Birth defect and risk factor surveillance in the northern and southwestern Netherlands

Objective: To survey the associations between several risk factors and birth defects, in order to detect potential new teratogens.Methods: Data of the two Dutch European Registration of Congenital Anomalies (EUROCAT) registries collected before January 1, 1998 were used to perform X2 tests for a large number of risk factors and birth defects. Defects caused by chromosomal or monogenic disorders were analyzed separately.Results: Cross- tabulations of 80 groups of birth defects with 303 risk factors were studied. Of these, 126 combinations had a p value under 0.05, and 34 had a p value under 0.001. Of these 34 associations, some are known in the literature, some were found before in the same databases and some were new associations.Conclusions: This is a good method for generating new hypotheses for associations between risk factors and birth defects. It can be a start for new, more in-depth studies of potential teratogens. Copyright (C) 2000 S. Karger AG, Basel.</p

GRACE and TIMI risk scores but not stress imaging predict long-term cardiovascular follow-up in patients with chest pain after a rule-out protocol

Objective To determine the long-term prognostic value of stress imaging and clinical risk scoring for cardiovascular mortality in chest pain patients after ruling out acute coronary syndrome (ACS). Methods A standard rule-out protocol was performed in emergency room patients with a normal or non-diagnostic admission electrocardiogram (ECG) within 6 h of chest 4 pain onset. ACS patients were identified by troponin T, recurrent angina and serial ECG. Dobutamine stress echocardiography (DSE) was performed after ACS was ruled out. Myocardial perfusion scintigraphy (MPS) was performed within 6 months in an outpatient setting according to the physician's discretion. Results 524 patients were included. GRACE and TIMI risk scores were 75 (57-96) and 1 (0-2) in the rule-out ACS group, and 89 (74-107) and 2 (1-3) in the ACS group, respectively (median, interquartile range). Follow-up (median 9.4 (8.9-10.0) years) was complete in 96%. 350 of 379 rule-out ACS patients had an interpretable DSE and 52 patients underwent an MPS. 21 of the rule-out ACS patients (6%) died of a cardiovascular cause compared with 24 (17%) ACS patients (p <0.001). For rule-out ACS patients, C-statistics were 0.829 and 0.803 for the GRACE and TIMI scores. In these patients, DSE and MPS outcome did not predict long-term cardiovascular mortality. In multivariate analysis, known chronic heart failure, ACE inhibitor use, and GRACE score were independent predictors of cardiovascular mortality. Conclusions TIMI and GRACE score but not DSE and MPS are accurate predictors of long-term cardiovascular mortality, even in chest pain patients with a normal or non-diagnostic electrocardiogram undergoing a rule-out protoco

Metabolism of ticagrelor in patients with acute coronary syndromes.

© The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio

Epidemiology of prenatal diagnosis and selective termination of pregnancy because of foetal neural tube defects in the Netherlands in comparison with other European countries

Objective. To describe the epidemiological impact of prenatal diagnosis and selective abortion on the frequency of neural tube defects (NTD) in the period 1980-1992 in the Northern Netherlands in comparison with data from other European regions. Design. Descriptive. Setting. 17 'European registration of congenital anomalies' (EUROCAT) registrations, localized in 10 European countries. Method. Data were collected actively and retrospectively from multiple sources fed by voluntary registration of congenital anomalies in live births, stillbirths and pregnancies terminated because of congenital anomalies. Results. In Europe the total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000 in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In live births the difference was ninefold: ranging from 2,0 per 10,000 in Paris to 18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence among live births, higher than in other regions in continental Europe. For spina bifida the live birth prevalence both in other continental regions and in Glasgow was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein screening apparently led to frequent early prenatal diagnosis of NTD and to frequent termination of pregnancy. In Paris the use of ultrasound screening appears to lead to frequent later prenatal diagnosis, as well as frequent termination of pregnancy. Conclusion. In the Netherlands the impact of prenatal diagnosis and selective abortion is limited, so that primary prevention (periconceptional use of folic acid) is more important than in some other European countries.</p

Epidemiology of prenatal diagnosis and selective termination of pregnancy because of foetal neural tube defects in the Netherlands in comparison with other European countries

Objective. To describe the epidemiological impact of prenatal diagnosis and selective abortion on the frequency of neural tube defects (NTD) in the period 1980-1992 in the Northern Netherlands in comparison with data from other European regions. Design. Descriptive. Setting. 17 'European registration of congenital anomalies' (EUROCAT) registrations, localized in 10 European countries. Method. Data were collected actively and retrospectively from multiple sources fed by voluntary registration of congenital anomalies in live births, stillbirths and pregnancies terminated because of congenital anomalies. Results. In Europe the total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000 in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In live births the difference was ninefold: ranging from 2,0 per 10,000 in Paris to 18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence among live births, higher than in other regions in continental Europe. For spina bifida the live birth prevalence both in other continental regions and in Glasgow was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein screening apparently led to frequent early prenatal diagnosis of NTD and to frequent termination of pregnancy. In Paris the use of ultrasound screening appears to lead to frequent later prenatal diagnosis, as well as frequent termination of pregnancy. Conclusion. In the Netherlands the impact of prenatal diagnosis and selective abortion is limited, so that primary prevention (periconceptional use of folic acid) is more important than in some other European countries.</p

