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Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model. [ABSTRACT FROM AUTHOR]

Peatlands have often been neglected in Earth system models (ESMs). Where they are included, they are usually represented via a separate, prescribed grid cell fraction that is given the physical characteristics of a peat (highly organic) soil. However, in reality soils vary on a spectrum between purely mineral soil (no organic material) and purely organic soil, typically with an organic layer of variable thickness overlying mineral soil below. They are also dynamic, with organic layer thickness and its properties changing over time. Neither the spectrum of soil types nor their dynamic nature can be captured by current ESMs. Here we present a new version of an ESM land surface scheme (Joint UK Land Environment Simulator, JULES) where soil organic matter accumulation – and thus peatland formation, degradation and stability – is integrated in the vertically resolved soil carbon scheme. We also introduce the capacity to track soil carbon age as a function of depth in JULES and compare this to measured peat age–depth profiles. The new scheme is tested and evaluated at northern and temperate sites. This scheme simulates dynamic feedbacks between the soil organic material and its thermal and hydraulic characteristics. We show that draining the peatlands can lead to significant carbon loss, soil compaction and changes in peat properties. However, negative feedbacks can lead to the potential for peatlands to rewet themselves following drainage. These ecohydrological feedbacks can also lead to peatlands maintaining themselves in climates where peat formation would not otherwise initiate in the model, i.e. displaying some degree of resilience. The new model produces similar results to the original model for mineral soils and realistic profiles of soil organic carbon for peatlands. We evaluate the model against typical peat profiles based on 216 northern and temperate sites from a global dataset of peat cores. The root-mean-squared error (RMSE) in the soil carbon profile is reduced by 35 %–80 % in the best-performing JULES-Peat simulations compared with the standard JULES configuration. The RMSE in these JULES-Peat simulations is 7.7–16.7 kg C m -3 depending on climate zone, which is considerably smaller than the soil carbon itself (around 30–60 kg C m -3). The RMSE at mineral soil sites is also reduced in JULES-Peat compared with the original JULES configuration (reduced by ∼ 30 %–50 %). Thus, JULES-Peat can be used as a complete scheme that simulates both organic and mineral soils. It does not require any additional input data and introduces minimal additional variables to the model. This provides a new approach for improving the simulation of organic and peatland soils and associated carbon-cycle feedbacks in ESMs. [ABSTRACT FROM AUTHOR]

Peatlands have often been neglected in Earth System Models (ESMs). Where they are included, they are usually represented via a separate, prescribed grid cell fraction that is given the physical characteristics of a peat (highly organic) soil. However, in reality soils vary on a spectrum between purely mineral soil (no organic material), and purely organic soil, typically with an organic layer of variable thickness overlying mineral soil below. They are also dynamic, with organic layer thickness and its properties changing over time. Neither the spectrum of soil types nor their dynamic nature can be captured by current ESMs. Here we present a new version of an ESM land surface scheme (Joint UK Land Environment Simulator, JULES) where soil organic matter accumulation - and thus peatland formation, degradation and stability - is integrated in the vertically-resolved soil carbon scheme. We also introduce the capacity to track soil carbon age as a function of depth in JULES, and compare this to measured peat age-depth profiles. This scheme simulates dynamic feedbacks between the soil organic material and its thermal and hydraulic characteristics. We show that draining the peatlands can lead to significant carbon loss along with soil compaction and changes in peat properties. However, negative feedbacks can lead to the potential for peatlands to rewet themselves following drainage. These ecohydrological feedbacks can also lead to peatlands maintaining themselves in climates where peat formation would not otherwise initiate in the model, i.e. displaying some degree of resilience. The new model produces similar results to the original model for mineral soils, and realistic profiles of soil organic carbon for peatlands. In particular the best performing configurations had root mean squared error (RMSE) in carbon density for peat sites of 7.7-16.7 kgC m−3 depending on climate zone, when compared against typical peat profiles based on 216 sites from a global dataset of peat cores. This error is considerably smaller than the soil carbon itself (around 30-60 kgC m−3) and reduced by 35-80 % compared with standard JULES. The RMSE at mineral soil sites is also smaller in JULES-Peat than JULES itself (reduced by ~30-50 %). Thus JULES-Peat can be used as a complete scheme that simulates both organic and mineral soils. It does not require any additional input data and introduces minimal additional variables to the model. This provides a new approach for improving the simulation of organic and peatland soils, and associated carbon-cycle feedbacks in ESMs, which other land surface models could follow. [ABSTRACT FROM AUTHOR]

Background: Effective management of patients with chronic kidney disease (CKD) relies on timely detection of clinical deterioration towards end stage kidney failure. We aimed to design an electronic Patient-Reported Outcome Measure (ePROM) system, which would allow patients with advanced CKD (pre-dialysis) to: (i) remotely self-report their symptoms using a simple and secure online platform; (ii) share the data with the clinical team in real-time via the electronic patient record to help optimise care. We adopted a staged development process which included: a systematic review of PROMs used in CKD; formation of a co-design team; prototype system design/development, user acceptance testing and refinement; finalisation of the system for testing in a pilot/feasibility trial. Results: A co-design team was convened, including patients with lived experience of CKD; clinical team members; IT/Informatics experts; academics; and Birmingham Clinical Trials Unit representatives. A prototype system was developed and iterative changes made before finalisation during a series of operational meetings. The system allows patients to remotely self-report their symptoms; provides tailored self-management advice; allows monitoring of real-time patient ePROM data; sends automated notifications to the patient/clinical team in the advent of a severe symptom report; and incorporates longitudinal ePROM symptom data into the electronic patient record. Feasibility of the system will be evaluated as part of the National Institute for Health Research funded RePROM (Renal electronic Patient-Reported Outcome Measure) pilot trial (ISRCTN12669006). Conclusions: Routine ePROM collection with real-time feedback has the potential to improve outcomes and reduce health service costs. We have successfully developed a trial-ready ePROM system for advanced CKD, the feasibility of which is currently being explored in a pilot trial. Assuming feasibility is demonstrated, formal evaluation of efficacy will take place in a future multi-centre randomised controlled trial. [ABSTRACT FROM AUTHOR]