Grijseels, E.W.M.

Comparable low-level mosaicism in affected and non affected tissue of a complex CDH patient (Article)

2010-12-01T00:00:00Z

In this paper we present the detailed clinical and cytogenetic analysis of a prenatally detected complex Congenital Diaphragmatic Hernia (CDH) patient with a mosaic unbalanced translocation (5;12). High-resolution whole genome SNP array confirmed a low-level mosaicism (20%) in uncultured cells, underlining the value of array technology for identification studies. Subsequently, targeted Fluorescence In-Situ Hybridization in postmortem collected tissues demonstrated a similar low-level mosaicism, independently of the affected status of the tissue. Thus, a higher incidence of the genetic aberration in affected organs as lung and diaphragm cannot explain the severe phenotype of this complex CDH patient. Comparison with other described chromosome 5p and 12p anomalies indicated that half of the features presented in our patient (including the diaphragm defect) could be attributed to both chromosomal areas. In contrast, a few features such as the palpebral downslant, the broad nasal bridge, the micrognathia, microcephaly, abnormal dermatoglyphics and IUGR better fitted the 5p associated syndromes only. This study underlines the fact that low-level mosaicism can be associated with severe birth defects including CDH. The contribution of mosaicism to human diseases and specifically to congenital anomalies and spontaneous abortions becomes more and more accepted, although its phenotypic consequences are poorly described phenomena leading to counseling issues. Therefore, thorough follow-up of mosaic aberrations such as presented here is indicated in order to provide genetic counselors a more evidence based prediction of fetal prognosis in the future.

Pre- and postnatal diagnosis and outcome of fetuses and neonates with esophageal atresia and tracheoesophageal fistula (Article)

2010-03-01T00:00:00Z

Objectives: Clinical symptoms and ultrasound signs during pregnancy could suggest the presence of esophageal atresia (EA). However, most often EA is diagnosed postnatally. The aim of our study is to evaluate the course and outcome for prenatally and postnatally diagnosed EA. In addition, we studied the outcome of isolated versus nonisolated EA. Methods: In a retrospective data analysis, ultrasound characteristics, maternal and neonatal variables as well as clinical outcome were compared for fetuses/neonates with prenatal (n = 30) or postnatal (n = 49) diagnosis of EA. Clinical outcome in terms of morbidity and mortality of isolated EA was compared with that of EA complicated by chromosomal or structural anomalies. Results: Prenatally diagnosed children were born 2 weeks earlier than postnatally diagnosed children (36.4 weeks vs 38.2 weeks; P = 0.02). The former had higher mortality rates (30 vs 12%; P = 0.05) and more associated anomalies (80 vs 59%; P = 0.04). In both subsets, there was a high morbidity rate in the survivors (not significant). Nonisolated EA was associated with greater occurrence of polyhydramnios (53 vs 27%; P = 0.04) and higher mortality rate (28 vs 0%; P = 0.002). Conclusions: Mortality was significantly higher in prenatally diagnosed infants and in infants with additional congenital anomalies. Isolated EA is associated with good outcome.

Cornelia de lange syndrome: A recognizable fetal phenotype (Article)

2009-10-01T00:00:00Z

We describe a fetus with Cornelia de Lange syndrome diagnosed after termination of pregnancy at 21 weeks. Prenatally, growth retardation, diaphragmatic hernia, cystic hygroma and a right hand with only three rays were diagnosed by ultrasound in the second trimester of pregnancy. Postnatal magnetic resonance imaging confirmed the prenatal findings, and the presence of the typical dysmorphic features led to the diagnosis of Cornelia de Lange syndrome. The diagnosis was confirmed by the finding of a truncating mutation in the NIPBL gene. This case illustrates that the diagnosis Cornelia the Lange syndrome can be suspected prenatally in the second trimester, and can be diagnosed in fetuses after induction or newborns at birth as the typical phenotype is present early.

