Topical pravibismane as adjunctive therapy for moderate or severe diabetic foot infections: A phase 1b randomized, multicenter, double‐blind, placebo‐controlled trial

Abstract

This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).

Physical activity and cognitive function in adults born very preterm or with very low birth weight–an individual participant data meta-analysis

by Kristina Anna Djupvik Aakvik, Silje Dahl Benum, Marjaana Tikanmäki, Petteri Hovi, Katri Räikkönen, Sarah L. Harris, Lianne J. Woodward, Brian A. Darlow, Marit S. Indredavik, Stian Lydersen, Paul Jarle Mork, Eero Kajantie, Kari Anne I. Evensen

Objective

Individuals born very preterm ( Study design

Cohorts with data on physical activity and cognitive function in adults born very preterm/very low birth weight and term-born controls were recruited from the Research on European Children and Adults Born Preterm, and the Adults Born Preterm International Collaboration Consortia. A systematic literature search was performed in PubMed and Embase.

Results

Five cohorts with 1644 participants aged 22–28 years (595 very preterm/very low birth weight and 1049 controls) were included. Adults born very preterm/very low birth weight reported 1.11 (95% CI: 0.68 to 1.54) hours less moderate to vigorous physical activity per week than controls, adjusted for cohort, age and sex. The difference between individuals born very preterm/very low birth weight and controls was larger among women than among men. Neither intelligence quotient nor self-reported executive function mediated the association between very preterm/very low birth weight and moderate to vigorous physical activity. Results were essentially the same when we excluded individuals with neurosensory impairments.

Conclusion

Adults born very preterm/very low birth weight, especially women, reported less moderate to vigorous physical activity than their term-born peers. Cognitive function did not mediate this association. Considering the risk of adverse health outcomes among individuals born preterm, physical activity could be a target for intervention.

Is there ‘trustworthy’ evidence for using manual therapy to treat patients with shoulder dysfunction?: A systematic review

by Daniel W. Flowers, Brian T. Swanson, Stephen M. Shaffer, Derek J. Clewley, Sean P. Riley

The primary objective of this review was to create a ‘trustworthy,’ living systematic review and meta-analysis for the application of manual therapy interventions in treating patients with shoulder dysfunction. Included studies were English-language randomized controlled trials published between 1/1/2010 and 8/3/2023, with searches performed in: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINHAL, ProQuest Nursing & Allied Health, EBSCO Medline, and PEDro. The population of focus included adults 18 years and older with musculoskeletal impairments related to shoulder dysfunction. Our primary outcomes included pain and region-specific outcome measures. We excluded trials, including participants having shoulder dysfunction resulting from surgery, radicular pain, instability/dislocation, fracture, lymphedema, and radiation. Our screening methodology was based upon a previously published ‘trustworthy’ systematic review protocol. This included the application of our PICOTS criteria in addition to screening for prospective clinical trial registration and following of prospective intent, as well as assessment of PEDro scores, risk-of-bias ratings, GRADE scoring, and examination of confidence in estimated effects. Twenty-six randomized controlled trials met our PICOTS criteria; however, only 15 of these were registered. Only three were registered prospectively. Two of these did not have discussions and conclusions that aligned with their primary outcome. The remaining single study was found to have a high risk-of-bias, meaning the remainder of the protocol could not be employed and that no randomized controlled trials could undergo further assessment or meta-analysis. The results of this systematic review indicate there are no ‘trustworthy’ randomized controlled trials examining the effectiveness of manual therapy interventions for the treatment of patients with shoulder dysfunction, as defined by the prospectively established methodology. Therefore, these findings signal that creating a ‘trustworthy,’ living systematic review on this clinically relevant topic is not yet possible due to a lack of ‘trustworthy’ randomized controlled trials.

Atrial fibrillation as a novel risk factor for retinal stroke: A protocol for a population-based retrospective cohort study

by Jay B. Lusk, Lauren Wilson, Vinit Nalwade, Ailin Song, Matthew Schrag, Valerie Biousse, Fan Li, Sven Poli, Jonathan Piccini, Ying Xian, Emily O’Brien, Brian Mac Grory

Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods.

The long-term impact of the Covid-19 pandemic on financial insecurity in vulnerable families: Findings from the Born in Bradford Covid-19 longitudinal study

by Sian Reece, Josie Dickerson, Brian Kelly, Rosemary R. C. McEachan, Kate E. Pickett

There is growing recognition that the public health measures employed to control the spread of the COVID-19 pandemic had unintended consequences on socioeconomic security and health inequalities, having the greatest impact on the most vulnerable groups. This longitudinal study aims to explore the medium to long-term impacts of the COVID-19 pandemic and subsequent public health measures on financial security for families living in the deprived and ethnically diverse city of Bradford. We collected data at four time points before and during the pandemic from mothers who participated in one of two prospective birth cohort studies in Bradford. The findings demonstrate that the risk of experiencing financial insecurity rose sharply during the pandemic and has not returned to pre-COVID-19 baseline levels. Several individual characteristics were found to be possible predictors of financial insecurity, including homeowner status, free school meal eligibility and not working. Protective factors against financial insecurity include: living in more affluent areas; greater levels of educational attainment; and families with two or more adults in the household. Notably, families of Pakistani Heritage were found to have the greatest risk of experiencing financial insecurity throughout the pandemic. Furthermore, this study demonstrated that there were strong associations between financial insecurity and maternal health and wellbeing outcomes, with mothers experiencing financial insecurity being more likely to report unsatisfactory general health and clinically important symptoms of depression and anxiety. The findings of this study highlight that the impact of financial insecurity experienced by mothers and their families throughout the pandemic was severe, wide ranging and affected the most vulnerable. In the wake of the pandemic, the emerging cost of living and energy crisis emphasises the urgent need for policy makers to act to support vulnerable families to prevent further widening of existing health and social inequalities.