Peanut allergen Ara h 6 is detectable in blood transfusion products

Peanut allergen Ara h 6 is known to maintain IgE‐binding capacity upon exposure to digestive enzymes1 and its presence in circulation after consumption of peanut has been demonstrated.2,3 Therefore, it has been speculated that food‐derived allergens could be transferred via blood transfusion products, causing an allergic reaction in food-allergic recipients.4,5 However, in published case reports, presence of food allergen in donated material could not be confirmed due to lack of remaining transfusion material and/or lack of sensitive analytical methods. Using a newly developed sensitive immune‐assay for detecting Ara h 6 in human serum, we now report to what extent consumed peanut allergens can be present in blood transfusion materials and estimate the associated risk for peanut‐allergic recipients

Evaluation of total body weight and body mass index cut-offs for increased cefazolin dose for surgical prophylaxis

AbstractFrench and American guidelines recommend increased dosage regimens of cefazolin (CFZ) for surgical prophylaxis in patients with a body mass index (BMI) ≥ 35 kg/m2 or with a total body weight (TBW) ≥ 120 kg. The objective of this study was to evaluate the accuracy of these cut-offs in identifying patients who require CFZ dose adjustment. A pharmacokinetic study was conducted in patients of varying TBW and BMI who received 2 g of CFZ intravenously for prophylaxis prior to digestive surgery. Adequacy of therapy, defined as a serum concentration of unbound CFZ (fCFZ) ≥ 4 mg/L, was evaluated 180 min (T180) and 240 min (T240) after the start of CFZ infusion. Possible factors associated with insufficient fCFZ levels were also assessed. A P-value of <0.05 was considered statistically significant. A total of 63 patients were included in the study, categorised according to BMI (<35 kg/m2, 20 patients; and ≥35 kg/m2, 43 patients) and TBW (<120 kg, 41 patients; and ≥120 kg, 22 patients). All patients had adequate drug levels at T180 but only 40/63 patients (63%) had adequate levels at T240. At T240, therapy was adequate in 15/20 patients (75%) and 25/43 patients (58%) with BMI <35 kg/m2 and ≥35 kg/m2, respectively (P = 0.20), and in 28/41 patients (68%) and 12/22 patients (55%) with TBW <120 kg and ≥120 kg, respectively (P = 0.28). No factor associated with insufficient fCFZ was identified. In conclusion, current BMI and TBW cut-offs are poor indicators of which patients could benefit from increased CFZ dosage regimens

Cannabidiol in clinical and preclinical anxiety research. A systematic review into concentration-effect relations using the IB-de-risk tool

BACKGROUND: Preclinical research suggests that cannabidiol (CBD) may have therapeutic potential in pathological anxiety. Dosing guidelines to inform future human studies are however lacking. AIM: We aimed to predict the therapeutic window for anxiety-reducing effects of CBD in humans based on preclinical models. METHODS: We conducted two systematic searches in PubMed and Embase up to August 2021, into pharmacokinetic (PK) and pharmacodynamic (PD) data of systemic CBD exposure in humans and animals, which includes anxiety-reducing and potential side effects. Risk of bias was assessed with SYRCLE's RoB tool and Cochrane RoB 2.0. A control group was an inclusion criterion in outcome studies. In human outcome studies, randomisation was required. We excluded studies that co-administered other substances. We used the IB-de-risk tool for a translational integration of outcomes. RESULTS: We synthesised data from 87 studies. For most observations (70.3%), CBD had no effect on anxiety outcomes. There was no identifiable relation between anxiety outcomes and drug levels across species. In all species (humans, mice, rats), anxiety-reducing effects seemed to be clustered in certain concentration ranges, which differed between species. DISCUSSION: A straightforward dosing recommendation was not possible, given variable concentration-effect relations across species, and no consistent linear effect of CBD on anxiety reduction. Currently, these results raise questions about the broad use as a drug for anxiety. Meta-analytic studies are needed to quantitatively investigate drug efficacy, including aspects of anxiety symptomatology. Acute and (sub)chronic dosing studies with integrated PK and PD outcomes are required for substantiated dose recommendations

Point-of-care testing in paediatric settings in the UK and Ireland: A cross-sectional study

Background: Point-of-care testing (POCT) is diagnostic testing performed at or near to the site of the patient. Understanding the current capacity, and scope, of POCT in this setting is essential in order to respond to new research evidence which may lead to wide implementation. Methods: A cross-sectional online survey study of POCT use was conducted between 6th January and 2nd February 2020 on behalf of two United Kingdom (UK) and Ireland-based paediatric research networks (Paediatric Emergency Research UK and Ireland, and General and Adolescent Paediatric Research UK and Ireland). Results: In total 91/109 (83.5%) sites responded, with some respondents providing details for multiple units on their site based on network membership (139 units in total). The most commonly performed POCT were blood sugar (137/139; 98.6%), urinalysis (134/139; 96.4%) and blood gas analysis (132/139; 95%). The use of POCT for Influenza/Respiratory Syncytial Virus (RSV) (45/139; 32.4%, 41/139; 29.5%), C-Reactive Protein (CRP) (13/139; 9.4%), Procalcitonin (PCT) (2/139; 1.4%) and Group A Streptococcus (5/139; 3.6%) and was relatively low. Obstacles to the introduction of new POCT included resources and infrastructure to support test performance and quality assurance. Conclusion: This survey demonstrates significant consensus in POCT practice in the UK and Ireland but highlights specific inequity in newer biomarkers, some which do not have support from national guidance. A clear strategy to overcome the key obstacles of funding, evidence base, and standardising variation will be essential if there is a drive toward increasing implementation of POCT

