Intranasal Dexmedetomidine for Procedural Distress in Children: A Systematic Review.

CONTEXT: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children. OBJECTIVE: To explore the effectiveness of IND for procedural distress in children. DATA SOURCES: We performed electronic searches of Medline (1946-2019), Embase (1980-2019), Google Scholar (2019), Cumulative Index to Nursing and Allied Health Literature (1981-2019), and Cochrane Central Register. STUDY SELECTION: We included randomized trials of IND for procedures in children. DATA EXTRACTION: Methodologic quality of evidence was evaluated by using the Cochrane Collaboration's risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. The primary outcome was the proportion of participants with adequate sedation. RESULTS: Among 19 trials (N = 2137), IND was superior to oral chloral hydrate (3 trials), oral midazolam (1 trial), intranasal midazolam (1 trial), and oral dexmedetomidine (1 trial). IND was equivalent to oral chloral hydrate (2 trials), intranasal midazolam (2 trials), and intranasal ketamine (3 trials). IND was inferior to oral ketamine and a combination of IND plus oral ketamine (1 trial). Higher doses of IND were superior to lower doses (4 trials). Adverse effects were reported in 67 of 727 (9.2%) participants in the IND versus 98 of 591 (16.6%) in the comparator group. There were no reports of adverse events requiring resuscitative measures. LIMITATIONS: The adequacy of sedation was subjective, which possibly led to biased outcome reporting. CONCLUSIONS: Given the methodologic limitations of included trials, IND is likely more effective at sedating children compared to oral chloral hydrate and oral midazolam. However, this must be weighed against the potential for adverse cardiovascular effects.

Probing fibroblast activation in response to extracellular cues with whole protein- or peptide-functionalized step-growth hydrogels.

Synthetic hydrogels with well-defined mechanical properties have become invaluable tools for probing cell response to extracellular cues including matrix stiffness and integrin binding. These synthetic matrices are often decorated with either proteins or integrin-binding peptides to promote cell adhesion and to direct or probe cell behavior. For example, both collagen I-functionalized polyacrylamide and peptide-functionalized poly(ethylene glycol) hydrogels have been instrumental in elucidating the role of the elasticity or 'stiffness' of the matrix in promoting fibroblast activation in wound healing and fibrosis. However, the two methods of promoting integrin binding are not often directly compared in the same system, partly owing to differences in material designs, despite the potential differences in the way cells interact with whole proteins and protein mimetic peptides. We hypothesized that such a comparison could provide insight into the ways integrin binding affects fibroblast activation within commonly utilized in vitro cell culture models, and more broadly, to inform the design of materials to modulate fibroblast activation in studies of wound healing and disease. To enable this comparison, we developed a method to conjugate whole proteins to step-growth poly(ethylene glycol) (PEG) hydrogels and investigated fibroblast response to protein-peptide pairs: fibronectin and PHSRN(G)10RGDS or collagen I and (POG)3POGFOGER(POG)4, which are important in matrix remodeling and relevant to fibroblast activation. With this approach, we observed that human pulmonary fibroblasts adopted a similar morphology on fibronectin and PHSRN(G)10RGDS, although with a slight increase in the percentage of alpha smooth muscle actin (αSMA) expressing cells on PHSRN(G)10RGDS. Interestingly, we observed that fibroblasts formed activated clusters on the collagen mimic (POG)3POGFOGER(POG)4 while exhibiting less activation on collagen I. This cell activation and clustering is reminiscent of fibroblast foci that are observed in lung fibrosis, suggesting the relevance of these well-defined polymer-peptide hydrogels for investigating fibrosis and decoupling biochemical and biophysical cues.