The Effects of Inspiratory Flows, Inspiratory Pause, and Suction Catheter on Aerosol Drug Delivery with Vibrating Mesh Nebulizers During Mechanical Ventilation.

Background: Some experts recommend specific ventilator settings during nebulization for mechanically ventilated patients, such as inspiratory pause, high inspiratory to expiratory ratio, and so on. However, it is unclear whether those settings improve aerosol delivery. Thus, we aimed to evaluate the impact of ventilator settings on aerosol delivery during mechanical ventilation (MV). Methods: Salbutamol (5.0 mg/2.5 mL) was nebulized by a vibrating mesh nebulizer (VMN) in an adult MV model. VMN was placed at the inlet of humidifier and 15 cm away from the Y-piece of the inspiratory limb. Eight scenarios with different ventilator settings were compared with endotracheal tube (ETT) connecting 15 cm from the Y-piece, including tidal volumes of 6-8 mL/kg, respiratory rates of 12-20 breaths/min, inspiratory time of 1.0-2.5 seconds, inspiratory pause of 0-0.3 seconds, and bias flow of 3.5 L/min. In-line suction catheter was utilized in two scenarios. Delivered drug distal to the ETT was collected by a filter, and drug was assayed by an ultraviolet spectrophotometry (276 nm). Results: Compared to the use of inspiratory pause, the inhaled dose without inspiratory pause was either higher or similar across all ventilation settings. Inhaled dose was negatively correlated with inspiratory flow with VMN placed at 15 cm away from the Y-piece (rs = -0.68, p < 0.001) and at the inlet of humidifier (rs = -0.83, p < 0.001). The utilization of in-line suction catheter reduced inhaled dose, regardless of the ventilator settings and nebulizer placements. Conclusions: When VMN was placed at the inlet of humidifier, directly connecting the Y-piece to ETT without a suction catheter improved aerosol delivery. In this configuration, the inhaled dose increased as the inspiratory flow decreased, inspiratory pause had either no or a negative impact on aerosol delivery. The inhaled dose was greater with VMN placed at the inlet of humidifier than 15 cm away the Y-piece.

Effect of Interrupting Heated Humidification on Nebulized Drug Delivery Efficiency, Temperature, and Absolute Humidity During Mechanical Ventilation: A Multi-Lab In Vitro Study.

Introduction: During mechanical ventilation (MV), inspired gases require heat and humidification. However, such conditions may be associated with reduced aerosol delivery efficiency. The practice of turning off heated humidification before nebulization and the impact of nebulization on humidity in a dry ventilator circuit remain topics of debate. This study aimed to assess the effect of turning off heated humidification on inhaled dose and humidity with nebulizer use during adult MV. Methods: A bronchodilator (albuterol) and two antibiotics (Colistimethate sodium and Amikacin sulfate) were nebulized with a vibrating mesh nebulizer placed at the humidifier inlet and in the inspiratory limb at the Y-piece. Additionally, albuterol was nebulized using a jet nebulizer in both placements. Aerosol particle size distribution was determined through a cascade impactor. Absolute humidity (AH) and temperature of inspired gases were determined with anemometer/hygrometers before, during, and after nebulization, before, during, and up to 60 minutes after interrupting active humidification. Aerosol collected on a filter distal to the endotracheal tube and on impactor stages were eluted and assayed by spectrophotometry. Results: The inhaled dose was greater when both nebulizers were placed at the humidifier inlet than the inspiratory limb at the Y-piece. Irrespective of the nebulizer types and placements, the inhaled dose either decreased or showed no significant change after the humidifier was turned off. The aerosol particle size ranged from 1.1 to 2.7 µm. With interruption of active humidification, humidity of inspired gas quickly dropped below recommended levels, and nebulization in dry ventilator circuit produced an AH between 10 and 20 mgH2O/L, lower than the recommended minimum of 30 mgH2O/L. Conclusion: Interrupting active humidification during MV before nebulization did not improve aerosol delivery efficiency for bronchodilator or antibiotics, but did reduce humidity below recommended levels.

Exploration of treatment in childhood Langerhans cell histiocytosis based on inflammatory and malignant symptoms: a pilot study.

