Local Delivery of Therapeutics to the Inner Ear: The State of the Science

BACKGROUND: Advances in the understanding of the genetic and molecular etiologies of inner ear disorders have enabled the identification of therapeutic targets and innovative delivery approaches to the inner ear. As this field grows, the need for knowledge about effective delivery of therapeutics to the inner ear has become a priority. This review maps all clinical and pre-clinical research published in English in the field to date, to guide both researchers and clinicians about local drug delivery methods in the context of novel therapeutics. METHODS: A systematic search was conducted using customized strategies in Cochrane, pubmed and EMBASE databases from inception to 30/09/2018. Two researchers undertook study selection and data extraction independently. RESULTS: Our search returned 12,200 articles, of which 837 articles met the inclusion criteria. 679 were original research and 158 were reviews. There has been a steady increase in the numbers of publications related to inner ear therapeutics delivery over the last three decades, with a sharp rise over the last 2 years. The intra-tympanic route accounts for over 70% of published articles. Less than one third of published research directly assesses delivery efficacy, with most papers using clinical efficacy as a surrogate marker. CONCLUSION: Research into local therapeutic delivery to the inner ear has undergone a recent surge, improving our understanding of how novel therapeutics can be delivered. Direct assessment of delivery efficacy is challenging, especially in humans, and progress in this area is key to understanding how to make decisions about delivery of novel hearing therapeutics

Clustering Analysis of SAGE Data using a Poisson Approach

Serial analysis of gene expression (SAGE) data have been poorly exploited by clustering analysis owing to the lack of appropriate statistical methods that consider their specific properties. We modeled SAGE data by Poisson statistics and developed two Poisson-based distances. Their application to simulated and experimental mouse retina data show that the Poisson-based distances are more appropriate and reliable for analyzing SAGE data compared to other commonly used distances or similarity measures such as Pearson correlation or Euclidean distance.Statistic

Early phase trials of novel hearing therapeutics: Avenues and opportunities

Novel hearing therapeutics are rapidly progressing along the innovation pathway and into the clinical trial domain. Because these trials are new to the hearing community, they come with challenges in terms of trial design, regulation and delivery. In this paper, we address the key scientific and operational issues and outline the opportunities for interdisciplinary and international collaboration these trials offer. Vital to the future successful implementation of these therapeutics is to evaluate their potential for adoption into healthcare systems, including consideration of their health economic value. This requires early engagement with all stakeholder groups along the hearing innovation pathway

What has been researched in childhood obstructive sleep-disordered breathing: a systematic review

BACKGROUND: Despite recent clinical guideline development, the best pathway of care for children with symptoms of obstructive sleep-disordered breathing (oSDB) is still debated. This systematic review aims to map research in childhood oSDB conducted so far, to support further guideline development, identify evidence gaps and guide future research. METHODS: Systematic search of PubMed, Embase, and Cochrane Library from inception to 26 November 2015. All publications on childhood oSDB were included, irrespective of type and language. The annual number of publications in the field of oSDB was counted over all years; for those published since 1 January 2011 (i.e. date of latest literature search of American Academy of Pediatrics guideline), total and annual numbers of publications across main research themes and methodologies were calculated. RESULTS: Of the 7637 unique records retrieved, 5871 publications were eligible for inclusion. There is an increase in annual publications since 2000, with 46% published since 2011. Most (61%) publications focused on individual treatment modalities, incidence or prognosis. Few (2.7%) publications focused on health service delivery, outcomes and health economics. 78.5% of publications were observational, 2.4% were randomised controlled trials and 0.4% used a qualitative approach as their main methodology. CONCLUSIONS: A recent surge in research activity in childhood oSDB has improved the knowledge base for this condition; the lack of health services, health economics and outcomes research however impacts on the applicability of evidence informing current guidance and leaves important questions for future research

Prognostic factors for outcomes of idiopathic sudden sensorineural hearing loss: protocol for the SeaSHeL national prospective cohort study

INTRODUCTION: The mainstay of treatment for idiopathic sudden sensorineural hearing loss (SSNHL) includes oral steroids, intratympanic steroid injections or a combination of both. The National Institute for Health and Care Excellence, in their recent hearing loss guidelines, highlighted the paucity of evidence assessing the comparative effectiveness of these treatments; and the National Institute for Health Research (NIHR) Health Technology Assessment Programme has since released a commissioned call for a trial to identify the most effective route of administration of steroids as a first-line treatment for idiopathic SSNHL. For such trials to be run effectively, reliable information is needed on patients with SSNHL: where they present, numbers, demographics, treatment pathways, as well as outcomes. This study will collect these data in a nationwide cohort study of patients presenting with SSNHL across 97 National Health Service (NHS) trusts. The study will be delivered through ear, nose and throat (ENT) trainee networks, the NIHR Clinical Research Network (CRN) Audiology Champions and the NIHR CRN. Importantly, this study will also provide a dataset to develop a prognostic model to predict recovery for patients with idiopathic SSNHL. The study objectives are to: (1) map the patient pathway and identify the characteristics of adult patients presenting to NHS ENT and hearing services with SSNHL, (2) develop a prognostic model to predict recovery for patients with idiopathic SSNHL and (3) establish the impact of idiopathic SSNHL on patients' quality of life (QoL). METHODS AND ANALYSIS: Study design: national multicentre prospective cohort study across 97 NHS trusts. INCLUSION CRITERIA: adult patients presenting to NHS ENT and hearing services with SSNHL. OUTCOMES: change in auditory function; change in QoL score. ANALYSIS: multivariable prognostic model, using prespecified candidate predictors. Mean change in QoL scores will be calculated from initial presentation to follow-up. ETHICS AND DISSEMINATION: Health Research Authority and NHS Research Ethics Committee approved the study. Publication will be on behalf of study sites and collaborators. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04108598)

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records

Background : The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. Methods : We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). Results : From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. Conclusions : While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records

BACKGROUND: The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. METHODS: We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). RESULTS: From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. CONCLUSIONS: While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management

The eventization of leisure and the strange death of alternative Leeds

The communicative potential of city spaces as leisure spaces is a central assumption of political activism and the creation of alternative, counter-cultural and subcultural scenes. However, such potential for city spaces is limited by the gentrification, privatization and eventization of city centres in the wake of wider societal and cultural struggles over leisure, work and identity formation. In this paper, we present research on alternative scenes in the city of Leeds to argue that the eventization of the city centre has led to a marginalization and of alternative scenes on the fringes of the city. Such marginalization has not caused the death of alternative Leeds or political activism associated with those scenes—but it has changed the leisure spaces (physical, political and social) in which alternative scenes contest the mainstream