Current practice for the treatment of acute paracetamol intoxication with N-acetylcysteine in Dutch hospitals

Background Nationally and internationally a discussion is ongoing on the effectiveness, the dose required and the treatment duration of N-acetylcysteine to treat acute paracetamol intoxication. Objective In this paper we present the results of a national survey among hospital pharmacists. In this research the present treatment duration and dosing of N-acetylcysteine is reviewed. Design and methods An electronic survey consisting of 15 questions on the treatment of acute paracetamol intoxications in hospitals has been sent to hospital pharmacists. Results Hospital pharmacists of 67 of the 69 Dutch hospitals (97%) have responded. The majority (52 centres, 78%) indicated to treat acute paracetamol intoxications according to the treatment guideline of the NVZA/NVKFB on toxicologie.org. 64 centres (96%) used the dosing regimen of the above-mentioned treatment guideline, namely 150 mg/kg in 1 hour, followed by 450 mg/kg in 24 hours. The toxicologie.org treatment guideline of 150 mg/L at 4 hours after intake, (or 75 mg/L at 4 hours after intake for sensitive patients) to start N-acetylcysteine therapy, is used by 61 centres (91%). 30% of the centres indicate that there are differences in the treatment of an acute paracetamol intoxication in children and adults. In general, in these centres, it is preferred to start early with N-acetylcysteine in children. Conclusion Despite local differences, in the majority of the hospitals acute paracetamol intoxications are treated according to the toxicologie.org treatment guideline. Because of this, toxicologie.org is an appropriate medium to implement possible future adaptations in the N-acetylcysteine dosing regime in Dutch hospitals.</p

Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial

Rifampicin; Tuberculosis; Vulnerable populationRifampicina; Tuberculosis; Población vulnerableRifampicina; Tuberculosi; Població vulnerablePrevious clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231.This study is part of the European South American TB Research Collaborative Network (EUSAT-RCS), a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 823890. A.S.M. is supported by a Juan Rodés (JR18/00022) postdoctoral fellowship from ISCIII

A Randomised Controlled Trial Assessing the Effect of Oral Diazepam on F-18-FDG Uptake in the Neck and Upper Chest Region

A distinctive pattern of physiological symmetrical uptake of F-18-fluorodeoxyglucose (F-18-FDG) in the neck and upper chest region is a phenomenon that is sometimes observed on positron emission tomography (PET) scans of some oncologic patients. Initially, it was assumed to be muscle uptake secondary to patient anxiety or tension, which could be prevented by diazepam treatment. However, PET-computed tomography data have shown that F-18-FDG uptake is not restricted to the musculature but is also localised within the non-muscular soft tissue, such as brown adipose tissue. The efficacy of benzodiazepine treatment to reduce this uptake has not been well established. Therefore, a randomised controlled trial was conducted to decide whether diazepam would decrease physiological F-18-FDG uptake in the neck and upper chest region (FDG-NUC). A randomised, double-blind, placebo-controlled trial was conducted to assess the effect on FDG-NUC of 5 mg diazepam, given orally 1 h before F-18-FDG injection. Patients younger than 40 years, having or suspected to have a malignancy, were eligible for inclusion. The primary endpoint was FDG-NUC, as assessed by visual analysis of whole-body PET scans by two independent observers. The secondary endpoint was clinical relevance of FDG-NUC. Fifty-two patients were included between September 2003 and January 2005. Twenty-eight patients (54%) received placebo; 24 (46%) received diazepam. FDG-NUC was seen in 25% of the patients in the diazepam group versus 29% in the placebo group. This difference was not statistically significant. No beneficial effect of administration of diazepam could be established. Pre-medication with benzodiazepines to diminish physiological uptake of F-18-FDG in the neck and upper chest region is not indicate

Malnutrition assessment methods in adult patients with tuberculosis:A systematic review

