Comparative in vitro evaluation of four corticosteroid metered dose inhalers:Consistency of delivered dose and particle size distribution

SummaryIntroductionRecent developments concerning pressurized metered dose inhalers (pMDIs) with inhaled corticosteroids (ICS) are the introduction of ciclesonide and the replacement of propellants. As the results of in vivo studies depend on pMDIperformance, it is necessary to evaluate pMDIs in vitro for delivered dose and particle size distributions under different conditions.MethodsFluticasone 125μg, budesonide 200μg, beclomethasone HFA100μg, and ciclesonide 160μg were compared for delivered dose and particle size using laser diffraction analysis with inspiratory flow rates of 10, 20 and 30l/s.ResultsThe volume median diameter of budesonide was 3.5μm, fluticasone 2.8μm, beclomethasone and ciclesonide both 1.9μm. The mouthpiece retention was up to 30% of the nominal dose for beclomethasone and ciclesonide, 11–19% for the other pMDIs. Lifespan, flow rate, and air humidity had no significant influence on particle size distribution. The delivered dose of beclomethasone, budesonide, and ciclesonide remained constant over the lifespan. The delivered dose of fluticasone 125 decreased from 106% to 63%; fluticasone 250 also decreased whereas fluticasone 50 remained constant.ConclusionsThere is a significant difference in median particle size distribution between the different ICS pMDIs. Air humidity and inspiratory flow rate have no significant influence on particle size distribution. Ciclesonide 160 and beclomethasone 100 deliver the largest fine particle fractions of 1.1–3.1μm. The changes in delivered dose during the lifespan for the fluticasone 125 and 250 may have implications for patient care

Trajectories of fatigue in cancer patients during psychological care

Objective Psycho-oncological institutions offer specialized care for cancer patients. Little is known how this care might impact fatigue. This study aimed to identify fatigue trajectories during psychological care, examined factors distinguishing these trajectories and predicted fatigue severity after nine months of psychological care. Design Naturalistic, longitudinal study of 238 cancer patients receiving psycho-oncological care in the Netherlands. Data were collected before initiation of psychological care (T1) and three (T2) and nine months (T3) afterwards. Latent class growth analysis, repeated measure analyses (RMA) and linear regression analysis were performed. Main Outcome Measures Fatigue severity: Checklist Individual Strength. Results Three fatigue trajectories were identified: high- (30%), moderate- (62%) and low-level fatigue (8%). While statistically significant decreases in fatigue were found, this decrease was not clinically relevant. RMA showed main effects for time for fatigue trajectories on depression, anxiety, personal control and illness cognitions. Fatigue severity and physical symptoms at T1, but not demographic or clinical factors, were predictive of fatigue severity at T3. Conclusions Fatigue is very common during psycho-oncological care, and notably not clinically improving. As symptoms of fatigue, depression, anxiety and physical symptoms often cluster, supplementary fatigue treatment should be considered when it is decided to treat other symptoms first

Elevated High-Sensitivity Troponin and NT-proBNP Values in Febrile Children

Objectives The COVID-19 pandemic and subsequent rise of multisystem inflammatory syndrome in children have raised interest in high-sensitivity troponin (hs-TnT) and N-terminal probrain natriuretic peptide (NT-proBNP) because these have been found to be elevated in many cases of multisystem inflammatory syndrome in children. Our aim was to study hs-TnT and NT-proBNP concentrations in febrile children not affected by COVID-19. Methods We retrospectively measured cardiac markers, hs-TnT, and NT-proBNP in leftover blood samples of febrile children (0-18 years) diagnosed and treated in a single-center emergency department (ED) (N = 67) and pediatric intensive care unit (PICU) (N = 19) that participated in a multicenter, prospective study of infection biomarkers (PERFORM). Results Concentrations of hs-TnT, median 1.8 ng/L (interquartile range [IQR], 0.0-15.1), and NT-proBNP, 194 pg/mL (IQR, 54.9-706), were higher in febrile children than in controls (N = 25, hs-TnT 0.0 [IQR, 0-0]; NT-proBNP 56.3 [IQR, 29.7-109], both P &lt; 0.001), whereas PICU patients had higher concentrations (hs-TnT 15.1 [IQR, 10.3-102] and NT-proBNP 828 [IQR, 657-4712], both P &lt; 0.001) than ED patients (hs-TnT 0 [IQR, 0-7.4] and NT-proBNP 104 [IQR, 39.5-363]). No differences were found between viral and bacterial infections. Highest concentrations were found in children with either comorbidity predisposing to elevated concentrations (eg, chronic cardiac or renal disease) or children with critical illness or multiorgan failure such as those with septic shock. Conclusions Concentrations of hs-TnT and NT-proBNP are often elevated in febrile children with different causes of fever. Concentrations were higher in children admitted to the PICU than in children attending the ED, and seem to reflect disease severity rather than the underlying cause of fever.</p

