The impact of liraglutide on diabetes-related foot ulceration and associated complications in patients with type 2 diabetes at high risk for cardiovascular events: Results from the LEADER trial

OBJECTIVE: Diabetes-related foot ulcers (DFUs) and their sequelae result in large patient and societal burdens. Long-term data determining the efficacy of individual glucose-lowering agents on DFUs are lacking. Using existing data from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, we conducted post hoc analyses assessing the impact of liraglutide versus placebo in people with type 2 diabetes and at high risk of cardiovascular (CV) events on the incidence of DFUs and their sequelae. RESEARCH DESIGN AND METHODS: The LEADER trial (NCT01179048) was a randomized, double-blind, multicenter, CV outcomes trial assessing liraglutide (1.8 mg/day) versus placebo, in addition to standard of care, for up to 5 years. Information on DFUs was collected systematically during the trial, and DFU complications were assessed post hoc through reviewing case narratives. RESULTS: During a median of 3.8 years' follow-up, similar proportions of patients reported at least one episode of DFU in the liraglutide and placebo groups (3.8% [176/4,668] versus 4.1% [191/4,672], respectively; hazard ratio [HR] 0.92 [95% CI 0.75, 1.13; P = 0.41]). Analysis of DFU-related complications demonstrated a significant reduction in amputations with liraglutide versus placebo (HR 0.65 [95% CI 0.45, 0.95; P = 0.03]). However, no differences were found for foot infections, involvement of underlying structures, or peripheral revascularization in the main analysis. CONCLUSIONS: Treatment with liraglutide in patients with type 2 diabetes and at high risk of CV events in the LEADER trial did not increase the risk of DFU events and was associated with a significantly lower risk of DFU-related amputations compared with placebo. This association, possibly due to chance, needs further investigation

Tetrazine-Triggered Release of Carboxylic-Acid-Containing Molecules for Activation of an Anti-inflammatory Drug.

In addition to its use for the study of biomolecules in living systems, bioorthogonal chemistry has emerged as a promising strategy to enable protein or drug activation in a spatially and temporally controlled manner. This study demonstrates the application of a bioorthogonal inverse electron-demand Diels-Alder (iEDDA) reaction to cleave trans-cyclooctene (TCO) and vinyl protecting groups from carboxylic acid-containing molecules. The tetrazine-mediated decaging reaction proceeded under biocompatible conditions with fast reaction kinetics (<2 min). The anti-inflammatory activity of ketoprofen was successfully reinstated after decaging of the nontoxic TCOprodrug in live macrophages. Overall, this work expands the scope of functional groups and the application of decaging reactions to a new class of drugs

Functionalized Poly(3-hexylthiophene)s via Lithium–Bromine Exchange

Poly(3-hexylthiophene) (P3HT) is one of the most extensively investigated conjugated polymers and has been employed as the active material in many devices including field-effect transistors, organic photovoltaics and sensors. As a result, methods to further tune the properties of P3HT are desirable for specific applications. Herein, we report a facile postpolymerization modification strategy to functionalize the 4-position of commercially available P3HT in two simple steps–bromination of the 4-position of P3HT (Br–P3HT) followed by lithium−bromine exchange and quenching with an electrophile. We achieved near quantitative lithium–bromine exchange with Br–P3HT, which requires over 100 thienyl lithiates to be present on a single polymer chain. The lithiated-P3HT is readily combined with functional electrophiles, resulting in P3HT derivatives with ketones, secondary alcohols, trimethylsilyl (TMS) group, fluorine, or an azide at the 4-position. We demonstrated that the azide-modified P3HT could undergo Cu-catalyzed or Cu-free click chemistry, significantly expanding the complexity of the structures that can be appended to P3HT using this method.National Science Foundation (U.S.) (ECCS-0939514

Silence as an element of care:A meta-ethnographic review of professional caregivers’ experience in clinical and pastoral settings

Background: In interactions between professional caregivers, patients and family members at the end of life, silence often becomes more prevalent. Silence is acknowledged as integral to interpersonal communication and compassionate care but is also noted as a complex and ambiguous phenomenon. This review seeks interdisciplinary experience to deepen understanding of qualities of silence as an element of care. Aim: To search for published papers which describe professional caregivers’ experience of silence as an element of care, in palliative and other clinical, spiritual and pastoral care settings and to synthesise their findings. Design: Meta-ethnography: employing a systematic search strategy and line-of-argument synthesis. Data sources: PsycINFO and seven other cross-disciplinary databases, supplemented by hand-search, review of reference lists and citation tracking. No date range was imposed. Inclusion criteria focused on reported experience of silence in professional caregiving. Selected papers (n = 18) were appraised; none were rejected on grounds of quality. Results: International, interdisciplinary research and opinion endorses the value of silence in clinical care. As a multi-functional element of interpersonal relationships, silence operates in partnership with speech to support therapeutic communication. As a caregiving practice, silence is perceived as particularly relevant in spiritual and existential dimensions of care when words may fail. Conclusion: Experience of silence as an element of care was found in palliative and spiritual care, psychotherapy and counselling supporting existing recognition of the value of silence as a skill and practice. Because silence can present challenges for caregivers, greater understanding may offer benefits for clinical practice