OBJECTIVES: Malnutrition is associated with a twofold higher risk of dying in patients with tuberculosis (TB) and considered an important potentially reversible risk factor for failure of TB treatment. The construct of malnutrition has three domains: intake or uptake of nutrition; body composition and physical and cognitive function. The objectives of this systematic review are to identify malnutrition assessment methods, and to quantify how malnutrition assessment methods capture the international consensus definition for malnutrition, in patients with TB. DESIGN: Different assessment methods were identified. We determined the extent of capturing of the three domains of malnutrition, that is, intake or uptake of nutrition, body composition and physical and cognitive function. RESULTS: Seventeen malnutrition assessment methods were identified in 69 included studies. In 53/69 (77%) of studies, body mass index was used as the only malnutrition assessment method. Three out of 69 studies (4%) used a method that captured all three domains of malnutrition. CONCLUSIONS: Our study focused on published articles. Implementation of new criteria takes time, which may take longer than the period covered by this review. Most patients with TB are assessed for only one aspect of the conceptual definition of malnutrition. The use of international consensus criteria is recommended to establish uniform diagnostics and treatment of malnutrition. PROSPERO REGISTRATION NUMBER: CRD42019122832

Physiological uptake of [f]fluorodeoxyglucose in the neck and upper chest region: are there predictive characteristics?

The purpose of this study was to assess (patient) characteristics that might influence the prevalence of physiological uptake of [F]fluorodeoxyglucose (FDG) in the neck and upper chest region (FDG NUC) in positron emission tomography (PET) imaging

Huidige praktijkvoering voor de behandeling van acute paracetamolintoxicaties met N-acetylcysteïne in de Nederlandse ziekenhuizen

Background Nationally and internationally a discussion is ongoing on the effectiveness, the dose required and the treatment duration of N-acetylcysteine to treat acute paracetamol intoxication. Objective In this paper we present the results of a national survey among hospital pharmacists. In this research the present treatment duration and dosing of N-acetylcysteine is reviewed. Design and methods An electronic survey consisting of 15 questions on the treatment of acute paracetamol intoxications in hospitals has been sent to hospital pharmacists. Results Hospital pharmacists of 67 of the 69 Dutch hospitals (97%) have responded. The majority (52 centres, 78%) indicated to treat acute paracetamol intoxications according to the treatment guideline of the NVZA/NVKFB on toxicologie.org. 64 centres (96%) used the dosing regimen of the above-mentioned treatment guideline, namely 150 mg/kg in 1 hour, followed by 450 mg/kg in 24 hours. The toxicologie.org treatment guideline of 150 mg/L at 4 hours after intake, (or 75 mg/L at 4 hours after intake for sensitive patients) to start N-acetylcysteine therapy, is used by 61 centres (91%). 30% of the centres indicate that there are differences in the treatment of an acute paracetamol intoxication in children and adults. In general, in these centres, it is preferred to start early with N-acetylcysteine in children. Conclusion Despite local differences, in the majority of the hospitals acute paracetamol intoxications are treated according to the toxicologie.org treatment guideline. Because of this, toxicologie.org is an appropriate medium to implement possible future adaptations in the N-acetylcysteine dosing regime in Dutch hospitals

Basic aspects of good manufacturing practice for PET-rediopharmaceuticals

Good manufacturing practice (GMP) is a cornerstone in the regulated production of pharmaceuticals. As a result of historical accidents like the thalidomide disaster around 1960, regulations have evolved into a quality system that is nowadays called GMP. The main focus of GMP is to control preparation of pharmaceuticals during all stages of the manufacturing process. Both traceability of the product as well as of all production parameters and quality control data are assured by a quality system. This quality system consists of standard procedures meant to guide personnel through its dedicated tasks as well as monitoring data forms to fill out. Furthermore, all batch documentation is used for proper registration of batch related data. This book chapter focuses on GMP dedicated to PETradiopharmaceuticals. Thus, all relevant items regarding this theme are briefly discussed, such as design and development of hotcells and cleanroom facilities, qualification and validation, starting materials and clothing procedures. We conclude that GMP is important in order to be able to ensure patient safety and manufacturing concistency. Furthermore, to sustain operational flexibility for PET-preparations, a pragmatic, risk-based approach regarding GMP is needed.</p