Elevated High-Sensitivity Troponin and NT-proBNP Values in Febrile Children

Objectives The COVID-19 pandemic and subsequent rise of multisystem inflammatory syndrome in children have raised interest in high-sensitivity troponin (hs-TnT) and N-terminal probrain natriuretic peptide (NT-proBNP) because these have been found to be elevated in many cases of multisystem inflammatory syndrome in children. Our aim was to study hs-TnT and NT-proBNP concentrations in febrile children not affected by COVID-19. Methods We retrospectively measured cardiac markers, hs-TnT, and NT-proBNP in leftover blood samples of febrile children (0-18 years) diagnosed and treated in a single-center emergency department (ED) (N = 67) and pediatric intensive care unit (PICU) (N = 19) that participated in a multicenter, prospective study of infection biomarkers (PERFORM). Results Concentrations of hs-TnT, median 1.8 ng/L (interquartile range [IQR], 0.0-15.1), and NT-proBNP, 194 pg/mL (IQR, 54.9-706), were higher in febrile children than in controls (N = 25, hs-TnT 0.0 [IQR, 0-0]; NT-proBNP 56.3 [IQR, 29.7-109], both P &lt; 0.001), whereas PICU patients had higher concentrations (hs-TnT 15.1 [IQR, 10.3-102] and NT-proBNP 828 [IQR, 657-4712], both P &lt; 0.001) than ED patients (hs-TnT 0 [IQR, 0-7.4] and NT-proBNP 104 [IQR, 39.5-363]). No differences were found between viral and bacterial infections. Highest concentrations were found in children with either comorbidity predisposing to elevated concentrations (eg, chronic cardiac or renal disease) or children with critical illness or multiorgan failure such as those with septic shock. Conclusions Concentrations of hs-TnT and NT-proBNP are often elevated in febrile children with different causes of fever. Concentrations were higher in children admitted to the PICU than in children attending the ED, and seem to reflect disease severity rather than the underlying cause of fever.</p

The pharmacokinetics of antibiotics in cystic fibrosis

Introduction Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. Areas covered The purpose of this work is to critically review original data as well as previous reviews and guidelines on pharmacokinetics of systemic and inhaled antibiotics in CF, with the aim to propose strategies for optimization of antibacterial therapy in both children and adults with CF. Expert opinion For systemic antibiotics, absorption is comparable in CF patients and non-CF controls. The volume of distribution (Vd) of most antibiotics is similar between people with CF with normal body composition and healthy individuals. However, there are a few exceptions, like cefotiam and tobramycin. Many antibiotic class-dependent changes in drug metabolism and excretion are reported, with an increased total body clearance for ss-lactam antibiotics, aminoglycosides, fluoroquinolones, and trimethoprim. We, therefore, recommend following class-specific guidelines for CF, mostly resulting in higher dosages per kg bodyweight in CF compared to non-CF controls. Higher local antibiotic concentrations in the airways can be obtained by inhalation therapy, with which eradication of bacteria may be achieved while minimizing systemic exposure and risk of toxicity

Attachment style and post-bariatric surgery health behaviours:the mediating role of self-esteem and health self-efficacy