BACKGROUND: Multisystem childhood Langerhans cell histiocytosis (LCH) patients, especially those with risk organ (RO) involved, had not been satisfactorily treated under the international traditional schemes as high incidences of reactivation with late sequelae were largely reported. Over years, we have observed that LCH patients with varied clinical symptoms responded differently to different drugs, suggesting the current grouping strategies based only on the number of organs involved might be inadequate. LCH has been defined as an inflammatory myeloid tumor, thus this study has innovatively divided LCH pediatric patients into inflammatory or malignant symptoms group, and given different intensity treatment regimens to different groups. AIM: This clinical study aimed to explore a more appropriate patient grouping system according to the LCH symptom presentations and examine the clinical outcomes of treatment strategies in different groups. METHODS: According to the clinical manifestations, 37 cases of children were divided into Group A (only inflammatory symptoms) and Group B (malignant symptoms with or without inflammatory symptoms). Patients in Group A and B were initially treated with vindesine (VDS) and methylprednisolone (PSL), and VDS, PSL, pirarubicin (THP) and cyclophosphamide (CTX), respectively. Treatment responses were evaluated six weeks after the induction therapy in all patients, and the criteria were disease status and clinical scores of symptoms. RESULTS: Pre- and post-treatment scores were 1.22 ± 0.547 and 0.00 ± 0.00 in Group A, and 14.79 ± 1.686 and 1.00 ± 1.563 in Group B, respectively. All patients had subsequentlly received maintenance therapy without progressive disease. The 4-year overall survival (OS) rate was 100% in both groups and the 4-year event-free survival (EFS) was 94.4% in Group A and 89.5% in Group B, respectively. There were no obvious adverse events (AE) in Group A, whereas the main AE in Group B were alopecia and non-lethal hematological toxicity. CONCLUSION: Stratification according to patients' clinical symptoms, with low-intensity treatment for inflammatory symptoms (mild manifestations) and intensive treatment with multiple drugs for malignant symptoms (severe manifestations), is a positive exploration that simplifies stratification method, achieves good long-term remission of the disease, and obtains a higher survival rate and quality of life, which seemed to be more appropriate for LCH patients.

Factors associated with continuing education needs in medication administration among school nurses.

AIM: To investigate the continuing education requirements and factors influencing school nurses' needs in relation to medication administration on school campuses. DESIGN: A total of 391 school nurses working in K-12 schools in Taiwan were invited to participate in an online questionnaire survey. METHODS: This cross-sectional study employed a probability proportionate to size technique along with a random sampling method. Data were collected from February to April 2023. RESULTS: School nurses reported a significant demand for continuing education and perceived moderate levels of stress and government support related to medication administration. Among the various dimensions, the highest demand was observed for 'definition of campus medication errors' and 'regulations for campus medical orders.' Moreover, the 'identifying drug interactions' and 'adverse drug effects and referrals' dimensions were identified as the most stressful aspects. Notably, perceived stress emerged as the sole predictive factor for continuing education demand, accounting for 16.1% of the variance. CONCLUSIONS: The study found that there was a significant demand for and moderate stress related to continuing education among school nurses. Therefore, it is crucial for the government and school nursing organizations to develop targeted programs focusing on medication administration. These initiatives should be designed to enhance nurses' capabilities and reduce their stress, thereby ensuring safe medication administration on campuses. IMPACT: Continuing education enables school nurses to acquire up-to-date knowledge and improve the workflow in their practice. This study highlights a strong need for education in medication administration with a focus on 'campus medication error definitions' and 'campus medical order regulations.' The government and relevant school nursing organizations should prioritize the development and implementation of continuing education programs to decrease the school nurses' stress related to medication administration. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. REPORTING METHOD: This study adhered to the relevant cross-sectional EQUATOR STROBE guidelines.

Competence and Stress of Medication Administration Practices for School Nurses in K-12 Taiwan Schools.

