Publications by authors named "Laura Peeters"

28 Publications

  • Page 1 of 1

An Accidental Repetitive 10-Fold Overdose of Sildenafil in a Young Infant with Pulmonary Hypertension.

Neonatology 2021 Mar 29:1-5. Epub 2021 Mar 29.

Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Sildenafil is a selective phosphodiesterase type-5 inhibitor that is increasingly used to treat pulmonary hypertension (PH) in neonates. Only little is known about the relation between the dose of sildenafil, plasma concentrations, and the degree of toxicity. Here, we present a young infant with congenital diaphragmatic hernia and PH who received an unintentional 10-fold overdose of oral sildenafil for 6 consecutive days. This overdose, compared to the therapeutic dose, resulted in increased plasma concentrations of sildenafil from 42 to 521 mcg/L and desmethylsildenafil from 81 to 393 mcg/L. However, the high exposure only led to diarrhea, without any other serious adverse events. This case describes the mild symptoms upon an overdose with the role of therapeutic drug monitoring to monitor exposure in relation to symptoms and therewith support clinical decision-making.
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http://dx.doi.org/10.1159/000514380DOI Listing
March 2021

Antiplasmodial Oleanane Triterpenoids from Root Bark.

J Nat Prod 2021 Mar 5;84(3):666-675. Epub 2021 Mar 5.

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.

Phytochemical investigation of the -BuOH extract of the roots of Sc. Elliot (Combretaceae) led to the isolation and identification of 10 oleanane triterpenoids (-), among which six new compounds, i.e., albidanoside A (), albidic acid A (), albidinolic acid (), albidienic acid (), albidolic acid (), and albidiolic acid (), and two triterpenoid aglycones, i.e., albidic acid B () and albidic acid C (), were isolated here for the first time from a natural source, along with two known compounds. The structures of these constituents were established by means of 1D and 2D NMR spectroscopy and ESI mass spectrometry. The isolated compounds were evaluated for their antiplasmodial and antimicrobial activity against the chloroquine-resistant strain K1, , and . Compounds -, , , and showed moderate antiplasmodial activity with IC values between 5 and 15 μM. None of the tested compounds were active against or . These findings emphasize the potential of as a source for discovery of new antiplasmodial compounds.
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http://dx.doi.org/10.1021/acs.jnatprod.0c01119DOI Listing
March 2021

Simulated Gastrointestinal Biotransformation of Chlorogenic Acid, Flavonoids, Flavonolignans and Triterpenoid Saponins in Cecropia obtusifolia Leaf Extract.

Planta Med 2020 Oct 2. Epub 2020 Oct 2.

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.

It is well known that biotransformation processes in the human body are crucial to form potentially bioactive metabolites from particular classes of natural products. However, little research has been conducted concerning the bioavailability of polyphenols, especially in the colon. The gastrointestinal stability and colonic biotransformation of the crude extract of the leaves of , rich in flavone -glycosides, was investigated under conditions, and the processing and interpretation of results were facilitated by using an automated machine learning model. This investigation revealed that flavone -glycosides and flavonolignans from were stable throughout their passage in the simulated gastrointestinal tract including the colon phase. On the other hand, the colon bacteria extensively metabolized chlorogenic acid, flavonol, and triterpenoid -glycosides. This investigation revealed that the colonic microbiota has an important role in the biotransformation of some chemical constituents of this extract.
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http://dx.doi.org/10.1055/a-1258-4383DOI Listing
October 2020

Aggrecan and COMP Improve Periosteal Chondrogenesis by Delaying Chondrocyte Hypertrophic Maturation.

Front Bioeng Biotechnol 2020 28;8:1036. Epub 2020 Aug 28.

Laboratory for Experimental Orthopedics, Department of Orthopedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Center, Maastricht, Netherlands.

The generation of cartilage from progenitor cells for the purpose of cartilage repair is often hampered by hypertrophic differentiation of the engineered cartilaginous tissue caused by endochondral ossification. Since a healthy cartilage matrix contains high amounts of Aggrecan and COMP, we hypothesized that their supplementation in the biogel used in the generation of subperiosteal cartilage mimics the composition of the cartilage extracellular matrix environment, with beneficial properties for the engineered cartilage. Supplementation of COMP or Aggrecan was studied during chondrogenic differentiation of rabbit periosteum cells and periosteum-derived chondrocytes. Low melting agarose was supplemented with bovine Aggrecan, human recombinant COMP or vehicle and was injected between the bone and periosteum at the upper medial side of the tibia of New Zealand white rabbits. Generated subperiosteal cartilage tissue was analyzed for weight, GAG and DNA content and ALP activity. Key markers of different phases of endochondral ossification were measured by RT-qPCR. For the experiments, no significant differences in chondrogenic marker expression were detected following COMP or Aggrecan supplementation, while favorable chondrogenic marker expression was detected. Gene expression levels of hypertrophic markers as well as ALP activity were significantly decreased in the Aggrecan and COMP supplemented conditions compared to controls. The wet weight and GAG content of the generated subperiosteal cartilage tissue was not significantly different between groups. Data demonstrate the potential of Aggrecan and COMP to favorably influence the subperiosteal microenvironment for the generation of cartilage for the optimization of cartilage regenerative approaches.
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http://dx.doi.org/10.3389/fbioe.2020.01036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483497PMC
August 2020

Quantitative description of upper extremity function and activity of people with spinal muscular atrophy.

J Neuroeng Rehabil 2020 09 11;17(1):126. Epub 2020 Sep 11.

Department of Rehabilitation, Radboud University Medical Center, Donders Centre for Neuroscience, Reinier Postlaan 4, 6525 GC, Nijmegen, the Netherlands.

Background: Therapeutic management of the upper extremity (UE) function of people with spinal muscular atrophy (SMA) requires sensitive and objective assessment. Therefore, we aimed to measure physiologic UE function of SMA patients with different functional abilities and evaluate the relation between these physiologic measures and functional UE scales.

Methods: 12 male and 5 female SMA patients (mean age 42 years; range 6-62 years) participated in this explorative study. Concerning the physiologic level, the maximal muscle torque, the maximal and normalized surface electromyography (sEMG) amplitudes, and the maximal passive and active joint angles were measured. Concerning the activity level, the Performance of the Upper Limb (PUL) scale was used, and hand function was examined using the Nine-Hole Peg Test and the Timed Test of In-Hand Manipulation (TIHM).

