Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned.
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ABSTRACT:
SUBMITTER: Bianco F
PROVIDER: S-EPMC7908012 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceSpontaneous breathing trials (SBTs) are used to determine extubation readiness in extremely preterm neonates (gestational age ≤28 weeks), but these trials rely on empirical combinations of clinical events during endotracheal continuous positive airway pressure (ET-CPAP).ObjectivesTo describe clinical events during ET-CPAP and to assess accuracy of comprehensive clinical event combinations in predicting successful extubation compared with clinical judgment alone.Design, setting, and participantsThis multicenter diagnostic study used data from 259 neonates seen at 5 neonatal intensive care units from the prospective Automated Prediction of Extubation Readiness (APEX) study from September 1, 2013, through August 31, 2018. Neonates with birth weight less than 1250 g who required mechanical ventilation were eligible. Neonates deemed to be ready for extubation and who underwent ET-CPAP before extubation were included.InterventionsIn the APEX study, cardiorespiratory signals were recorded during 5-minute ET-CPAP, and signs of clinical instability were monitored.Main outcomes and measuresFour clinical events were documented during ET-CPAP: apnea requiring stimulation, presence and cumulative durations of bradycardia and desaturation, and increased supplemental oxygen. Clinical event occurrence was assessed and compared between extubation pass and fail (defined as reintubation within 7 days). An automated algorithm was developed to generate SBT definitions using all clinical event combinations and to compute diagnostic accuracies of an SBT in predicting extubation success.ResultsOf 259 neonates (139 [54%] male) with a median gestational age of 26.1 weeks (interquartile range [IQR], 24.9-27.4 weeks) and median birth weight of 830 g (IQR, 690-1019 g), 147 (57%) had at least 1 clinical event during ET-CPAP. Apneas occurred in 10% (26 of 259) of neonates, bradycardias in 19% (48), desaturations in 53% (138), and increased oxygen needs in 41% (107). Neonates with successful extubation (71% [184 of 259]) had significantly fewer clinical events (51% [93 of 184] vs 72% [54 of 75], P = .002), shorter cumulative bradycardia duration (median, 0 seconds [IQR, 0 seconds] vs 0 seconds [IQR, 0-9 seconds], P < .001), shorter cumulative desaturation duration (median, 0 seconds [IQR, 0-59 seconds] vs 25 seconds [IQR, 0-90 seconds], P = .003), and less increase in oxygen (median, 0% [IQR, 0%-6%] vs 5% [0%-18%], P < .001) compared with neonates with failed extubation. In total, 41 602 SBT definitions were generated, demonstrating sensitivities of 51% to 100% (median, 96%) and specificities of 0% to 72% (median, 22%). Youden indices for all SBTs ranged from 0 to 0.32 (median, 0.17), suggesting low accuracy. The SBT with highest Youden index defined SBT pass as having no apnea (with desaturation requiring stimulation) or increase in oxygen requirements by 15% from baseline and predicted extubation success with a sensitivity of 93% and a specificity of 39%.Conclusions and relevanceThe findings suggest that extremely preterm neonates commonly show signs of clinical instability during ET-CPAP and that the accuracy of multiple clinical event combinations to define SBTs is low. Thus, SBTs may provide little added value in the assessment of extubation readiness.
| S-EPMC6990705 | biostudies-literature
Project description:BackgroundThere is an increasing interest in safely delivering high dose of inhaled nitric oxide (NO) as an antimicrobial and antiviral therapeutics for spontaneously breathing patients. A novel NO delivery system is described.MethodsWe developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide. The performance of the system was tested using a mechanical lung, assessing the NO concentration delivered at varying inspiratory flows. Safety was assessed in vitro and in vivo by measuring nitrogen dioxide (NO2) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO2 of this system in 5 healthy subjects during a 15-min administration of high dose NO (160 parts-per-million, ppm) using our delivery system.ResultsThe system demonstrated stable delivery of prescribed NO levels at various inspiratory flow rates (0-50 L/min). The reservoir bag and a high flow of entering air minimized the oscillation of NO concentrations during inspiration on average 4.6 ppm for each 10 L/min increment in lung inspiratory flow. The calcium hydroxide scavenger reduced the inhaled NO2 concentration on average 0.9 ppm (95% CI -1.58, -0.22; p = .01). We performed 49 NO administrations of 160 ppm in 5 subjects. The average concentration of inspired NO was 164.8±10.74 ppm, with inspired NO2 levels of 0.7±0.13 ppm. The subjects did not experience any adverse events; transcutaneous methemoglobin concentrations increased from 1.05±0.58 to 2.26±0.47%.ConclusionsThe system we developed to administer high-dose NO for inhalation is easy to build, reliable, was well tolerated in healthy subjects.
