Creating new guidelines on how best to treat foot symptoms in people with EB.

Epidermolysis bullosa (EB) is a complex rare condition that affects the skin and many parts of the body. Those born with EB have skin so fragile they are called 'butterfly children', their skin is quite simply as fragile as the wing of a butterfly. In the UK it is estimated that there are more than 5,000 people living with EB and 500,000 worldwide. Little clinical guidance for care existed until DEBRA International started a programme to develop clinical practice guidelines (CPGs). There were no previous guidelines and few published studies on foot care in EB so treatment decisions were largely based on individual opinion and experience. The panel - made up of clinical experts and people living with EB representing Australia, the UK, and the USA - aimed to describe foot problems in people of all ages with EB, and summarise current evidence and management. The authors used a logical podiatric (foot) care literature review focussed on patients with EB. The authors found that the evidence in this area was limited but several interventions (treatments) currently practised by podiatrists show positive outcomes. The study allowed the group to make recommendations on how to treat foot and nail disorders in patients with EB. Furthermore, the authors concluded that further research is needed. This is a summary of the study: Foot care in epidermolysis bullosa: evidence-based guideline.

Foot care in epidermolysis bullosa: evidence-based guideline.

This guideline was designed to provide service providers and users with an evidence-based set of current best practice guidelines for people and their families and carers, living with epidermolysis bullosa (EB). A systematic literature review relating to the podiatric care of patients with EB was undertaken. Search terms were used, for which the most recent articles relating to podiatric treatment were identified from as early as 1979 to the present day, across seven electronic search engines: MEDLINE, Wiley Online Library, Google Scholar, Athens, ResearchGate, Net and PubFacts.com. The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used. The first guideline draft was analysed and discussed by clinical experts, methodologists and patients and their representatives at four panel meetings. The resulting document went through an external review process by a panel of experts, other healthcare professionals, patient representatives and lay reviewers. The final document will be piloted in three different centres in the U.K. and Australia. Following an EB community international survey the outcomes indicated six main areas that the community indicated as a priority to foot management. These include blistering and wound management, exploring the most suitable footwear and hosiery for EB, management of dystrophic nails, hyperkeratosis (callus), maintaining mobility and fusion of toes (pseudosyndactyly). The evidence here is limited but several interventions currently practised by podiatrists show positive outcomes.

Psychosocial recommendations for the care of children and adults with epidermolysis bullosa and their family: evidence based guidelines.

Epidermolysis Bullosa (EB) is a group of rare genetic disorders resulting in skin fragility and other symptoms. Commissioned by DEBRA International and funded by DEBRA Norway, this evidence-bases guideline provides recommendations to optimise psychosocial wellbeing in EB.An international multidisciplinary panel of social and health care professionals (HCP) and people living with EB was formed. A systematic international literature review was conducted by the panel following the Scottish Intercollegiate Guidelines Network (SIGN) methodology. The resulting papers underwent systematic selection and critique processes. Included papers were allocated to 6 different outcome groups to allow data synthesis and exploration: quality of life, coping, family, wellbeing, access to HCP and pain. Based on the evidence in those papers, recommendations were made for individuals living with EB, family and caregivers and HCP working in the field.Few studies have investigated interventions and which factors lead to better outcomes, but general recommendations can be made. EB is a complex disease impacting enormously on every aspect of psychosocial life. People and families living with EB need access to multidisciplinary support, including psychological guidance, in order to improve quality of life and psychosocial wellbeing. Interventions should stimulate social participation to prevent isolation. People with EB and their families should be able to access a supportive network. HCP should be well supported and educated about the complexity of EB. They should work collaboratively with those around the individual with EB (e.g. schools, employers etc.) to provide psychosocial opportunity and care.Attention should be paid to the psychosocial impact of EB as well as physical needs. Directions for research are indicated.

Subanaesthetic ketamine and altered states of consciousness in humans.