Results: Outcome measures that significantly related to the functional ability were: the PUL score (all dimensions); the finger to palm task of the Timed TIHM; biceps, triceps, and forearm extensor strength; and the active range of motion of shoulder abduction, shoulder flexion, and wrist extension. In addition, the following physiologic variables were related to the activity level (PUL score): hand function (the Nine-Hole Peg Test; R = - 0.61), the Timed TIHM (R = - 0.53), the maximal muscle torque (R = 0.74), the maximal sEMG amplitude (R = 0.79), and the maximal active joint angle (R = 0.88).

Conclusions: Muscle functions in SMA patients are already affected before activity limitations are noticeable. Consequently, monitoring the maximal muscle strength and the normalized muscle activity during task performance could play a role in the early detection of UE limitations. The mechanism behind the loss of arm activities due to SMA is primarily caused by decreasing muscle capacity, which influences the ability to move an arm actively. In clinical practices, these dimensions should be considered separately when monitoring disease progression in order to better evaluate the need for interventions.
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http://dx.doi.org/10.1186/s12984-020-00757-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488714PMC
September 2020

Exploring physiological signals on people with Duchenne muscular dystrophy for an active trunk support: a case study.

BMC Biomed Eng 2019 9;1:31. Epub 2019 Dec 9.

Department Biomechanical Engineering, University of Twente, Drienerlolaan 5, 7522 NB Enschede, the Netherlands.

Background: Arm support devices are available to support people with Duchenne muscular dystrophy (DMD), but active trunk support devices are lacking. An active trunk support device can potentially extend the reach of the arm and stabilize the unstable trunk of people with DMD. In a previous study, we showed that healthy people were able to control an active trunk support using four different control interfaces (based on joystick, force on feet, force on sternum and surface electromyography). All four control interfaces had different advantages and disadvantages. The aim of this study was to explore which of the four inputs is detectably used by people with DMD to control an active trunk support.

Results: The results were subject-dependent in both experiments. In the active experiment, the joystick was the most promising control interface. Regarding the static experiment, surface electromyography and force on feet worked for two out of the three subjects.

Conclusions: To our knowledge, this is the first time that people with DMD have engaged in a control task using signals other than those related to their arm muscles. According to our findings, the control interfaces have to be customised to every DMD subject.
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http://dx.doi.org/10.1186/s42490-019-0032-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422594PMC
December 2019

A comparative study on the in vitro biotransformation of medicagenic acid using human liver microsomes and S9 fractions.

Chem Biol Interact 2020 Sep 23;328:109192. Epub 2020 Jul 23.

Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Wilrijk, Belgium. Electronic address:

Many natural products are prodrugs which are biotransformed and activated after oral administration. The investigation of gastrointestinal and hepatic biotransformation can be facilitated by in vitro screening methods. This study compares two widely used in vitro models for hepatic biotransformation: 1) human S9 fractions and 2) human liver microsomes and cytosolic fractions in a two-step sequence, with the purpose of identifying differences in the biotransformation of medicagenic acid, the putative precursor of active metabolites, responsible for the medicinal effects of the herb Herniaria hirsuta. The combination of liquid chromatography coupled to high-resolution mass spectrometry with subsequent suspect and non-target data analysis allowed the identification of thirteen biotransformation products, four of which are reported here for the first time. Eight biotransformation products resulting from oxidative Phase I reactions were identified. Phase II conjugation reactions resulted in the formation of three glucuronidated and two sulfated biotransformation products. No major differences could be observed between incubations with human liver S9 or when utilizing human microsomal and cytosolic fractions. Apart from two metabolites, both methods rendered the same qualitative metabolic profile, with minor quantitative differences. As a result, both protocols applied in this study can be used to study in vitro human liver biotransformation reactions.
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http://dx.doi.org/10.1016/j.cbi.2020.109192DOI Listing
September 2020

Clinical Applicability of Monitoring Antihypertensive Drug Levels in Blood.

Hypertension 2020 07 18;76(1):80-86. Epub 2020 May 18.

Department of Internal Medicine (L.E.J.P., T.v.G., J.V.), Erasmus MC, University Medical Center Rotterdam, the Netherlands.

Dried blood spot (DBS) analysis is a novel analytical method for therapeutic drug monitoring to identify nonadherence to antihypertensive drugs. This study was conducted to evaluate the clinical applicability of measuring drug concentrations of 8 antihypertensive drugs, using DBS and venipuncture. Furthermore, this study aimed to provide more insight into the between-patient variability in drug concentrations. False-negative values from DBS compared with a venipuncture were determined to assess drug adherence. A generalized estimating equation was used to estimate the model parameters, including sex, dose, age, weight, and the time interval, between drug intake and sampling, on the C (drug concentration in plasma). No false-negative values were found when measuring nonadherence using DBS compared with venipuncture. A high variability in C between patients was observed, especially at peak concentrations with a fold change reaching from 2.3 to 35.2. The time of intake was significantly related to the height of the C in 7 of the 8 measured drugs with a <0.05, but the influence of dose, weight, age, and sex on drug levels differed largely between the measured drugs. DBS is a reliable and convenient method to assess nonadherence to antihypertensive drugs in clinical practice. The C of the 8 antihypertensive drugs in this study show a large interindividual difference, and therefore, low plasma concentrations do not necessarily mean nonadherence. Nonadherence can only be confirmed if drug levels are undetectable, that is, values below the lower limit of detection.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15038DOI Listing
July 2020

Compound Characterization and Metabolic Profile Elucidation after In Vitro Gastrointestinal and Hepatic Biotransformation of an Extract Using Unbiased Dynamic Metabolomic Data Analysis.

Metabolites 2020 Mar 16;10(3). Epub 2020 Mar 16.

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.

