An FCER2 polymorphism is associated with increased oral leukotriene receptor antagonists and allergic rhinitis prescribing

The Fc Fragment of IgE Receptor II (FCER2) is expressed in several cells, such as macrophages, eosinophils, B cells and platelets. Studies have suggested that FCER2 is involved in the regulation of IgE responses, growth and differentiation of T and B cells, cellular adherence and antigen presentation. The activation of the receptor results in down-regulation of IgE-mediated immune responses. Two studies found that individuals with asthma on inhaled corticosteroids (ICS) with the CC genotype of the rs28364072 polymorphism had a two-fold increased odds of asthma exacerbations and uncontrolled asthma than individuals with at least one copy of the T allele (CT/TT)

Prior elicitation of the efficacy and tolerability of Methotrexate and Mycophenolate Mofetil in Juvenile Localised Scleroderma

BackgroundEvidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered.MethodsAn international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial.ResultsAn international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF.ConclusionsKey factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available

Why Don't We Ask? A Complementary Method for Assessing the Status of Great Apes

Species conservation is difficult. Threats to species are typically high and immediate. Effective solutions for counteracting these threats, however, require synthesis of high quality evidence, appropriately targeted activities, typically costly implementation, and rapid re-evaluation and adaptation. Conservation management can be ineffective if there is insufficient understanding of the complex ecological, political, socio-cultural, and economic factors that underlie conservation threats. When information about these factors is incomplete, conservation managers may be unaware of the most urgent threats or unable to envision all consequences of potential management strategies. Conservation research aims to address the gap between what is known and what knowledge is needed for effective conservation. Such research, however, generally addresses a subset of the factors that underlie conservation threats, producing a limited, simplistic, and often biased view of complex, real world situations. A combination of approaches is required to provide the complete picture necessary to engage in effective conservation. Orangutan conservation (Pongo spp.) offers an example: standard conservation assessments employ survey methods that focus on ecological variables, but do not usually address the socio-cultural factors that underlie threats. Here, we evaluate a complementary survey method based on interviews of nearly 7,000 people in 687 villages in Kalimantan, Indonesia. We address areas of potential methodological weakness in such surveys, including sampling and questionnaire design, respondent biases, statistical analyses, and sensitivity of resultant inferences. We show that interview-based surveys can provide cost-effective and statistically robust methods to better understand poorly known populations of species that are relatively easily identified by local people. Such surveys provide reasonably reliable estimates of relative presence and relative encounter rates of such species, as well as quantifying the main factors that threaten them. We recommend more extensive use of carefully designed and implemented interview surveys, in conjunction with more traditional field methods

Children with asthma and eczema carrying filaggrin loss-of-function mutations have increased antibiotic use through to adulthood

Summary boxChildren with asthma and eczema carrying FLG loss-of-function mutations have greater risk of antibiotic use.The dysfunctional skin barrier might contribute to increased bacterial entry, reflected in increased antibiotic use</p

Cutaneous squamous cell carcinoma in epidermolysis bullosa:A 28-year retrospective study

Epidermolysis bullosa (EB), notably severe recessive dystrophic EB (RDEB-S), is associated with increased risk of aggressive mucocutaneous squamous cell carcinomas, the major cause of mortality in early adulthood. This observational, retrospective case review describes a series of EB patients with cutaneous squamous cell carcinomas over a 28-year period. Forty-four EB patients with squamous cell carcinomas were identified with a total of 221 primary tumours. They comprised: 31 (70%) with RDEB-S, 4 (9%) with other RDEB subtypes, 5 (11.4%) with dominant dystrophic EB, 3 (6.8%) with intermediate junctional EB and 1 (2.3%) with Kindler EB. Squamous cell carcinomas occurred earlier in RDEB-S (median age 29.5 years; age range 13–52 years) than other groups collectively (median age 47.1 years; age range 30–89 years) and most had multiple tumours (mean 5.8; range 1–44). Squamous cell carcinoma-associated mortality was high in RDEB-S (64.5%), with median survival after first squamous cell carcinoma of 2.4 years (range 0.5–12.6 years), significantly lower than previous reports, highlighting the need for early surveillance and better treatments