Nasal Airway Obstruction Study (NAIROS): a phase III, open-label, mixed-methods, multicentre randomised controlled trial of septoplasty versus medical management of a septal deviation with nasal obstruction

Background Septoplasty (surgery to straighten a deviation in the nasal septum) is a frequently performed operation worldwide, with approximately 250,000 performed annually in the US and 22,000 in the UK. Most septoplasties aim to improve diurnal and nocturnal nasal obstruction. The evidence base for septoplasty clinical effectiveness is hitherto very limited. Aims To establish, and inform guidance for, the best management strategy for individuals with nasal obstruction associated with a deviated septum. Methods/design A multicentre, mixed-methods, open label, randomised controlled trial of septoplasty versus medical management for adults with a deviated septum and a reduced nasal airway. Eligible patients will have septal deflection visible at nasendoscopy and a nasal symptom score ≥ 30 on the NOSE questionnaire. Surgical treatment comprises septoplasty with or without reduction of the inferior nasal turbinate on the anatomically wider side of the nose. Medical management comprises a nasal saline spray followed by a fluorinated steroid spray daily for six months. The recruitment target is 378 patients, recruited from up to 17 sites across Scotland, England and Wales. Randomisation will be on a 1:1 basis, stratified by gender and severity (NOSE score). Participants will be followed up for 12 months post randomisation. The primary outcome measure is the total SNOT-22 score at 6 months. Clinical and economic outcomes will be modelled against baseline severity (NOSE scale) to inform clinical decision-making. The study includes a recruitment enhancement process, and an economic evaluation. Discussion The NAIROS trial will evaluate the clinical effectiveness and cost-effectiveness of septoplasty versus medical management for adults with a deviated septum and symptoms of nasal blockage. Identifying those individuals most likely to benefit from surgery should enable more efficient and effective clinical decision-making, and avoid unnecessary operations where there is low likelihood of patient benefit

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Feasibility of trial procedures for a randomised controlled trial of a community based group exercise intervention for falls prevention for visually impaired older people: the VIOLET study

Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial

Occupational, domestic and environmental mesothelioma risks in the British population: a case–control study

We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8–96.8) for carpenters (LR 1 in 17), 17.1 (10.3–28.3) for plumbers, electricians and painters, 7.0 (3.2–15.2) for other construction workers, 15.3 (9.0–26.2) for other recognised high-risk occupations and 5.2 (3.1–8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (∼1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3–3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture

Occupational cancer in Britain: Statistical methodology

An approach using the attributable fraction (AF) has been developed to estimate the current burden of occupational cancer in Britain. The AF combines the relative risk (RR) associated with exposure with the proportion exposed. For each cancer–exposure pairing, the RR is selected from key epidemiological literature such as an industry, or population-based study, meta-analysis or review. The CARcinogen EXposure (CAREX) database provides point estimates for the number of workers exposed to a range of carcinogens; alternative sources are national surveys such as the Labour Force Survey and Census of Employment. The number of workers exposed are split between high and low exposure levels matched to appropriate RRs from the literature. The relevant period for cancer development during which exposure occurred is defined as the risk exposure period (REP). Estimation of the numbers ever exposed over the REP takes into account the changes in the number of people employed in primary and manufacturing industry and service sectors in Britain where appropriate, and adjustment is made for staff turnover over the period and for life expectancy. National estimates of the population ever of working age during the REP are used for the proportion denominator. Strategies have been developed to combine exposure AFs correctly while avoiding double counting and minimising bias. The AFs are applied to national cancer deaths and registrations to obtain occupation-attributable cancer numbers. The methods are adaptable for other diseases and other geographies, and are also adaptable to more sophisticated modelling if better exposure and dose–response data are available