| S-EPMC7441999 | biostudies-literature
Project description:An effective delivery strategy coupled with relevant social and behaviour change communication (SBCC) have been identified as central to the implementation of micronutrient powders (MNP) interventions, but there has been limited documentation of what works. Under the auspices of "The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance," three working groups were formed to summarize experiences and lessons across countries regarding MNP interventions for young children. This paper focuses on programmatic experiences related to MNP delivery (models, platforms, and channels), SBCC, and training. Methods included a review of published and grey literature, interviews with key informants, and deliberations throughout the consultation process. We found that most countries distributed MNP free of charge via the health sector, although distribution through other platforms and using subsidized fee for product or mixed payment models have also been used. Community-based distribution channels have generally shown higher coverage and when part of an infant and young child feeding approach, may provide additional benefit given their complementarity. SBCC for MNP has worked best when focused on meeting the MNP behavioural objectives (appropriate use, intake adherence, and related infant and young child feeding behaviours). Programmers have learned that reincorporating SBCC and training throughout the intervention life cycle has allowed for much needed adaptations. Diverse experiences delivering MNP exist, and although no one-size-fits-all approach emerged, well-established delivery platforms, community involvement, and SBCC-centred designs tended to have more success. Much still needs to be learned on MNP delivery, and we propose a set of implementation research questions that require further investigation.
| S-EPMC5656897 | biostudies-literature
Project description:Recently, the isolation and elucidation of a series of polyhydroxyanthraquinones were reported from an organic extract of a solid phase culture of an endophytic fungus, Penicillium restrictum (strain G85). One of these compounds, ω-hydroxyemodin (1: ), showed promising quorum-sensing inhibition against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) in both in vitro and in vivo models. The initial supply of 1: was 19 mg, and this amount needed to be scaled by a factor of 30 to 50 times, in order to generate material for further in vivo studies. To do so, improvements were implemented to enhance both the fermentation of the fungal culture and the isolation of this compound, with the target of generating > 800 mg of study materials in a period of 13 wk. Valuable insights, both regarding chemistry and mycology, were gained during the targeted production of 1: on the laboratory-scale. In addition, methods were modified to make the process more environmentally friendly by judicious choice of solvents, implementing procedures for solvent recycling, and minimizing the use of halogenated solvents.
| S-EPMC7511429 | biostudies-literature
Project description:AimWe compared effects of infant positioning and feed-rate interventions on respiratory events and oximetry parameters in spontaneously breathing preterm infants born <32 weeks gestation managed in a neonatal unit.MethodsA randomised triple crossover design was employed. n = 68 infants underwent three test conditions A: control (supine/flat, gravity bolus feeds), B: position intervention (propped/prone) and C: feed-rate intervention (continuous pump feeds) in randomised sequence over three consecutive days. Primary outcomes were number of events (apnoea, bradycardia and desaturation) and percentage time SpO2 < 80% over 24 h. The secondary outcome was percentage time SpO2 ≥ 88%. Treatment effects were estimated using linear mixed-effects models.ResultsPropped/prone positioning significantly reduced events and improved percentage time SpO2 < 80% and ≥88% compared to both other conditions (all P < 0.001). Outcomes for the feed-rate intervention were not significantly different to control.ConclusionsAlternative infant positioning should be considered in preterm infants managed in the neonatal unit.