Isolated or non-isolated duodenal obstruction: Perinatal outcome following prenatal or postnatal diagnosis (Article)

2008-11-01T00:00:00Z

Objectives To determine whether the pre- or postnatal diagnosis of either isolated or non-isolated duodenal obstruction (DO) is associated with different outcomes. Methods A single-center retrospective analysis was carried out of 91 cases diagnosed with a DO between January 1991 and June 2003. Data on the diagnosis, treatment and outcomes of the cases were gathered, and differences between the groups were analyzed. Results Twenty-eight cases of DO were diagnosed before and 63 after birth. Of 15 presumed isolated cases in the prenatally diagnosed group, four revealed associated or chromosomal anomalies after birth. The types of obstruction present were significantly different between the prenatally (n = 11) and postnatally (n = 27) detected subsets of isolated DO. The prenatally detected subset displayed a lower median gestational age at delivery, lower median birth weight and a higher prematurity rate (8/11 vs. 8/27). The diagnosis of DO occurred significantly later in the postnatally detected subset than the postnatal confirmation of the diagnosis in the prenatally detected cases. In the non-isolated cases of DO, no difference was found in the type of chromosomal or associated anomaly or the type of obstruction between the prenatally detected (n = 17) and postnatally detected subsets (n = 36). Trisomy 21 was present in 7/17 (41%) vs. 22/36 (61%) cases, respectively. Two terminations and three intrauterine deaths occurred in the prenatal non-isolated subset. The liveborn infants from the prenatally detected non-isolated subset (n = 12) showed a significantly higher prematurity rate (9/12 vs.14/36), lower median birth weight and earlier confirmation of diagnosis after delivery. After surgery, outcome was similar between both subsets of isolated and non-isolated DO. All the infants with an isolated DO survived. Neonatal death occurred in three prenatally and five postnatally diagnosed cases with non-isolated DO. Conclusions The outcome of prenatally and postnatally diagnosed DO is not essentially different despite more prematurity and a lower birth weight in the former. Of the prenatally detected cases of DO assumed to be isolated, 25% revealed additional chromosomal or associated anomalies after delivery, which influenced outcome. Copyright

Costs and effects of various analgesic treatments for patients with rheumatoid arthritis and osteoarthritis in The Netherlands (Article)

2008-07-01T00:00:00Z

Objective: To assess the balance between costs and upper gastrointestinal (GI) side effects of treatment with celecoxib, nonsteroidal antiinflammatory drugs (NSAIDs) alone, NSAID plus misoprostol, NSAID plus histamine-2 receptor antagonist (H2RA), NSAID plus proton pump inhibitor (PPI), and Arthrotec in The Netherlands. Methods: A model was used to convene data from various sources on the probability of GI side effects and resource use. The probabilities of GI side effects for celecoxib and NSAIDs alone were derived from trial data. Calculations were based on 6 months of treatment, and were from a societal perspective. Distinction was made between low-, medium-, and high-risk patients. An extensive probabilistic sensitivity analysis was performed to address uncertainty. Results: Assuming an average patient, the total costs per 6 months of therapy were: celecoxib €255, NSAIDs alone €166, NSAID plus misoprostol €285, NSAID plus H2RA €284, NSAID plus PPI €243, and Arthrotec €187. Treatment with celecoxib was associated with the lowest number of GI side effects and related deaths. Incremental costs per life-year saved for Arthrotec compared to NSAIDs alone were €5676 for all patients and €526 for medium-to-high-risk patients, whereas for high-risk patients, Arthrotec dominated NSAID alone. For celecoxib compared to Arthrotec, the incremental cost-effectiveness ratios (ICERs) were €56,667, €33,684, and €15,429, respectively. Conclusion: Assuming a limit of €20,000 per life-year gained, from an economic point of view, Arthrotec is the preferred treatment when all patients or medium-to-high-risk patients are considered. In high-risk patients, celecoxib is the preferred treatment strategy.