BACKGROUND: Despite its designation as a 'dissociative anaesthetic,' the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine. METHODS: High-density EEG was recorded in 15 human volunteers before, during, and after subanaesthetic ketamine infusion (0.5 mg kg-1 over 40 min), with self-reported measures of altered states of consciousness obtained after ketamine exposure. Sensor- and source-level EEG changes were analysed with a focus on spectral power and regional changes. RESULTS: Ketamine-induced altered states were characterised predominantly by dissociative experiences such as disembodiment and ego transcendence; sensory disturbances were also common. Ketamine broadly decreased low-frequency power, with mean reductions largest at alpha (8-12 Hz) in parietal (-0.94 dB, P<0.001) and occipital (-1.8 dB, P<0.001) channel clusters. Significant decreases in alpha were identified in the precuneus and temporal-parietal junction. CONCLUSIONS: Ketamine induces altered states of consciousness during periods of reduced alpha power in the precuneus and temporal-parietal junction. Modulation of these temporal-parietal loci are candidate mechanisms of the psychoactive effects of ketamine, given that this region is involved in multisensory integration, body representation, and consciousness.

Different experiences and perspectives between head and neck cancer patients and their care-givers on their daily impact of a gastrostomy tube.

BACKGROUND: Gastrostomy feeding in head and neck cancer patients is recognised standard practice in some cancer centres with beneficial effects on outcomes for appropriately selected patients. However, the impact on patients and care-givers needs consideration. The present study aimed to understand the daily impact of gastrostomy feeding on head and neck cancer patients and their care-givers to identify improvements to services. METHODS: Twenty-one adult patients were randomly selected from the Head and Neck centre at University College London Hospital. Six head and neck cancer patients and three care-givers participated in focus groups. The sessions were recorded, fully transcribed and qualitatively thematically analysed, and the resulting data were tabulated. RESULTS: Patients and care-givers expressed opposite experiences within knowledge and understanding of why the tube was necessary; their personal perceptions and objectives of nutritional support. Themes expressing similar experiences included: developing positive coping strategies; preventing nutritional decline; tube dependency; dentures; finance; active care; and psychological support. Furthermore, both groups expressed the benefits of retaining a support network for rehabilitation with the hospital-based specialist team. Also patients and carers recognised that the gastrostomy tube helped patient survival and, with timely dietetic management, helped them wean off the tube reliance with more confidence. CONCLUSIONS: It is essential that patients and care-givers attend pretreatment clinics to discuss nutritional support via the artificial route; their quality of life can be enhanced if guided through a specialist support pathway based at the clinical site where they initiated their care, with links to key agencies.

Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism.

Bisphosphonates (BPs) are an important class of antiresorptive drugs used in the treatment of bone diseases, including osteoporosis. Although their mechanism of action has not been identified at the molecular level, there is substantial evidence that BPs can have a direct effect on osteoclasts by mechanisms that may lead to osteoclast cell death by apoptosis. BPs can also inhibit proliferation and cause cell death in macrophages in vitro. We have now shown that the toxic effect of BPs on macrophages is also due to the induction of apoptotic, rather than necrotic, cell death. Morphological and biochemical features that are definitive of apoptosis (chromatin condensation, nuclear fragmentation, and endonuclease-mediated internucleosomal cleavage of DNA) could be identified in mouse macrophage-like J774 and RAW264 cells, following treatment with 100 microM pamidronate, alendronate, and ibandronate for 24 h or more. Clodronate was much less potent, even at 2000 microM, while 2000 microM etidronate did not cause apoptosis. Apoptosis was not due to increased synthesis of nitric oxide and could not be prevented by inhibitors of nitric oxide synthases. Since macrophages, like osteoclasts, are particularly susceptible to BPs, these observations support the recent suggestion that the mechanism by which BPs inhibit bone resorption may involve osteoclast apoptosis. Furthermore, the macrophage-like cell lines used in this study may be a convenient model with which to identify the molecular mechanisms by which BPs promote apoptosis in osteoclasts. Induction of macrophage apoptosis by BPs in vivo may also account, at least in part, for the anti-inflammatory properties of BPs as well as the ability of BPs to cause an acute phase response.