Oxygenated polycyclic aromatic hydrocarbons in atmospheric particulate matter: Molecular characterization and occurrence.

Particulate matter (PM) has become a major research issue receiving increasing attention because of its significant negative impact on human health. There are main indicators that next to the morphological characteristics of the particle, also the chemical composition plays an important role in the adverse health effects of PM. In this context, the rather polar organic fraction of PM is expected to play a major role, and advanced analytical techniques are developed to improve the knowledge on the molecular composition of this fraction. One component class that deserves major attention consists of the oxygenated polycyclic aromatic hydrocarbons (PAHs). Those compounds are considered to be among the key compounds in PM toxicity. This paper presents a comprehensive review focusing on the analysis, fate and behavior of oxygenated PAHs in the atmosphere. The first part of the paper briefly introduces (i) the main sources and atmospheric pathways of oxygenated PAHs. (ii) available physical chemical properties and (iii) their health effects. The second and main part of this paper gives a thorough discussion on the entire analytical sequence necessary to identify and quantify oxygenated PAHs on atmospheric PM. Special attention is given to critical parameters and innovations related to (i) sampling, (ii) sample preparation including both extraction and clean-up, and (iii) separation and detection. Third, the state-of-the-art knowledge about the atmospheric occurrence of oxygenated PAHs is discussed, including an extended overview of reported concentrations presented as a function of sampling season and geographical location. A clear seasonal effect is observed with the median of the oxygenated PAHs concentrations during winter being a factor of 3-4 higher than during summer. However, the oxygenated PAH/parent PAH ratio is about 20 times higher during summer, indicating the importance of photochemical activity in the atmosphere

Implementation of patient-tailored contrast volumes based on body surface area and heart rate harmonizes contrast enhancement and reduces contrast load in small patients in portal venous phase abdominal CT

Purpose: The aim of this study was to evaluate the impact of a patient-tailored contrast volume protocol on portal venous phase abdominal CT-images compared to a fixed volume protocol in daily radiological practice. Method: Data of 77 patients who underwent two contrast-enhanced CT-examinations were collected. The first examination was performed with a fixed contrast volume (95 ml), the follow-up examination was performed with a patient-tailored contrast volume based on patient's BSA and heart rate. The patient-tailored volume was calculated by a software application integrated in the interface of the injection pump. Two independent radiologists assessed subjective and objective image quality. Differences in enhancement and contrast volumes between both protocols were analysed. Results: Despite a significant contrast volume reduction in women and in patients with low to normal BMI, enhancement was more consistent over different BMI-categories in the patient-tailored contrast volume protocol and there was no significant difference in subjective image quality between both injection protocols. Conclusions: A patient-tailored contrast volume protocol based on BSA and heart rate can be considered in daily radiological practice to decrease contrast volumes in women and in low to normal BMI patients and to achieve more consistent contrast enhancement across different BMI-categories in venous phase abdominal CT

Selective accurate-mass-based analysis of 11 oxy-PAHs on atmospheric particultate matter by pressurized liquid extraction followed by highperformance liquid chromatography and magnetic sector mass spectrometry

An innovative analytical method based on high-performance liquid chromatography and atmospheric pressure chemical ionization magnetic sector mass spectrometry was developed and optimized to determine trace concentrations of 11 compounds belonging to the group of the seldom-analyzed oxy-PAHs (phenanthrene-9,10-dione, chrysene-5,6-dione, benzo[a]pyrene-4,5-dione, benzo[a]pyrene-1,6-dione, benzo[a]pyrene-3,6-dione, benzo[a]pyrene-6,12-dione, 4-oxa-benzo[def]chrysene-5-one, pyrene-1-carboxaldehyde, benzo[de]anthracene-7-one, benzo[a]anthracene-7,12-dione, and napthacene-5,12-dione) on airborne particulate matter (PM10). The mass spectrometer was operated in multiple ion detection mode, allowing for selective accurate mass detection (mass resolution of 12,000 full width at half maximum) of the oxy-PAHs characteristic ions. Optimization of both the vaporizer (450 degrees C) and capillary temperature (350 degrees C) resulted into instrumental detection limits in the range between 7 (benzo[a]pyrene-1,6-dione) and 926 pg (benzo[a]anthracene-7,12-dione). The advanced pressurized liquid extraction (PLE) and the more traditionally used ultrasonic extraction (USE) were compared using ethyl acetate as an extraction solvent. For both techniques, high recoveries from spiked quartz fiber filters (PLE, 82-110%; USE, 67-97%) were obtained. Recoveries obtained from real PM10 samples were also high (76-107%), and no significant matrix effects (ME) on the ionization process (enhancement or suppression) were found (ME, 89-123%). Method limits of quantification (S/N=10) were in the range between 2 and 336 pg/m(3). This method was used to analyze real PM samples collected at several urban and rural locations in the Antwerp area. For the first time, concentrations for Belgium are provided. Concentrations of individual oxy-PAHs are in the lower pictograms per cubic meter to 6 ng/m(3) range. High concentration differences between individual compounds are found as exemplified by the 75th percentile of the phenanthrene-9,10-dione and benzo[de]anthracene-7-one concentrations being a factor of 4 to 22 higher compared with the other target oxy-PAHs

Rationalisatie van slaapmiddelen: een sisyfusarbeid?

