Diabetic foot ulcer photography study: a study within a trial to assess the reliability of two-dimensional (2D) photography for the assessment of ulcer healing in patients with diabetes-related foot ulcers-protocol paper.

Background: The primary endpoint in diabetes-related foot ulcer (DFU) trials is often time to healing, defined as complete re-epithelialisation with absence of drainage, requiring clinical expert assessment as the gold standard. Central blinded photograph review for confirmation of healing is increasingly being undertaken for internal validity. The Diabetic Foot Ulcer Photography study aims to determine the agreement between blinded independent review panel members for assessing ulcer healing status in patients with DFUs.

Theoretically-informed vs standard cover letter to improve participant response to mailed questionnaire: results of an embedded randomised retention trial.

Background: Participant non-response is a source of bias in all research, especially in randomised controlled trials. Participants followed up remotely can have high non-response rates. Four such trials have been conducted of a cover letter with content informed by behaviour change theory to overcome hypothesised barriers to responding to a mailed questionnaire.

Enhanced surveillance for the detection of psoriatic arthritis in a UK primary care psoriasis population: results from the TUDOR trial.

Background: Our objective was to determine whether early detection of undiagnosed psoriatic arthritis (PsA) in a primary care psoriasis population improves outcome in physical function at 24 months post-registration.

Methods: A multicentre, prospective, parallel group cluster randomised controlled trial in patients with psoriasis was conducted. Participants with suspected inflammatory arthritis on screening were referred for an assessment of PsA (enhanced surveillance (ES) arm: at baseline, 12 and 24 months; standard care (SC) arm: at 24 months).

Approaches and experiences implementing remote, electronic consent at the Leeds Clinical Trials Research Unit.

Background: Use of electronic methods to support informed consent ('eConsent') is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK.

Main Text: We implemented a remote eConsent process using the REDCap platform.

Fluorinated Isoindolinone-Based Glucosylceramide Synthase Inhibitors with Low Human Dose Projections.

Inhibition of glucosylceramide synthase (GCS) has been proposed as a therapeutic strategy for the treatment of Parkinson's Disease (PD), particularly in patients where glycosphingolipid accumulation and lysosomal impairment are thought to be contributing to disease progression. Herein, we report the late-stage optimization of an orally bioavailable and CNS penetrant isoindolinone class of GCS inhibitors. Starting from advanced lead , we describe efforts to identify an improved compound with a lower human dose projection, minimal P-glycoprotein (P-gp) efflux, and acceptable pregnane X receptor (PXR) profile through fluorine substitution.

Posterior cervical foraminotomy versus anterior cervical discectomy for Cervical Brachialgia: the FORVAD RCT.

Background: Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking.

Objective: The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome.

Design: This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy.

, an allele of , causes tissue overgrowth in the eye.

Mutant , generated via EMS mutagenesis in , was studied by undergraduate students participating in the Fly-CURE. After inducing genetically mosaic tissue in the adult eye, mutant tissue displays a robust increase in cell division and a rough appearance. Complementation mapping and sequence analysis identified a nonsense mutation in the gene , which we named ( ) due to observed increases in red-pigmented mutant tissue compared to controls.

Perioperative exposure to volatile organic compounds in neonates undergoing cardiac surgery.

Objective: Volatile organic compounds (VOCs) are used in the sterilization and manufacture of medical equipment. These compounds have high vapor pressures with low water solubility and are emitted as gases from solids or liquids. They can be mutagenic, neurotoxic, genotoxic, and/or carcinogenic.

Improvement in Palivizumab Administration Prior to Discharge for Hospitalized Infants with Hemodynamically Significant Congenital Heart Disease: A Quality Improvement Initiative.

In this quality improvement initiative, we aimed to increase provider adherence with palivizumab administration guidelines for hospitalized infants with hemodynamically significant congenital heart disease. We included 470 infants over four respiratory syncytial virus (RSV) seasons from 11/2017 to 03/2021 (baseline season: 11/2017-03/2018). Interventions included the following: education, including palivizumab in the sign-out template, identifying a pharmacy expert, and a text alert (seasons 1 and 2: 11/2018-03/2020) that was replaced by an electronic health record (EHR) best practice alert (BPA) in season 3 (11/2020-03/2021).

Functional crosstalk between chromatin and hypoxia signalling.

Eukaryotic genomes are organised in a structure called chromatin, comprising of DNA and histone proteins. Chromatin is thus a fundamental regulator of gene expression, as it offers storage and protection but also controls accessibility to DNA. Sensing and responding to reductions in oxygen availability (hypoxia) have recognised importance in both physiological and pathological processes in multicellular organisms.

Pyrazole Ureas as Low Dose, CNS Penetrant Glucosylceramide Synthase Inhibitors for the Treatment of Parkinson's Disease.