| S-EPMC10092656 | biostudies-literature
Project description:Purpose: Dysfunctional breathing behaviors are prevalent in chronic obstructive pulmonary disease (COPD). Although these behaviors contribute to dyspnea, abnormal carbon dioxide (CO2) levels, and COPD exacerbations, they are modifiable. Current dyspnea treatments for COPD are suboptimal, because they do not adequately address dysfunctional breathing behaviors and anxiety together. We developed a complementary mind-body breathlessness therapy, called capnography-assisted respiratory therapy (CART), that uses real-time CO2 biofeedback at the end of exhalation (end-tidal CO2 or ETCO2), to target dysfunctional breathing habits and improve dyspnea treatment and pulmonary rehabilitation (PR) adherence in COPD. The study aim was to test the feasibility of integrating CART with a traditional, clinic-based PR program in an urban setting. Methods: We used a feasibility pre- and post-test design, with 2:1 randomization to CART+PR or control (PR-alone) groups, to test and refine CART. Multi-component CART consisted of six, 1-h weekly sessions of slow breathing and mindfulness exercises, ETCO2 biofeedback, motivational counseling, and a home program. All participants were offered twice weekly, 1-h sessions of PR over 10 weeks (up to 20 sessions). Results: Thirty-one participants with COPD were enrolled in the study. Approximately a third of participants had symptoms of psychological distress. Results showed that CART was feasible and acceptable based on 74% session completion and 91.7% homework exercise completion (n = 22). Within-group effect sizes for CART+PR were moderate to large (Cohen's d = 0.51-1.22) for reduction in resting Borg dyspnea (anticipatory anxiety) and respiratory rate, St. George's Respiratory Questionnaire (SGRQ) respiratory symptoms; and increase in Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and physical activity; all p < 0.05. Conclusions: CART is a new mind-body breathing therapy that targets eucapnic breathing, interoceptive function, and self-regulated breathing to relieve dyspnea and anxiety symptoms in COPD. Study findings supported the feasibility of CART and showed preliminary signals that CART may improve exercise tolerance, reduce dyspnea, and enhance PR completion by targeting reduced dysfunctional breathing patterns (CTR No. NCT03457103).
| S-EPMC10024272 | biostudies-literature
Project description:PurposeNearly one in three US adolescents meet the criteria for anxiety, an issue that has worsened with the COVID-19 pandemic. We developed a video-based slow diaphragmatic breathing stress-reduction curriculum for high school students and evaluated its feasibility, tolerability, and preliminary effectiveness.MethodsThis cluster-randomized feasibility pilot compared 5-min slow diaphragmatic breathing for 5 weeks with treatment-as-usual control among four 12th-grade public high school classes. Students individually participated after school during COVID-19-related hybrid teaching, with slow diaphragmatic breathing three times/week and breath science education once/week. Feasibility was based on completion of breathing exercises, breath science education, and preliminary effectiveness assessments, and ease/tolerability was based on qualitative assessments. Preliminary effectiveness was measured with the State-Trait Anxiety Inventory (STAI) and a timed-exhale carbon dioxide tolerance test (CO2TT) of physiological stress response. Descriptive statistics and repeated analysis of variance were performed to quantify and compare outcomes between time periods. Human subjects research approval was granted through Western IRB-Copernicus Group (WCG IRB) [ClinicalTrials.gov, Identifier: NCT05266833.].ResultsForty-three students consented to participate. Breath practice compliance ranged from 29 to 83% across classes and weeks, and decreased on average over the 5 weeks. Compliance with the breath science videos ranged from 43 to 86%, and that with the weekly STAI-State and CO2TT measures varied from 36 to 86%. Compliance with ease/tolerability assessments ranged from 0 to 60%. Preliminary effectiveness assessments' compliance varied across classes from 83 to 89% during baseline, and 29 to 72% at follow-up. The curriculum was rated as somewhat-to-definitely useful/beneficial, and definitely-to-very easy/tolerable. Students reported enjoying the diaphragmatic breathing, CO2TT, and breath science education; some found the extended exhales challenging and the curriculum and assessments time-consuming. Preliminary effectiveness analyses indicated no significant changes in STAI or CO2TT from baseline to followup or from before to after breathing exercises (p > 0.05 for all).ConclusionsImplementation of this 5-week slow breathing curriculum was feasible and tolerable to this cohort. Compliance, tolerability, and effectiveness may be improved with in-class participation. Future research on simple and accessible slow-breathing exercises is warranted to address today's adolescent stress-management crisis.Trial registrationClinicalTrials.gov, Identifier: NCT05266833.
