Plasma anandamide and other N-acylethanolamines are correlated with their corresponding free fatty acid levels under both fasting and non-fasting conditions in women

N-acylethanolamines (NAEs), such as anandamide (AEA), are a group of endogenous lipids derived from a fatty acid linked to ethanolamine and have a wide range of biological activities, including regulation of metabolism and food intake. We hypothesized that i) NAE plasma levels are associated with levels of total free fatty acids (FFAs) and their precursor fatty acid in fasting and non-fasting conditions and ii) moderate alcohol consumption alters non-fasting NAE levels. In a fasting and non-fasting study we sampled blood for measurements of specific NAEs and FFAs. In the fasting study blood was drawn after an overnight fast in 22 postmenopausal women. In the non-fasting study blood was sampled before and frequently after a standardized lunch with beer or alcohol-free beer in 19 premenopausal women. Fasting AEA levels correlated with total FFAs (r = 0.84; p <0.001) and arachidonic acid levels (r = 0.42; p <0.05). Similar results were observed for other NAEs with both total FFAs and their corresponding fatty acid precursors. In addition, AEA (r = 0.66; p <0.01) and OEA levels (r = 0.49;

Outpatient parenteral antifungal therapy (OPAT) for invasive fungal infections with intermittent dosing of liposomal amphotericin B

Triazole resistant A. fumigatus has been documented in many parts of the world. In the Netherlands, incidence is now above 10% and results in the need for long-term parenteral therapy with liposomal amphotericin B (LAmB). The long terminal half-life of LAmB suggests that intermittent dosing could be effective, making the application of outpatient antifungal therapy (OPAT) possible. Here, we report our experience with the use of OPAT for Invasive Fungal Infections (IFI). All adult patients treated with LAmB with a 2 or 3 times weekly administration via the outpatient departments in four academic tertiary care centers in the Netherlands and Belgium since January 2010 were included in our analysis. Patient characteristics were collected,\ud as well as information about diagnostics, therapy dose and duration, toxicity, treatment history and outcome of the IFI. In total, 18 patients were included. The most frequently used regimen (67%) was 5 mg/kg 3 times weekly. A partial response to the daily treatment prior to discharge was confirmed by CT-scan in 17 (94%) of patients. A favorable outcome was achieved in 13 (72%) patients. Decrease in renal function occurred in 10 (56%) cases but was reversible in all and was treatment limiting in one patient only. The 100-day mortality and 1-year mortality after initiation of OPAT were 0% and 6%, respectively. In a selected population, and after confirmation of initial response to treatment, our data support the use of OPAT with LAmB for treatment of IFI in an intermittent dosing regimen

Presence, formation and putative biological activities of N-acyl serotonins, a novel class of fatty-acid derived mediators in the intestinal tract

Following the discovery of the endocannabinoid arachidonoyl ethanolamide (anandamide) and other N-acyl-ethanolamines, several other compounds have been found in which amino acids or neurotransmitters rather than ethanolamide are linked to fatty acids. Studies have shown that the local availability of fatty acid precursors, which in turn is modulated by dietary intake of lipids, determines the pattern of conjugates formed. Less information is available whether the same might be true for the amines or neurotransmitters involved. We hypothesized that N-arachidonoyl-serotonin (AA-5-HT) and its analogs could be endogenously present in those tissues that have high contents of serotonin. We investigated the endogenous presence of N-acyl serotonins in different parts of the gastro-intestinal tract of pigs and mice. We discovered that AA-5-HT, oleoyl-serotonin, palmitoyl-serotonin, and stearoyl-serotonin were endogenously present, particularly in the jejunum and ileum. Their formation in vitro was stimulated by the addition of serotonin to intestinal tissue incubations. Furthermore, in a mouse study we showed that the pattern of formation is dependent on the relative amount of fatty acids in the diet. The formation of docosahexaenoyl-serotonin and eicosapentaenoyl-serotonin was elevated in mice fed with a diet containing fish oil. Preliminary data showed that several of the serotonin conjugates are able to inhibit glucagon-like peptide-1 secretion and FAAH activity in vitro. Taken together, our data suggest that N-acyl serotonins are a novel class of lipid mediators present in the gut with highly promising biological propertie

In conversation with politically dissatisfied citizens. Political discontent in the Netherlands in the first decade of the 21st century

This dataset - consisting of twenty interviews with politically dissatisfied Dutch citizens- is one of the datasources on which the thesis 'Political discontent in the Netherlands in the first decade of the 21st century' is based upon.The original audio files as well as the transcriptions of the interviews are available. The interviews reveal that there is a persistent image problem of a privileged political class, resulting in an urgent call for political virtue and moral leadership. Information about the selection of the interviewees and the interview format is available in the documentation files

In conversation with politically dissatisfied citizens. Political discontent in the Netherlands in the first decade of the 21st century

This dataset - consisting of twenty interviews with politically dissatisfied Dutch citizens- is one of the datasources on which the thesis 'Political discontent in the Netherlands in the first decade of the 21st century' is based upon.The original audio files as well as the transcriptions of the interviews are available. The interviews reveal that there is a persistent image problem of a privileged political class, resulting in an urgent call for political virtue and moral leadership. Information about the selection of the interviewees and the interview format is available in the documentation files

