scholarly journals Continuous Aerosol Medication Therapy in an in vitro High-Flow System Using Wire Mesh Technology

2020 ◽  
Author(s):  
Jhaymie Cappiello ◽  
Carla Bremenour ◽  
Jason Boyle ◽  
Jessica Lumbard ◽  
Kamrouz Ghadimi
Keyword(s):  
Success Rate ◽  
Primary Endpoint ◽  
Flow System ◽  
Wire Mesh ◽  
Secondary Endpoint ◽  
Residual Volume ◽  
Fluid Level ◽  
Medication Therapy ◽  
Jet Nebulizers

AbstractBACKGROUNDJet nebulizers are commonly used to provide continuous aerosolized medication therapy (CAMT). We observed the function of our CAMT system that utilizes the Aeroneb Solo nebulizer system (Aerogen Ltd, Galway, Ireland). METHODS: An observational study was performed on 2 CAMT systems with 15 Aeroneb nebulizers for each system. CAMT was simulated for 1, 2 and 3 hours. Continuous nebulization was monitored and residual volumes were recorded at the end of each simulation. Our primary endpoint was established as intermittent nebulization observed by nebulizer filling of > 1 ml during CAMT simulation. Secondary endpoint was a residual volume of < 0.1 ml.RESULTSOut of 30 simulations in two arms, a fluid level was observed to accumulate intermittently in three nebulizers with a residual volume of 0.7 mls in one of these three. This produced a total success rate of 90%, Arm-A 80%, Arm B-100%, for our primary endpoint. Our secondary endpoint was achieved in 29 of the 30 nebulizers for an overall 97% success rate, Arm A-93%, Arm B-100%. CONCLUSION: Our Aerogen Solo CAMT system successfully emitted the set dose with 90% accuracy.

scholarly journals Observational study of haloperidol in hospitalized patients with COVID-19

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247122 ◽  
Author(s):  
Nicolas Hoertel ◽  
Marina Sánchez-Rico ◽  
Raphaël Vernet ◽  
Anne-Sophie Jannot ◽  
Antoine Neuraz ◽  
...  
Keyword(s):  
Observational Study ◽  
Primary Endpoint ◽  
Regression Models ◽  
Cox Regression ◽  
Adult Patients ◽  
Secondary Endpoint ◽  
Sensitivity Analyses ◽  
University Hospitals ◽  
Discharge Home

Background Haloperidol, a widely used antipsychotic, has been suggested as potentially useful for patients with COVID-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2, possibly through sigma-1 receptor antagonist effect. Methods We examined the associations of haloperidol use with intubation or death and time to discharge home among adult patients hospitalized for COVID-19 at Assistance Publique-Hôpitaux de Paris (AP-HP) Greater Paris University hospitals. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. In the primary analyses, we compared these two outcomes between patients receiving and not receiving haloperidol using univariate Cox regression models in matched analytic samples based on patient characteristics and other psychotropic medications. Sensitivity analyses included propensity score analyses with inverse probability weighting and multivariable Cox regression models. Results Of 15,121 adult inpatients with a positive COVID-19 PT-PCR test, 39 patients (0.03%) received haloperidol within the first 48 hours of admission. Over a mean follow-up of 13.8 days (SD = 17.9), 2,024 patients (13.4%) had a primary end-point event and 10,179 patients (77.6%) were discharged home at the time of study end on May 1st. The primary endpoint occurred in 9 patients (23.1%) who received haloperidol and 2,015 patients (13.4%) who did not. The secondary endpoint of discharge home occurred in 16 patients (61.5%) who received haloperidol and 9,907 patients (85.8%) who did not. There were no significant associations between haloperidol use and the primary (HR, 0.80; 95% CI, 0.39 to 1.62, p = 0.531) and secondary (HR, 1.30; 95% CI, 0.74 to 2.28, p = 0.355) endpoints. Results were similar in multiple sensitivity analyses. Conclusion Findings from this multicenter observational study suggest that haloperidol use prescribed at a mean dose of 4.5 mg per day (SD = 5.2) for a mean duration of 8.4 days (SD = 7.2) may not be associated with risk of intubation or death, or with time to discharge home, among adult patients hospitalized for COVID-19.

scholarly journals Observational Study of Haloperidol in Hospitalized Patients with Covid-19

2020 ◽  
Author(s):  
Nicolas HOERTEL ◽  
Marina SANCHEZ RICO ◽  
Raphael VERNET ◽  
Anne-Sophie JANNOT ◽  
Antoine NEURAZ ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Observational Study ◽  
Primary Endpoint ◽  
Cox Regression ◽  
Adult Patients ◽  
Secondary Endpoint ◽  
Sensitivity Analyses ◽  
University Hospitals ◽  
Discharge Home