Parkinson's disease is the second most prevalent progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. Loss-of-function mutations in GBA, the gene that encodes for the lysosomal enzyme glucosylcerebrosidase, are a major genetic risk factor for the development of Parkinson's disease potentially through the accumulation of glucosylceramide and glucosylsphingosine in the CNS. A therapeutic strategy to reduce glycosphingolipid accumulation in the CNS would entail inhibition of the enzyme responsible for their synthesis, glucosylceramide synthase (GCS).

First Hard X-Ray Imaging Results by Solar Orbiter STIX.

The Spectrometer/Telescope for Imaging X-rays (STIX) is one of six remote sensing instruments on-board Solar Orbiter. The telescope applies an indirect imaging technique that uses the measurement of 30 visibilities, i.e.

Evaluation of Sirolimus Dosing in Neonates and Infants With Lymphatic Disorders: A Case Series.

Objective: Literature in pediatric patients suggests dosing sirolimus 1.6 mg/m2/day divided twice daily for lymphatic disorders with limited evidence available for dosing in neonates and infants. The objective of this research was to determine the sirolimus dose required to achieve therapeutic trough concentrations in infants with lymphatic disorders at Children's Hospital of Philadelphia.

Selection of an Optimal In Vitro Model to Assess P-gp Inhibition: Comparison of Vesicular and Bidirectional Transcellular Transport Inhibition Assays.

The multidrug resistance protein 1 (MDR1) P-glycoprotein (P-gp) is a clinically important transporter. In vitro P-gp inhibition assays have been routinely conducted to predict the potential for clinical drug-drug interactions (DDIs) mediated by P-gp. However, high interlaboratory and intersystem variability of P-gp IC data limits accurate prediction of DDIs using static models and decision criteria recommended by regulatory agencies.

Pressure Relieving Support Surfaces: a Randomised Evaluation 2 (PRESSURE 2): using photography for blinded central endpoint review.

Background: PRESSURE 2 is a randomised evaluation of the clinical and cost-effectiveness of two types of mattress for the prevention of pressure ulcers (PUs). The primary clinical endpoint was time to development of a category ≥2 PU. The current 'gold standard' for PU identification is expert clinical assessment.

Patterns of Medication Exposure in Children on Extracorporeal Membrane Oxygenation: A Step in Prioritizing Future Pharmacologic Studies.

Unlabelled: To identify medications administered to pediatric patients on extracorporeal membrane oxygenation and to review the available pharmacokinetics and pharmacodynamics literature for the most commonly administered medications.

Design: Retrospective single-center study.

Setting: ICUs at Children's Hospital of Philadelphia.

Registered nurses' perspectives on medically safe practices and sound ethical standards in aesthetic nursing: An interview study.

Aims And Objectives: To explore the views of registered nurses experienced in aesthetic nursing regarding medically safe practices and sound ethical standards.

Background: Aesthetic nursing is an emerging field of modern-day healthcare encompassed within aesthetic medicine. There is a distinct lack of research regarding how registered nurses who specialise in this area of care view medically safe practices and sound ethical standards.

Pressure Relieving Support Surfaces for Pressure Ulcer Prevention (PRESSURE 2): Clinical and Health Economic Results of a Randomised Controlled Trial.

Background: Pressure ulcers (PUs) are complications of serious acute/chronic illness. Specialist mattresses used for prevention lack high quality effectiveness evidence. We aimed to compare clinical and cost effectiveness of 2 mattress types.

Comparing alternating pressure mattresses and high-specification foam mattresses to prevent pressure ulcers in high-risk patients: the PRESSURE 2 RCT.

Background: Pressure ulcers (PUs) are a burden to patients, carers and health-care providers. Specialist mattresses minimise the intensity and duration of pressure on vulnerable skin sites in at-risk patients.

Primary Objective: Time to developing a new PU of category ≥ 2 in patients using an alternating pressure mattress (APM) compared with a high-specification foam mattress (HSFM).

Comparison of generic and disease-specific measures in their ability to detect differences in pressure ulcer clinical groups.

Patient-reported outcomes can be included as end points in pressure ulcer (PU) intervention trials to provide information to inform decision-making and improve the lives of patients. However, the challenge for researchers and clinicians is identifying and choosing an appropriate instrument for each particular application that suits their research questions and clinical context. To provide researchers and clinicians with the information needed to inform choice of patient-reported outcome measures, we compared a generic and disease-specific measures' ability to discriminate between clinical groups known to differ, and determined their responsiveness to change.

Evaluation of IV to Enteral Benzodiazepine Conversion Calculations in a Pediatric Intensive Care Setting.

Objectives: To evaluate if institutionally established calculations for transitioning continuous IV midazolam to enteral benzodiazepines maintain Withdrawal Assessment Tool-Version 1 scores equal to or less than preconversion values.

Design: Retrospective cohort study evaluating the effectiveness and safety of benzodiazepine conversion calculations embedded within an institution-specific clinical pathway for sedation and weaning of mechanically ventilated pediatric patients.

Setting: A 55-bed, mixed-medical, noncardiac surgical PICU in a tertiary care children's hospital.