We investigated school nurses' experiences, perceived government support, school nurses' acceptance of responsibility for medication administration, perceived stress, and perceived competence of medication administration and analyzed factors associated with perceived competence. In this cross-sectional study, from February to April 2023, we conducted an online survey of 269 school nurses serving at K-12 schools in Taiwan. The results revealed that although 71% of the participants had prior experience with medication administration, they reported low competence and high stress in areas such as drug interactions, adverse drug effects, and referrals. The school nurses' disagreement with responsibilities for medication administration emerged as the only factor to be significantly associated with perceived medication administration competence, accounting for 22.8% of the variance. We recommend implementing continuing training programs to provide school nurses with up-to-date medication information. Additionally, the development of practice guidelines is suggested as a means of enhancing nurses' competence and reducing their stress levels for the administration of medications.

Aerosol therapy in adult critically ill patients: a consensus statement regarding aerosol administration strategies during various modes of respiratory support.

BACKGROUND: Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence. OBJECTIVES: To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research. METHODS: A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus. RESULTS: We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings. CONCLUSIONS: We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.

[Reducing the Incidence of Postoperative Hypothermia in Patients Undergoing Robotic-Assisted Mitral Valve Surgery].

BACKGROUND & PROBLEMS: Post-operation hypothermia tends to induce complications. Sixty percent of robotic-assisted mitral valve surgery patients experienced hypothermia while admitted to our intensive care unit (ICU), resulting in prolonged ICU stays and 57% (eight) of those patients with hypothermia also experiencing cardiac arrhythmia. The causes of hypothermia in our ICU included low temperature in the operating room, delayed initiation of blanket coverage after surgery, and lack of postoperative thermal blankets, insufficient cardiopulmonary bypass rewarming time, cold ICU beds, lack of in-service training for hypothermia, and lack of procedure auditing. PURPOSE: This intervention was designed to reduce the incidence of hypothermia in ICU patients undergoing robotic-assisted mitral valve surgery upon ICU admission from 60% to 36% and the one-hour hypothermia rate from 43.3% to 26%. RESOLUTIONS: We implemented several measures including increasing the room temperature, pre-heating the ICU bed, achieving team consensus regarding prolonging the rewarming time after cardiopulmonary bypass, establishing a blanket warming area for postoperative patient use, and holding in-service training to enhance the awareness of the nurses were implemented. RESULTS: The incidence of hypothermia in ICU patients receiving robotic-assisted mitral valve surgery upon ICU admission decreased from 60% to 19.4%, while the one-hour hypothermia rate decreased from 43.3% to 19.4%. CONCLUSIONS: Using systemic interprofessional collaboration, combined thermal care can be achieved to significantly reduce the incidence of postoperative hypothermia in patients undergoing robotic-assisted mitral valve surgeries resulting in higher patient care quality and shorter ICU stays. We recommend applying this combined method to improve the quality of perioperative care for long-duration and major surgical procedures that involve large postoperative wounds and for patients who may require wider exposure during their operation.

Influence of Aerosol Mask Design on Fugitive Aerosol Concentrations During Nebulization.

BACKGROUND: Secondhand exposure to fugitive aerosols may cause airway diseases in health providers. We hypothesized that redesigning aerosol masks to be closed-featured would reduce the fugitive aerosol concentrations during nebulization. This study aimed to evaluate the influence of a mask designed for a jet nebulizer on the concentration of fugitive aerosols and delivered doses. METHODS: An adult intubation manikin was attached to a lung simulator to mimic normal and distressed adult breathing patterns. The jet nebulizer delivered salbutamol as an aerosol tracer. The nebulizer was attached to 3 aerosol face masks: an aerosol mask, a modified non-rebreathing mask (NRM, with no vent holes), and an AerosoLess mask. An aerosol particle sizer measured aerosol concentrations at parallel distances of 0.8 m and 2.2 m and a frontal distance of 1.8 m from the manikin. The drug dose delivered distal to the manikin's airway was collected, eluted, and analyzed using a spectrophotometer at a 276 nm wavelength. RESULTS: With a normal breathing pattern, the trends of aerosol concentrations were higher with an NRM followed by an aerosol mask and AerosoLess mask (P < .001) at 0.8 m; however, the concentrations were higher with an aerosol mask followed by NRM and AerosoLess mask at 1.8 m (P < .001) and 2.2 m (P < .001). With a distressed breathing pattern, the aerosol concentrations were higher with an aerosol mask followed by an NRM and AerosoLess mask at 0.8 m, 1.8 m (P < .001), and 2.2 m (P = .005). The delivered drug dose was significantly higher with AerosoLess mask with a normal breathing pattern and with an aerosol mask with a distressed breathing pattern. CONCLUSIONS: Mask design influences fugitive aerosol concentrations in the environment, and a filtered mask reduces the concentration of aerosols at 3 different distances and with 2 breathing patterns.