L. (Caryophyllaceae) is used for treatment of urinary stones and as a diuretic. Little is known about the active compounds and the mechanism of action. The phytochemical composition of was comprehensively characterized using UHPLC-UV-HRMS (Ultrahigh-Performance Liquid Chromatography-Ultraviolet-High Resolution Mass Spectrometry) data. An in vitro gastrointestinal model was used to simulate biotransformation, which allowed the monitoring of the relative abundances of individual compounds over time. To analyze the longitudinal multiclass LC-MS data, XCMS, a platform that enables online metabolomics data processing and interpretation, and EDGE, a statistical method for time series data, were used to extract significant differential profiles from the raw data. An interactive Shiny app in R was used to rate the quality of the resulting features. These ratings were used to train a random forest model. The most abundant aglycone after gastrointestinal biotransformation was subjected to hepatic biotransformation using human S9 fractions. A diversity of compounds was detected, mainly saponins and flavonoids. Besides the known saponins, 15 new saponins were tentatively identified as glycosides of medicagenic acid, acetylated medicagenic acid and zanhic acid. It is suggested that metabolites of phytochemicals present in , most likely saponins, are responsible for the pharmaceutical effects. It was observed that the relative abundance of saponin aglycones increased, indicating loss of sugar moieties during colonic biotransformation, with medicagenic acid as the most abundant aglycone. Hepatic biotransformation of this aglycone resulted in different metabolites formed by phase I and II reactions.
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http://dx.doi.org/10.3390/metabo10030111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142424PMC
March 2020

Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites.

Ther Drug Monit 2020 06;42(3):460-467

Departments of Hospital Pharmacy.

Background: Drug nonadherence is one of the major challenges faced by resistant hypertension patients, and identification of this problem is needed for optimizing pharmacotherapy. Dried blood spot (DBS) sampling is a minimally invasive method designed to detect and determine the degree of nonadherence. In this study, a DBS method for qualifying 8 antihypertensive drugs (AHDs) and 4 active metabolites was developed and validated using ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

Method: The DBS assay was validated analytically and clinically, in accordance with FDA requirements. Analytical validation was accomplished using UHPLC-MS/MS. For clinical validation, paired peak and trough levels of DBS and plasma samples were simultaneously collected and comparatively analyzed using Deming regression and Bland-Altman analyses. All concentrations below the set lower limit were excluded. Deming regression analysis was used to predict comparison bias between the collected plasma and DBS samples, with DBS concentrations corrected accordingly.

Results: The UHPLC-MS/MS method for simultaneously measuring 8 AHDs and their metabolites in DBS, was successfully validated. With Deming regression no bias was observed in N = 1; constant bias was seen in N = 6 and proportional bias in N = 11 of the AHDs and metabolites. After correction for bias, only one metabolite (canrenone) met the 20% acceptance limit for quantification, after Bland-Altman analyses. In addition, amlodipine, valsartan, and [enalaprilate] met the 25% acceptance limit.

Conclusions: A novel DBS assay for simultaneously qualifying and quantifying 8 AHDs and their metabolites, has been successfully developed and validated. The DBS assay is therefore a suitable method to detect drug nonadherence. However, with the exception of canrenone, the interchangeable use of plasma and DBS sampling to interpret drug quantities should be avoided.
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http://dx.doi.org/10.1097/FTD.0000000000000703DOI Listing
June 2020

Patients With Spinal Muscular Atrophy Use High Percentages of Trunk Muscle Capacity to Perform Seated Tasks.

Am J Phys Med Rehabil 2019 12;98(12):1110-1117

From the Department of Rehabilitation, Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands (LHCP, MMHPJ, IJMdG); and Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands (IK, JHvD).

Objective: The aim of the study was to investigate trunk function during seated upper limb tasks in patients with spinal muscular atrophy types 2 and 3.

Design: Seventeen persons with spinal muscular atrophy and 15 healthy controls performed several tasks when sitting unsupported, such as reaching (and placing) forward and sideward. Joint torque and muscle activity were measured during maximum voluntary isometric contractions. Three-dimensional kinematics and normalized muscle activity were analyzed when performing tasks.

Results: Trunk joint torques were significantly decreased, approximately 45%, in patients with spinal muscular atrophy compared with healthy controls. Active range of trunk motion was also significantly decreased in all directions. When performing tasks, the average back muscle activity was 27% and 56% of maximum voluntary isometric contractions for healthy controls and spinal muscular atrophy and for abdominal muscles 10% and 44% of maximum voluntary isometric contractions, respectively. Trunk range of motion did not differ when performing daily tasks.

Conclusions: The trunk of patients with spinal muscular atrophy is weaker compared with healthy controls, reflected by reduced trunk torques and decreased active range of motion. In addition, patients with spinal muscular atrophy use high percentages of their trunk muscle capacity to perform tasks. Clinicians should take this into account for intervention development, because using high percentages of the maximum muscle capacity results in fatigue and muscle overloading.
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http://dx.doi.org/10.1097/PHM.0000000000001258DOI Listing
December 2019

Current care for victims of sexual violence and future sexual assault care centres in Belgium: the perspective of victims.

BMC Int Health Hum Rights 2019 06 27;19(1):21. Epub 2019 Jun 27.

International Centre for Reproductive Health (ICRH), Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, UZP114, B-9000, Ghent, Belgium.

Background: Sexual violence is a global health problem. After ratifying the Convention of Istanbul in 2016, this Belgian study was set up to map the perspective of victims of rape on the current sexual violence care provision in Belgium and to inquire on their need for more specialised and holistic care in future Sexual Assault Care Centres.

Methods: Sixteen rape victims participated in this sub-study. A mixed-method design (questionnaire, in-depth interview or small focus group) was applied depending on the time elapsed between rape and participation. Descriptive Thematic Framework Analysis was performed in duo.

Results: The participants thought it of utmost importance that every victim should receive all medical, psychological and forensic care without necessarily having to involve the police first. They stated that the current Belgian sexual violence care provision could be much more patient-centred, specifically the forensic examination and psychological care. Alongside medical and psychological consequences, victims emphasised the high personal financial and relational burden of sexual violence. The holistic care offered in Sexual Assault Care Centres was perceived to enhance the recovery process of victims of sexual violence. Their doors should be open to all victims and their relatives. They should not only provide acute care for the victim, but also improve victims' reintegration into society while reducing their personal costs significantly.

Conclusion: All care for victims of sexual violence, especially forensic and psychological care, needs drastic improvement in Belgium. All participants agreed that having specialised, multidisciplinary and longitudinal care in a Sexual Assault Care Centre that would be open 24/7 for everyone, victims and their significant others, would be an improvement to the currently available care all over Belgium.