Background: Haloperidol, a widely used antipsychotic, has been suggested as potential effective treatment for Covid-19 on the grounds of its in-vitro antiviral effects against SARS-CoV-2. Methods: We examined the association between haloperidol use and respiratory failure at AP-HP Greater Paris University hospitals. Data were obtained regarding all adult patients hospitalized with Covid-19 since the beginning of the epidemic. Study baseline was defined as the date of hospital admission. The primary endpoint was a composite of intubation or death and the secondary endpoint was discharge home among survivors in time-to-event analyses. We compared outcomes between patients who were exposed to haloperidol and those who were not, using a multivariable Cox regression model with inverse probability weighting according to the propensity score. Results: Of the 13,279 hospitalized adult patients with positive Covid-19 RT-PCR test, 667 patients (5.0%) were excluded because of missing data. Of the remaining 12,612 patients, 104 (0.8%) were exposed to haloperidol. Over a mean follow-up of 20.8 days, the primary endpoint of respiratory failure respectively occurred in 27 patients (26.0%) exposed to haloperidol and 1,700 patients (13.6%) who were not. Among survivors, the secondary endpoint of discharge home occurred in 26 patients (32.1%) who received haloperidol and 6,110 patients (55.3%) who did not. In the main analysis, there were no significant associations between haloperidol use and the primary (HR, 1.09; 95% CI, 0.60 to 1.97, p=0.772) and secondary (HR, 0.88; 95% CI, 0.50 to 1.53, p=0.643) endpoints. Results were similar in multiple sensitivity analyses. Conclusion: In this observational study involving patients with Covid-19 who had been admitted to the hospital, haloperidol use was not associated with risk of intubation or death, or with time to hospital discharge home. These results suggest that haloperidol is unlikely to have a clinical efficacy for Covid-19.

Discovery of New AKT1 Inhibitors by Combination of In silico Structure Based Virtual Screening Approaches and Biological Evaluations

2019 ◽  
Author(s):  
Filip Fratev ◽  
Denisse A. Gutierrez ◽  
Renato J. Aguilera ◽  
suman sirimulla
Keyword(s):  
Virtual Screening ◽  
Success Rate ◽  
Protein Interactions ◽  
In Silico ◽  
Biological Data ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Screening Protocol ◽  
Screening Approaches

AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>

Functional precision medicine in colorectal cancer based on patient-derived tumoroids and in-vitro sensitivity drug testing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
Lars Henrik Jensen ◽  
Anders Kristian Moeller Jakobsen ◽  
Birgitte Mayland Havelund ◽  
Cecilie Abildgaard ◽  
Chris Vagn-Hansen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Primary Endpoint ◽  
Drug Testing ◽  
Progression Free Survival ◽  
Patient Specific ◽  
Precision Oncology ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity

e15567 Background: Precision oncology based on in-vitro, functional assays has potential advantages compared to the much more common molecular approach, but the clinical benefit is unknown. We here report the results from the largest prospective interventional clinical trial testing the clinical outcome in colorectal cancer patients treated with drugs showing cytotoxic effect in matched patient-derived tumoroids. Methods: This single-center, phase II trial included patients with metastatic colorectal cancer previously exposed to all standard therapies. Specimens from one to three 18-16 G core needle biopsies were manually dissected, enzymatically treated, cultivated, and incubated to form 3D spherical microtumors, i.e. tumoroids. In the assay for in-vitro sensitivity testing, the tumoroids were challenged with single drugs and combinations thereof to determine patient-specific responses. Using tumoroid screening technology (IndiTreat, 2cureX, Copenhagen, Denmark), results were generated by comparing the sensitivity of the individual patient’s tumoroids with a reference panel from other patients. The testing included standard cytostatics and drugs with proven effect in previous early-phase clinical trials, a total of 15 drugs. The primary endpoint was the fraction of patients with progression-free survival (PFS) at two months. Based on placebo arms in randomized last-line trials, a minimal relevant difference of 20% (20% to 40%) was stated. Using Simon's two-stage design, a sample size of 45 patients was calculated with at least 14 PFS at two months (significance 5%, power 90%). Results: Ninety patients were enrolled from 9/2017 to 9/2020. Biopsies from 82 patients were obtained and sent for tumoroid formation of which 44 (54%, 95% CI 42-65) were successful and at least one treatment was suggested. Thirty-four patients initiated treatment according to the response obtained in the drug assays within a median of 51 days from inclusion (IQR 39-63). The primary endpoint, PFS at two months, was met in 17 of 34 patients (50%, 95%CI 32-68). There were no radiological responses. Median PFS was 81 days (95% CI 51-112) and median OS was 189 days (95% CI 103-277). Conclusions: Precision oncology using a functional approach with patient-derived tumoroids and in-vitro drug sensitivity testing seems feasible. The approach is limited by the fraction of patients with successful tumoroid development. The primary endpoint was met, as half of the patients were without progression at two months. Further clinical studies are justified. Clinical trial information: NCT03251612.

