Exploring the role of oxidative stress and the effect of N-acetylcysteine in thiopurine-induced liver injury in inflammatory bowel disease: A randomized crossover pilot study.

Thiopurine treatment is regularly complicated by drug-induced liver injury. It has been suggested that oxidative stress may play a synergistic role. To assess whether thiopurine-induced liver injury coincides with increased oxidative stress and whether co-administration with N-acetylcysteine is protective, we performed a randomized open label crossover pilot study in inflammatory bowel disease patients with thiopurine-induced increased serum liver tests.

Neonatal pain score after use of paracetamol: Is there a relationship with serum trough concentration at steady state in preterm and term neonates?

Objective: An easy to establish and patient-friendly biomarker to guide dosing of paracetamol in neonates is currently not available. The aim of this study was to determine the potential association between the serum trough concentration and area under the curve (AUC) of paracetamol at steady state and differences in pain scores in preterm and term neonates.

Materials And Methods: A retrospective observational study was performed, using an academic hospital database to identify neonates treated with intravenous or rectal paracetamol for at least 48 hours.

Predicting treatment response to vancomycin using bacterial DNA load as a pharmacodynamic marker in premature and very low birth weight neonates: A population PKPD study.

While positive blood cultures are the gold standard for late-onset sepsis (LOS) diagnosis in premature and very low birth weight (VLBW) newborns, these results can take days, and early markers of possible treatment efficacy are lacking. The objective of the present study was to investigate whether the response to vancomycin could be quantified using bacterial DNA loads (BDLs) determined by real-time quantitative polymerase chain reaction (RT-qPCR). VLBW and premature neonates with suspected LOS were included in a prospective observational study.

Optimizing Antiviral Dosing for HSV and CMV Treatment in Immunocompromised Patients.

Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be challenging because these drugs have a narrow therapeutic window and show significant pharmacokinetic variability.

Bayesian geostatistical modelling of stunting in Rwanda: risk factors and spatially explicit residual stunting burden.

Background: Stunting remains a significant public health issue in Rwanda and its prevalence exhibits considerable geographical variation. We apply Bayesian geostatistical modelling to study the spatial pattern of stunting in children less than five years considering anthropometric, socioeconomic and demographic risk factors in Rwanda. In addition, we predict the spatial residuals effects to quantify the burden of stunting not accounted for by our geostatistical model.

Stunting spatial pattern in Rwanda: An examination of the demographic, socio-economic and environmental determinants.

Stunting is recognised as a major public health problem in Rwanda. We therefore aimed to study the demographic, socio-economic and environmental factors determining the spatial pattern of stunting. A cross-sectional study using the data from the 2014- 2015 Rwanda Demographic and Health Survey and environmental data from external geospatial datasets were conducted.

Predictors of stunting with particular focus on complementary feeding practices: A cross-sectional study in the northern province of Rwanda.

Objectives: The aim of this study was to review the factors associated with stunting in the northern province of Rwanda by assessing anthropometric status, dietary intake, and overall complementary feeding practices.

Methods: This was a cross-sectional study with 138 children 5 to 30 mo of age. A structured questionnaire was used to collect information on sociodemographic characteristics of each mother and child and breastfeeding and complementary feeding practices.

Data on child complementary feeding practices, nutrient intake and stunting in Musanze District, Rwanda.

Stunting prevalence in Rwanda is still a major public health issue, and data on stunting is needed to plan relevant interventions. This data, collected in 2015, presents complementary feeding practices, nutrient intake and its association with stunting in infants and young children in Musanze District in Rwanda. A household questionnaire and a 24-h recall questionnaire were used to collect the data.

Schistosomiasis mansoni incidence data in Rwanda can improve prevalence assessments, by providing high-resolution hotspot and risk factors identification.

Background: Schistosomiasis mansoni constitutes a significant public health problem in Rwanda. The nationwide prevalence mapping conducted in 2007-2008 revealed that prevalence per district ranges from 0 to 69.5% among school children.

An UPLC-MS detection method for the quantification of five antibiotics in human plasma.

Background: An UPLC-MS detection method for the quantification of amikacin, flucloxacillin, meropenem, penicillin G and vancomycin was developed and validated.

Results: The calibration curves were found to be linear from 0.47 to 50 mg/l for amikacin, 1.

Clinical validation of dried blood spot sampling in therapeutic drug monitoring of ciclosporin A in allogeneic stem cell transplant recipients: direct comparison between capillary and venous sampling.

Background: The immunosuppressive drug ciclosporin A has a narrow therapeutic window and a large inter- and intraindividual pharmacokinetic variability. Therapeutic drug monitoring of ciclosporin is usually performed in ethylenediaminetetraacetic acid blood, obtained by venous sampling. Dried blood spot sampling (DBS) could be a useful alternative sampling method, which also easily allows multiple sampling, for example, for obtaining area under the curve.

Rapid quantification of gabapentin, pregabalin, and vigabatrin in human serum by ultraperformance liquid chromatography with mass-spectrometric detection.

Background: Gabapentin (GBP), pregabalin (PRG), and vigabatrin (VIG) are used for the prevention and treatment of epileptic seizures. The developed method was applied to samples from subjects participating in a pharmacokinetic study of GBP.

