Fallow time determination in dentistry using aerosol measurement

AbstractAimTo calculate fallow time (FT) required following dental aerosol generating procedures (AGPs) in both a dental hospital (mechanically ventilated) and primary care (non-mechanically ventilated). Secondary outcomes were to identify spread and persistence of aerosol in open clinics compared to closed surgeries (mechanically ventilated environment), and identify if extra-oral scavenging (EOS) reduces production of aerosol and FT.MethodsIn vitro simulation of fast handpiece (FHP) cavity preparations using a manikin was conducted in a mechanically and non-mechanically ventilated environment using Optical Particle Sizer™ and NanoScan™ at baseline, during the procedure and fallow period.ResultsAGPs carried out in the non-mechanically, non-ventilated environment failed to achieve baseline particle levels after one hour. In contrast, when windows were opened after AGP, there was an immediate reduction in all particle sizes.In mechanically ventilated environments the baseline levels of particles were very low and particle count returned to baseline within 10 minutes following AGP. There was no detectable difference between particles in mechanically ventilated open bays and closed surgeries.The effect of the EOS was greater in non-mechanically ventilated environment on reducing the particle count; additionally, it also reduced the spikes in particle counts in mechanically ventilated environments.ConclusionHigh-efficiency particulate air filtered mechanical ventilation along with mitigating factors (high-volume suction) resulted in reduction of FT (10 minutes). Non-ventilated rooms failed to reach baseline level even after one hour of FT. There was no difference in particle counts in open bay or closed surgeries in mechanically ventilated settings. The use of an EOS device can reduce the particulate spikes during procedures in both mechanical and non-mechanical environments.This study confirms that AGPs are not recommended in dental surgeries where no ventilation is possible. No difference was demonstrated in FT required in open bays and closed surgeries in mechanically ventilated settings.Clinical significanceAGPs should not be carried out in surgeries where ventilation is not possible. Mechanical ventilation for AGPs should be gold standard; where not available or practical then the use of natural ventilation with EOS helps reduce FT. AGPs can be carried out in open bay environment with a minimum of 6 air changes per hour of mechanical ventilation. Four-handed dentistry with high-volume suction and saliva ejector are essential mitigating factors during AGPs.

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Novel Toxicology Program to Support the Development of Inhaled VentaProst

International Journal of Toxicology ◽

10.1177/1091581820945985 ◽

2020 ◽

Vol 39 (5) ◽

pp. 433-442

Author(s):

Jeffrey Tepper ◽

Juergen Pfeiffer ◽

Kim Bujold ◽

James B. Fink ◽

Richard Malcolmson ◽

...

Keyword(s):

Mechanical Ventilation ◽

Dose Rate ◽

Mitral Valve Surgery ◽

Continuous Exposure ◽

Continuous Administration ◽

Inhalation Study ◽

Mechanically Ventilated ◽

Off Label ◽

Toxicology Study

Currently, off-label continuous administration of inhaled epoprostenol is used to manage hemodynamics during mitral valve surgery. A toxicology program was developed to support the use of inhaled epoprostenol during mechanical ventilation as well as pre- and postsurgery via nasal prongs. To support use in patients using nasal prongs, a Good Laboratory Practice (GLP), 14-day rat, nose-only inhalation study was performed. No adverse findings were observed at ∼50× the dose rate received by patient during off-label use. To simulate up to 48 hours continuous aerosol exposure during mechanical ventilation, a GLP toxicology study was performed using anesthetized, intubated, mechanically ventilated dogs. Dogs inhaled epoprostenol at approximately 6× and 13× the dose rate reported in off-label human studies. This novel animal model required establishment of a dog intensive care unit providing sedation, multisystem support, partial parenteral nutrition, and management of the intubated mechanically ventilated dogs for the 48-hour duration of study. Aerosol was generated by a vibrating mesh nebulizer with novel methods required to determine dose and particle size in-vitro. Continuous pH 10.5 epoprostenol was anticipated to be associated with lung injury; however, no adverse findings were observed. As no toxicity at pH 10.5 was observed with a formulation that required refrigeration, a room temperature stable formulation at pH 12 was evaluated in the same ventilated dog model. Again, there were no adverse findings. In conclusion, current toxicology findings support the evaluation of inhaled epoprostenol at pH 12 in surgical patients with pulmonary hypertension for up to 48 hours continuous exposure.

