[Online tool to prepare patient for colonoscopy; development and implementation of a patient-education app]. / Digitaal de patiënt voorbereiden op coloscopie.

Optimal patient education prior to colonoscopy is essential for an optimal outcome of the procedure. Patients benefit from adequate information regarding laxatives, risks and alternatives, and must provide informed consent. The endoscopist also has to have access to patient data in advance of the procedure in order to carry out an adequate risk assessment for the use of sedation. Most centres in the Netherlands usually make use of a pre-endoscopy consultation to exchange this information, but here is now pressure on this practice because the number of colonoscopies is increasing rapidly as a result of the introduction of the national screening programme for colorectal cancer.

Intelligence Assessment Instruments in Adult Prison Populations: A Systematic Review.

Detection of intellectual disability (ID) in the penitentiary system is important for the following reasons: (a) to provide assistance to people with ID in understanding their legal rights and court proceedings; (b) to facilitate rehabilitation programs tailored to ID patients, which improves the enhancement of their quality of life and reduces their risk of reoffending; and (c) to provide a reliable estimate of the risk of offence recidivism. It requires a short assessment instrument that provides a reliable estimation of a person's intellectual functioning at the earliest possible stage of this process. The aim of this systematic review is (a) to provide an overview of recent short assessment instruments that provide a full-scale IQ score in adult prison populations and (b) to achieve a quality measurement of the validation studies regarding these instruments to determine which tests are most feasible in this target population. The Preferred Reporting Items for Systematic reviews and Meta-Analyses Statement is used to ensure reliability. The Satz-Mögel, an item-reduction short form of the Wechsler Adult Intelligence Scale, shows the highest correlation with the golden standard and is described to be most reliable. Nevertheless, when it comes to applicability in prison populations, the shorter and less verbal Quick Test can be preferred over others. Without affecting these conclusions, major limitations emerge from the present systematic review, which give rise to several important recommendations for further research.

Catechol-O-methyltransferase (COMT) gene variants and pain in chronic pancreatitis.

BACKGROUND: Pain is the major symptom of chronic pancreatitis. The role of genetics in pancreatic pain is unclear. Catechol-O-methyltransferase (COMT) regulates enkephalin levels and influences pain perception. The COMT gene contains functional polymorphisms that have been found to influence human pain perception. The aim of our study was to investigate COMT single-nucleotide polymorphisms (SNP s) and diplotypes in chronic pancreatitis patients and healthy controls. METHODS: We genotyped four COMT gene SNP s: c.1-98A>G (rs6269), c.186C>T (p.=) (rs4633), c.408C>G (p.=) (rs4818) and c.472G>A (p.Val158Met) (rs4680) using a dual-colour discrimination assay in 240 chronic pancreatitis patients and 445 controls. We generated five diplotypes with a frequency >0.5% and compared prevalence between patients and controls. RESULTS: There was no significant association between the SNPs in the COMT gene and chronic pancreatitis. The diplotype ATCA÷ACCG was more prevalent in controls compared with patients (OR 0.48, 95% CI 0.24 to 0.93, p=0.03) where the most common diplotype GCGG ÷ATCA served as reference. However, after correction for multiple testing, this is not a significant difference. The distribution of other diplotypes was not significantly different between patients and controls. CONCLUSION: COMT SNP s and diplotypes are not associated with chronic pancreatitis. As a consequence, our results do not support a significant role for the COMT gene in chronic pancreatitis.

Practical guidelines for routine intensity-modulated radiotherapy verification: pre-treatment verification with portal dosimetry and treatment verification with in vivo dosimetry.