Predicting Inhaled Drug Dose Generated by Mesh Nebulizers.

Background: The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for measuring breath patterns and a formula for estimating inhaled drugs, and then to validate the hypothesized prediction formula. Methods: An in vitro model was first used to determine correlations among the delivered dose, breath patterns, and doses deposited on the accessories and reservoirs testing with a breathing simulator to generate 12 adult breathing patterns (n = 5). A pressure sensor was developed to measure breathing parameters and used along with a prediction formula that accounted for the initial charge dose, respiratory pattern, and dose on the accessory and reservoir of a nebulizer. Three brands of nebulizers were tested by placing salbutamol (5.0 mg/2.5 mL) in the drug holding chamber. Ten healthy individuals participated in the ex vivo study to validate the prediction formula. The agreement between the predicted and inhaled doses was analyzed using the Bland-Altman plot. Results: The in vitro model showed that the inspiratory time to total respiratory cycle time (Ti/Ttotal; %) was significantly directly correlated with the delivered dose among the respiratory factors, followed by inspiratory flow, respiratory rate, and tidal volume. The ex vivo model showed that Ti/Ttotal was significantly directly correlated with the delivered dose among the respiratory factors, in addition to the nebulization time and accessory dose. The Bland-Altman plots for the ex vivo model showed similar results between the two methods. Large differences in inhaled dose measured at the mouth were observed among the subjects, ranging from 12.68% to 21.68%; however, the difference between the predicted dose and inhaled dose was lower, at 3.98%-5.02%. Conclusions: The inhaled drug dose could be predicted with the hypothesized estimation formula, which was validated by the agreement between the inhaled and predicted doses of breathing patterns of healthy individuals.

Comparison of Hemodynamic and Cerebral Oxygenation Responses during Exercise between Normal-Weight and Overweight Men.

Obesity has negative impacts on cardiovascular function and may increase cerebrovascular complications during exercise. We compared hemodynamic and cerebral oxygen changes during high-intensity exercise between overweight (OW) and normal-weight (NW) individuals. Eighteen NW and fourteen OW male individuals performed high-intensity (70% of peak oxygen uptake, VO2peak) cycling exercises for 30 min. Hemodynamics were measured using a bioelectrical impedance device, and cerebral oxygenation status was measured using a near-infrared spectrophotometer during and after exercise. The VO2peak of NW individuals was significantly higher than that of OW individuals (41.3 ± 5.7 vs. 30.0 ± 5.0 mL/min/kg, respectively; p < 0.05). During the 30 min exercise, both groups exhibited an increase in oxygenated hemoglobin (O2Hb) (p < 0.001), deoxygenated hemoglobin (p < 0.001), and cardiac output with increasing time. Post-exercise, cardiac output and systemic vascular resistance were significantly higher in the OW group than in the NW group (p < 0.05). The O2Hb in the NW group was significantly higher at post-exercise times of 20 min (13.9 ± 7.0 µmol/L) and 30 min (12.3 ± 8.7 µmol/L) than that in the OW group (1.0 ± 13.1 µmol/L and 0.6 ± 10.0 µmol/L, respectively; p = 0.024 vs. 0.023, respectively). OW participants demonstrated lower cerebral oxygenation and higher vascular resistance in the post-exercise phase than non-OW subjects. These physiological responses should be considered while engaging OW and obese individuals in vigorous exercise.

Burnout and Mental Health and Well-Being of School Nurses After the First Wave of the COVID-19 Pandemic: A National Cross-Sectional Survey.