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Gradual Reduction of Endotracheal Tube Diameter during Mechanical Ventilation via Different Humidification Devices

Anesthesiology ◽

10.1097/00000542-199612000-00015 ◽

1996 ◽

Vol 85 (6) ◽

pp. 1341-1349. ◽

Cited By ~ 95

Author(s):

Maria Cristina Villafane ◽

Gilda Cinnella ◽

Frederic Lofaso ◽

Daniel Isabey ◽

Alain Harf ◽

...

Keyword(s):

Mechanical Ventilation ◽

Prolonged Mechanical Ventilation ◽

Water System ◽

Hot Water ◽

Mechanically Ventilated ◽

Mean Diameter ◽

The Mean ◽

Heat And Moisture

Background Limited data suggest that increased resistance to flow within endotracheal tubes (ETT) may occur in patients whose lungs are mechanically ventilated for more than 48 h, especially when airway humidification is inadequate. This could lead to sudden ETT obstruction or induce excessive loading during spontaneous breathing. Methods Twenty-three such patients were randomly assigned to three types of airway humidifier based on three different working principles: a Fisher Paykell hot water system (n = 7), a Pall BB2215 heat and moisture exchanger (HME) hydrophobic filter (n = 8), and a Dar Hygrobac 35254111 HME hygroscopic filter (n = 8). The decrease in internal pressure along the ETT and the flow rate were measured in each patient every 2 days. An "effective inner diameter" was derived from these measurements and allowed the inner ETT configuration to be monitored. Results On the first day of intubation, the mean diameter was similar in the three groups, and was slightly smaller than the in vitro diameter (mean +/- SD: 7.6 +/- 0.6 mm for Fisher-Paykell, 7.7 +/- 0.4 for Pall, and 7.5 +/- 0.4 for Dar). The mean diameter tended to decrease from day to day. At the end of the study, the overall reduction in mean diameter was significantly greater with the hydrophobic HME (Pall) than with the two other systems (Pall: -6.5 +/- 4% vs. 2.5 +/- 2.5% for Dar and 1.5 +/- 3% for Fisher-Paykell; P < 0.01 with analysis of variance). The same was true of the mean reduction in effective inner ETT diameter expressed per day of ventilation (-1.6 +/- 1.5% per day for Pall vs. -0.5 +/- 0.4% for Dar and -0.2 +/- 0.4% for Fisher-Paykell; P < 0.01). In four patients, the ETT became obstructed and emergency repeated tracheal intubation was required. The Pall HME and the Fisher-Paykell system were being used in three and one patient, respectively. Before obstruction, the reduction in ETT diameter was significantly greater for these four patients than for the remaining 23 patients (7.8 +/- 1.4% vs. 3.1 +/- 4.1%; P < 0.01). Conclusions During prolonged mechanical ventilation, significant alterations in inner ETT configuration occur frequently and are influenced by the type of humidification device used. In vivo monitoring of ETT mechanical properties might be clinically useful.

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Quantitative evaluation of dental bio-aerosols using particle count values. Part 1: the effect of High Volume Aspiration and natural ventilation.

10.21203/rs.3.rs-55265/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Andre Haigh ◽

Ronuk Vasant ◽

Dominic O'Hooley

Keyword(s):