The purpose of this work is to provide guidelines for the routine use of portal dosimetry and in vivo diode measurements to verify intensity-modulated radiotherapy (IMRT) treatments. To achieve tolerance levels that are sensitive enough to intercept problems, both the portal dosimetry and the in vivo procedure must be optimised. Portal dosimetry was improved by the introduction of an optimised two-dimensional (2D) profile correction, which also accounted for the effect of backscatter from the R-arm. The scaled score, indicating the fraction of points not meeting the desired gamma evaluation criteria within the field opening, was determined as the parameter of interest. Using gamma criteria of a 3% dose difference and 3 mm distance to agreement, a "scaled score" threshold value of 1.5% was chosen to indicate excessive tongue and groove and other problems. The pre-treatment portal dosimetry quality assurance (QA) does not encompass verification of the patient dose calculation or position, and so it is complemented by in vivo diode measurements. Diode positioning is crucial in IMRT, and so we describe a method for diode positioning at any suitable point. We achieved 95% of IMRT field measurements within ±5% and 99% within ±8%, with improved accuracy being achieved over time owing to better positioning. Although the careful preparation and setup of the diode measurements can be time-consuming, this is compensated for by the time efficiency of the optimised procedure. Both methods are now easily absorbed into the routine work of the department.

Automatic segmentation of thoracic and pelvic CT images for radiotherapy planning using implicit anatomic knowledge and organ-specific segmentation strategies.

Automatic segmentation of anatomical structures in medical images is a valuable tool for efficient computer-aided radiotherapy and surgery planning and an enabling technology for dynamic adaptive radiotherapy. This paper presents the design, algorithms and validation of new software for the automatic segmentation of CT images used for radiotherapy treatment planning. A coarse to fine approach is followed that consists of presegmentation, anatomic orientation and structure segmentation. No user input or a priori information about the image content is required. In presegmentation, the body outline, the bones and lung equivalent tissue are detected. Anatomic orientation recognizes the patient's position, orientation and gender and creates an elastic mapping of the slice positions to a reference scale. Structure segmentation is divided into localization, outlining and refinement, performed by procedures with implicit anatomic knowledge using standard image processing operations. The presented version of algorithms automatically segments the body outline and bones in any gender and patient position, the prostate, bladder and femoral heads for male pelvis in supine position, and the spinal canal, lungs, heart and trachea in supine position. The software was developed and tested on a collection of over 600 clinical radiotherapy planning CT stacks. In a qualitative validation on this test collection, anatomic orientation correctly detected gender, patient position and body region in 98% of the cases, a correct mapping was produced for 89% of thorax and 94% of pelvis cases. The average processing time for the entire segmentation of a CT stack was less than 1 min on a standard personal computer. Two independent retrospective studies were carried out for clinical validation. Study I was performed on 66 cases (30 pelvis, 36 thorax) with dosimetrists, study II on 52 cases (39 pelvis, 13 thorax) with radio-oncologists as experts. The experts rated the automatically produced structures on the scale 1-excellent (no corrections necessary, maximum time saving), 2-good (corrections necessary for up to 1/3 of slices), 3-acceptable (major corrections necessary, but still time saving), 4-not acceptable (manual redrawing more efficient, no time saving). A rating

Inhibition of complement factor C5 protects against anti-myeloperoxidase antibody-mediated glomerulonephritis in mice.

In mice, administration of murine anti-myeloperoxidase (MPO) IgG induces pauci-immune necrotizing crescentic glomerulonephritis. Recent studies in this model indicate a crucial role for complement activation in disease induction. Here, we investigated the effect of pretreatment or intervention with a C5-inhibiting monoclonal antibody (BB5.1) in the mouse model of anti-MPO IgG-induced glomerulonephritis. Mice received BB5.1 8 h before or 1 day after disease induction with anti-MPO IgG and lipopolysaccharide. Mice were killed after 1 or 7 days. Control antibody-pretreated mice developed hematuria, leukocyturia and albuminuria, and glomerulonephritis with a mean of 21.0+/-8.8% glomerular crescents and 12.8+/-5.5% glomerular capillary necrosis. BB5.1 pretreatment prevented disease development, as evidenced by the absence of urinary abnormalities, a marked reduction in glomerular neutrophil influx at day 1 and normal renal morphology at day 7. Importantly, BB5.1 administration 1 day after disease induction also resulted in a marked attenuation of urinary abnormalities and a more than 80% reduction in glomerular crescent formation. In conclusion, inhibition of C5 activation attenuates disease development in a mouse model of anti-MPO IgG-induced glomerulonephritis. These results favor further investigations into the role of complement activation in human MPO-anti-neutrophil cytoplasmic autoantibody-mediated glomerulonephritis, and indicate that inhibition of C5 activation is a potential therapeutic approach in this disease.