Ondanks meerdere sensibilisatiecampagnes gedurende de afgelopen jaren blijft langdurig gebruik van slaapmiddelen een prevalent probleem. Gezien de snelle tolerantie voor het effect in combinatie met de bijwerkingen is langdurig gebruik veelal schadelijk voor de patiënt. Indien er geen andere mogelijkheid is dan het gebruik van slaapmiddelen, moet men de duur beperken tot twee weken en moet er systematisch getracht worden om bij langdurig gebruik deze middelen af te bouwen en finaal te stoppen. De afbouw van slaapmiddelen is een uitdaging gezien de psychologische en de fysieke afhankelijkheid aan deze middelen. De winst na afbouw treedt echter snel op. Bij het gebruik van deze geneesmiddelen bij ouderen is het risico op ongewenste effecten groter, met name een verminderd cognitief vermogen en verminderde motorische functies, met als gevolg een grotere kans op ongewenste sedatie, vallen en fracturen.status: publishe

Pharmacokinetics of 2 oral paracetamol formulations in hospitalized octogenarians

Aims: It is currently unclear how paracetamol should be dosed in order to increase its efficacy while warranting safety in very old adults. The objective was to evaluate the pharmacokinetics of 2 oral paracetamol formulations and its metabolites in hospitalized octogenarians. Methods: Geriatric inpatients aged 80 years and older received a 1000-mg paracetamol tablet or granulate at 08.00, 14.00 and 20.00. After at least 4 consecutive gifts, plasma samples were collected around the 08.00 dose (trough, +0.5, +1, +2, +4, +5 and +6 h). Plasma concentrations of paracetamol and its metabolites were determined and individual pharmacokinetic parameters were derived. The Edmonton Frail Scale was used to assess frailty. An analgesic plasma target was defined as an average plasma concentration (C avg) of 10 mg/L. Results: The mean (±standard deviation) age was 86.78 (±4.20) years. The majority (n = 26/36, 72%) received the tablet, 10 (28%) the granulate. Thirty patients (85%) were classified with moderate to severe frailty. Seven (21%) patients had a C avg above 10 mg/L. The median [interquartile range] time to reach the peak concentration was 50.5 [31.50–92.50] and 42.50 [33.75–106.75] min for the tablet and granulate, respectively. The coefficient of variation was 95% for time to reach the peak concentration and 30% for C avg of paracetamol. A correlation of C avg of paracetamol was observed with female sex and total serum bilirubin. Conclusion: Large interindividual differences were found for pharmacokinetic parameters of oral paracetamol in frail inpatients after multiple dosing. Female sex and higher total serum bilirubin concentrations were associated with paracetamol exposure. No significant differences were observed between the tablet and granulate

Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial

Background: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. Methods: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (>= 18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computergenerated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2.5 x 10. colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0.7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. Findings: Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40.1 years [SD 14.4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1.95 [95% CI 1.07-4.11]; p=0.028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. Interpretation: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets

Highly Variable Paracetamol Pharmacokinetics After Multiple Oral Dosing in Frail Older People:A Population Pharmacokinetic Analysis

Introduction: Paracetamol pharmacokinetics (PK) is highly variable in older fit adults after intravenous administration. Frailty and oral administration likely result in additional variability. The aim was to determine oral paracetamol PK and variability in geriatric inpatients. Methods: A population PK analysis, using NONMEM 7.2, was performed on 245 paracetamol samples in 40 geriatric inpatients (median age 87 [range 80–95] years, bodyweight 66.4 [49.3–110] kg, 92.5% frail [Edmonton Frail Scale]). All subjects received paracetamol 1000 mg as tablet (72.5%) or granulate (27.5%) three times daily. Simulations of dosing regimens (1000 mg every 6 hours [q6h] or q8h) were performed to determine target attainment, using mean steady-state concentration (Css-mean) of 10 mg/L as target. Results: A one-compartment model with first order absorption and lag time best described the data. The inter-individual variability was high, with absorption rate constant containing the highest variability. The inter-individual variability could not be explained by covariates. Simulations of 1000 mg q6h and q8h resulted in a Css-mean of 10.8 [25–75th percentiles 8.2–12.7] and 8.13 [6.3–9.6] mg/L, respectively, for the average geriatric inpatient. The majority of the population remained off-target (22.2% [q6h] and 52.2% [q8h] 12 mg/L). Conclusion: A population of average geriatric inpatients achieved target Css-mean with paracetamol 1000 mg q6h, while q8h resulted in underexposure for the majority of them. Due to high unexplained variability, a relevant proportion remained either above or below the target concentration of 10 mg/L. Research focusing on PK, efficacy and safety is needed to recommend dosing regimens