Time Series ◽

Natural Ventilation ◽

High Volume ◽

Sample Standard Deviation ◽

Particle Count ◽

Aerosol Generation ◽

Dependent Variables ◽

The Mean ◽

Post Hoc ◽

Mean Time

Abstract AimRoutine dental treatments are frequently associated with aerosol generating procedures (AGP). Recently dental AGP have attracted significant attention as a possible vector for the transmission of SARS-CoV-2 and attempts have been made to establish when a surgery may be safely decontaminated following a dental AGP — the ‘fallow time’. There is a paucity of research in the dental literature regarding the near real time generation and dispersion of dental aerosol following a dental AGP. Study aims are to: (1) monitor dental aerosol generation and dispersal through semi-continuous particle count values (PCV), and (2) use this information to delineate a range of suitable fallow times.MethodFollowing baseline measurements, five identical dental AGP were conducted on a dental manikin for each of three groups: (SEO) saliva ejector only, (HVA) high volume aspiration, (WO) high volume aspiration with windows open. For each procedure PCV were recorded every 2.2 minutes with a Light Scattering Airborne Particle Counter (LSAPC) for 3.3 hours. Eleven dependent variables were analysed, including baseline PCV, total PCV, peak PCV, time taken to return to one sample standard deviation of baseline PCV, and a time series extending from 15 minutes to 3 hours after cessation of AGP. Due to heterogeneity, the data was analysed with Krushkall-Wallis test and Dunn-Bonferroni post hoc.ResultsBetween group mean baseline PCV were not statistically significant. Compared with SEO, WO had a statistically significant impact on peak PCV (p=.009) and HVA had a statistically significant impact on total PCV (p=.006). With the exception at 2 and 3 hours, PCV throughout the time series were statistically significantly lower for WO and HVA in comparison with SEO. WO PCV were influenced by outdoor aerosol levels.Four of the five SEO procedures failed to return to baseline PCV within 3.3 hours. Following AGP, the mean time for the HVA procedures to return to baseline PCV was 17.12 minutes, 95% CI [4.96 to 29.28]. The effect of HVA on the time taken to return to baseline PCV was very large (Glass’s Δ= -4.943, CLES=1.00).ConclusionThere is a significant benefit in opening windows during AGP. The effect of HVA on reducing fallow time is very large. Under the conditions of this study, PCV suggest that it might be safe to consider a fallow time of 29.28 minutes.

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Investigation of Ventilation Behaviors in Mechanically Ventilated Residential Buildings in China

E3S Web of Conferences ◽

10.1051/e3sconf/201911106048 ◽

2019 ◽

Vol 111 ◽

pp. 06048

Author(s):

Yue Qi ◽

Junjie Liu ◽

Xilei Dai ◽

Lei Zhao ◽

Dayi Lai ◽

...

Keyword(s):

Mechanical Ventilation ◽

Energy Efficient ◽

Natural Ventilation ◽

Residential Buildings ◽

Ventilation System ◽

Outdoor Air ◽

Climate Zones ◽

Mechanically Ventilated ◽

Ventilation Duration ◽

Site Monitoring

Mechanical ventilation system provides a more reliable, controllable, and comfortable way of ventilation than natural ventilation through an opened window. However, the operation of mechanical ventilation system cost energy. This study investigated the usage of natural and mechanical ventilation in 46 apartments in ten cities across five different climate zones in China by on-site monitoring and questionnaire survey. On average, the daily natural and mechanical ventilation durations were 11 hours and 7.2 hours, respectively. Large differences existed among climate regions and seasons. From north to south, as the climate became warmer, the usage of natural ventilation increased. From seasonal perspectives, natural ventilation duration was the longest in summer and the shortest in winter. The trend of mechanical ventilation usage was opposite to that of natural ventilation. Generally, as the outdoor air temperature increased, the duration of natural ventilation increased and the duration of mechanical ventilation decreased. This study proposed an outline to use thermal comfort, health, and energy saving as three motivations to analyze ventilation behaviors. Based on the obtained results, suggestions were made for achieving healthy, thermally comfortable, and energy efficient ventilation in residential buildings.

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Check the gap: Facemask performance and exhaled aerosol distributions around the wearer

PLoS ONE ◽

10.1371/journal.pone.0243885 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0243885

Author(s):

Emily L. Kolewe ◽

Zachary Stillman ◽

Ian R. Woodward ◽

Catherine A. Fromen

Keyword(s):