Three-dimensional sonography of prenatal skull base development (Article)

2007-04-01T00:00:00Z

Objective: To explore longitudinally the development of the fetal skull base using three-dimensional (3D) sonography. Methods: Serial 3D sonographic measurements of anterior skull base length, posterior cranial fossa length and skull base angle were made in 126 normal singleton pregnancies at 18-34 weeks of gestation. In a sub-study of 22 pregnancies, intraobserver variability was determined. Regression analysis for repeated measurements was performed by means of the random coefficients model. Results from an earlier publication on brain volume were extended to the total patient cohort. Results: Measurements were technically successful in 69-94% of cases. The coefficient of variation for differences between repeated tests within women was 3.5-7.6% and between repeated analyses of the same recorded volume it was 3.0-5.1%. A statistically significant gestational age-related increase was established for both the anterior skull base length and the posterior cranial fossa length and the skull base angle showed a small but significant flexion of about 6°. A higher increment in posterior cranial fossa length relative to anterior skull base angle was established. A significant quadratic relationship could be established for both anterior skull base length (P < 0.0001) and posterior cranial fossa length (P < 0.0001) but not for skull base angle, relative to brain volume. Conclusion: The reproducibility was acceptable for all fetal skull base measurements. The more pronounced growth in posterior cranial fossa length relative to anterior skull base length is influenced by brain growth. The small flexion of the skull base angle, however, may be caused by other factors. Copyright

Economic analysis for clinical practice - The case of 31 national consensus guidelines in the Netherlands (Article)

2007-02-01T00:00:00Z

Rationale, aims and objective: Evidence on the cost-effectiveness of health interventions in the development of practice guidelines has become of interest in many countries. Challenges are the quality of economic data, the use of cost-effectiveness criteria, and the consensus process. Our paper aims to assess the quality and use of economic information in the formulation of consensus guidelines in a Dutch pilot programme and to recommend improvements. Methods: Retrospective qualitative review of economic evaluations and formulated recommendations, using a checklist based on international standards. Results: The national programme to support the development of guidelines with economic analysis in multidisciplinary consensus groups run from 1998 to 2002. It has included 31 medical guidelines, addressing 23 conditions across seven International Classification of Diseases (ICD)-disease groups. Experts in health technology assessment have participated in the guidelines groups. Economic information in all guidelines varies by all criteria in the level of evidence used. Information on quality-adjusted life years gained is limited as is statistical analysis in most studies. Highest cost-effectiveness ratios reported are between €20 000 and €30 000. However, there is no uniformity in the definitions of acceptable cost-effectiveness ratios. Conclusions: Economic recommendations can be included in guidelines. Interaction between clinicians and health economists promotes a balance between medical and economic arguments. Among panellists there appears to be agreement on the level of the cost-effectiveness ratios that is acceptable. It is recommended that economic analysis is used to strengthen the evidence-base of guidelines. An evidence-grading system should include the quality of economic evaluation. Roles of policymakers and providers need to be defined.

Richtlijnenprogramma (1997-2002). Deelprogramma iMTA; Eindrapportage maart 2002 (Research Paper)

