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Biomechanics and Modeling in... Jun 2024Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and...
Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and development. Variability in stenosis onset, duration, and severity result in variable growth and remodeling of the pulmonary vasculature. Computational fluid dynamics (CFD) models enable investigation into the hemodynamic impact and altered mechanics associated with PAS. In this study, a one-dimensional (1D) fluid dynamics model was used to simulate hemodynamics throughout the pulmonary arteries of individual animals. The geometry of the large pulmonary arteries was prescribed by animal-specific imaging, whereas the distal vasculature was simulated by a three-element Windkessel model at each terminal vessel outlet. Remodeling of the pulmonary vasculature, which cannot be measured in vivo, was estimated via model-fitted parameters. The large artery stiffness was significantly higher on the left side of the vasculature in the left pulmonary artery (LPA) stenosis group, but neither side differed from the sham group. The sham group exhibited a balanced distribution of total distal vascular resistance, whereas the left side was generally larger in the LPA stenosis group, with no significant differences between groups. In contrast, the peripheral compliance on the right side of the LPA stenosis group was significantly greater than the corresponding side of the sham group. Further analysis indicated the underperfused distal vasculature likely moderately decreased in radius with little change in stiffness given the increase in thickness observed with histology. Ultimately, our model enables greater understanding of pulmonary arterial adaptation due to LPA stenosis and has potential for use as a tool to noninvasively estimate remodeling of the pulmonary vasculature.
PubMed: 38918266
DOI: 10.1007/s10237-024-01850-6 -
International Journal of Antimicrobial... Jun 2024Insufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance....
BACKGROUND
Insufficient exposure and poor compliance with anti-tuberculosis (TB) medications are risk factors for treatment failure and the development of drug resistance. Measurement of drugs in biological samples, such as blood and saliva, can be used to assess adherence and make dose adjustments by therapeutic drug monitoring (TDM). Finger sweat testing is a convenient and non-invasive method to monitor patients.
OBJECTIVES
To assess the feasibility of finger sweat testing for medication adherence and as a semi-quantitative tool for TDM analysis.
METHODS
Ten patients provided finger sweat, blood and saliva samples following a controlled dose of isoniazid. Samples were analysed by liquid chromatography-mass spectrometry.
RESULTS
Isoniazid can be detected in finger sweat 1-6 h following administration at typically prescribed dosages. The normalisation of isoniazid to creatinine increases the correlation between finger sweat and serum isoniazid concentration and provides a means to account for inconsistent sample volumes.
CONCLUSION
We describe the time-course measurement of isoniazid (or drug-to-creatinine ratio) in finger sweat compared to the pharmacokinetic profile in blood for the first time. This technique, adaptable for other drugs, could reduce the burden on clinics and improve patient experience.
PubMed: 38918168
DOI: 10.1016/j.ijantimicag.2024.107231 -
International Journal of Pharmaceutics Jun 2024A challenge in development of peptide and protein therapeutics is rapid elimination from the body, necessitating frequent dosing that may lead to toxicities and/or poor...
A challenge in development of peptide and protein therapeutics is rapid elimination from the body, necessitating frequent dosing that may lead to toxicities and/or poor patient compliance. To solve this issue, there has been great investment into half-life extension of rapidly eliminated drugs using approaches such as albumin binding, fusion to albumin or Fc, or conjugation to polyethylene glycol. Despite clinical successes of half-life extension products, no clear relationship has been drawn between properties of drugs and the pharmacokinetic parameters of their half-life extended analogues. In this study, non-compartmentally derived pharmacokinetic parameters (half-life, clearance, volume of distribution) were collected for 186 half-life extended drugs and their unmodified parent molecules. Statistical testing and regression analysis was performed to evaluate relationships between pharmacokinetic parameters and a matrix of variables. Multivariate linear regression models were developed for each of the three pharmacokinetic parameters and model predictions were in good agreement with observed data with r values for each parameter being: half-life: 0.879, clearance: 0.820, volume of distribution: 0.937. Significant predictors for each parameter included the corresponding pharmacokinetic parameter of the parent drug and descriptors related to molecular weight. This model represents a useful tool for prediction of the potential benefits of half-life extension.