Trial Registration: This research was registered on April 1st 2016. Registration number B670201628242.
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http://dx.doi.org/10.1186/s12914-019-0207-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598354PMC
June 2019

Using Expert Driven Machine Learning to Enhance Dynamic Metabolomics Data Analysis.

Metabolites 2019 Mar 20;9(3). Epub 2019 Mar 20.

Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, 2000 Antwerp, Belgium.

Data analysis for metabolomics is undergoing rapid progress thanks to the proliferation of novel tools and the standardization of existing workflows. As untargeted metabolomics datasets and experiments continue to increase in size and complexity, standardized workflows are often not sufficiently sophisticated. In addition, the ground truth for untargeted metabolomics experiments is intrinsically unknown and the performance of tools is difficult to evaluate. Here, the problem of dynamic multi-class metabolomics experiments was investigated using a simulated dataset with a known ground truth. This simulated dataset was used to evaluate the performance of tinderesting, a new and intuitive tool based on gathering expert knowledge to be used in machine learning. The results were compared to EDGE, a statistical method for time series data. This paper presents three novel outcomes. The first is a way to simulate dynamic metabolomics data with a known ground truth based on ordinary differential equations. This method is made available through the MetaboLouise R package. Second, the EDGE tool, originally developed for genomics data analysis, is highly performant in analyzing dynamic case vs. control metabolomics data. Third, the tinderesting method is introduced to analyse more complex dynamic metabolomics experiments. This tool consists of a Shiny app for collecting expert knowledge, which in turn is used to train a machine learning model to emulate the decision process of the expert. This approach does not replace traditional data analysis workflows for metabolomics, but can provide additional information, improved performance or easier interpretation of results. The advantage is that the tool is agnostic to the complexity of the experiment, and thus is easier to use in advanced setups. All code for the presented analysis, MetaboLouise and tinderesting are freely available.
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http://dx.doi.org/10.3390/metabo9030054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468718PMC
March 2019

Revelation of the metabolic pathway of hederacoside C using an innovative data analysis strategy for dynamic multiclass biotransformation experiments.

J Chromatogr A 2019 Jun 25;1595:240-247. Epub 2019 Feb 25.

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.

Although some herbal remedies have been used for decades, little is known about the active compounds and the mechanism of action. Many natural products, such as glycosides, can be considered as prodrugs, which become active after biotransformation. To optimize the workflow of in vitro biotransformation followed by automated data analysis, hederacoside C was used as a model compound for saponins. Hederacoside C was subjected to gastrointestinal enzymes and fecal microflora. Samples were analyzed with UHPLC-PDA-HRMS before, during and after in vitro biotransformation, which allowed the monitoring of the relative abundances of the compound and its metabolites. The data-analysis workflow was optimized to render as much information as possible from the longitudinal LCMS data. XCMS was used to convert the raw data into features via peak-picking, followed by grouping, and EDGE was used for the extraction of significant differential profiles. To evaluate if the workflow was suitable for dynamic multiclass metabolomics data, an interactive Shiny web app was developed in R to rate the quality of the resulting features. These ratings were used to train a random forest model for predicting experts response. A performance analysis revealed that the random forest model was capable of correctly predicting the reviewers response in most cases (AUC 0.926 with 10 fold cross validation). The automated data analysis workflow was used for unbiased screening for metabolites and revealed the biotransformation of hederacoside C. As expected, a decrease in relative abundance of hederacoside C was observed over time. Additionally, the relative abundance of metabolites increased, illustrating the biotransformation of hederacoside C, especially in the colon phase, where microbial fermentation takes place. Stepwise progressive elimination of sugar moieties was the major metabolic pathway.
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http://dx.doi.org/10.1016/j.chroma.2019.02.055DOI Listing
June 2019

Drug nonadherence is a common but often overlooked cause of hypertensive urgency and emergency at the emergency department.

J Hypertens 2019 05;37(5):1048-1057

Department of Internal Medicine.

Objectives: Over 70% of patients who visit the emergency department with a hypertensive emergency or a hypertensive urgency have previously been diagnosed with hypertension. Drug nonadherence is assumed to play an important role in development of hypertensive urgency and hypertensive emergency, but exact numbers are lacking. We aimed to retrospectively compare characteristics of patients with hypertensive urgency and hypertensive emergency and to prospectively quantify the attribution of drug nonadherence.

Methods: We retrospectively analysed clinical data including information on nonadherence obtained by treating physicians of patients with SBP at least 180 mmHg and DBP at least 110 mmHg visiting the emergency department between 2012 and 2015. We prospectively studied drug adherence among patients admitted to the emergency department with severely elevated BP by measuring plasma drug levels using liquid chromatography tandem mass spectrometry from September 2016 to March 2017.

Results: Of the 1163 patients retrospectively analysed, 257 (22.0%) met the criteria for hypertensive urgency and 356 (30.6%) for hypertensive emergency. Mean SBP (SD) was 203 (19) mmHg and mean DBP 121 (12) mmHg. Mean age was 60.1 (14.6) years; 55.1% were men. In 6.3% of patients with hypertensive urgency or hypertensive emergency, nonadherence was recorded as an attributing factor. Of the 59 patients prospectively analysed, 18 (30.5%) were nonadherent for at least one of the prescribed antihypertensive drugs.

Conclusion: Hypertensive urgency and hypertensive emergency are common health problems resulting in frequent emergency department admissions. Workup of patients with a hypertensive urgency or hypertensive emergency should include an assessment of drug adherence to optimize treatment strategy.
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http://dx.doi.org/10.1097/HJH.0000000000002005DOI Listing
May 2019

Establishing Sexual Assault Care Centres in Belgium: health professionals' role in the patient-centred care for victims of sexual violence.

BMC Health Serv Res 2018 Oct 22;18(1):807. Epub 2018 Oct 22.

International Centre for Reproductive Health (ICRH), Department of Uro-Gynaecology, Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, UZP114, 9000, Ghent, Belgium.