2002-01-01T00:00:00Z

Deze rapportage beschrijft de activiteiten die door het iMTA zijn uitgevoerd om samen met (para-) medische beroepsgroepen richtlijnen voor kosten-effectieve patiëntenzorg te ontwikkelen. Dit Richtlijnenproject vormde een onderdeel van het programma "bevordering doelmatig handelen", dat in het najaar van 1997 van start is gegaan. Het iMTA heeft uitgebreid overlegd met de betrokken richtlijnontwikkelaars over de keuze van richtlijnonderwerpen. Daarbij werden naast de gebruikelijke criteria voor de keuze van onderwerpen voor richtlijnontwikkeling mede in beschouwing genomen of een kosten-effectiviteitsanalyse een duidelijk toegevoegde waarde bood en of er voldoende gegevens op dat terrein beschikbaar waren. Uiteindelijk werden 17 onderwerpen geselecteerd. Dit rapport geeft een korte beschrijving van elk van de richtlijnen en beschrijft het doel van de richtlijnontwikkeling, een samenvatting van de uiteindelijke aanbevelingen en de toegevoegde waarde van het kosten-effectiviteitsonderdeel. Aanvullend hierop heeft het iMTA een apart onderzoek geïnitieerd, waarin de evaluatie van zowel het proces als de uitkomsten van het richtlijnenprogramma centraal stonden. Dit onderzoek heeft geleid tot concrete aanbevelingen, welke tevens in dit rapport beschreven zijn. Naast de werkzaamheden aan de richtlijnontwikkeling op zich heeft het iMTA twee producten vervaardigd, die bij de richtlijnontwikkeling in de toekomst van nut kunnen zijn. Er is een handboek voor evaluatie- studies in de gezondheidszorg gepubliceerd, dat met name goed toegankelijk is voor die leden van richtlijncommissies, die nog geen kennis hebben genomen van het terrein van kosten-effectiviteitsanalyses. Daarnaast is een meetinstrument ontwikkeld voor het waarderen van productieverliezen bij betaald en onbetaald werk, hetgeen kan worden ingezet voor het schatten van indirecte kosten.

Implementation of a pre-hospital decision rule in general practice. Triage of patients with suspected myocardial infarction (Article)

1996-01-01T00:00:00Z

OBJECTIVE: To improve pre-hospital triage of patients with suspected acute cardiac disease. DESIGN: Prospective study. SUBJECTS. Patients with symptoms suggestive of acute cardiac pathology, who were seen by a general practitioner, for whom acute admission into hospital was requested, and in whom a pre-hospital electrocardiogram was recorded by the ambulance service. METHODS: The study consisted of two phases. In the first phase, a decision rule was developed based on clinical characteristics and electrocardiographic findings in 1005 patients with suspected acute cardiac pathology. In the second phase, the decision rule was prospectively validated. Symptoms were recorded by a standardized questionnaire by the general practitioner and a computerized electrocardiogram was made by the ambulance nurses at the patient's home. Three electrocardiographic outcomes were available: 'normal electrocardiogram', 'possible myocardial infarction' or 'extensive myocardial infarction'. By use of the predictive model, the general practitioner could decide if hospitalization was necessary or not. MAIN OUTCOME MEASUREMENTS: Identification of patients at low (stable angina, atypical chest pain, other pathology) and high (myocardial infarction, unstable angina) probability of acute cardiac pathology. RESULTS: Among 977 patients with a complete pre-hospital evaluation in the validation phase of the study, the decision rule recommended 'no hospitalization' in 227 patients (23%). The general practitioner followed this advice in 44% of these patients. Although seven of them developed a non-Q wave myocardial infarction, no complications occurred in patients not admitted. In addition, the general practitioner did not hospitalize 19 (2%) of 750 patients for whom the decision rule recommended admission. Pre-hospital triage by the general practitioner resulted in a 12% (118 of 977 patients) reduction of the number of patients admitted to the Coronary Care Units. CONCLUSIONS: Pre-hospital triage by the general practitioner was facilitated using a standardized questionnaire and pre-hospital electrocardiography, and resulted in a reduction in the number of patients admitted to the Coronary Care Unit, and proved to be safe.

Bevordering van snelle en gerichte verwijzing van patienten met een mogelijk hartinfarct door ECG thuis (Article)

1995-01-01T00:00:00Z

Snelle en adequate behandeling van patiënten met een hartinfarct is levensreddend en beperkt de schade aan de hartspier (infarctgrootte). Niet alleen de duur, maar ook de kwaliteit van het leven na een infarct wordt zo verbeterd. Levensbedreigende ritmestoornissen, met name ventrikelfibrilleren, kunnen worden gedetecteerd door middel van elektrocardiografische bewaking, en kunnen doorgaans adequaat worden behandeld met defibrillatie en resuscitatie. Reperfusie van de bij het infarct afgesloten coronairarterie leidt tot herstel van de bloedtoevoer naar het bedreigde myocard, zodat de ischemische myocyten kunnen herstellen en de infarctgrootte wordt beperkt. Indien reperfusietherapie kan worden gestart binnen 3 h na het begin van de klachten van een infarct, daalt het sterfterisico met maar liefst gemiddeld 50. Toediening tussen 3 en 6 h vermindert het sterfterisico met ongeveer 25 en latere toediening, tot 12 h, met ongeveer 12,5.1 Hoe vroeger, hoe ... etc.