Pharmacological management of pain in chronic pancreatitis.

Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.

Comparison of build-up dose between Elekta and Varian linear accelerators for high-energy photon beams using radiochromic film and clinical implications for IMRT head and neck treatments.

Skin toxicity has been reported for IMRT of head and neck cancer. The purpose of this study was to investigate the dose in the build-up region delivered by a 6 MV treatment plan for which important skin toxicity was observed. We also investigated if the different designs of the treatment head of an Elekta and a Varian linear accelerator, especially the lower position of the Varian multi-leaf collimator, give rise to different build-up doses. For regular square open beams, the build-up dose along the central beam axis is higher for the Varian machine than for the Elekta machine, both for 6 MV and 18 MV. At the Elekta machine at 18 MV, the superficial dose of a diamond shaped 10 x 10 cm2 field is 3.6% lower than the superficial dose of a regular 10 x 10 cm2 field. This effect is not seen at 6 MV. At the Varian machine, the superficial dose of the diamond shaped field is respectively 3.5 and 14.2% higher than the superficial dose of the regular 10 x 10 cm2 field for 6 MV and 18 MV. Despite the differences measured in build-up dose for single beams between the Elekta and the Varian linear accelerator, there were no measurable differences in superficial dose when a typical IMRT dose plan of 6 MV for a head and neck tumour is executed at the two machines.

Pre-treatment dosimetric verification by means of a liquid-filled electronic portal imaging device during dynamic delivery of intensity modulated treatment fields.

BACKGROUND AND PURPOSE: Although intensity modulated radiation therapy is characterized by three-dimensional dose distributions which are often superior to those obtained with conventional treatment plans, its routine clinical implementation is partially held back by the complexity of the beam verification. This is even more so when a dynamic multileaf collimator (dMLC) is used instead of a segmented beam delivery. We have therefore investigated the possibility of using a commercially available, liquid-filled electronic portal imaging device (EPID) for the pre-treatment quality assurance of dynamically delivered dose distributions. METHODS AND MATERIALS: A special acquisition mode was developed to optimize the image acquisition speed for dosimetry with the liquid-filled EPID. We investigated the accuracy of this mode for 6 and 18 MV photon beams through comparison with film and ion chamber measurements. The impact of leaf speed and pulse rate fluctuations was quantified by means of dMLC plans especially designed for this purpose. Other factors influencing the accuracy of the dosimetry (e.g. the need for build-up, remanence of the ion concentration in the liquid and bulging of the liquid at non-zero gantry angles) were studied as well. We finally compared dosimetric EPID images with the corresponding image prediction delivered without a patient in the beam. RESULTS: The dosimetric accuracy of the measured dose distribution is approximately 2% with respect to film and ion chamber measurements. The accuracy declines when leaf speed is increased beyond 2 cm/s, but is fairly insensitive to accelerator pulse rate fluctuations. The memory effect is found to be of no clinical relevance. When comparing the acquired and expected distributions, an overall agreement of 3% can be obtained, except at areas of steep dose gradients where slight positional shifts are translated into large errors. CONCLUSIONS: Accurate dosimetric images of intensity modulated beam profiles delivered with a dMLC can be obtained with a commercially available, liquid-filled EPID. The developed acquisition mode is especially suited for fast and accurate pre-treatment verification of the intensity modulated fields.

Quality assurance in radiotherapy by identifying standards and monitoring treatment preparation.