PubMed: 38917959
DOI: 10.1016/j.ijpharm.2024.124382 -
Scientific Reports Jun 2024Estimating the change rates in body size following the weight loss programs is very important in the compliance of those programs. Although, there is enough evidence on...
Estimating the change rates in body size following the weight loss programs is very important in the compliance of those programs. Although, there is enough evidence on the significant association of body weight change with the other anthropometric indices and/ or body composition, there is so limited studies that have depicted this relationship as mathematical formulas. Therefore, the present research designed to use a mathematical model to predict changes of anthropometric indices following a weight-loss diet in the overweight and obese women. In this longitudinal study, 212 overweight/obese women who received an individualized low-calorie diet (LCD) were selected and followed-up for five months. Anthropometric measurements such as weight, waist circumference (WC), hip circumference (HC), and body composition (lean mass and fat mass) were performed. Then, body mass index, waist to hip ratio (WHR), waist to height ratio (WHtR), a body shape index (ABSI), abdominal volume index (AVI), and body adiposity index (BAI) were calculated using the related formula. Following the LCD led to the substantial and consistent changes in various anthropometric indices over time. All of these anthropometric variations were significantly related with the percent change (PC) of body weight except than WHR. Moreover, according to the mathematical formulas, weight loss was closely related to the decrease of WC (PC-WC = - 0.120 + 0.703 × PC-WT), HC (PC-HC = - 0.350 + 0.510 × PC-WT), body fat percentage (PC-Body Fat = - 0.019 + 0.915 × PC-WT), WHtR (PC-WHtR = - 0.113 + 0.702 × PC-WT), and improvements in ABSI (PC-ABSI = - 0.112 + 0.034 × PC-WT) and AVI (PC-AVI = - 0.324 + 1.320 × PC-WT). The decreasing rates of WC, HC, body fat percentage, WHtR, ABSI, and AVI in relation to the weight loss were clinically and statistically significant. This means that a healthy weight lowering diet would be accompanied by decreasing the body fat, body size and also the risk of morbidities.
Topics: Humans; Female; Obesity; Adult; Weight Loss; Diet, Reducing; Middle Aged; Overweight; Anthropometry; Models, Theoretical; Longitudinal Studies; Body Mass Index; Waist Circumference; Waist-Hip Ratio; Body Composition; Caloric Restriction
PubMed: 38914732
DOI: 10.1038/s41598-024-65586-0 -
Scientific Reports Jun 2024Normally aerated lung tissue on computed tomography (CT) is correlated with static respiratory system compliance (C) at zero end-expiratory pressure. In clinical...
Normally aerated lung tissue on computed tomography (CT) is correlated with static respiratory system compliance (C) at zero end-expiratory pressure. In clinical practice, however, patients with acute respiratory failure are often managed using elevated PEEP levels. No study has validated the relationship between lung volume and tissue and C at the applied positive end-expiratory pressure (PEEP). Therefore, this study aimed to demonstrate the relationship between lung volume and tissue on CT and C during the application of PEEP for the clinical management of patients with acute respiratory distress syndrome due to COVID-19. Additionally, as a secondary outcome, the study aimed to evaluate the relationship between CT characteristics and C, considering recruitability using the recruitment-to-inflation ratio (R/I ratio). We analyzed the CT and respiratory mechanics data of 30 patients with COVID-19 who were mechanically ventilated. The CT images were acquired during mechanical ventilation at PEEP level of 15 cmHO and were quantitatively analyzed using Synapse Vincent system version 6.4 (Fujifilm Corporation, Tokyo, Japan). Recruitability was stratified into two groups, high and low recruitability, based on the median R/I ratio of our study population. Thirty patients were included in the analysis with the median R/I ratio of 0.71. A significant correlation was observed between C at the applied PEEP (median 15 [interquartile range (IQR) 12.2, 15.8]) and the normally aerated lung volume (r = 0.70 [95% CI 0.46-0.85], P < 0.001) and tissue (r = 0.70 [95% CI 0.46-0.85], P < 0.001). Multivariable linear regression revealed that recruitability (Coefficient = - 390.9 [95% CI - 725.0 to - 56.8], P = 0.024) and C (Coefficient = 48.9 [95% CI 32.6-65.2], P < 0.001) were significantly associated with normally aerated lung volume (R-squared: 0.58). In this study, C at the applied PEEP was significantly correlated with normally aerated lung volume and tissue on CT. Moreover, recruitability indicated by the R/I ratio and C were significantly associated with the normally aerated lung volume. This research underscores the significance of C at the applied PEEP as a bedside-measurable parameter and sheds new light on the link between recruitability and normally aerated lung.