The aim of this study was to examine the associations between job stressors, COVID-19-related concerns, burnout, and mental health and well-being among school nurses, and whether any of these associations are mediated by burnout. Based on stratified proportional sampling, data collection was conducted by an online questionnaire distributed to 600 school nurses in Taiwan. A total of 256 participants aged between 27 and 62 years (mean = 47.08; standard deviation = 7.28) returned questionnaires. Results showed that burnout was the main mediating variable that fully mediated the relationship between COVID-19-related concerns and mental health and well-being. The effects of job stressors on mental health and well-being included direct negative effects (ß = -.29) and indirect negative effects (ß = -.67) through mediating factors. School health managers should be more aware of burnout and mental health and well-being among school nurses under the impact of COVID-19.

Analysis of predictive parameters for extubation in very low birth weight preterm infants.

BACKGROUND: Mechanical ventilation is the primary treatment for preterm infants with respiratory failure. Prolonged intubation may lead to complications; thus, early extubation is desirable. No standard criteria exist for determining the appropriateness of extubating very-low-birth-weight (VLBW) infants. This study explored the predictors of successful extubation in preterm VLBW infants. METHODS: This retrospective cohort study included 60 preterm VLBW infants who underwent their first extubation in the neonatal intensive care unit in a regional hospital in Hsinchu, Taiwan, between January 2017 and November 2020. Successful extubation was defined as having no requirement of reintubation within 3 days of extubation. Potentially predictive variables, including demographics, prenatal characteristics, and ventilator parameters were compared between a successful extubation group and failed extubation group. RESULTS: Of the 60 infants, 47 (78.33%) underwent successful extubation. The successful extubation group had higher Apgar scores at 1 (7 vs. 6, P = 0.02) and 5 min (9 vs. 7, P = 0.007) than those of the failed extubation group. Ventilator inspiratory pressure and mean airway pressure were significantly lower at 24, 16, 8, and 1 h before extubation and upon its completion in the successful extubation group. The areas under a number of the receiver operating characteristic curve curves in this study were moderate, specifically, 0.72, 0.74, and 0.69. Statistical analysis revealed an association between ventilator parameters before 1 h extubation (IP > 17.5cmH2O, MAP >7.5 cmH2O, RSS >1.82) and extubation failure (odds ratio 1.73, 2.27, 2.46 and 95% confidence interval:1.16-2.6, 1.26-4.08, 1.06-5.68, respectively). CONCLUSION: Higher Apgar scores at birth, lower ventilator inspiratory pressure, and mean airway pressure 24, 16, 8, and 1 h and 1 h RSS prior to extubation are associated with successful extubation in VLBW preterm infants.

Treponema pallidum protein Tp0136 promoting MMPs/TIMPs imbalance via PI3K, MAPK and NF-κB signalling pathways in HDVSMCs.

The invasive capability of Treponema. pallidum is central to its infection process. Matrix metalloproteinases (MMPs), which are specifically inhibited by the tissue inhibitors of metalloproteinases (TIMPs), play a pivotal role in promoting pathogenic invasion by destroying tissue barriers within the body. This study aimed to explore the effect of T. pallidum protein Tp0136 on the balance of MMPs/TIMPs in human dermal vascular smooth muscle cells (HDVSMCs) and the related underlying mechanisms. A number of in vitro studies were conducted to access the impact of recombinant Tp0136 protein on the balance of MMPs/TIMPs in HDVSMCs. The involvement of the PI3K, MAPK, and NF-κB signaling pathways in this process was also investigated. Tp0136 induced the mRNA and protein expressions of MMP1 in HDVSMCs in a concentration-dependent way. In addition, MMP1/TIMP1 and MMP1/TIMP2 ratios were also increased. Furthermore, the study demonstrated that treatment of HDVSMCs with Tp0136 activated the PI3K, MAPK, and NF-κB signaling pathways. Inhibition of PI3K, JNK, P38, and NF-κB, suppressed MMP1 expression and reduced the induction of MMP1/TIMP1 and MMP1/TIMP2 ratios by Tp0136. These findings demonstrate that Tp0136 enhanced the expression of MMP1 involving the PI3K, MAPK, and NF-κB signaling pathways in HDVSMCs, and thus generated the unbalance of MMPs/TIMP, which could contribute to the early spread of T. pallidum and pathogenesis of syphilis.