Methods: Sample pretreatment consisted of adding 20 μL of trichloroacetic acid (30%; vol/vol) and 200 μL of GBP-d4 in acetonitrile as an internal standard to 20 μL of serum.

A multi-scale modelling approach for analysing landscape service dynamics.

Shifting societal needs drive and shape landscapes and the provision of their services. This paper presents a modelling approach to visualize the regional spatial and temporal dynamics in landscape service supply as a function of changing landscapes and societal demand. This changing demand can result from different policy targets.

Population pharmacokinetics of ciclosporin in haematopoietic allogeneic stem cell transplantation with emphasis on limited sampling strategy.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The population pharmacokinetics and limited sampling strategies for ciclosporin monitoring have been extensively studied in renal and liver transplant recipients. Little is known about the pharmacokinetics of ciclosporin in patients undergoing haematopoietic allogeneic stem cell transplantation (HSCT). • It is anticipated that there is a difference in pharmacokinetics in patients after kidney or liver transplantation compared with patients undergoing stem cell transplantation, because of mucositis and interacting drugs (e.

The lopinavir/ritonavir-associated rise in lipids is not related to lopinavir or ritonavir plasma concentration.

Background: The relationship between lopinavir plasma concentration and the magnitude of lipid elevation after initiation of lopinavir/ritonavir-containing antiretroviral therapy is unclear. The aim of this study was to determine the relationship between drug concentration and lipid changes in two patient cohorts.

Methods: First, we analysed, in an outpatient cohort, the correlation between percentage lipid changes and lopinavir concentration, measured at least 2 weeks or more after initiation of lopinavir/ritonavir.

Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy.

Background And Purpose: 5-aminosalicylate (5-ASA) raises levels of 6-thioguanine nucleotides (6-TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN - 6-thioguanosine mono-, di- and triphosphate (6-TGMP, 6-TGDP, 6-TGTP) - and of 6-methylmercaptopurine ribonucleotides (6-MMPR) after 5-ASA are not known.

Experimental Approach: Effects of increasing 5-ASA doses on AZA metabolites were investigated prospectively in 22 patients with inflammatory bowel disease in 4-week study periods.

Limited stability of thiopurine metabolites in blood samples: relevant in research and clinical practise.

Background: Monitoring of thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) is used to assess compliance and explain adverse reactions in IBD-patients. Correlations between dosage, metabolite concentrations and therapeutic efficacy or toxicity are contradictive. Research is complicated by analytical problems as matrices analyzed and analytical procedures vary widely.

On therapeutic drug monitoring of thiopurines in inflammatory bowel disease; pharmacology, pharmacogenomics, drug intolerance and clinical relevance.

Thiopurines such as azathioprine, 6-mercaptopurine and 6-thioguanine are antimetabolites that have been used for several decades in the treatment of several diseases including inflammatory bowel diseases. Additional anti-inflammatory properties of these thiopurines have been discovered in recent years. Thiopurine metabolism is complex due to the involvement of multiple enzymes, of which the activities are genetically determined and cell type dependent.

From land cover change to land function dynamics: a major challenge to improve land characterization.

Land cover change has always had a central role in land change science. This central role is largely the result of the possibilities to map and characterize land cover based on observations and remote sensing. This paper argues that more attention should be given to land use and land functions and linkages between these.

Effects of cyclosporine a on single-dose pharmacokinetics of intravenous itraconazole in patients with hematologic malignancies.

An open-label, clinical pilot study was performed to study the effect of cyclosporine A (CsA) on single-dose pharmacokinetics of itraconazole in patients with a hematologic malignancy. Patients (n = 10), admitted for allogeneic stem cell transplantation, received a single dose of 200 mg itraconazole in a 1-hour intravenous infusion during their treatment period before initiation of CsA. This was repeated during the period that CsA was administered and a steady-state concentration of CsA was achieved (trough whole blood level 200-400 ng/mL).

Modelling land use change and environmental impact.

Land use change models are tools for understanding and explaining the causes and consequences of land use dynamics. Recently, new models, combining knowledge and tools from biophysical and socio-economic sciences, have become available. This has resulted in spatially explicit models focussed on patterns of change as well as agent-based models focused on the underlying decision processes.

Hepatotoxicity following nevirapine-containing regimens in HIV-1-infected individuals.

To determine the incidence of hepatotoxicity and to investigate whether plasma concentrations of nevirapine, in addition to other risk factors, could predict hepatotoxicity during treatment with nevirapine-containing regimens, we conducted a retrospective analysis with data from 174 individuals infected with human immunodeficiency virus-1 (HIV-1). During regular visits to the clinic, blood samples were collected for the determination of nevirapine plasma concentrations and clinical chemistry parameters including liver enzymes (LEs) and total bilirubin (TBR). Severe hepatotoxicity was defined as a grade > or =3 elevation in at least one of the tested LEs or TBR levels while on therapy.

Modeling the spatial dynamics of regional land use: the CLUE-S model.

Land-use change models are important tools for integrated environmental management. Through scenario analysis they can help to identify near-future critical locations in the face of environmental change. A dynamic, spatially explicit, land-use change model is presented for the regional scale: CLUE-S.