PAMAM versus PEI complexation for siRNA delivery: interaction with model lipid membranes and cellular uptake

Pharmaceutical Research - Cationic polymers have many advantages as vectors for mediated cellular entry and delivery of siRNA. However, toxicity related to their cationic charge has compromised...     

Worry as a mechanism of the relationship between perceived new knowledge and discouragement to smoke elicited from graphic cigarette warnings

Journal of Behavioral Medicine - Evidence supports the use of graphic warnings to educate the public about the health harms of smoking and suggests warnings eliciting negative emotional responses...     

High-flow via a tracheostomy tube and speaking valve during weaning from mechanical ventilation and tracheostomy

Background

Weaning from mechanical ventilation and tracheostomy after prolonged intensive care consume enormous resources with optimal management not currently well described. Restoration of respiratory flow via the upper airway is essential and early cuff-deflation using a one-way valve (OWV) is recommended. However, extended OWV use may cause dry airways and thickened secretions which challenge the weaning process. High-flow therapy via the tracheostomy tube (HFT-T) humidifies inspired air and may be connected via an in-line OWV (HFT-T-OWV) alleviating these problems. We aim to provide clinical and experimental data on the safety of HFT-T-OWV along with a practical guide to facilitate clinical use during weaning from mechanical ventilation and tracheostomy.

Methods

Data on adverse events of HFT-T-OWV were retrieved from a quality register for patients treated at an intensive care rehabilitation center between 2019 and 2022. Benchtop experiments were performed to measure maximum pressures and pressure support generated by HFT-T-OWV at 25–60 L/min flow using two different HFT-T adapters (interfaces). In simulated airway obstruction using a standard OWV (not in-line) maximum pressures were measured with oxygen delivered via the side port at 1–3 L/min.

Results

Of 128 tracheostomized patients who underwent weaning attempts, 124 were treated with HFT-T-OWV. The therapy was well tolerated, and no adverse events related to the practice were detected. The main reason for not using HFT-T-OWV was partial upper airway obstruction using a OWV. Benchtop experiments demonstrated HFT-T-OWV maximum pressures <4 cmH₂O and pressure support 0–0.6 cmH₂O. In contrast, 1–3 L/min supplemental oxygen via a standard OWV caused pressures between 84 and 148 cmH₂O during simulated airway obstruction.

Conclusions

Current study clinical data and benchtop experiments indicate that HFT-T-OWV was well tolerated and appeared safe. Pressure support was low, but humidification may enable extended use of a OWV without dry airway mucosa and thickened secretions. Results suggest the treatment could offer advantages to standard OWV use, with or without supplementary oxygen, as well as to HFT-T without a OWV, for weaning from mechanical ventilation and tracheostomy. However, for definitive treatment recommendations, randomized clinical trials are needed.     

A Review of Aerosol Generation Mitigation in International Dental Guidance

IntroductionThe coronavirus disease 2019 (COVID-19) led to the worldwide closure of dental practices or reduction of dental services. By the end of April 2020, governments and professional organisations were publishing recommendations or guidance for the reopening/restructuring of dental services. The aim of this study was to assess how dental aerosol-generating procedures (AGPs) were defined in international dental guidelines, what mitigation processes were advised, and whether they were linked to COVID-19 epidemiology.MethodsElectronic searches of a broad range of databases, along with grey literature searches, without language restriction were conducted up to 13 July 2020. Recommendations for the use of face masks and fallow times with patients without COVID-19 were assessed against the deaths per 1 million population in the included countries and country income level using Pearson Chi-squared statistics.ResultsSixty-three guidance documents were included. Most (98%) indicated that AGPs can be performed with patients without COVID-19 with caveats, including advice to restrict AGPs where possible, with 21% only recommending AGPs for dental emergencies. Face masks were recommended by most documents (94%), with 91% also specifying the use of goggles or face shields. Fallow periods for patients without COVID-19 were mentioned in 48% of documents, ranging from 2 to 180 minutes. There were no significant differences in recommendations for face masks or fallow time in patients without COVID-19 by country death rate (P = .463 and P = .901) or World Bank status (P = .504 and P = .835). Most documents recommended procedural or environmental mitigations such as preprocedural mouthwash (82%) and general ventilation (52%). Few documents provided underpinning evidence for their recommendations.ConclusionsWhile the amount of high-quality direct evidence related to dentistry and COVID-19 remains limited, it is important to be explicit about the considered judgements for recommendations as well as generate new evidence to face this challenge.     

Influence of Classroom-Level Factors on Implementation Fidelity During Scale-up of Evidence-Based Interventions

Prevention Science - As evidence-based interventions (EBIs) become more widely disseminated, fidelity of implementation (FOI) often wanes. This study explores the association between FOI and...