| S-EPMC9397716 | biostudies-literature
Project description:There are concerns regarding the risk and the course of COVID-19 in pregnancy and in the neonates. In this review, we aimed to present the current understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and neonatal periods considering diagnosis, treatment, prognosis, and prevention. Few studies on pregnant women with COVID-19 have been conducted between December 2019 and April 2020. The majority of patients applied in the third trimester and presented with fever and cough. Ground-glass opacities and consolidation on computed tomography were reported to be common. COVID-19 was proposed to have a milder course than SARS and the Middle East respiratory syndrome coronavirus in pregnant women. Hydroxychloroquine and antiproteases (lopinavir/ritonavir) were reported to be safe; however, therapeutic efficacy and safety of remdesivir still lack evidence. As ribavirin and favipiravir have teratogenic effects, there are some debates on the use of ribavirin in severe cases. There is still no clear evidence of vertical transmission of SARS-CoV-2 during delivery. Occupational safety issues of pregnant healthcare workers on the frontline should be considered as their risk to develop severe pneumonia is higher because of altered maternal immune response. Knowledge about neonatal outcomes of COVID-19 was based on studies of the last trimester of pregnancy. There is much to be learnt about COVID-19 in pregnant women and in the neonates, especially concerning prognosis- and treatment-related issues.
| S-EPMC7311134 | biostudies-literature
Project description:Complex three-dimensional (3D) in vitro model systems that recapitulate human tumor biology are essential to better understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellula communication, nutrient and oxygen gradients, and cell polarity that is lacking in traditional two-dimensional (2D) monolayer cultures. In the present study, we could demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents. Changes in the kinase activities of Erb family members and differential expression of apoptosis- and survival-associated genes before and after drug treatment may account for the differential drug sensitivities. Importantly, EGFR oncoprotein addiction was evident only in the 3D cultures mirroring the effect of EGFR inhibition in the clinic. Furthermore, targeted drug efficacy was strongly increased when incorporating cancer-associated fibroblasts into the 3D cultures. Taken together, we could provide conclusive evidence that complex 3D cultures are more predictive of the clinical outcome than their 2D counterparts. In the future, 3D cultures will be instrumental for understanding the mode of action of drugs, identifying genotype-drug response relationships and developing patient-specific and personalized cancer treatments.
2017-11-30 | GSE102722 | GEO
Project description:Vaginal delivery of antimicrobial drugs is the most effective method for the local treatment of the vaginal infections. However, current vaginal drug delivery systems (VDDS), including gel, lotion, aerosol and cream, are suffering from low penetration in the deep vaginal rugae and easy elimination by self-cleaning of vaginal canal. To address these issues, a foam aerosol based on the thermal transformation was designed to improve penetration efficiency and achieve the extended retention. The expansible thermal gelling foam aerosol (ETGFA) consisting of thermal sensitive matrix, silver nanoparticle, adhesive agent and propellant, was optimized by evaluations of precursor viscosity, foam expansion, thermal gelation, gel adhesiveness, antimicrobial effects and tissue irritation. The ETGFA would penetrate to the deep vaginal rugae to cover the infectious sites by foam expansion. Drug leakage was intended to be avoided by the thermal gelation at physiological temperature before foam collapse. The gel could be retained in the vaginal canal for extended time due to its superior adhesiveness when compared to the commercial gel Asimi®. The ETGFA provided extended drug release for over 4 h and maintained effective drug concentrations at the infectious sites. The ETGFA containing silver nanoparticles showed dose-dependent antimicrobial effects on the vaginal floras and irritation reduction to the vaginal tissues. The results demonstrated that the ETGFA could overcome the limitations of conventional dosage forms, including poor drug penetration, carrier retention and patient compliance and satisfied the requirements for vaginal drug delivery.
| S-EPMC8241080 | biostudies-literature