Lactam dosage regimens in septic patients with augmented renal clearance

Augmented renal clearance is commonly observed in septic patients and may result in insufficient -lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of -lactam antibiotics and measured creatinine clearance and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance. We reviewed 256 antibiotic measurements (512 drug concentrations) from a cohort of 215 critically ill patients who had a measured creatinine clearance of 120 ml/min and who received therapeutic drug monitoring of meropenem, cefepime, ceftazidime, or piperacillin from October 2009 until December 2014 at Erasme Hospital. Population pharmacokinetic (PK) analysis of the data was performed using the Pmetrics software package for R. Fifty-five percent of drug concentrations showed insufficient -lactam serum concentrations to treat infections due to Pseudomonas aeruginosa. There were significant, yet weak, correlations between measured creatinine clearance and trough concentrations of meropenem (r 0.21, P 0.01), trough concentrations of piperacillin (r 0.28, P 0.0071), concentrations at 50% of the dosage interval (r 0.41, P 0.0001), and total body clearance of piperacillin (r 0.39, P 0.0002). Measured creatinine clearance adequately explained changes in drug concentrations in population pharmacokinetic models for cefepime, ceftazidime, and meropenem but not for piperacillin. Therefore, specific PK modeling can predict certain -lactam concentrations based on renal function but not on absolute values of measured creatinine clearance, easily available for clinicians. Currently, routine therapeutic drug monitoring is required to adjust daily regimens in critically ill patients receiving standard dosing regimens.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Investigation of unbound colistin A and B in clinical samples using a mass spectrometry method.

Colistin, used as a last resort drug, has a narrow therapeutic range that justifies therapeutic drug monitoring. Few data are available in the literature concerning the in vivo unbound fraction of colistin. The objectives of this study were to develop a method to isolate unbound colistin in clinical samples by ultrafiltration and to quantify it. The association between unbound colistin and biological parameters (total protein, albumin, alpha-1-acid glycoprotein, and creatinine) was investigated. The measured ranges were 0.036-7.160 mg/L for colistin A and 0.064-9.630 mg/L for colistin B. The process of isolation and determination of unbound colistin was applied to clinical samples (n=30) within 40 minutes and no non-specific binding was observed during the ultracentrifugation step. The median unbound fractions of colistin measured were 34.3% (12.8%-51.0%) and 53.4% (27.0%-77.8%) for colistin A and colistin B, respectively. High inter-individual biological variation of binding was observed for colistin A and B which was not explained by the biochemical parameters studied. The method developed could be useful to improve outcomes for patients

Beta-Lactams Clearance Is Related to the Intensity of Continuous Renal Replacement Therapy in Septic Patients

Introduction: Severe sepsis may alter the pharmacokinetics (PKs) of B-lactams, and the use of continuous renal replacement therapy (CRRT) may further compromise them.Hypothesis: The aim of this study was to evaluate the correlation between B-lactams clearance and CRRT intensity.Methods: We reviewed the data of all patients undergoing CRRT and treated with ceftazidime/cefepime (CEF, 2gq8h), meropenem (MEM, 1gq8h) or piperacillin-tazobactam (TZP, 4gq6h) since January 2010. Serum drug concentrations were measured by high-performance liquid chromatography (HPLC-UV), twice during the elimination phase after a 30-min intravenous drug administration. Antibiotic PKs were calculated using a one-compartment model and the percentage of time spent above four times the MIC (%T>4xMIC) for Pseudomonas aeruginosa was obtained. CRRT data (blood flow, dialysate and ultrafiltrate rates) were collected and CRRT intensity was calculated as (dialysate + ultrafiltrate)/weight (kgs). Results are expressed as median [ranges].Results: A total of 73 serum levels were obtained in 50 patients (CEF = 10; MEM = 44; TZP = 19). There was considerable variability in B-lactam serum concentrations and pharmacokinetic variables. We found a weak, although significant, correlation of CRRT intensity with both B-lactams clearance (r=0.31, p = 0.007) and the %T>4xMIC (r= -0.27, p = 0.02). B-lactams clearance was increased in patients with higher CRRT intensity (45 ml/kg.h = 74.7 [51.3-131.7] ml/min; p = 0.02). Also, the %T > 4xMIC significantly decreased in patients with higher CRRT intensity (p=0.04).Conclusions: B-lactams concentrations and clearances during CRRT are quite variable. The intensity of CRRT may influence drug levels and elimination and should be taken into account when drug regimens are prescribed.info:eu-repo/semantics/publishedCommunication at the 42st SCCM Congress (19-23 January 2013 – San Juan, USA)

Beta-lactam serum levels are inadequate in most critically ill patients

info:eu-repo/semantics/nonPublishe