The Effect of Aerosol Devices and Administration Techniques on Drug Delivery in a Simulated Spontaneously Breathing Pediatric Model with a Tracheostomy

Background: Evidence on aerosol delivery via tracheostomy is lacking. The purpose of this study was to evaluate the effect of aerosol device and administration technique on drug delivery in a simulated spontaneously breathing pediatric model with tracheostomy. Methods: Delivery efficiencies during spontaneous breathing with assisted and unassisted administration techniques were compared using the jet nebulizer (JN- MicroMist), vibrating mesh nebulizer (VMN- Aeroneb Solo) and pressurized metered-dose inhaler (pMDI- ProAirHFA). The direct administration of aerosols in spontaneously breathing patients (unassisted technique) was compared to administration of aerosol therapy via a manual resuscitation bag (assisted technique) attached to the aerosol delivery device and synchronized with inspiration. An in-vitro lung model consisted of an uncuffed tracheostomy tube (4.5 mmID) was attached to a collecting filter (Respirgard) which was connected to a dual-chamber test lung (TTL) and a ventilator (Hamilton). The breathing parameters of a 2 years-old child were set at an RR of 25 breaths/min, a Vt of 150 mL, a Ti of 0.8 sec and PIF of 20 L/min. Albuterol sulfate was administered with each nebulizer (2.5 mg/3 ml) and pMDI with spacer (4 puffs, 108 µg/puff). Each aerosol device was tested five times with both administration techniques (n=5). Drug collected on the filter was eluted with 0.1 N HCl and analyzed via spectrophotometry. Results: The amount of aerosol deposited in the filter was quantified and expressed as inhaled mass and inhaled mass percent. The pMDI with spacer had the highest inhaled mass percent, while the VMN had the highest inhaled mass. The results of this study also found that JN had the least efficient aerosol device used in this study. The trend of higher deposition with unassisted versus assisted administration of aerosol was not significant (p\u3e0.05). Conclusions: Drug deposited distal to the tracheostomy tube with JN was lesser than either VMN or pMDI. Delivery efficiency was similar with unassisted and assisted aerosol administration technique in this in vitro pediatric model

Cell-free DNA for the detection of kidney allograft rejection

Donor-derived cell-free DNA (dd-cfDNA) is an emerging noninvasive biomarker that has the potential to detect allograft injury. The capacity of dd-cfDNA to detect kidney allograft rejection and its added clinical value beyond standard of care patient monitoring is unclear. We enrolled 2,882 kidney allograft recipients from 14 transplantation centers in Europe and the United States in an observational population-based study. The primary analysis included 1,134 patients. Donor-derived cell-free DNA levels strongly correlated with allograft rejection, including antibody-mediated rejection (P \u3c 0.0001), T cell-mediated rejection (P \u3c 0.0001) and mixed rejection (P \u3c 0.0001). In multivariable analysis, circulating dd-cfDNA was significantly associated with allograft rejection (odds ratio 2.275; 95% confidence interval (CI) 1.902-2.739; P \u3c 0.0001) independently of standard of care patient monitoring parameters. The inclusion of dd-cfDNA to a standard of care prediction model showed improved discrimination (area under the curve 0.777 (95% CI 0.741-0.811) to 0.821 (95% CI 0.784-0.852); P = 0.0011) and calibration. These results were confirmed in the external validation cohorts (n = 1,748) including a cohort of African American patients (n = 439). Finally, dd-cfDNA showed high predictive value to detect subclinical rejection in stable patients. Our study provides insights on the potential value of assessing dd-cfDNA, in addition to standard of care monitoring, to improve the detection of allograft rejection. ClinicalTrials.gov registration: NCT05995379

Medicines as common commodities or powerful potions? What makes medicines reusable in people’s eyes

Abstract: Background: Medicines reuse involves dispensing quality-checked, unused medication returned by one patient for another, instead of disposal as waste. This is prohibited in UK com-munity pharmacy because storage conditions in a patient’s home could potentially impact on the quality, safety and efficacy of returned medicines. Our 2017 survey examining patients’ intentions to reuse medicines found many favoured medicines reuse. Our aim was to analyse the qualitative comments to explore people’s interpretations of what makes medicines (non-)reusable. Methods: Thematic analysis was used to scrutinize 210 valid qualitative responses to the survey to deline-ate the themes and super-ordinate categories. Results: Two categories were “medicines as com-mon commodities” versus “medicines as powerful potions”. People’s ideas about medicines aligned closely with other common commodities, exchanged from manufacturers to consumers, with many seeing medicines as commercial goods with economic value sanctioning their reuse. Fewer of the comments aligned with the biomedical notion of medicines as powerful potions, regulated and with legal and ethical boundaries limiting their (re)use. Conclusion: People’s pro-medicines-reuse beliefs align with perceptions of medicines as common commodities. This helps explain why patients returning their medicines to community pharmacies want these to be recycled. It could also explain why governments permit medicines reuse in emergencies

