Role of ABCB1 C3435T variant in response to antiepileptic drugs in epilepsy: a review

Over-expression of P-glycoprotein (P-gp), the encoded product of the ATP-binding cassette (ABC), sub-family B, member 1 (ABCB1/MDR1) gene, plays an important role in mediating multidrug resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation may in part explain inter-individual differences in phenotype-genotype relationships in the pharmacological response of epilepsy patients to AEDs. The synonymous C3435T polymorphism is one of the most common allelic variants in the ABCB1/MDR1 gene, proposed in the causation of refractory epilepsy. Many studies have shown the relationship between C3435T polymorphism and refractoriness to AEDs in epilepsy. However, there is controversy between the findings of various studies, that is, whether ABCB1/MDR1 C3435T gene polymorphism is associated with response to AEDs in epilepsy patients. This review provides a background and discusses the results of investigations on possible confounding factors affecting the interpretation and implementation of association studies in this area

A man with hypophosphataemia

Case report; A section on BMJ, 2011, v. 342, p. 715published_or_final_versio

An exploration of running as metaphor, methodology, material through the RUN! RUN! RUN! Biennale #r3fest 2016

© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group. This paper runs through the RUN! RUN! RUN! Biennale’s origins, curatorial framework, and its potential future impact. Also known as #r3fest, the Biennale is an interdisciplinary programme exploring running as an arts and humanities discourse. Exploring running as creative material, metaphor and methodology, the 2016 edition threw a spotlight on live art, drawings, films and activities by practitioners in the arts, academia and NGOs which have hitherto been underrepresented in dominant discourses in the emerging field of ‘Running Studies’. The paper raises philosophical questions about the synergies between arts and sport. Examples of practice across visual and performance art locate RUN! RUN! RUN! and the paper in the area of curating, suggesting a new way of considering how arts and sports can be organized, considered and presented. My aims include:  widening the current discourse,  inviting curators, artists and academics to consider and generate yet other experiments that activate running as creative material, metaphor and methodology, and challenging existing assumptions in the arts about sport

Using behavioural insights to increase HIV self-sampling kit returns: a randomized controlled text message trial to improve England's HIV self-sampling service.

OBJECTIVES: The aim of the study was to determine whether behaviourally informed short message service (SMS) primer and reminder messages could increase the return rate of HIV self-sampling kits ordered online. METHODS: The study was a 2 × 2 factorial design randomized control trial. A total of 9585 individuals who ordered a self-sampling kit from www.freetesting.hiv different SMS combinations: 1) standard reminders sent days 3 and 7 after dispatch (control); 2) primer sent 1 day after dispatch plus standard reminders; 3) behavioural insights (BI) reminders (no primer); or 4) primer plus BI reminders. The analysis was restricted to individuals who received all messages (n = 8999). We used logistic regression to investigate independent effects of the primer and BI reminders and their interaction. We explored the impact of sociodemographic characteristics on kit return as a secondary analysis. RESULTS: Those who received the primer and BI reminders had a return rate 4% higher than that of those who received the standard messages. We found strong evidence of a positive effect of the BI reminders (odds ratio 1.13; 95% confidence interval 1.04-1.23; P = 0.003) but no evidence for an effect of the primer, or for an interaction between the two interventions. Odds of kit return increased with age, with those aged ≥ 65 years being almost 2.5 times more likely to return the kit than those aged 25-34 years. Men who have sex with men were 1.5-4.5 times more likely to return the kit compared with other sexual behaviour and gender identity groups. Non-African black clients were 25% less likely to return the kit compared with other ethnicities. CONCLUSIONS: Adding BI to reminder messages was successful in improving return rates at no additional cost

Qualitative study exploring which research outcomes best reflect women's experiences of heavy menstrual bleeding: stakeholder involvement in development of a core outcome set.