Factors Associated With Follow-Up Visits in Parents With Myopic Children Wearing Orthokeratology Lens.

BACKGROUND: Orthokeratology (Ortho-k) is an effective method for slowing the progression of myopia and correcting refractive error in school children. Although parents of children aged < 10 years play a major role in Ortho-k lens care, they have a generally low level of compliance in performing regular follow-up visits. PURPOSE: This study was developed to analyze the associations between follow-up visits by parents of Ortho-k lens wearers aged < 10 years and, respectively, the Ortho-k-related knowledge of these parents and information resources promoting Ortho-k use. METHODS: A cross-sectional study design was used. Parents of children who wear Ortho-k lenses were recruited through a private Facebook group with 3,500 members in 2020 that was created in 2018 for information sharing and exchange among parents of these children. The following data were collected: demographics of the parents and their children, four-item Ortho-k-related knowledge, information resources that prompted the decision to use Ortho-k, and the regularity of follow-up visits. These data were presented in terms of means, standard deviations, and percentages. Logistic regression was performed to compute the odds ratios ( OR s) and 95% confidence intervals (CIs). RESULTS: The study showed that 83.11% had regular follow-up visits. The correct response rate on Ortho-k-related knowledge was > 80%. However, 15.51% of the participants did not recognize axial length as an indicator for monitoring myopia progress, and 10.76% did not know that at least 6 hours of nighttime sleep is required for myopia control with Ortho-k. The most common information resource leading to Ortho-k use was self-acquisition from Internet sources. The spherical equivalent refraction of < -2.0 D was 2.58 times higher in participants with regular follow-up visits than in their peers with irregular follow-up visits ( OR = 2.58, 95% CI [0.22, 5.63]). In addition, acknowledgment of "There is no need to change the Ortho-k lenses regularly as long as there is no discomfort" was 7.19 times higher in participants with regular follow-up visits than in their peers with irregular follow-up visits ( OR = 7.19, 95% CI [1.26, 13.93]). However, participants with regular follow-up visits did not receive Internet ophthalmology advertisements prompting their decision to use Ortho-k 2.62 times higher than their peers with irregular follow-up visits ( OR = 2.62, 95% CI [0.04, 4.29]). CONCLUSIONS: The results support that both information sources and knowledge of Ortho-k use influence the frequency of follow-up visits among parents of Ortho-k lens wearers aged < 10 years. Related support from health professionals in terms of providing appropriate information and guidance is recommended to promote higher rates of regular follow-up visit attendance.

Identifying Novel Clusters of Patients With Prolonged Mechanical Ventilation Using Trajectories of Rapid Shallow Breathing Index.

Objective: Patients with prolonged mechanical ventilation (PMV) are comprised of a heterogeneous population, creating great challenges for clinical management and study design. The study aimed to identify subclusters of PMV patients based on trajectories of rapid shallow breathing index (RSBI), and to develop a machine learning model to predict the cluster membership based on baseline variables. Methods: This was a retrospective cohort study conducted in respiratory care center (RCC) at a tertiary academic medical center. The RCC referral criteria were patients with mechanical ventilation for at least 21 days with stable hemodynamic and oxygenation status. Patients admitted to the RCC from April 2009 to December 2020 were screened. Two-step clustering through linear regression modeling and k-means was employed to find clusters of the trajectories of RSBI. The number of clusters was chosen by statistical metrics and domain expertise. A gradient boosting machine (GBM) was trained, exploiting variables on RCC admission, to predict cluster membership. Results: A total of 1371 subjects were included in the study. Four clusters were identified: cluster A showed persistently high RSBI; cluster B was characterized by a constant low RSBI over time; Cluster C was characterized by increasing RSBI; and cluster D showed a declining RSBI. Cluster A showed the highest mortality rate (72%), followed by cluster D (63%), C (62%) and B (61%; p = 0.005 for comparison between 4 clusters). GBM was able to predict cluster membership with an accuracy of > 0.95 in ten-fold cross validation. Highly ranked variables for the prediction of clusters included thyroid-stimulating hormone (TSH), cortisol, platelet, free thyroxine (T4) and serum magnesium. Conclusions: Patients with PMV are composed of a heterogeneous population that can be classified into four clusters by using trajectories of RSBI. These clusters can be easily predicted with baseline clinical variables.