BACKGROUND AND PURPOSE: Due to the complexity of the treatment preparation in radiotherapy, a number of errors go undetected until after the first treatment session. Some of these errors could easily have been noticed before treatment if an objective filter existed in addition to human supervision. With this in mind, a conceptually novel extension to conventional quality assurance procedures was explored to create a global platform monitoring treatment preparation by comparison with the existing local standards. MATERIALS AND METHODS: The feasibility of developing such a platform was evaluated for a test case on a cohort of 202 patients having received breast irradiation. By statistical analysis of the treatment parameters, mean values and tolerance levels could be defined for most parameters based on the observed standard deviations. Useful correlations were traced providing us with a means to automatically track errors, the detection of which would otherwise solely depend upon the alertness of the supervisor. RESULTS AND CONCLUSIONS: Apart from its possibilities as a mere quality control tool, the platform, developed in the framework of EQUART (European Quality Assurance Program in Radiotherapy by Monitoring Treatment Preparation), can be incorporated in the treatment preparation chain, providing standard setup values for the simulation. A crucial achievement of EQUART lies in the fact that filtering out of errors occurs prior to treatment initiation.

A method to estimate the transit dose on the beam axis for verification of dose delivery with portal images.

PURPOSE AND BACKGROUND: A feasibility study is performed to evaluate the possibility of using the transit dose of portal images on the beam axis to measure the accuracy in dose delivery. The algorithm and the method are tested on a breast phantom and on patients with a breast disease. MATERIALS AND METHODS: To estimate the transit dose at various air gaps behind the patient, a method is proposed which applies, for a given air gap, the inverse square law to the primary component of the exit dose and an experimentally determined function for the scatter component of the exit dose. It is assumed that the primary component and the scattered component of the exit dose are given by the treatment planning system. The experimental function for the variation of the scattered component with the air gap, determined by phantom measurements, is modelled by an analytical function which contains only field size, air gap and one energy-dependent parameter. RESULTS: The measurements on the breast phantom yield a maximum deviation between measured and estimated transit doses of 4.5%. The mean deviation is 0.9% with a standard deviation of the distribution of 2.3%. In vivo diode measurements on the same phantom yield a maximum deviation of 2.7%. Transit dose measurements on the beam axis for 45 portal images of breast patients show a mean deviation of 0.0% between the measured transit dose and the estimated transit dose. The standard deviation of the distribution is 4.4%. The method seems to be very sensitive to patient positioning and to discrepancies in breast thicknesses used for treatment planning. CONCLUSION: Preliminary results on breast patients show that the method proposed to evaluate transit doses on the beam axis from portal images may be a valuable alternative to conventional in vivo exit dosimetry. The method can be implemented in a simple way and does not require additional time during the irradiation session, as exit dosimetry with diodes does. The transit dose is only considered in one point. Nevertheless, in the framework of quality assurance of treatment delivery, this study is an example of the possibilities of monitoring at the same time the visual evaluation of the irradiated volume as well as the dosimetric control (i.e. in Gy) of treatment delivery with portal images.

Evaluation of an electronic portal imaging device for transit dosimetry.

The possibility of using a commercially available electronic portal imaging device for transit dosimetry was investigated. The detection unit of the device comprises a metal plate/fluorescence screen and a camera. Basic parameters of this system were investigated: stability, detector uniformity, dose-response curve, field-size dependence and phantom-thickness dependence. It was found that in terms of relative dosimetry, portal images corrected for detector non-uniformity are in good agreement (within 5%) with transit dose distributions measured by film dosimetry. For dose determination, it was found that the use of the device is hampered by an important field-size dependence and phantom-thickness dependence. Both correction factors should be applied if the device is to be used for this purpose.

Prediction of febrile seizures in siblings: a practical approach.

UNLABELLED: To quantify the risk of febrile seizures (FS) in relatives of children with FS and to predict the risk of FS in siblings, we calculated cumulative risks of FS in first degree relatives of 129 children with FS. The study was conducted as a prospective follow up study of FS recurrences at the outpatient clinic of the Sophia Children's Hospital in Rotterdam. Thirteen parents and 12 siblings had experienced FS, accounting for a 6-year cumulative risk of 7%. The risk of FS was increased in relatives of children with recurrent FS (12%). The risk of FS in siblings (10%) in our study was more than twice the average risk in a similar population (4%). A positive FS history in a parent, young age at onset in the proband, and recurrences in the proband were selected in a multivariable prediction model. If two or more of these risk factors were present, the risk of West European siblings to develop FS was 46% (hazard ratio 5.4). CONCLUSION: The cumulative risk of FS in siblings of children with FS is increased. The age attained risk of FS can be estimated using a practical model incorporating three readily available risk factors.