Background: Having ratified the Convention of Istanbul, the Belgian federal government commits itself to the foundation of Sexual Assault Care Centres (SACC). In the light of researching the feasibility of these centres, this study aimed to evaluate the care for victims of sexual violence (SV) in Belgian hospitals anno 2016 as well as to formulate recommendations for the intended model.

Methods: Between April and October 2016, a questionnaire was distributed to 159 key health professionals active in 17 different hospitals attached to an AIDS Referral Centre. The survey covered four parts, i.e. the health professionals' profile, their knowledge, attitude and practices, an assessment of the hospital's policy and the caregivers' opinion on the care for victims of SV and on the intended SACCs. Subsequently, a descriptive analysis using 'IBM SPSS Statistics 23' was performed.

Results: A total of 60 key health professionals representing 15 different hospitals completed the questionnaire resulting in a response rate of 38%. The results showed a lack of knowledge and practical experience of caregivers' regarding the care for SV victims. Approximately 30% of responders face personal or professional difficulties upon provision of care to victims of SV. Participants evaluate the current care as good, despite the limited psychosocial support, follow-up, insight for the needs of vulnerable groups and support for family, relatives and health professionals. Yet, the majority of health professionals appraise the SACCs as the best approach for both victims and caregivers.

Conclusions: By introducing a SACC, the Belgian federal government aims to provide holistic and patient-centred care for victims of SV. Essential in patient-centred health care is an extensive and continuous education, training and supervision of health professionals concerning the care for victims, support for family, relatives and caregivers. At the end and as a result of a participatory process with many professional experts as well as victims, a specific Belgian model, adjusted to the health care system anno 2016 was developed for piloting. The main challenges in establishing SACCs are situated at the institutional and policy level. Collaborating with other institutions and further research are herewith required.
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http://dx.doi.org/10.1186/s12913-018-3608-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196455PMC
October 2018

Towards a more integrated and gender-sensitive care delivery for victims of sexual assault: key findings and recommendations from the Belgian sexual assault care centre feasibility study.

Int J Equity Health 2018 09 24;17(1):152. Epub 2018 Sep 24.

International Centre for Reproductive Health (ICRH), Department of Uro-Gynaecology, Faculty of Medicine and Health Sciences, Ghent University, Corneel Heymanslaan 10, UZP114, B-9000, Ghent, Belgium.

Background: Sexual assault remains a major threat to public health, affecting every gender, gender identity and sexual orientation. Following the Belgian ratification of the Istanbul Convention in 2016, the feasibility of a Belgian sexual assault centre model was investigated, aiming to provide more integrated and patient-centred health and judiciary services to victims of sexual assault. By actively involving health professionals, police and judiciary system representatives, as well as victims themselves, this feasibility study eventually fed into the Belgian Sexual Assault Care Centre model. In this process, this paper assessed current Belgian health services and the degree to which the implementation of this model could contribute to both a more integrated and gender-sensitive care delivery. Findings from this study and the subsequent recommendations aim to contribute to similar reforms in other countries that have already taken or are about to take steps towards an integrated, multi-agency support framework for victims of sexual assault.

Methods: A qualitative, descriptive analysis of the survey response of 60 key health professionals (N = 60) representing 15 major Belgian hospitals was first conducted. Comparing their approach with the international guidelines and standards, a Strengths Weaknesses Opportunities and Threats analysis of the current sexual assault health services and their potential transition to the Sexual Assault Care Centre model was then executed.

Results: Despite adequate equipment, the clear fragmentation of health services and limited follow-up hamper an integrated care delivery in most hospitals. Only three hospitals differentiated their sexual assault care protocol based on the victim's gender, gender identity and sexual orientation. A striking unawareness among health professionals of sexual assault in male victims, as well as in gender and sexual minorities further hampers a gender-sensitive care delivery.

Conclusions: The Sexual Assault Care Centre model aims to counter most of the current sexual assault health services' weaknesses and threats hampering an integrated care for victims of sexual assault. Further research and training of health professionals are however required in order to tune this integrated form of care to sexuality and gender-based differences in victims' already multi-faceted healthcare needs.
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http://dx.doi.org/10.1186/s12939-018-0864-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154874PMC
September 2018

Evaluation of Control Interfaces for Active Trunk Support.

IEEE Trans Neural Syst Rehabil Eng 2018 10 23;26(10):1965-1974. Epub 2018 Aug 23.

A feasibility study was performed to evaluate the control interfaces for a novel trunk support assistive device (Trunk Drive), namely, joystick, force on sternum, force on feet, and electromyography (EMG) to be used by adult men with Duchene muscular dystrophy. The objective of this paper was to evaluate the performance of the different control interfaces during a discrete position tracking task. We built a one degree of freedom flexion-extension active trunk support device that was tested on 10 healthy men. An experiment, based on the Fitts law, was conducted, whereby subjects were asked to steer a cursor representing the angle of the Trunk Drive into a target that was shown on a graphical user interface, using the above-mentioned control interfaces. The users could operate the Trunk Drive via each of the control interfaces. In general, the joystick and force on sternum were the fastest in movement time (more than 40%) without any significant difference between them, but there was a significant difference between force on sternum on the one hand, and EMG and force on feet on the other. All control interfaces proved to be feasible solutions for controlling an active trunk support, each of which had specific advantages.
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http://dx.doi.org/10.1109/TNSRE.2018.2866956DOI Listing
October 2018

Development and evaluation of a passive trunk support system for Duchenne muscular dystrophy patients.

J Neuroeng Rehabil 2018 03 14;15(1):22. Epub 2018 Mar 14.

Dept of Human Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands.

Background: Patients with Duchenne muscular dystrophy gradually lose the ability to use different muscles of their body. Consequently, they lose the ability to stabilize their trunk against gravity. This hinders them to effectively perform different daily activities. In this paper, we describe the design, realization and evaluation of a trunk orthosis for these patients that should allow them to move their trunk and maintain stability.

Method: This study aimed to primarily assess the effectiveness of the trunk support system in terms of unloading of trunk muscles, so only healthy participants were recruited for this phase of the study. Measurements were done on 10 healthy participants (23.4±2.07 [M±SD] years old, average body weight 68.42±24.22 [M±SD] kg). The experiment comprised maintaining a constant trunk posture in three different device conditions (control without orthosis and two conditions with different configurations of the orthosis), at four different flexion angles (10°, 20°, 30°, 40°) for each device condition and for two load conditions (with and without stretching the arms). Electromyography (EMG) signals from the trunk muscles were measured to estimate activation levels of the trunk muscles (iliocostalis, longissimus, external oblique and rectus abdominis) and a motion capture system was used to record the movement of the participants during the experiment.