Topics: Humans; COVID-19; Positive-Pressure Respiration; Male; Female; Aged; Lung; Middle Aged; Tomography, X-Ray Computed; SARS-CoV-2; Respiratory Mechanics; Respiratory Distress Syndrome; Lung Compliance; Aged, 80 and over
PubMed: 38914620
DOI: 10.1038/s41598-024-64622-3 -
Expert Opinion on Pharmacotherapy Jun 2024The efficacy of non-pharmacotherapeutic treatment of obstructive sleep apnea, a highly prevalent condition with serious cardiometabolic and neurocognitive health... (Review)
Review
INTRODUCTION
The efficacy of non-pharmacotherapeutic treatment of obstructive sleep apnea, a highly prevalent condition with serious cardiometabolic and neurocognitive health consequences, is well established. Supplementing traditional treatment strategies with medications can improve symptoms and reduce side effects. Efforts to identify medications that target the causes of sleep apnea have met with mixed success. However, this remains a worthwhile objective for researchers to pursue, given the potential benefit pharmacotherapy could bring to those patients who reject or struggle to adhere to existing treatments.
AREAS COVERED
This article presents the case for obstructive sleep apnea pharmacotherapy including drugs that reduce the occurrence of apnea events, such as weight loss agents, ventilation activators and muscle and nervous system stimulants, drugs that alleviate symptoms, such as wake-promoting agents for excessive daytime sleepiness, and drugs that improve adherence to existing treatments, such as hypnotics. Literature was accessed from PubMed between 1 March 2024 and 18 April 2024.
EXPERT OPINION
Exciting recent advances in both our understanding of obstructive sleep apnea pathology and in the techniques used to identify therapeutic agents and their targets combine to embolden a positive outlook for the expanded use of drugs in tackling this consequential disease.
Topics: Sleep Apnea, Obstructive; Humans; Medication Adherence; Hypnotics and Sedatives; Animals; Wakefulness-Promoting Agents
PubMed: 38913403
DOI: 10.1080/14656566.2024.2365329 -
Allergy, Asthma & Immunology Research May 2024Concerns regarding the safety of beta-2 agonists have led to revisions of the major asthma guidelines to better address these issues. Although these updates allow for a... (Review)
Review
Concerns regarding the safety of beta-2 agonists have led to revisions of the major asthma guidelines to better address these issues. Although these updates allow for a combination of previous and current strategies, they may confuse clinical practitioners. Beta-2 agonists are vital for alleviating asthma symptoms by relaxing smooth muscles; however, they also pose significant risks by inducing pro-inflammatory mediators both and . In addition to the risks of overuse and symptom masking, the use of beta-agonists alone at therapeutic doses can worsen airway inflammation and enhance virus-induced inflammation during asthma exacerbation. Inhaled corticosteroids (ICS) can effectively prevent these adverse effects. With new insights into the mechanisms of these adverse events, reserving short-acting beta-agonists for acute symptom relief during exacerbations and only for those who are already on ICS or oral steroids represents a careful approach to using beta-agonists with least adverse effects in patients with asthma. However, a major drawback of this approach is the potential non-compliance with ICS, leading to beta-agonist use without the necessary counteraction by ICS. An optimal strategy, both during and outside exacerbations, would integrate beta-agonists into an anti-inflammatory regimen that includes ICS, ideally combined with the same inhaler to ensure their concurrent use where finances allow. This would maintain the beneficial effects of beta-agonists, such as bronchodilation, while preventing the adverse effects from the induction of inflammatory mediators. This method is aligned with diverse clinical settings, maximizes the safe use of beta-agonists, and supports a comprehensive guideline-compliant management strategy.