Prescription opioid use before and after kidney transplant: Implications for posttransplant outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146648/1/AJT14714-sup-0001-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146648/2/ajt14714_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146648/3/ajt14714.pd

Analysis and Design Methodology of a Novel Integration Topology of Storageless Off-Grid PV Systems

In this manuscript, a novel topology is proposed to integrate on-grid and off-grid PV systems supplying the same load premises. The load side is investigated and analyzed, and critical and non-critical loads are separated in terms of power supply. Critical and seasonal loads usually place stress on the grid’s point of common coupling (PCC). In the proposed topology, they are supplied by a novel topology for an off-grid solar pump PV system that lacks energy storage integration. The lack of energy storage batteries requires a novel design and sizing scheme for the off-grid PV system, and a methodology is proposed in this manuscript. The on-grid PV system is conventionally designed and coupled with the storage-less off-grid PV system to maintain load supply. The proposed methodology minimizes the ratings of the PCC and hence relieves stress on congested grids with renewable energy penetration, especially in condensed urban areas. The proposed structure enables the operation of microgrids with high penetration levels of renewable energy resources and minimizes dependance on storage batteries for off-grid systems. A case study is presented and thoroughly analyzed with the proposed methodology. The outcomes of the design process are evaluated economically and were found to be feasible, as is detailed and supported with simulation results

The impact of direct‐acting antiviral agents on liver and kidney transplant costs and outcomes

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146297/1/ajt14895_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146297/2/ajt14895.pd

Performance Comparisons of Jet and Mesh Nebulizers Using Different Interfaces in Simulated Spontaneously Breathing Adults and Children

Background: Different types of nebulizers and interfaces are used for the treatment of adults and children with pulmonary diseases. The purpose of this study was to determine the efficiency of a mesh nebulizer (MN) with a proprietary adapter and a jet nebulizer (JN) under different configurations in adult and pediatric models of spontaneous breathing. We hypothesize that delivery efficiency of JN and MN will differ depending on the interface used during aerosol therapy in simulated spontaneously breathing adult and pediatric models. While we expect that aerosol delivery with JN will be less efficient than MN, we also hypothesize that lung deposition obtained with the adult lung model will be more than that with the pediatric lung model in all conditions tested in this study. Methods: A lung model using a teaching manikin connected to a sinusoidal pump via a collecting filter at the level of the bronchi simulating a spontaneously breathing adult (Vt 500 mL, RR 15 bpm, I:E ratio 1:2) or pediatric patient (Vt 150 mL, RR 25 bpm, I:E ratio 1:2). Albuterol sulfate (2.5 mg/3 mL) was aerosolized with JN (Mistymax 10, Airlife) or MN (Aerogen Solo®, Aerogen) with the Adapter (Aerogen Solo® Adapter, Aerogen Ltd, Galway, Ireland) using mouthpiece, aerosol mask, and valved-mask in adults and the dragon mask, aerosol mask, and valved-mask in pediatrics (n=3). The Adapter, specifically designed for MN, was attached to all the interfaces used in this study with supplemental oxygen of 2 lpm, and in addition, the MP was tested with no additional flow in the adult model. The JN was driven with 10 lpm based on the manufacturer\u27s label. Drug was eluted from the filter and analyzed via spectrophotometry. Descriptive statistics, dependent t-test and one-way analysis of variance were used for data analysis. Significant level was set at 0.05. Results: In adults, delivery efficiency of JN with the valved mask was significantly greater than that with the aerosol mask (p=0.01). Aerosol delivery of JN with the mouthpiece was not statistically significant from the valved mask (p=0.123) and the aerosol mask (p=0.193). Drug delivery with MN with mouthpiece (15.42±1.4%) and valved-mask (15.15±1.1%) was greater than the open aerosol mask (7.54±0.39%; p=0.0001) in the adult lung model. With no flow mouthpiece delivery increased\u3e2 fold (34.9±3.1%; p=.0001) compared to use of 2 lpm of flow. Using the JN with the pediatric model deposition with valved-mask (5.3±0.8%), dragon mask (4.7±0.9%), and aerosol mask (4.1±0.3%) were similar (p\u3e0.05); while drug delivery with MN via valved-mask (11.1±0.7%) was greater than the dragon mask (6.44±0.3%; p=0.002) and aerosol mask (4.6±0.4%; p=0.002), and the dragon mask was more efficient than the open aerosol mask (p=0.009) Conclusion: The type of nebulizer and interface used for aerosol therapy affects delivery efficiency in these simulated spontaneously breathing adult and pediatric models. Drug delivery was greatest with the valved-mouthpiece and mask with JN and MN, while the standard aerosol mask was least efficient in these simulated spontaneously breathing adult and pediatric lung models. Delivery efficiency of JN was less than MN in all conditions tested in this study except in the aerosol mask. Lung deposition obtained with the adult lung model was more than that with the pediatric lung model