OBJECTIVE: This work contributed to the development of a core outcome set (COS) for heavy menstrual bleeding (HMB). The objective was to determine which research outcomes best reflect how HMB affects women's lives and to identify additional research outcomes, not previously reported. It was important to explore and record participants' reasoning for prioritising outcomes and use this information to reinforce the patients' voice during later phases of the COS development. DESIGN: Patient workshop discussions and telephone interviews. SETTING: East London teaching hospital. PARTICIPANTS: Inclusion criteria were that participants must be over 18 years old, that either they or their partner had a history of HMB and that they had a good understanding of written and spoken English. RESULTS: 41 participants were recruited for the study. 8 women and 1 man completed the study. The eight female participants were representative of the different underlying causes and treatments for HMB. Participants ranged in age from their early 20s to their 60s and represented a range of ethnic groups. The five main themes that were identified as being important to patients were: 'restriction', 'relationships and isolation', 'emotions and self-perception', 'pain' and 'perceptions of treatment'. We identified eight coding nodes that did not correspond with our list of previously reported outcomes in studies of HMB. These nodes were consolidated and became five new outcomes for potential inclusion in the COS. CONCLUSIONS: HMB stops women living their lives as they would wish. It affects their relationships, education, careers, reproductive wishes, social life and mental health. This is a condition of girls and women in the prime of their lives, but for many, the constant threat of a heavy period starting means that they sacrifice that freedom. The societal and economic costs of women being incapacitated every month has an effect on everyone. TRIAL REGISTRATION: The COS study is registered with the COMET (Core Outcome Measures in Effectiveness Trials) Initiative-project reference number 789

Running into each other: Run! run! run! a festival and a collaboration

© The Author(s) 2017. artists and geographers frequently work together. the following essay explores one such on-going collaboration. centering on a festival organized by an artist and a geographer, it explores the productive antagonisms that working through and along disciplinary borders produces

Respiratory viral infections in exacerbation of chronic airway inflammatory diseases: novel mechanisms and insights from the upper airway epithelium.

Respiratory virus infection is one of the major sources of exacerbation of chronic airway inflammatory diseases. These exacerbations are associated with high morbidity and even mortality worldwide. The current understanding on viral-induced exacerbations is that viral infection increases airway inflammation which aggravates disease symptoms. Recent advances in in vitro air-liquid interface 3D cultures, organoid cultures and the use of novel human and animal challenge models have evoked new understandings as to the mechanisms of viral exacerbations. In this review, we will focus on recent novel findings that elucidate how respiratory viral infections alter the epithelial barrier in the airways, the upper airway microbial environment, epigenetic modifications including miRNA modulation, and other changes in immune responses throughout the upper and lower airways. First, we reviewed the prevalence of different respiratory viral infections in causing exacerbations in chronic airway inflammatory diseases. Subsequently we also summarized how recent models have expanded our appreciation of the mechanisms of viral-induced exacerbations. Further we highlighted the importance of the virome within the airway microbiome environment and its impact on subsequent bacterial infection. This review consolidates the understanding of viral induced exacerbation in chronic airway inflammatory diseases and indicates pathways that may be targeted for more effective management of chronic inflammatory diseases

Updated clinical recommendations for the use of tibolone in Asian women

Tibolone, which is indicated for the relief of climacteric symptoms and the prevention of osteoporosis in postmenopausal women, has a tissue-specific mode of action different to that of conventional hormone replacement therapy (HRT). A large proportion of Asian postmenopausal women experience symptoms that most frequently include musculoskeletal pain, insomnia, forgetfulness, hot flushes and sexual dysfunction, and there is a need to address their specific requirements. Recent studies show that, in comparison to HRT, tibolone is as effective in alleviating menopausal symptoms and preventing bone loss, has a greater positive effect on sexual dysfunction and is associated with less vaginal bleeding, but it is rarely mentioned in guidelines for menopausal treatment. Levels of awareness amongst women about treatments for menopausal symptoms vary between Asian countries but, even in countries where awareness is high, HRT usage is much lower than in the West. To provide a practical approach to the use of tibolone in Asian postmenopausal women, a panel of experts in the management of menopause from 11 Asia Pacific countries has developed recommendations for its use, based on the evidence from clinical studies published since 2005. However, as much of the clinical data reviewed are from international studies, the recommendations and the treatment algorithm presented here are widely applicable

Ethics roundtable debate: Child with severe brain damage and an underlying brain tumour

A young person presents with a highly malignant brain tumour with hemiparesis and limited prognosis after resection. She then suffers an iatrogenic cardiac and respiratory arrest that results in profound anoxic encephalopathy. A difference in opinion between the treatment team and the parent is based on a question of futile therapy. Opinions from five intensivists from around the world explore the differences in ethical and legal issues. A Physician-ethicist comments on the various approaches