PubMed: 38910281
DOI: 10.4168/aair.2024.16.3.217 -
Medical Dosimetry : Official Journal of... Jun 2024Respiratory motion management is the crucial challenge for safe and effective application of lung stereotactic body radiotherapy (SBRT). The present study implemented...
Respiratory motion management is the crucial challenge for safe and effective application of lung stereotactic body radiotherapy (SBRT). The present study implemented lung SBRT treatment in voluntary deep inspiration breath-hold (DIBH) with surface-guided radiotherapy (SGRT) system and evaluated the geometric and dosimetric benefits of DIBH to organs-at-risk (OARs), aiming to advising the choice between DIBH technology and conventional free breathing 4 dimensions (FB-4D) technology. Five patients of lung SBRT treated in DIBH with SGRT at our institution were retrospectively analyzed. CT scans were acquired in DIBH and FB-4D, treatment plans were generated for both respiratory phases. The geometric and dosimetry of tumor, ipsilateral lung, double lungs and heart were compared between the DIBH and FB-4D treatment plans. In terms of target coverage, utilizing DIBH significantly reduced the mean plan target volume (PTV) by 21.9% (p = 0.09) compared to FB-4D, the conformity index (CI) of DIBH and FB-4D were comparable, but the dose gradient index (DGI) of DIBH was higher. With DIBH expanding lung, the volumes of ipsilateral lung and double lungs were 2535.1 ± 403.0cm and 4864.3 ± 900.2cm, separately, 62.2% (p = 0.009) and 73.1% (p = 0.009) more than volumes of ipsilateral lung (1460.03 ± 146.60cm) and double lungs (2811.25 ± 603.64cm) in FB-4D. The heart volume in DIBH was 700.0 ± 146.1cm, 11.6% (p = 0.021) less than that in FB-4D. As for OARs protection, the mean dose, percent of volume receiving > 20Gy (V20) and percent of volume receiving > 5Gy (V5) of ipsilateral lung in DIBH were significantly lower by 33.2% (p = 0.020), 44.0% (p = 0.022) and 24.5% (p = 0.037) on average, separately. Double lungs also showed significant decrease by 31.1% (p = 0.019), 45.5% (p = 0.024) and 20.9% (p = 0.048) on average for mean dose, V20 and V5 in DIBH. Different from the lung, the mean dose and V5 of heart showed no consistency between DIBH and FB-4D, but lower maximum dose of heart was achieved in DIBH for all patients in this study. Appling lung SBRT in DIBH with SGRT was feasibly performed with high patient compliance. DIBH brought significant dosimetric benefits to lung, however, it caused more or less irradiated heart dose that depend on the patients' individual differences which were unpredictable.
PubMed: 38910070
DOI: 10.1016/j.meddos.2024.05.003 -
Veterinary Anaesthesia and Analgesia May 2024To compare static compliance of the respiratory system (C) and the ratio of partial pressure of end-tidal to arterial carbon dioxide (Pe'CO/PaCO), in healthy dogs using...
Tidal volume selection in volume-controlled ventilation guided by driving pressure versus actual body weight in healthy anesthetized and mechanically ventilated dogs: A randomized crossover trial.
OBJECTIVE
To compare static compliance of the respiratory system (C) and the ratio of partial pressure of end-tidal to arterial carbon dioxide (Pe'CO/PaCO), in healthy dogs using two approaches for tidal volume (V) selection during volume-controlled ventilation: body mass based and driving pressure (ΔPaw) guided.