Results: Wearing the orthosis caused reductions in longissimus and iliocostalis activity. The average muscle activity level was 5%-10% of maximum voluntary contraction in the unsupported conditions for those particular muscles. This level was reduced to 3%-9% of maximal voluntary contraction for the supported conditions. No effect on external oblique and rectus abdominis activity was observed. Moreover, no pain or discomfort was reported by any of the participants during the experiment. The results from the current experiment also suggests the necessity of lumber stabilizing systems while using trunk orthosis.

Conclusion: The developed orthosis reduces trunk muscle activation level and provides a solid step for further development of support systems for Duchenne muscular dystrophy patients.

Trial Registration: The current study was approved by the medical ethics committee Arnhem-Nijmegen (study number: NL53143.091.15 ), The Netherlands.
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http://dx.doi.org/10.1186/s12984-018-0353-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853074PMC
March 2018

Trunk involvement in performing upper extremity activities while seated in neurological patients with a flaccid trunk - A review.

Gait Posture 2018 05 6;62:46-55. Epub 2018 Mar 6.

Radboud University Medical Center, Donders Centre for Neuroscience, Department of Rehabilitation, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Background: Trunk control is essential during seated activities. The trunk interacts with the upper extremities (UE) and head by being part of a kinematic chain and by providing a stable basis. When trunk control becomes impaired, it may have consequences for the execution of UE tasks.

Aim: To review trunk involvement in body movement and stability when performing seated activities and its relation with UE and head movements in neurological patients with a flaccid trunk, with a focus on childhood and development with age.

Methods And Procedures: A search using PubMed was conducted and 32 out of 188 potentially eligible articles were included.

Outcomes And Results: Patients with a flaccid trunk (e.g. with spinal cord injury or cerebral palsy) tend to involve the trunk earlier while reaching than healthy persons. Different balance strategies are observed in different types of patients, like using the contralateral arm as counterweight, eliminating degrees of freedom, or reducing movement speed.

Conclusions And Implications: The key role of the trunk in performing activities should be kept in mind when developing interventions to improve seated task performance in neurological patients with a flaccid trunk.
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http://dx.doi.org/10.1016/j.gaitpost.2018.02.028DOI Listing
May 2018

Effect of residual doxycycline concentrations on resistance selection and transfer in porcine commensal Escherichia coli.

Int J Antimicrob Agents 2018 Jan 28;51(1):123-127. Epub 2017 Jun 28.

Department of Pathology, Bacteriology and Avian Diseases, Ghent University, 9820 Merelbeke, Belgium.

Pig feed may contain various levels of antimicrobial residues due to cross-contamination. A previous study showed that a 3% carry-over level of doxycycline (DOX) in the feed results in porcine faecal concentrations of approximately 4 mg/L. The aim of this study was to determine the effect of residual DOX concentrations (1 and 4 mg/L) in vitro on selection of DOX-resistant porcine commensal Escherichia coli and transfer of their resistance plasmids. Three different DOX-resistant porcine commensal E. coli strains and their plasmids were characterised. These strains were each brought in competition with a susceptible strain in a medium containing 0, 1 and 4 mg/L DOX. Resistant bacteria, susceptible bacteria and transconjugants were enumerated after 24 h and 48 h. The tet(A)-carrying plasmids showed genetic backbones that are also present among human E. coli isolates. Ratios of resistant to susceptible bacteria were significantly higher at 1 and 4 mg/L DOX compared with the blank control, but there was no significant difference between 1 and 4 mg/L. Plasmid transfer frequencies were affected by 1 or 4 mg/L DOX in the medium for only one of the resistance plasmids. In conclusion, DOX concentrations of 1 and 4 mg/L can select for resistant E. coli in vitro. Further research is needed to determine the effect of these concentrations in the complex environment of the porcine intestinal microbiota.
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http://dx.doi.org/10.1016/j.ijantimicag.2017.04.018DOI Listing
January 2018

A 3D-printed anatomical pancreas and kidney phantom for optimizing SPECT/CT reconstruction settings in beta cell imaging using In-exendin.

EJNMMI Phys 2016 Dec 7;3(1):29. Epub 2016 Dec 7.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, P.O. Box: 9101, 6500 HB, Nijmegen, The Netherlands.

Background: Quantitative single photon emission computed tomography (SPECT) is challenging, especially for pancreatic beta cell imaging with In-exendin due to high uptake in the kidneys versus much lower uptake in the nearby pancreas. Therefore, we designed a three-dimensionally (3D) printed phantom representing the pancreas and kidneys to mimic the human situation in beta cell imaging. The phantom was used to assess the effect of different reconstruction settings on the quantification of the pancreas uptake for two different, commercially available software packages.

Methods: 3D-printed, hollow pancreas and kidney compartments were inserted into the National Electrical Manufacturers Association (NEMA) NU2 image quality phantom casing. These organs and the background compartment were filled with activities simulating relatively high and low pancreatic In-exendin uptake for, respectively, healthy humans and type 1 diabetes patients. Images were reconstructed using Siemens Flash 3D and Hermes Hybrid Recon, with varying numbers of iterations and subsets and corrections. Images were visually assessed on homogeneity and artefacts, and quantitatively by the pancreas-to-kidney activity concentration ratio.

Results: Phantom images were similar to clinical images and showed comparable artefacts. All corrections were required to clearly visualize the pancreas. Increased numbers of subsets and iterations improved the quantitative performance but decreased homogeneity both in the pancreas and the background. Based on the phantom analyses, the Hybrid Recon reconstruction with 6 iterations and 16 subsets was found to be most suitable for clinical use.

Conclusions: This work strongly contributed to quantification of pancreatic In-exendin uptake. It showed how clinical images of In-exendin can be interpreted and enabled selection of the most appropriate protocol for clinical use.
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http://dx.doi.org/10.1186/s40658-016-0165-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143330PMC
December 2016

Residues of chlortetracycline, doxycycline and sulfadiazine-trimethoprim in intestinal content and feces of pigs due to cross-contamination of feed.

