The effect of high protein dosing in critically ill patients: an exploratory, secondary Bayesian analyses of the EFFORT Protein trial.

Background: The EFFORT Protein trial assessed the effect of high vs usual dosing of protein in adult ICU patients with organ failure. This study provides a probabilistic interpretation and evaluates heterogeneity in treatment effects (HTE).

Methods: We analysed 60-day all-cause mortality and time to discharge alive from hospital using Bayesian models with weakly informative priors.

Clinician assessment of kidney function from plasma creatinine values during critical illness: A scenario-based international multi-professional survey.

Purpose: During critical illness interpretation of serum creatinine is affected by non-steady state conditions, reduced creatinine generation, and altered distribution. We evaluated healthcare professionals' ability to adjudicate underlying kidney function, based on simulated creatinine values.

Methods: We developed an online survey, incorporating 12 scenarios with simulated trajectories of creatinine based on profiles of muscle mass, GFR and fluid balance using bespoke kinetic modelling.

Effects of Ionic Liquids on the Nucleofugality of Dimethyl Sulfide.

The nucleofugality of dimethyl sulfide was measured in solvent mixtures containing ionic liquids. The first-order rate constants of the solvolysis of sulfonium salts were determined in mixtures containing different proportions of 1-butyl-3-methylimidazolium (trifluoromethanesulfonyl)imide in ethanol, representing the first report on the solvolysis of a charged species in an ionic liquid. Temperature-dependent kinetic studies allowed determination of activation parameters and rationalization of observed solvent effects in different ionic liquid mixtures.

Distinct regulatory mechanisms by the nuclear Argonautes HRDE-1 and NRDE-3 in the soma of .

Unlabelled: RNA interference is a conserved silencing mechanism that depends on the generation of small RNA molecules that disrupt synthesis of their corresponding transcripts. Nuclear RNA interference is a unique process that triggers regulation through epigenetic alterations to the genome. This pathway has been extensively characterized in and involves the nuclear recruitment of H3K9 histone methyltransferases by the Argonautes HRDE-1 and NRDE-3.

In vitro activity of Western Australian honeys and Manuka honey against clinically important yeasts.

With the steady rise in antifungal resistance amongst clinically important yeasts, antifungal drug discovery remains of the utmost importance. To determine the potential of some honeys as alternative antifungal agents, we quantified the antifungal activity of 12 Western Australian honey samples, two Manuka honey samples and an artificial honey against 10 yeast isolates including clinical and reference strains. Results showed that the tested honeys varied in activity, and yeasts species also differed in susceptibility, with minimum inhibitory concentrations (MICs) determined by broth microdilution ranging from 8% to >44% w/v honey.

Prevalence and risk factors for milk allergy overdiagnosis in the BEEP trial cohort.

Background: Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA overdiagnosis and identify individual-level and primary care practice-level risk factors.

Methods: We analysed data from 1394 children born in England in 2014-2016 (BEEP trial, ISRCTN21528841).

Telephone consulting for 'Personalised Care and Support Planning' with people with long-term conditions: a qualitative study of healthcare professionals' experiences during COVID-19 restrictions and beyond.

Background: Personalised Care and Support Planning (PCSP) replaces conventional annual reviews for people with long-term conditions. It is designed to help healthcare professionals (HCPs) and patients engage in conversations as equals and collaboratively plan actions oriented to each patient's priorities, alongside biomedical concerns. Little is known about how the shift to remote consulting initiated with COVID-19 restrictions has impacted PCSP.

Effects of Ionic Liquids on the Nucleofugality of Bromide.

The nucleofugality of bromide was measured in solvent mixtures containing ionic liquids. The solvolysis rate constants of the bromides of well-defined electrofuges were determined in mixtures containing different proportions of 1-butyl-3-methylimidazolium (trifluoromethanesulfonyl)imide in ethanol. Temperature-dependent kinetic studies allowed an explanation of the observed solvent effects in different mixtures in terms of interactions in solution.

Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT).

Background: Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein.

Emollients for preventing atopic eczema: Cost-effectiveness analysis of the BEEP trial.

Background: Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy.

Objective: To determine the cost-effectiveness of daily all-over-body application of emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis.

The effects of ionic liquids on the ethanolysis of a chloroacenaphthene. Evaluation of the effectiveness of nucleofugality data to predict reaction outcome.

The reaction of a chlorobenzene in mixtures containing ethanol and eight different ionic liquids was investigated in order to understand the effects of varying proportions and constituent ions of an ionic liquid on the rate constant of the process. The results were found to be generally consistent with previously studied reactions of the same type, with small proportions of an ionic liquid resulting in a rate constant increase compared to ethanol and large proportions causing a rate constant decrease. Temperature dependent kinetic studies were used to interpret the changes in reaction outcome, particularly noting an entropic cost on moving to high proportions of ionic liquid, consistent with organisation of solvent around the transition state.

Comparison of Cystatin C and Creatinine in the Assessment of Measured Kidney Function during Critical Illness.

Background: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction.

Methods: To assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center.

Effectiveness and cost effectiveness of digital hearing aids in patients with tinnitus and hearing loss: a randomised feasibility trial (THE HUSH Trial).

Background: Education and advice is provided for tinnitus management in all UK audiology clinics. Sound therapy, including provision of hearing aids may be offered, but this is often dependent on a clinician's decision rather than UK policy. This inconsistent management reflects a lack of evidence around the effectiveness of hearing aids for tinnitus.

Emollients for prevention of atopic dermatitis: 5-year findings from the BEEP randomized trial.

Background: The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years.

Methods: 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls).

Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa.

Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF).

Antibacterial interactions between two monofloral honeys and several topical antiseptics, including essential oils.

Background: Honey has broad spectrum antibacterial activity against clinically important organisms and may be suitable for treating superficial bacterial infections. However, very little data are available describing potential interactions between honey and other topically applied agents such as antiseptics or essential oils.

Methods: Interactions between pairs of antibacterial agents were investigated by performing checkerboard assays and determining the fractional inhibitory concentration indices (FICIs).

In vitro antibacterial activity of Western Australian honeys, and manuka honey, against bacteria implicated in impetigo.

Impetigo is a contagious skin disease caused by Staphylococcus aureus and Streptococcus pyogenes. Without treatment, impetigo may be recurrent, develop into severe disease, or have serious, life-threatening sequelae. Standard treatment consists of topical or systemic antibiotic therapy (depending on severity), however, due to antibiotic resistance some therapies are increasingly ineffective.

Prescribing and using vitiligo treatments: lessons from a nested process evaluation within the HI-Light vitiligo randomized controlled trial.

Background: The HI-Light Trial demonstrated that for active, limited vitiligo, combination treatment with potent topical corticosteroid (TCS) and handheld narrowband ultraviolet B offers a better treatment response than potent TCS alone. However, it is unclear how to implement these findings.

Aim: We sought to answer three questions: (i) Can combination treatment be used safely and effectively by people with vitiligo?; (ii) Should combination treatment be made available as routine clinical care?; and (iii) Can combination treatment be integrated within current healthcare provision?

Methods: This was a mixed-methods process evaluation, including semi-structured interviews with a purposive sample of trial participants, structured interviews with commissioners, and an online survey and focus groups with trial staff.

Dual roles for nuclear RNAi Argonautes in Caenorhabditis elegans dosage compensation.

Dosage compensation involves chromosome-wide gene regulatory mechanisms which impact higher order chromatin structure and are crucial for organismal health. Using a genetic approach, we identified Argonaute genes which promote dosage compensation in Caenorhabditis elegans. Dosage compensation in C.

Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial.

Objectives: Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay.