Use of weekly, low dose, high frequency ultrasound for hard to heal venous leg ulcers: the VenUS III randomised controlled trial

Objective To assess the clinical effectiveness of weekly delivery of low dose, high frequency therapeutic ultrasound in conjunction with standard care for hard to heal venous leg ulcers

Human Immunodeficiency Virus and Risk of Type 2 Diabetes in a Large Adult Cohort in Jos, Nigeria

BACKGROUND HIV infection and the use of anti-retroviral therapy (ART) may increase the risk of type 2 diabetes mellitus (T2DM). However, data from regions with a high burden of HIV/AIDS is limited. We determined the prevalence of T2DM at the time of presentation to a large HIV Clinic in Nigeria, as well as the incidence of diabetes 12 months following ART initiation. METHODS Data from patients enrolled for ART from 2011 to 2013 was analyzed, including 2632 patients on enrollment and 2452 re-evaluated after 12 months of ART commencement. The presence of diabetes, demographic, clinical and biochemical data were retrieved from standardized databases. CD4+, HIV viral load, and hepatitis C virus (HCV) status were noted. Bivariate and logistic regressions were used to identify risk factors for T2DM. RESULTS Baseline T2DM prevalence was 2.3% (95%CI: 1.8% - 2.9%), and age, but not body mass index (BMI) was a risk factor for diabetes. After 12 months of ART, a further 5.3% had developed T2DM. Newly developed diabetes was not associated with age, but was associated with BMI. There were no significant associations between prevalent or incident diabetes and CD4+, viral load or type of ART. CONCLUSIONS Diabetes is not uncommon in HIV infected individuals at the time of presentation to HIV services. Patients initiating ART then have a high risk of developing diabetes in the first year of ART. Incident diabetes was associated with a BMI≥25.0, and excessive weight gain should be avoided

A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor

© 2020 The Author(s). Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and a significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, in participants with IPF. Methods: This was a phase 1b, randomised, double-blind (sponsor unblind) study, conducted in the UK (two clinical sites, one imaging unit) between June 2017 and July 2018 (NCT03069989). Participants with a definite or probable diagnosis of IPF received a single nebulised dose of 1000 mcg GSK3008348 or placebo (ratio 5:2) in two dosing periods. In period 1, safety and PK assessments were performed up to 24 h post-dose; in period 2, after a 7-day to 28-day washout, participants underwent a total of three positron emission tomography (PET) scans: Baseline, Day 1 (~ 30 min post-dosing) and Day 2 (~ 24 h post-dosing), using a radiolabelled αvβ6-specific ligand, [18F]FB-A20FMDV2. The primary endpoint was whole lung volume of distribution (VT), not corrected for air volume, at ~ 30 min post-dose compared with pre-dose. The study success criterion, determined using Bayesian analysis, was a posterior probability (true % reduction in VT > 0%) of ≥80%. Results: Eight participants with IPF were enrolled and seven completed the study. Adjusted posterior median reduction in uncorrected VT at ~ 30 min after GSK3008348 inhalation was 20% (95% CrI:-9 to 42%). The posterior probability that the true % reduction in VT > 0% was 93%. GSK3008348 was well tolerated with no reports of serious adverse events or clinically significant abnormalities that were attributable to study treatment. PK was successfully characterised showing rapid absorption followed by a multiphasic elimination. Conclusions: This study demonstrated engagement of the αvβ6 integrin target in the lung following nebulised dosing with GSK3008348 to participants with IPF. To the best of our knowledge this is the first time a target-specific PET radioligand has been used to assess target engagement in the lung, not least for an inhaled drug. Trial registration: Clinicaltrials.gov: NCT03069989; date of registration: 3 March 2017