Histone Deacetylase 3: A Potential Therapeutic Target for Atherosclerosis.

Atherosclerosis, the pathological basis of most cardiovascular disease, is characterized by plaque formation in the intima. Secondary lesions include intraplaque hemorrhage, plaque rupture, and local thrombosis. Vascular endothelial function impairment and smooth muscle cell migration lead to vascular dysfunction, which is conducive to the formation of macrophage-derived foam cells and aggravates inflammatory response and lipid accumulation that cause atherosclerosis. Histone deacetylase (HDAC) is an epigenetic modifying enzyme closely related to chromatin structure and gene transcriptional regulation. Emerging studies have demonstrated that the Class I member HDAC3 of the HDAC super family has cell-specific functions in atherosclerosis, including 1) maintenance of endothelial integrity and functions, 2) regulation of vascular smooth muscle cell proliferation and migration, 3) modulation of macrophage phenotype, and 4) influence on foam cell formation. Although several studies have shown that HDAC3 may be a promising therapeutic target, only a few HDAC3-selective inhibitors have been thoroughly researched and reported. Here, we specifically summarize the impact of HDAC3 and its inhibitors on vascular function, inflammation, lipid accumulation, and plaque stability in the development of atherosclerosis with the hopes of opening up new opportunities for the treatment of cardiovascular diseases.

Positive Airway Pressure at Extubation Minimizes Subglottic Secretion Leak In Vitro.

Accumulated secretion above the endotracheal tube cuff can be aspirated during extubation after deflation. The possible techniques for minimizing pulmonary aspiration from subglottic secretion during extubation have not been well explored. This study aimed to determine the effect of different extubation techniques on secretion leakage. An endotracheal tube was placed in a tube mimicking an airway. We measured the leak volume of water or artificial sputum of different viscosities with three extubation techniques-negative pressure with suctioning; positive pressure with a resuscitator; and continuous positive airway pressure set at 5, 10, and 20 cm H2O. Extubation with continuous positive airway pressure resulted in lower secretion leakage than that with negative pressure with suctioning and positive pressure with a resuscitator. Increasing the continuous positive airway pressure level decreased secretion leakage volume during extubation. We further determined a correlation of leak volume with sputum viscosity. Continuous positive airway pressure at 5 cm H2O produced lower volume secretion leakage than the other two techniques, even with higher secretion viscosity. Based on these results, using continuous positive airway pressure with a previous ventilator continuous positive airway pressure/positive end-expiratory pressure setting for extubation is recommended.

Effects of high flow nasal cannula on exercise endurance in patients with chronic obstructive pulmonary disease.

BACKGROUND: Ventilation limitation has a significant adverse effects on cardiovascular function and tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). High flow nasal cannula (HFNC) improve ventilation by washing out the anatomical dead space and providing oxygen at constant concentration. This study aimed to examine the effects of HFNC on the exercise performance and hemodynamic status in COPD patients. METHODS: Fifteen patients with COPD performed two constant load exercise tests (CLET) at the 70% of maximum workload achieved at a previous incremental exercise test on arm ergometer. The CLET were performed with HFNC and with nasal cannula (NC) in random order. The hemodynamics parameters of subjects during exercises were measured by a bioelectrical impedance device. The tissue oxygenation status (oxygenated hemoglobin, deoxygenated hemoglobin (hHb), total hemoglobin) was measured by a near infrared spectrophotometer. RESULTS: The exercise duration was longer for HFNC test than NC test (962.9 ± 281.7 s, vs 823.9 ± 184.9 s, p < 0.05). At the end of CLET, the PetCO2 was lower for HFNC than NC (29.3 ± 5.1 mmHg vs 32.1 ± 5.5 mmHg, p < 0.05). There was no difference in cardiac output (NC: 7.5 ± 1.8 vs HFNC: 7.4 ± 3.0 L,p > 0.05), stroke volume (NC:73.5 ± 21.0 vs HFNC 67.5 ± 16.3 ml, p > 0.05). The changes of hHb in muscle tissues was significantly lower in HFNC test than that in NC test (p < 0.05). CONCLUSION: HFNC resulted in a significant decrease in CO2 production and increase in exercise duration. The application of HFNC may improve the efficiency of exercise training by allowing patients to sustain exercise for longer time.