Outcome after febrile status epilepticus.

The neurological outcome after a first febrile status epilepticus (FSE) was retrospectively studied in 57 children. Patients were aged six to 57 months at first seizure and had had no previous seizures or neurological abnormalities. 12 children (24 percent: 2-year Kaplan-Meier estimate) had subsequent neurological sequelae varying from speech deficit (n = 9) to severe neurological sequelae and epilepsy (n = 3). Speech deficit was detected after a mean period of six months. The most important predictors for sequelae were the number of different drugs needed for seizure termination and the duration of the seizure. The authors recommend that children with FSE should be followed up for at least one year so that potential speech disorders can be detected and treated.

Antipyretic efficacy of ibuprofen and acetaminophen in children with febrile seizures.

OBJECTIVE: To compare the antipyretic efficacy of ibuprofen syrup (5 mg/kg per dose) and acetaminophen syrup (10 mg/kg per dose) in children with a history of febrile seizures. DESIGN: Randomized, multiple-dose, double-blind, cross-over trial. SETTING: The outpatient department of a university-affiliated teaching hospital. PATIENTS: Seventy outpatients (mean age, 2.1 years; range, 10 months to 4 years) who had visited the hospital because of a febrile seizure were randomized to treatment at a temperature of 38.5 degrees C or higher. INTERVENTIONS: Study medication was given every 6 hours for 1 to 3 days. Rectal temperatures were recorded at 0, 2, 4, 6, 12, and 24 hours after the first dose. MAIN OUTCOME MEASURES: The temperature 4 hours after the first dose, the mean temperature during treatment, and the highest temperature during treatment were evaluated. Analysis of covariance corrected for the initial temperature, age, weight, and cause of the fever. RESULTS: Ibuprofen lowered the initial temperature from 39.1 degrees C to a mean temperature of 37.7 degrees C during treatment; acetaminophen lowered the initial temperature from 39.2 degrees C to 38.0 degrees C. Ibuprofen reduced fever 0.50 degree C more than did acetaminophen at 4 hours (95% confidence interval [CI], -0.98 to -0.02). The mean temperature was 0.26 degree C lower during ibuprofen treatment (95% CI, -0.59 to 0.07); the highest temperature was 0.30 degree C lower (95% CI, -0.73 to 0.13). In 22 patients, a second fever was treated with the opposite medication than the first. In the cross-over analysis, the respective differences were 0.66 degree C (95% CI, -1.29 to -0.06), 0.40 degree C (95% CI, -0.83 to 0.03), and 0.36 degree C (95% CI, -0.81 to 0.08) in favor of ibuprofen. CONCLUSIONS: Ibuprofen and acetaminophen are effective antipyretic agents in children with a history of febrile seizures. Ibuprofen yielded significantly greater fever reduction than did acetaminophen 4 hours after the first dose. Research is needed on the value of antipyretic agents for the prevention of febrile seizure recurrence.

Family history and recurrence of febrile seizures.

To determine the value of a detailed family history for the assessment of the risk of recurrence of febrile seizures, 115 children who visited the emergency room of an academic children's hospital were studied prospectively. The recurrence risk of febrile seizures was analysed in relation to the child's family history and the proportion of relatives affected by febrile seizures using Kaplan-Meier estimates and Cox proportional hazard models. A first degree family history positive for febrile seizures (parents or siblings affected by febrile seizures) increased a child's two year recurrence risk from 27 to 52%. No significant increase of recurrence risk for febrile seizures was found in children with second degree relatives (grandparents and uncles/aunts) or cousins only affected by febrile seizures. Recurrence risk was significantly correlated with the proportion of first degree relatives affected by febrile seizures: risks were 27, 40, and 83% in children whose proportion was 0, 0-0.5, and > or = 0.5 respectively. Analysis of the recurrence risk in relation to a weighted proportion, adjusted for the attained age and sex of first degree relatives, showed similar results. It is concluded that the application of the proportion of first degree relatives affected by febrile seizures generates a more differentiated assessment of the recurrence risk of febrile seizures.