STUDY DESIGN
Randomized, nonblinded, crossover, clinical trial.
ANIMALS
A total of 19 client-owned dogs anesthetized for castration and ovariohysterectomy.
METHODS
After a stable 10 minute baseline, each dog was mechanically ventilated with a V selection strategy, randomized to a constant V of 15 mL kg of actual body mass (V) or ΔPaw-guided V (V) of 7-8 cmHO. Both strategies used an inspiratory time of 1 second, 20% end-inspiratory pause, 4 cmHO positive end-expiratory pressure and fraction of inspired oxygen of 0.4. Respiratory frequency was adjusted to maintain Pe'CO between 35 and 40 mmHg. Respiratory mechanics, arterial blood gases and Pe'CO/PaCO were assessed. Continuous variables are presented as mean ± SD or median (interquartile range; quartiles 1-3), depending on distribution, and compared with Wilcoxon signed-rank tests.
RESULTS
The V was significantly higher in dogs ventilated with V than with V strategy (17.20 ± 4.04 versus 15.03 ± 0.60 mL kg, p = 0.036). C was significantly higher with V than with V strategy [2.47 (1.86-2.86) versus 2.25 (1.79-2.58) mL cmHO kg, p = 0.011]. There were no differences in Pe'CO/PaCO between V and V strategies (0.94 ± 0.06 versus 0.92 ± 0.06, p = 0.094). No discernible difference in ΔPaw was noted between the strategies.
CONCLUSIONS AND CLINICAL RELEVANCE
While no apparent difference was observed in the Pe'CO/PaCO between the V selection strategies employed, C significantly increased during the V approach. A future trial should explore if V improves perioperative gas exchange and prevents lung damage.
PubMed: 38910061
DOI: 10.1016/j.vaa.2024.05.006 -
Medicine Jun 2024Although medical emergency teams (METs) have been widely introduced, studies on the importance of a dedicated intensivist staffing to METs are lacking. A single-center... (Observational Study)
Observational Study
Although medical emergency teams (METs) have been widely introduced, studies on the importance of a dedicated intensivist staffing to METs are lacking. A single-center retrospective before-and-after study was performed. Deteriorating patients who required emergency airway management in general wards by MET were included in this study. We divided the study period according to the presence of a dedicated intensivist staff in MET: (1) non-staffed period (from January 2016 to February 2018, n = 971) and (2) staffed period (from March 2018 to December 2019, n = 651), and compared emergency airway management-related variables and outcomes between the periods. Among 1622 patients included, mean age was 63.0 years and male patients were 64.2% (n = 1042). The first-pass success rate was significantly increased in the staffed period (85.9% in the non-staffed vs 89.2% in the staffed; P = .047). Compliance to rapid sequence intubation was increased (9.4% vs 34.4%; P < .001) and vocal cords were more clearly open (P < .001) in the staffed period. The SpO2/FiO2 ratio (median [interquartile range], 125 [113-218] vs 136 [116-234]; P = .007) and the ROX index (4.6 [3.4-7.6] vs 5.1 [3.6-8.5]; P = .013) at the time of intubation was higher in the staffed period, suggesting the decision on intubation was made earlier. The post-intubation hypoxemia was less commonly occurred in the staffed period (7.2% vs 4.2%, P = .018). In multivariate analysis, the rank of operator was a strong predictor of the first-pass success (adjusted OR [95% CI], 2.280 [1.639-3.172]; P < .001 for fellow and 5.066 [1.740-14.747]; P < .001 for staff, relative to resident). In our hospital, a dedicated intensivist staffing to MET was associated with improved emergency airway management in general wards. Staffing an intensivist to MET needs to be encouraged to improve the performance of MET and the patient safety.
Topics: Humans; Male; Middle Aged; Retrospective Studies; Female; Airway Management; Aged; Intubation, Intratracheal; Personnel Staffing and Scheduling
PubMed: 38905417
DOI: 10.1097/MD.0000000000038571