In Vitro Evaluation of Aerosol Delivery by Hand-Held Mesh Nebulizers in an Adult Spontaneous Breathing Lung Model.

Background: Drug inhalation is common mode of treatment for chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the efficiency of aerosol devices in a simulated COPD adult lung model using five commercially available hand-held mesh nebulizers. Materials and Methods: Five nebulizers (PARI VELOX®, Omron NE-U22, Aeroneb® Go, APEX PY001, and Pocket Air®) were tested with a unit dose of 5.0 mg/2.5 mL salbutamol. An in vitro lung model (compliance: 0.06 L/cm H2O, resistance: 20 cm H2O/L/sec) was constructed to simulate parameters (tidal volume of 500 mL, respiratory rate of 15 breaths/min, inspiratory time of 1 second) of an adult patient with COPD. A bacterial filter was attached at the bronchi level for drug collection, referring as inhaled mass. After nebulization, the inhaled mass (%), dose remaining on each component (%), particle size characteristics, and nebulizer performances were analyzed. Particle size characteristics were analyzed using an 8-stage Anderson Cascade Impactor. The salbutamol particles deposited were eluted and analyzed using a spectrophotometer at 276 nm. The inhaled mass (%), dose remaining on each component (%), particle size distribution, and nebulizer performance were statistically analyzed using analysis of variance (ANOVA) with Sheffee post hoc tests. Results: Pocket Air and APEX PY001 showed the greatest inhaled mass and the lowest dose in the mouthpiece connection. The largest and smallest mass median aerodynamic diameters were found with Omron NE-U22 and PARI VELOX, respectively. In addition, the output rate and inhaled aerosol rate (IAR) of PARI VELOX were higher than those of other nebulizers. Conclusions: This study showed that the performance of commercially available mesh nebulizers varied. Aerosol particles deposited on different auxiliary equipment directly influenced the output rate and IAR of the mesh nebulizer. Clinical validation of the drug IAR is necessary to avoid overdose and reduce drug wastage.

The Effects of a Scenario-Based Spiritual Care Course on Spiritual Care Competence among Clinical Nurses: A Quasi-Experimental Study.

Across their lifespans, and in many clinical settings, patients have spiritual care needs. Many nurses lack competence related to providing spiritual care. Popular educational strategies, such as simulated educational programs and objective structured clinical examinations (OSCE), have not been widely adopted in nursing spiritual care education. The purpose of this study was to explore the effects of a scenario-based spiritual care course on spiritual care competence in nurses. This quasi-experimental study employed a repeated-measures pre-test/post-test design with assessments immediately before, immediately after, and 3 months post-intervention. Nurses providing direct patient care in diverse clinical settings were recruited from a large medical foundation in northern Taiwan. The intervention was a one day scenario-based spiritual care course and OSCE. The experimental group (n = 53) and controls (n = 85) were matched for their similar units, ages, working experience, and clinical ladder status. The Spiritual Care Competence Scale (SCCS), Spiritual Perspective Scale (SPS), Spiritual Care Perspective Scale-Revised (SCPS-R), and reflection logs were completed by both experimental and control groups. The Course Satisfaction Scale, OSCE Checklist, and Standardized Patient Feedback Scale (SPFS) were completed by the experimental group only. The experimental group had significantly higher SPS scores and self-evaluated SCCS scores, and lower SCPS-R scores (more positive spiritual perspectives), than controls at 3 months post-intervention. The experimental group showed significant within-subject effects at three time points on SPS scores, SCPS-R scores, and self-evaluated SCCS scores. Mean global performance of OSCE was 3.40 ± 0.91, and SP feedback indicated strengths and areas for improvement. In conclusion, the scenario-based spiritual care course effectively enhanced nurses' spiritual care competence, competence, and skills. Blended education techniques can therefore enhance nurses' ability to support patients with spiritual care needs.