Background: Attachment avoidance and anxiety have been linked to overweight and poor health behaviours, yet the mechanisms that underpin the relationship between attachment and health behaviours are not fully understood. Self-esteem and self-efficacy have been found to differ between attachment styles, rendering these variables potential mediators of the relationship. This longitudinal study investigated the serial mediation between preoperative attachment and 2-year post-operative health behaviours through self-esteem and health self-efficacy. Methods: Participants were 263 bariatric surgery patients (75.7% females, aged 47.7 ± 10.4 years, BMI 38.9 ± 3.6 kg/m2) assessed before the operation and again one and two years after the surgery. Patients completed the Experiences for Close Relationships Brief Scale, Rosenberg Self-esteem scale, Weight Efficacy Lifestyle Questionnaire, Bariatric Surgery Self-Management Questionnaire, Exercise Self-Efficacy Scale and the Exercise Behaviour Scale. Results: Higher preoperative attachment anxiety and avoidance were associated with lower self-esteem one year after bariatric surgery and poorer health self-efficacy two years after the surgery. Self-esteem and health self-efficacy mediated the relationships between preoperative anxious and avoidant attachment and 2- year post-operative diet adherence and physical activity. Conclusions: Helping patients to feel more worthy and reinforcing their beliefs about their own competences could lead to higher engagement with healthy lifestyle and adherence to treatment protocols, ultimately helping patients to achieve their goals for bariatric surgery. Clinical trial registration: BARIA: Netherlands Trial Register: NL5837 (NTR5992) https://www.trialregister.nl/trial/5837 . Diabaria: ClinicalTrials.gov identifier (NCT number): NCT03330756.</p

How Do Different Motives for R&D Cooperation Affect Firm Performance? An Analysis Based on Swiss Micro Data

Starting point of our analysis is the empirical fact that firms pursue different goals when getting engaged in R&D collaborations, often more than one goal at the same time. Given that firms are driven by different motives for R&D cooperation, the aim of this article is to investigate the differences related to different motives with respect (a) to the factors influencing the likelihood of R&D cooperation as postulated by theory; and (b) to the impact of R&D cooperation on firm innovativeness and firm productivity. On the whole, distinguishing various cooperation motives appears to be fruitful because it allows more differentiated insights with respect to the importance of factors determining cooperation that would remain hidden behind the overall variable R&D cooperation yes/no. Not only R&D cooperation in general but also cooperation driven by each of the seven motives considered in this paper correlate positively with the sales share of innovative products. With respect to innovativeness the characterization of cooperation by the driving motive did not add much more insights that it could be gained through the overall variable R&D cooperation yes/no. Technology-motivated collaborative activities show a weaker tendency to positive direct effects on productivity than cost-motivated cooperation. In this case, the distinction of several cooperation motives yields some additional insights as compared to the overall cooperation variable

Low Physical Activity in Patients with Complicated Type 2 Diabetes Mellitus Is Associated with Low Muscle Mass and Low Protein Intake

Objective: In order to promote physical activity (PA) in patients with complicated type 2 diabetes, a better understanding of daily movement is required. We (1) objectively assessed PA in patients with type 2 diabetes, and (2) studied the association between muscle mass, dietary protein intake, and PA. Methods: We performed cross-sectional analyses in all patients included in the Diabetes and Lifestyle Cohort Twente (DIALECT) between November 2016 and November 2018. Patients were divided into four groups: = 10,000 steps/day. We studied the association between muscle mass (24 h urinary creatinine excretion rate, CER) and protein intake (by Maroni formula), and the main outcome variable PA (steps/day, Fitbit Flex device) using multivariate linear regression analyses. Results: In the 217 included patients, the median steps/day were 6118 (4115-8638). Of these patients, 48 patients (22%) took 7000-9999 steps/day, 37 patients (17%) took >= 10,000 steps/day, and 78 patients (36%) took = 10,000 steps/day, a higher body mass index (BMI) (33 +/- 6 vs. 30 +/- 5 kg/m(2), p = 0.009), lower CER (11.7 +/- 4.8 vs. 14.8 +/- 3.8 mmol/24 h, p = 0.001), and lower protein intake (0.84 +/- 0.29 vs. 1.08 +/- 0.22 g/kg/day, p < 0.001). Both creatinine excretion (beta = 0.26, p < 0.001) and dietary protein intake (beta = 0.31, p < 0.001) were strongly associated with PA, which remained unchanged after adjustment for potential confounders. Conclusions: Prevalent insufficient protein intake and low muscle mass co-exist in obese patients with low physical activity. Dedicated intervention studies are needed to study the role of sufficient protein intake and physical activity in increasing or maintaining muscle mass in patients with type 2 diabetes