Epidemiology of prenatal diagnosis and selective termination of pregnancy because of foetal neural tube defects in the Netherlands in comparison with other European countries

Objective. To describe the epidemiological impact of prenatal diagnosis and selective abortion on the frequency of neural tube defects (NTD) in the period 1980-1992 in the Northern Netherlands in comparison with data from other European regions. Design. Descriptive. Setting. 17 'European registration of congenital anomalies' (EUROCAT) registrations, localized in 10 European countries. Method. Data were collected actively and retrospectively from multiple sources fed by voluntary registration of congenital anomalies in live births, stillbirths and pregnancies terminated because of congenital anomalies. Results. In Europe the total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000 in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In live births the difference was ninefold: ranging from 2,0 per 10,000 in Paris to 18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence among live births, higher than in other regions in continental Europe. For spina bifida the live birth prevalence both in other continental regions and in Glasgow was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein screening apparently led to frequent early prenatal diagnosis of NTD and to frequent termination of pregnancy. In Paris the use of ultrasound screening appears to lead to frequent later prenatal diagnosis, as well as frequent termination of pregnancy. Conclusion. In the Netherlands the impact of prenatal diagnosis and selective abortion is limited, so that primary prevention (periconceptional use of folic acid) is more important than in some other European countries.</p

Antiinflammatory therapy with canakinumab for atherosclerotic disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering

Epidemiology of prenatal diagnosis and selective termination of pregnancy because of foetal neural tube defects in the Netherlands in comparison with other European countries

Objective. To describe the epidemiological impact of prenatal diagnosis and selective abortion on the frequency of neural tube defects (NTD) in the period 1980-1992 in the Northern Netherlands in comparison with data from other European regions. Design. Descriptive. Setting. 17 'European registration of congenital anomalies' (EUROCAT) registrations, localized in 10 European countries. Method. Data were collected actively and retrospectively from multiple sources fed by voluntary registration of congenital anomalies in live births, stillbirths and pregnancies terminated because of congenital anomalies. Results. In Europe the total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000 in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In live births the difference was ninefold: ranging from 2,0 per 10,000 in Paris to 18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence among live births, higher than in other regions in continental Europe. For spina bifida the live birth prevalence both in other continental regions and in Glasgow was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein screening apparently led to frequent early prenatal diagnosis of NTD and to frequent termination of pregnancy. In Paris the use of ultrasound screening appears to lead to frequent later prenatal diagnosis, as well as frequent termination of pregnancy. Conclusion. In the Netherlands the impact of prenatal diagnosis and selective abortion is limited, so that primary prevention (periconceptional use of folic acid) is more important than in some other European countries.</p

Epidemiology of prenatal diagnosis and selective termination of pregnancy because of foetal neural tube defects in the Netherlands in comparison with other European countries

Objective. To describe the epidemiological impact of prenatal diagnosis and selective abortion on the frequency of neural tube defects (NTD) in the period 1980-1992 in the Northern Netherlands in comparison with data from other European regions. Design. Descriptive. Setting. 17 'European registration of congenital anomalies' (EUROCAT) registrations, localized in 10 European countries. Method. Data were collected actively and retrospectively from multiple sources fed by voluntary registration of congenital anomalies in live births, stillbirths and pregnancies terminated because of congenital anomalies. Results. In Europe the total birth prevalence of NTD in the period 1980-1992 ranged from 5.3 per 10,000 in Switzerland to 29.0 per 10,000 in Glasgow, a difference of a factor 5.5. In live births the difference was ninefold: ranging from 2,0 per 10,000 in Paris to 18.8 per 10,000 in Dublin. The Netherlands had a conspicuously high prevalence among live births, higher than in other regions in continental Europe. For spina bifida the live birth prevalence both in other continental regions and in Glasgow was also lower than in the Netherlands. In Glasgow serum alpha-foetoprotein screening apparently led to frequent early prenatal diagnosis of NTD and to frequent termination of pregnancy. In Paris the use of ultrasound screening appears to lead to frequent later prenatal diagnosis, as well as frequent termination of pregnancy. Conclusion. In the Netherlands the impact of prenatal diagnosis and selective abortion is limited, so that primary prevention (periconceptional use of folic acid) is more important than in some other European countries.</p