Pre-hospital thrombolytic therapy with either alteplase or streptokinase. Practical applications, complications and long-term results in 529 patients (Article)

1995-01-01T00:00:00Z

OBJECTIVE: To assess the practical application, safety and long-term outcome of pre-hospital thrombolytic intervention with either alteplase or streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more than 30 min duration, presenting within 6 h of symptom onset and with electrocardiographic evidence of extensive evolving myocardial infarction. METHODS: Eligibility of patients was established by the general practitioner or the ambulance nurse using a standardized questionnaire with (contra-) indications for thrombolytic therapy. Computerized ECG was recorded by ambulance nurses. In the presence of extensive ST segment elevation (sum ST deviation of at least 1.0 mV), eligible patients received either 100 mg alteplase (n = 246) or 50 mg alteplase in the ambulance followed by 0.75 x 10(6) IE streptokinase in hospital (n = 90), or 1.5 x 10(6) IE streptokinase intravenously (n = 193). MAIN OUTCOME MEASUREMENTS: Death and life-threatening complications (ventricular fibrillation, cardiac arrest) and side effects (hypotension, allergic reactions) during transportation to hospital and in the first 24 h following hospitalization, and survival up to 5 years follow-up. RESULTS: From 1988-1993, 529 patients received thrombolytic treatment initiated pre-hospital. The time gained by pre-hospital administration of thrombolysis amounted to 50 min. The rate of complications during transportation and during the first 24 h after hospitalization was low. Hospital mortality was 2% and 1-year mortality 3%. Cumulative survival at 5 years was 92%. This was superior to the 84% 5-year survival observed in a matched group of 239 patients with similar baseline characteristics treated with alteplase in hospital. CONCLUSIONS: Pre-hospital administration of either alteplase or streptokinase is feasible and safe and results in significant time gain. The long-term prognosis is excellent in spite of extensive evolving myocardial infarction upon admission.

Prehospital triage to improve diagnostic and therapeutic decisions in patients with suspected myocardial infarction (Doctoral Thesis)

1994-10-26T00:00:00Z

The organisation of cardiac assistance for the general practitioner in the municipality of Rotterdam is well organised, due to an intensive co-operation between the general practitioners, the cardiologists, the Central Doktors Laboratorium (STA.R.) and the ambulance department of the Municipal Heallh Service. The first initiative towards a more intensive cooperation between cardiologists and general practitioners originated by the inititation of the Imminent Myocardial Infarction Rotterdam (IMIR) study, which started in 1972.'·3 The study was initiated and executed by the departments of Cardiology and General Practice of the Erasmus University of Rotterdam. In that study, the significance of prodromal symptoms, identified by means of history taking and physical examination, were studied prospectively in patients who visited their general practitioner wilh symptoms suggestive of myocardial infarction. Detailed history and physical findings were recorded on a standardized questionnaire by the general practitioner. Subsequently, the patient was referred to a special diagnostic centre (the IMIR centre, which was located at the department of Cardiology of the Thoraxcentre of the University Hospital of Rotterdam), where a standard 12-lead ECG was recorded by technicians and blood was drawn for cardiac enzyme determinations (CPK, a-HBDH, SGOT). An additional purpose of the study included the evaluation of this diagnostic centre provided by the study program to the participating general practitioners.

Verbetering opname-beleid op de hartbewakingseenheden (Article)

1993-03-05T00:00:00Z