Cues to improve antibiotic-allergy registration: A mixed-method study

BackgroundApproximately 2% of patients in primary care practice and up to 25% of hospital patients are registered as being allergic to an antibiotic. However, up to 90% of these registrations are incorrect, leading to unnecessary prescription of 2(nd) choice antibiotics with the attendant loss of efficacy, increased toxicity and antibiotic resistance. To improve registration, a better understanding is needed of how incorrect labels are attributed.ObjectiveTo investigate the quality of antibiotic allergy registration in primary care and identify determinants to improve registration of antibiotic allergies.DesignRegistration of antibiotic allergies in primary care practices were analysed for 1) completeness and 2) correctness. To identify determinants for improvement, semi-structured interviews with healthcare providers from four healthcare domains were conducted.ParticipantsA total of 300 antibiotic allergy registrations were analysed for completeness and correctness. Thirty-four healthcare providers were interviewed.Main measuresA registration was defined as complete when it included a description of all symptoms, time to onset of symptoms and the duration of symptoms. It was defined as correct when the conclusion was concordant with the Salden criteria. Determinants of correct antibiotic allergy registrations were divided into facilitators or obstructers.Key resultsRates of completeness and correctness of registrations were 0% and 29.3%, respectively. The main perceived barriers for correct antibiotic allergy registration were insufficient knowledge, lack of priority, limitations of registration features in electronic medical records (EMR), fear of medical liability and patients interpreting side-effects as allergies.ConclusionsThe quality of antibiotic allergy registrations can be improved. Potential interventions include raising awareness of the consequences of incomplete and the importance of correct registrations, by continued education, and above all simplifying registration in an EMR by adequate ICT support

Implementation of a clinical decision rule for selecting empiric treatment for invasive aspergillosis in a setting with high triazole resistance

World-wide, emerging triazole resistance increasingly complicates treatment of invasive aspergillosis (IA). In settings with substantial (>10%) prevalence of triazole resistance, empiric combination therapy with both a triazole and liposomal amphotericin B (LAmB) can be considered because of the low yields of susceptibility testing. To avoid toxicity while optimizing outcome, a strategy with monotherapy would be preferable. A newly designed treatment algorithm based on literature and expert consensus provided guidance for empiric monotherapy with either voriconazole or LAmB. Over a four and a half year period, all adult patients in our hospital treated for IA were included and patient data were collected. An independent committee reviewed the attributability of death to IA for each patient. Primary outcomes were 30- and 100-day crude mortality and attributable mortality. In total, 110 patients were treated according to the treatment algorithm. Fifty-six patients (51%) were initially treated with voriconazole and 54 patients (49%) with LAmB. Combined attributable and contributable mortality was 13% within 30 days and 20% within 100 days. Treatment switch to LAmB was made in 24/56 (43%) of patients who were initially treated with voriconazole. Combined contributable and attributable 100-day mortality in this subgroup was 21% and was not increased when compared with patients initially treated with LAmB (P = 0.38). By applying a comprehensive clinical decision algorithm, an antifungal-sparing regime was successfully introduced. Further research is warranted to explore antifungal treatment strategies that account for triazole-resistance. Lay summary Due to resistance of Aspergillus against triazoles, combination therapy with liposomal amphotericin B (LAmB) is applied more often as primary therapy against invasive aspergillosis. This study presents the results of a decision tool which differentiated between triazole or LAmB monotherapy.Immunogenetics and cellular immunology of bacterial infectious disease

The Dutch Working Party on Antibiotic Policy (SWAB) guideline for the approach to suspected antibiotic allergy

ObjectivesPrudent handling of reported antibiotic allergies is an important aspect of antibiotic stewardship. The Dutch Working Party on Antibiotic Policy (SWAB) constituted a multidisciplinary expert committee to provide evidence-based recommendations for bedside decision-making in antibiotic therapy in patients that report an antibiotic allergy.MethodsThe guideline committee generated 12 key questions, most of which were population, intervention, comparison, and outcome questions relevant to both children and adults with suspected antibiotic allergies. For each question, a systematic literature search was performed and reviewed for the best available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The quality of evidence was graded from very low to high, and recommendations were formulated in structured discussions as strong or weak.ResultsSixty recommendations were provided for suspected allergy to β-lactam antibiotics (BLAs) and non–β-lactam antibiotics. Owing to the absence of randomized controlled trials in this field, the underlying evidence was predominantly graded as low or very low. Available data support that a detailed allergy history should always be performed and critically appraised. When cross-allergy between BLA groups is not to be expected due to the absence of molecular similarity of the side chains, the patient can be safely exposed to the alternative BLA. An exception to this rule is severe delayed-type reactions in which re-exposure to a BLA should only be considered after consultation with a multidisciplinary team.ConclusionsAccumulated scientific data now support a more liberal approach that better balances the benefits of treatment with first choice and usually smaller spectrum antibiotics with appropriate avoidance of antibiotics in case of a truly high risk of a (severe) allergic reaction. In The Netherlands, a formal guideline was developed that provides recommendations for the approach toward suspected allergy to BLA and frequently used non–β-lactam antibiotics, thereby strongly supporting antimicrobial stewardship.Immunogenetics and cellular immunology of bacterial infectious disease