BMC Vet Res 2016 Sep 20;12:209. Epub 2016 Sep 20.

Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, 9820, Merelbeke, Belgium.

Background: Cross-contamination of feed with low concentrations of antimicrobials can occur at production, transport and/or farm level. Concerns are rising about possible effects of this contaminated feed on resistance selection in the intestinal microbiota. Therefore, an experiment with pigs was set up, in which intestinal and fecal concentrations of chlortetracycline (CTC), doxycycline (DOX) and sulfadiazine-trimethoprim (SDZ-TRIM) were determined after administration of feed containing a 3 % carry-over level of these antimicrobials.

Results: The poor oral bioavailability of tetracyclines resulted in rather high concentrations in cecal and colonic content and feces at steady-state conditions. A mean concentration of 10 mg/kg CTC and 4 mg/kg DOX in the feces was reached, which is higher than concentrations that were shown to cause resistance selection. On the other hand, lower mean levels of SDZ (0.7 mg/kg) and TRIM (< limit of detection of 0.016 mg/kg) were found in the feces, corresponding with the high oral bioavailability of SDZ and TRIM in pigs.

Conclusions: The relation between the oral bioavailability and intestinal concentrations of the tested antimicrobials, may be of help in assessing the risks of cross-contaminated feed. However, future research is needed to confirm our results and to evaluate the effects of these detected concentrations on resistance selection in the intestinal microbiota of pigs.
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http://dx.doi.org/10.1186/s12917-016-0803-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028959PMC
September 2016

Antimicrobial resistance and population structure of Staphylococcus aureus recovered from pigs farms.

Vet Microbiol 2015 Oct 29;180(1-2):151-6. Epub 2015 Aug 29.

Department of Pathology, Bacteriology, and Avian Diseases, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium; University, School of Veterinary Medicine, Department of Biomedical Sciences, Basseterre, P.O. Box 334, St. Kitts and Nevis, West Indies, Cote d'Ivoire.

Staphylococcus aureus is a burden in human and veterinary medicine. During the last decade, an increasing number of studies reported the presence of livestock-associated methicillin-resistant S. aureus (LA-MRSA) clonal complex (CC) 398 in pigs. During 2013, a survey was performed in pig farms (n=328) randomly selected over Belgium, to monitor the current epidemiological situation of LA-MRSA among asymptomatic pigs and compare with former data to determine possible evolutions. Per farm, nose swabs were taken from 20 animals and pooled. MRSA was detected in 215 farms. Most isolates belonged to CC398 (n=211), and the remaining were ST9/t337 (n=1), ST80/t044 (n=2) and ST239/t4150 (n=1). A large diversity (n=19) of spa-types was found in the CC398 isolates. More than 90% of the isolates were non-wild type (NWT) to tetracycline and trimethoprim. NWT isolates were also found for ciprofloxacin (61.1%), clindamycin (64.4%), erythromycin (57.8%), kanamycin (43.1%) and gentamicin (45.5%). Microarray analysis showed that most CC398 isolates carried genes encoding resistance to tetracycline [tet(M)], macrolide-lincosamide-streptogramin group [erm(B), erm(C), lnu(A), vga(A)], aminoglycosides (aacA-aphD,aa dD, aphA3, sat) and/or phenicols (fexA). One CC398 isolate carried the multi-resistance gene cfr. The non-CC398 isolates carried virulence genes, as the egc-like cluster. The ST80 strain carried the Panton-Valentine leukocidin gene and corresponded to the community-acquired (CA-)MRSA ST80-IV European clone. The MRSA prevalence among pigs in Belgium remains similar to previous studies but a larger diversity in spa-types has been detected in this study. The recovery of CA-MRSA from livestock indicates that one should remain vigilant to the evolution of LA-MRSA in pigs.
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http://dx.doi.org/10.1016/j.vetmic.2015.08.018DOI Listing
October 2015

Susceptibility of avian pathogenic Escherichia coli from laying hens in Belgium to antibiotics and disinfectants and integron prevalence.

Avian Dis 2014 Jun;58(2):271-8

Avian pathogenic Escherichia coli (APEC) causes huge annual losses in the poultry industry worldwide. Multiresistance against antibiotics of APEC strains is increasingly seen in broilers, although much is still unknown about strains from laying hens where use of antibiotics is limited. Disinfection can reduce the infection burden. However, little is known about the presence of resistance against these products. Ninety-seven APEC strains were isolated from Belgian laying hens. The resistance to different classes of antibiotics was determined as well as the minimum inhibitory concentrations (MIC; agar and broth dilution) and minimum bactericidal concentrations (MBC) of five disinfectants most often used in the poultry industry (formaldehyde, glutaraldehyde, glyoxal, hydrogen peroxide, and a quaternary ammonium compound). The presence of integrons was determined by PCR Resistance to ampicillin (35.1%), nalidixic acid (38.1%), sulfonamides (SULFA, 41.2%), and tetracycline (TET, 53.6%) was high but resistance to other tested antibiotics was low. Nevertheless, two extended spectrum beta-lactamase producers were found. The MIC of the disinfectants for the APEC strains showed a Gaussian distribution, indicating that there was no acquired resistance. MBCs were similar to MICs via the broth dilution method, showing the bactericidal effect of the disinfectants. Twenty-one strains (21.6%) were found positive for class 1 integrons and a positive association between integron presence and resistance to trimethoprim, SULFA, and TET was found. No association could be found between integron presence and phylogenetic group affiliation. Susceptibility of APEC strains from laying hens to antibiotics is, in general, very high. Phenotypic resistance to commonly used disinfectants could not be found, indicating that the current use of disinfectants in the laying hen industry did not select for resistance.
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http://dx.doi.org/10.1637/10680-100113-RegRDOI Listing
June 2014

Body positioning and medical therapy for infantile gastroesophageal reflux symptoms.

J Pediatr Gastroenterol Nutr 2014 Aug;59(2):237-43

*Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, AMC, Amsterdam, The Netherlands †School of Medicine, Flinders University, Adelaide ‡Pediatric Gastroenterology, Royal Children's Hospital, Brisbane §Neonatal Intensive Care Unit, Women's and Children's Health Network, Adelaide ||North Western Academic Centre University of Melbourne, Melbourne, Australia.