Viability and growth of mouse embryos after in vitro culture and fusion

Development ◽  
1970 ◽  
Vol 23 (3) ◽  
pp. 693-704
Author(s):  
Patricia Bowman ◽  
Anne McLaren
Keyword(s):  
In Vitro Culture ◽  
Success Rate ◽  
Zona Pellucida ◽  
Growth Regulation ◽  
Excess Mortality ◽  
Blastocyst Stage ◽  
Mouse Embryos ◽  
Foster Mothers ◽  
Mouse Eggs

About 80 % of 8-cell mouse eggs developed to the blastocyst stage in culture, whether the zona pellucida was left intact, or removed with pronase (pre-incubated and dialysed) and the eggs then cultured singly or as fused pairs. When pronase was used without prior incubation and dialysis, the success rate was reduced to 50 %. After transfer to uterine foster-mothers, 20–30 % of apparently normal blastocysts cultured with or without the zona, singly or fused, developed into live foetuses, compared with over 50 % of control blastocysts taken directly from the uterus. Some of the excess mortality of cultured embryos took place before implantation and some soon after. The foetuses derived from cultured blastocysts averaged 0·1 g lighter than those derived from control uterine blastocysts similarly transferred. No differences in the weights of the placentae were observed. Foetal and placental weights were unaffected by whether the eggs had been cultured singly or fused, implying that growth regulation of fused embryos is complete by the 17th day of gestation. The longer the eggs were maintained in culture, the lower was their viability after transfer, and the lighter were the foetuses derived from them.

scholarly journals Study of anatomical feature of in vitro and ex vitro regeneration plant of Sophora Alopecuroides l.

2019 ◽  
pp. 32-40
Author(s):  
Tsolmon M ◽  
Bayarmaa B ◽  
Oyunbileg Yu
Keyword(s):  
Success Rate ◽  
Ex Vitro Rooting ◽  
Vascular Cylinder ◽  
Ex Vitro ◽  
Anatomical Feature ◽  
Plant Survival ◽  
Anatomical Changes ◽  
Sophora Alopecuroides

The success of shoot and rooting from the nodal shoot segments of Sophora alopecuroides L. were induced in vitro condition. However, transferring and acclimatizing the plantlets to under soil or ex vitro condition were difficult. This study investigated plant survival with anatomical changes in plantlets while transferring from in vitro to ex vitro conditions to investigate vascular cylinder variations. The ex vitro rooting of the in vitro regenerated shoots, after having been treated with 500 mg/L IBA, showed a success rate of 80 per cent. These plantlets were rooted and acclimatized simultaneously in ex vitro condition.

Abstract 15091: Significant Reductions in Both Adjudicated and Investigator-Reported Ischemic Events in REDUCE-IT

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Deepak L Bhatt ◽  
Robert Giugliano ◽  
Philippe G Steg ◽  
Michael Miller ◽  
Eliot A Brinton ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Coronary Revascularization ◽  
Hazard Ratio ◽  
Secondary Endpoint ◽  
Icosapent Ethyl ◽  
Clinical Events ◽  
High Degree ◽  
Ischemic Events ◽  
Fatal Myocardial Infarction

Introduction: REDUCE-IT was an event-driven trial that randomized 8,179 statin-treated patients with controlled LDL-C and moderately elevated triglycerides to icosapent ethyl (IPE) 4g daily or placebo, with a median of 4.9 years of follow-up. There was a significant reduction in the prespecified adjudicated rates of the primary endpoint (cardiovascular [CV] death, non-fatal myocardial infarction [MI], non-fatal stroke, coronary revascularization, and unstable angina requiring hospitalization) and of the key secondary endpoint (CV death, MI, stroke), as well as in all the primary endpoint components. We sought to determine the effect of IPE on investigator-reported events. Methods: The Clinical Endpoint Committee (CEC) blindly adjudicated investigator-reported events according to a prespecified charter. Medical records and reports were also reviewed to assess for clinical events not reported by investigators. An endpoint management team compiled and electronically provided event packets to the CEC via an adjudication database. The CEC Chair provided final adjudication if the two primary adjudicators could not reach consensus. Results: IPE significantly reduced the rate of the primary endpoint (hazard ratio 0.74, p=0.0000000002) and the key secondary endpoint (hazard ratio 0.75, p=0.000007) as reported by the site investigators, with consistent benefits in each component of the primary endpoint (Table). There was a high degree of concordance between investigator-reported and adjudicated endpoints. Conclusions: Icosapent ethyl significantly reduced multiple types of ischemic events, both by independent, blinded adjudication as well as by investigator-reported assessment. These results underscore the robustness of the benefits of icosapent ethyl seen in REDUCE-IT.

Development of elastic artificial vessels with a digital pulse flow system to investigate the risk of restenosis and vasospasm

Lab on a Chip ◽  
2020 ◽  
Vol 20 (16) ◽  
pp. 3051-3059
Author(s):  
Yalei Lv ◽  
Guoqiang Li ◽  
Hongyu Peng ◽  
Yanping Liu ◽  
Jingru Yao ◽  
...  
Keyword(s):  
Quantitative Study ◽  
Flow System ◽  
Pulse Flow ◽  
Digital Pulse ◽  
Research Platform

We constructed elastic artificial vessels with a digital pulse flow system, which provide an in vitro research platform that approaches the in vivo microenvironment and facilitates a quantitative study on investigating the risk of restenosis and vasospasm.

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