Social Distance ◽

Material Characterization ◽

Critical Element ◽

Hygroscopic Growth ◽

Particle Count ◽

Industry Standard ◽

3D Printed ◽

Reproducible Method ◽

Particle Counts

Current facemask research focuses on material characterization and efficiency; however, facemasks are often not tested such that aerosol distributions are evaluated from the gaps in the sides, bottom, and nose areas. Poor evaluation methods could lead to misinformation on optimal facemasks use; a high-throughput, reproducible method which illuminates the issue of fit influencing aerosol transmission is needed. To this end, we have created an in vitro model to quantify particle transmission by mimicking exhalation aerosols in a 3D printed face-nose-mouth replica via a nebulizer and quantifying particle counts using a hand-held particle counter. A sewn, sewn with pipe cleaner nose piece, and sewn with a coffee filter facemask were used to evaluate current common homemade sewn facemask designs, benchmarked against industry standard surgical, N95 respirator tightly fit, and N95 respirator loosely fit facemasks. All facemasks have significantly reduced particle counts in front of the facemask, but the side and top of the facemask showed increases in particle counts over the no facemask condition at that same position, suggesting that some proportion of aerosols are being redirected to these gaps. An altered size distribution of aerosols that escape at the vulnerable positions was observed; escaped particles have larger count median diameters, with a decreased ratio of smaller to larger particles, possibly due to hygroscopic growth or aggregation. Of the homemade sewn facemasks, the facemask with a coffee filter insert performed the best at reducing escaped aerosols, with increased efficiency also observed for sewn masks with a pipe cleaner nose piece. Importantly, there were minimal differences between facemasks at increasing distances, which supports that social distance is a critical element in reducing aerosol transmission. This work brings to light the importance of quantifying particle count in positions other than directly in front of the facemask and identifies areas of research to be explored.

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Mechanical Ventilation Stimulates Expression of ACE2, the Receptor for SARS-Cov-2

10.20944/preprints202005.0429.v1 ◽

2020 ◽

Author(s):

Sui Huang ◽

Arja Kaipainen ◽

Michael Strasser ◽

Sergio Baranzini

Keyword(s):

Mechanical Ventilation ◽

Animal Studies ◽

Prolonged Mechanical Ventilation ◽

Surface Protein ◽

Mechanical Stretch ◽

Alveolar Cells ◽

Alveolar Cell ◽

Mechanically Ventilated ◽

Viral Propagation

The SARS-Cov-2 virus, which causes COVID 19, uses the cell surface protein ACE2 as receptor for entry into cells. Critically ill COVID-19 patients often require prolonged mechanical ventilation which can cause mechanical stress to lung tissue. In vitro studies have shown that expression of ACE2 in alveolar cells is increased following mechanical stretch and inflammation. Therefore, we analyzed transcriptome datasets of 480 (non-COVID-19) lung tissues in the GTex tissue gene expression database. We found that mechanical ventilation of the tissue donors increased the expression of ACE2 by more than two-fold (p<10-6). Analysis of transcriptomes of mechanically ventilated mice deposited in the GEO database indicates that this alveolar cell response to stretch and inflammation is mediated by the chemokine midkine. We also found in transcriptomes of the LINCS database of pharmacological perturbations that corticosteroids down-regulate midkine in pulmonal cells, consistent with transcriptome data of animal studies in GEO. Thus, mechanical ventilation of patients with COVID-19 pneumonia may eo ipso facilitate viral propagation in the lung, further accelerating the pulmonal pathology that has necessitated mechanical ventilation in the first place. This vicious cycle offers a possible rationale for interventions that disrupt the corticosteroid-midkine-ACE2 axis and provides a mechanism that supports the calls for gentler ventilation protocols.

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Effects of lung injury on pulmonary surfactant aggregate conversion in vivo and in vitro

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.5.l872 ◽

1997 ◽

Vol 272 (5) ◽

pp. L872-L878 ◽

Cited By ~ 10

Author(s):

R. A. Veldhuizen ◽

Y. Ito ◽

J. Marcou ◽

L. J. Yao ◽

L. McCaig ◽

...

Keyword(s):

Mechanical Ventilation ◽

Lung Injury ◽

Surface Area ◽

Pulmonary Surfactant ◽

Breathing Pattern ◽

Mechanically Ventilated ◽

Surface Active ◽

Spontaneously Breathing

Within the alveolar space pulmonary surfactant is converted from the surface active large aggregates (LA) to the inactive small aggregates (SA). This conversion is affected by a change in surface area, lung injury, breathing pattern, and protease activity. This study examined the effect of N-nitroso-N-methylurethane-induced acute lung injury on aggregate conversion in mechanically ventilated and spontaneously breathing rabbits. Both the in vitro surface area cycling techniques and the in vivo technique of intratracheally injecting radiolabeled LA were used for analyzing aggregate conversion. Mechanical ventilation of injured lungs resulted in increased aggregate conversion and increased surfactant aggregate ratios compared with controls. Spontaneously breathing injured animals had aggregate conversion and aggregate ratios that were not significantly different from controls. In vitro aggregate conversion was slower for LA obtained from injured animals compared with normal animals. We conclude that the mechanical stress of mechanical ventilation results in increased aggregate conversion and aggregate ratios. Furthermore, in vitro conversion of isolated LA does not necessarily reflect the conversion of aggregates within the alveoli.