Objective: Proton-pump inhibitors (PPIs) reduce acid gastroesophageal reflux (GER) and esophageal acid exposure in infants; however, they do not reduce total GER or symptoms attributed to GER. Reflux is reduced in the left lateral position (LLP). We hypothesize that the effect of LLP in combination with acid suppression is most effective in reducing GER symptoms in infants.

Methods: In this prospective sham-controlled trial, infants (0-6 months) with symptoms suggestive of gastroesophageal reflux disease were studied using 8-hour pH-impedance, cardiorespiratory and video monitoring, direct nurse observation, and a validated questionnaire. Infants demonstrating a positive GER symptom association were randomized to 1 of 4 groups; PPI + LLP, PPI + head of cot elevation (HE), antacid (AA) + LLP, or AA + HE. HE and AA were considered "sham" therapies. After 2 weeks the 8-hour studies were repeated on-therapy.

Results: Fifty-one patients were included (aged 13.6 [2-26] weeks). PPI + LLP was most effective in reducing GER episodes (69 [13] to 46 [10], P < 0.001) and esophageal acid exposure (median [interquartile range] 8.9% [3.1%-18.1%] to 1.1% [0%-4.4%], P = 0.02). No treatment group showed improvement in crying/irritability, although vomiting was reduced in AA + LLP (from 7 [2] to 2 [0] episodes P = 0.042). LLP compared with HE produced greater reduction in total GER (-21 [4] vs -10 [4], P = 0.056), regardless of acid-suppressive therapy. Acid exposure was reduced on PPI compared with AA (-6.8 [2.1] vs -0.9 [1.4]%, pH < 4, P = 0.043) regardless of positional intervention. A post-hoc analysis using automated analysis software revealed a significant reduction in crying symptoms in the PPI + LLP group (99 [65-103] to 62 [32-96] episodes, P = 0.018).

Conclusions: "Symptomatic gastroesophageal reflux disease" implies disease causation for distressing infant symptoms. In infants with symptoms attributed to GER, LLP produced a significant reduction in total GER, but did not result in a significant improvement in symptoms other than vomiting; however, automated analysis appeared to identify infants with GER-associated crying symptoms who responded to positioning therapy. This is an important new insight for future research.
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http://dx.doi.org/10.1097/MPG.0000000000000395DOI Listing
August 2014

Outcomes of endoscopy and novel pH-impedance parameters in children: is there a correlation?

J Pediatr Gastroenterol Nutr 2013 Feb;56(2):196-200

Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital AMC, Amsterdam, The Netherlands.

Objectives: Discordance exists between outcomes of endoscopy, multichannel intraluminal impedance monitoring (pH-MII), MII baselines, and gastroesophageal reflux symptoms. The aim of the present study was to determine the association between endoscopy, pH-MII and MII baselines, in children with gastroesophageal reflux symptoms.

Methods: Endoscopies were graded for reflux esophagitis (RE). Biopsies of the distal esophagus were assessed for signs suggestive of esophagitis. Reflux index (RI), symptom association probability (SAP), number of reflux episodes, and mean baseline values were calculated. pH-MII was considered positive in children when RI was ≥ 3% and/or SAP was ≥ 95% and for infants when RI was ≥ 10% and/or SAP was ≥ 95%. Baselines were manually calculated and compared with an automated analysis. For MII baselines, patients were divided in 3 groups: normal endoscopy and negative overall pH-MII; normal endoscopy and an overall positive pH-MII; and RE.

Results: A total of 26 children and 14 infants were included, median age: 26.5 months (2 months-16.2 years). Thirteen (32.5%) had RE. A significant negative association was found for RI and MII baselines (P = 0.009) and between SAP and RE (P = 0.039, odds ratio 1.018). MII baseline values were predictive for neither conventional pH-MII parameters nor RE. Manual analysis and automated calculation of MII baselines showed a perfect correlation. Distal MII baselines were significantly lower in children with a positive overall pH-MII outcome compared with the proximal esophagus (P = 0.049). No significant changes were found in baselines among the different groups 1 to 3.

Conclusions: Acid-related parameters are significantly related to MII baselines. A perfect correlation between manual- and automated analysis of MII baselines was found. Large prospective studies are needed to confirm the exact role of endoscopy and MII baselines.
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http://dx.doi.org/10.1097/MPG.0b013e31827167e2DOI Listing
February 2013

Interobserver and intraobserver variability in pH-impedance analysis between 10 experts and automated analysis.

J Pediatr 2012 Mar 15;160(3):441-446.e1. Epub 2011 Sep 15.

Department of Pediatric Gastroenterology and Nutrition, Emma Kinderziekenhuis, Academic Medical Centre, Amsterdam, The Netherlands.

Objective: To determine interobserver and intraobserver variability in pH-impedance interpretation between experts and accuracy of automated analysis (AA).

Study Design: Ten pediatric 24-hour pH-impedance tracings were analyzed by 10 observers from 7 world groups and with AA. Detection of gastroesophageal reflux (GER) episodes was compared between observers and AA. Intraobserver agreement was assessed in 3 observers after 3 to 5 months.

Results: Overall, 1242 liquid and mixed GER events were detected, 490 (42%) were scored by the majority of observers, yielding moderate agreement (Cohen's kappa [κ] = 0.46). Intraclass co-efficient for numbers of GER per study was 0.84 (P < .001). AA has 94% sensitivity rate and 74% specificity rate compared with majority consensus (≥6 observers). Agreement for gas GER was poor (κ = 0.11). Intraobserver agreement was κ = 0.49, κ = 0.71, and κ = 0.85 in 3 observers.

Conclusion: Interobserver agreement in combined pH-multichannel intraluminal impedance analysis in experts is moderate; only 42% of GER episodes were detected by the majority of observers. Detection of total GER numbers is more consistent. Considering these poor outcomes, AA seems favorable compared with manual analysis because of its reproducibility. However, the lower specificity rate suggests the need for refinement of AA before widespread use can be advocated.
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http://dx.doi.org/10.1016/j.jpeds.2011.08.017DOI Listing
March 2012