Disclosing ambiguous gene aliases by automatic literature profiling

Submitted by Nuzia Santos ([email protected]) on 2015-01-14T10:55:18Z No. of bitstreams: 1 Disclosing ambiguous gene aliases by automatic.pdf: 217573 bytes, checksum: ce54aa2c4ea49eb989f9e7308d827ce6 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-01-14T10:55:25Z (GMT) No. of bitstreams: 1 Disclosing ambiguous gene aliases by automatic.pdf: 217573 bytes, checksum: ce54aa2c4ea49eb989f9e7308d827ce6 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-01-14T11:01:59Z (GMT) No. of bitstreams: 1 Disclosing ambiguous gene aliases by automatic.pdf: 217573 bytes, checksum: ce54aa2c4ea49eb989f9e7308d827ce6 (MD5)Made available in DSpace on 2015-01-14T11:01:59Z (GMT). No. of bitstreams: 1 Disclosing ambiguous gene aliases by automatic.pdf: 217573 bytes, checksum: ce54aa2c4ea49eb989f9e7308d827ce6 (MD5) Previous issue date: 2010Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Centro de Excelência em Bioinformática. Belo Horizonte, MG, Brasil/Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Grupo de Genômica e Biologia Computacional. Belo Horizonte, MG, BrasilGlaxoSmithKline Moore Dr. Molecular Discovery Research. Research Triangle Park, NC, USAFundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Centro de Excelência em Bioinformática. Belo Horizonte, MG, Brasil/Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Grupo de Genômica e Biologia Computacional. Belo Horizonte, MG, BrasilBackground Retrieving pertinent information from biological scientific literature requires cutting-edge text mining methods which may be able to recognize the meaning of the very ambiguous names of biological entities. Aliases of a gene share a common vocabulary in their respective collections of PubMed abstracts. This may be true even when these aliases are not associated with the same subset of documents. This gene-specific vocabulary defines a unique fingerprint that can be used to disclose ambiguous aliases. The present work describes an original method for automatically assessing the ambiguity levels of gene aliases in large gene terminologies based exclusively in the content of their associated literature. The method can deal with the two major problems restricting the usage of current text mining tools: 1) different names associated with the same gene; and 2) one name associated with multiple genes, or even with non-gene entities. Important, this method does not require training examples. Results Aliases were considered “ambiguous” when their Jaccard distance to the respective official gene symbol was equal or greater than the smallest distance between the official gene symbol and one of the three internal controls (randomly picked unrelated official gene symbols). Otherwise, they were assigned the status of “synonyms”. We evaluated the coherence of the results by comparing the frequencies of the official gene symbols in the text corpora retrieved with their respective “synonyms” or “ambiguous” aliases. Official gene symbols were mentioned in the abstract collections of 42 % (70/165) of their respective synonyms. No official gene symbol occurred in the abstract collections of any of their respective ambiguous aliases. In overall, querying PubMed with official gene symbols and “synonym” aliases allowed a 3.6-fold increase in the number of unique documents retrieved. Conclusions These results confirm that this method is able to distinguish between synonyms and ambiguous gene aliases based exclusively on their vocabulary fingerprint. The approach we describe could be used to enhance the retrieval of relevant literature related to a gen

Randomised controlled trial of welfare rights advice accessed via primary health care: pilot study [ISRCTN61522618]

BACKGROUND: Little research has directly evaluated the impact of increasing financial or material resources on health. One way of assessing this lies with assisting people to obtain full welfare benefit entitlements. In 2000–1, 2.3 million pensioners were living in poverty in the UK and estimates suggest that around one million do not claim the financial support to which they are entitled. The effectiveness of welfare rights advice services delivered via primary health care to promote health and reduce health inequalities is unknown. METHODS: The main objectives of this study were to assess the feasibility and acceptability of a randomised controlled trial of welfare rights advice in a community setting and identify appropriate health and social outcome measures in order to plan a definitive trial. This was a single blind, community-based, pilot randomised controlled trial. 126 men and women aged 60 years and over, recruited from 4 general practices in Newcastle upon Tyne, UK, participated. The intervention comprised a structured welfare rights assessment followed by active assistance with welfare benefit claims over the following 24 months. The control group received the intervention after a six month delay. A range of socio-economic, health, behavioural and psycho-social outcomes were measured. RESULTS: 126 out of 400 people invited agreed to participate and 109 were followed up at 24 months. Both the intervention and research procedures were feasible and acceptable to participants and professionals involved. 68 (58%) of all participants received a welfare benefit award (31 financial, 16 non-financial and 21 both). Median time to receipt of benefits from initial assessment was 14 (range 1 to 78) weeks and median financial award was £55 (€81, $98) per household per week. There was little evidence of health-related differences between groups or over time, which could be due to limitations of the study design. CONCLUSION: Modification of the study design, including selection of study participants, timing of interventions and length of follow up are recommended for a definitive trial. More appropriate health and psycho-social outcome measures relevant to the elderly population should be sought, particularly focussing on those issues highlighted in the accompanying qualitative study