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Influence of Certain Drugs on the Adhesiveness of Human, Rat, and Rabbit Blood Platelets in Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656242 ◽

1965 ◽

Vol 13 (02) ◽

pp. 428-438 ◽

Cited By ~ 2

Author(s):

K Reber ◽

A Studer

Keyword(s):

Sodium Citrate ◽

Blood Platelets ◽

Drug Application ◽

Normal Range ◽

Blood Samples ◽

Serotonin Antagonist ◽

Thrombocyte Count ◽

Particle Count ◽

Rabbit Blood

SummaryThis is a comparative study of the methods described by H. P. Wright and O’Brien for determining the adhesiveness of thrombocytes. An attempt is made to characterize and statistically correlate both techniques. With the aid of a Coulter Counter for thrombocyte counts, a normal range is presented for human, rat, and rabbit blood. Anticoagulants used are sodium citrate and Heparin.The influence of Cocaine and the Serotonin antagonist Ro 3-0837 was studied on these same substrates, to determine a pharmacological interference with results of either Wright’s test or O’Brien’s. Both drugs are found to induce a statistically significant increase in the “thrombocyte count” as compared to the corresponding controls. These effects are not real but to be attributed to an increase in particle count due to thrombocyte fragmentation as a consequence of drug application. There is no evidence for the claim that these drugs decrease the adhesiveness of thrombocytes.Numerical results of both tests often show a high and statistically significant correlation, especially following the addition of Ro 3-0837. Such is not true of individual blood samples to which no drug has been added. Evidentally, both tests are not specific for the same characteristic of normal blood platelets. But, when Ro 3-0837 is added, the breakdown of unstable platelets is induced; and the corresponding increase in count of thrombocyte fragments is expressed by both tests in the same fashion.

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Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation

Annals of Intensive Care ◽

10.1186/s13613-020-00793-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Laurent Papazian ◽

◽

Samir Jaber ◽

Sami Hraiech ◽

Karine Baumstarck ◽

...

Keyword(s):

Mechanical Ventilation ◽

Invasive Mechanical Ventilation ◽

Double Blind ◽

Intravenous Ganciclovir ◽

Subdistribution Hazard ◽

Mechanically Ventilated ◽

Cytomegalovirus Reactivation ◽

Secondary Outcomes ◽

To Receive ◽

Cmv Reactivation

Abstract Background The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation. Methods This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37). Results The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0–51] and 0 [0–43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups. Conclusions In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

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Rapid target validation in a Cas9-inducible hiPSC derived kidney model

Scientific Reports ◽

10.1038/s41598-021-95986-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yasaman Shamshirgaran ◽

Anna Jonebring ◽

Anna Svensson ◽

Isabelle Leefa ◽

Mohammad Bohlooly-Y ◽

...

Keyword(s):

High Efficiency ◽

Disease Modeling ◽

Genetic Manipulation ◽

Disease Model ◽

Genetically Engineered ◽

Model Systems ◽

Target Validation ◽

Direct Differentiation ◽

Kidney Organoids

AbstractRecent advances in induced pluripotent stem cells (iPSCs), genome editing technologies and 3D organoid model systems highlight opportunities to develop new in vitro human disease models to serve drug discovery programs. An ideal disease model would accurately recapitulate the relevant disease phenotype and provide a scalable platform for drug and genetic screening studies. Kidney organoids offer a high cellular complexity that may provide greater insights than conventional single-cell type cell culture models. However, genetic manipulation of the kidney organoids requires prior generation of genetically modified clonal lines, which is a time and labor consuming procedure. Here, we present a methodology for direct differentiation of the CRISPR-targeted cell pools, using a doxycycline-inducible Cas9 expressing hiPSC line for high efficiency editing to eliminate the laborious clonal line generation steps. We demonstrate the versatile use of genetically engineered kidney organoids by targeting the autosomal dominant polycystic kidney disease (ADPKD) genes: PKD1 and PKD2. Direct differentiation of the respective knockout pool populations into kidney organoids resulted in the formation of cyst-like structures in the tubular compartment. Our findings demonstrated that we can achieve > 80% editing efficiency in the iPSC pool population which resulted in a reliable 3D organoid model of ADPKD. The described methodology may provide a platform for rapid target validation in the context of disease modeling.

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