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Please cite this paper as: Ravelli A, Jager K, de Groot M, Erwich J, Rijninks-van Driel G, Tromp M, Eskes M, Abu-Hanna A, Mol B. Travel time from home to hospital and adverse perinatal outcomes in women at term in the Netherlands. BJOG 2011;118:457-465. To study the effect of travel time, at the start or during labour, from home to hospital on mortality and adverse outcomes in pregnant women at term in primary and secondary care. Population-based cohort study from 2000 up to and including 2006. The Netherlands Perinatal Registry. A total of 751 926 singleton term hospital births. We assessed the impact of travel time by car, calculated from the postal code of the woman's residence to the 99 maternity units, on neonatal outcome. Logistic regression modelling with adjustments for gestational age, maternal age, parity, ethnicity, socio-economic status, urbanisation, tertiary care centres and volume of the hospital was used. Mortality (intrapartum, and early and late neonatal mortality) and adverse neonatal outcomes (mortality, Apgar <4 and/or admission to a neonatal intensive care unit). The mortality was 1.5 per 1000 births, and adverse outcomes occurred in 6.0 per 1000 births. There was a positive relationship between longer travel time (≥20 minutes) and total mortality (OR 1.17, 95% CI 1.002-1.36), neonatal mortality within 24 hours (OR 1.51, 95% CI 1.13-2.02) and with adverse outcomes (OR 1.27, 95% CI 1.17-1.38). In addition to travel time, both delivery at 37 weeks of gestation (OR 2.23, 95% CI 1.81-2.73) or 41 weeks of gestation (OR 1.52, 95% CI 1.29-1.80) increased the risk of mortality. A travel time from home to hospital of 20 minutes or more by car is associated with an increased risk of mortality and adverse outcomes in women at term in the Netherlands. These findings should be considered in plans for the centralisation of obstetric care. [ABSTRACT FROM AUTHOR]

To assess experiences related to antidepressant use reported to an internet-based medicine reporting system and to compare the nature of the side effects reported by patients with those reported by health care professionals (HCPs). All reports submitted from May 2004 to May 2005 to an internet-based medicine reporting system in The Netherlands related to the use of antidepressants were analysed. Spontaneous reports of adverse drug reactions on antidepressants from HCPs received by The Netherlands Pharmacovigilance Centre Lareb from May 2004 to May 2005 were included for comparison. Of the 2232 individuals who submitted a report to the internet-based medicine reporting system, 258 submitted a report on antidepressants. Of these, 92 individuals (36%) reported on effectiveness, 40 (16%) of whom reported on ineffectiveness, and 217 (84%) submitted a report on side effects, with 202 (78%) reporting a total of 630 side effects that were experienced as negative. Fourteen individuals (5%) reported a practical issue and four (2%) reported a reimbursement issue. Of all 630 side effects reported, 48% resulted in the patient discontinuing the antidepressant therapy; of these 29% did not inform their HCP. Of all the side effects reported, 52% were perceived as “very negative”. In comparison to the side effects reported by HCPs, patients more often reported apathy, excessive sweating, ineffectiveness, somnolence, insomnia, sexual problems and weight increase. Patients report the ineffectiveness and side effects of antidepressant therapy as negative and leading to discontinuation of the therapy. Patients and HCPs differ in the nature of the reported side effects. Patient experiences should be included in the evaluation of antidepressant treatment in clinical practice. [ABSTRACT FROM AUTHOR]

Background Etanercept and efalizumab recently became available and reimbursed for routine use in severe psoriasis in the Netherlands. The criteria for reimbursement are Psoriasis Area and Severity Index (PASI) ≥ 10 (or Skindex-29 ≥ 35 if PASI ≥ 8 and < 10) and ineffectiveness of ultraviolet (UV) B/psoralen plus UVA, methotrexate and ciclosporin, or a contraindication to or serious side-effect(s) during these treatments. Objectives We hypothesized: (i) that efficacy would be lower than that obtained in published phase II and III studies because (a) resistance to all conventional therapies as a reimbursement condition would select for more resistant cases and (b) inclusion would be more restricted to severe cases (higher PASI), and (ii) that efficacy would be lower in obese patients due to the possible role of adipose tissue in tumour necrosis factor (TNF)- α homeostasis. Methods We treated 50 patients (38 men, 12 women; mean PASI 15·8) with etanercept 25 mg or 50 mg twice weekly and evaluated in a retrospective analysis the efficacy and safety in comparison with data from published trials. Additionally, we related the clinical effect to the body mass index (BMI), for adipose tissue is thought to have a possible role in TNF- α homeostasis. Results Based on the literature, 30% and 49% of the patients treated with etanercept 25 mg and 50 mg twice weekly, respectively, should have achieved 75% or more improvement in PASI compared with baseline (PASI 75), and 10% and 21%, respectively, should have achieved 90% or more improvement (PASI 90). Our data showed that 21% in the 2 × 25 mg group and 23% in the 2 × 50 mg group achieved PASI 75. PASI 90 was only attained in 7% of patients treated with 2 × 25 mg and 6% of those treated with 2 × 50 mg. Contrary to our hypothesis, the mean initial PASI was comparable with the mean PASI mentioned in the phase II and III clinical trials. Although fatigue is not identified as a side-effect of etanercept, 10% of our patients reported fatigue as an adverse event during etanercept treatment. High BMI, indicating overweight or obesity, was found both in patients with little efficacy and in patients achieving PASI 75 or better. Conclusions Use of etanercept in real practice gives impressive results, but these are generally less favourable than those published in clinical trial reports. This is probably due to the stringent conditions for reimbursement, which select for more treatment-resistant patients. Fatigue as a possible side-effect of etanercept should also be an issue for further investigation. Finally, the BMI does not seem to influence the patients’ response to etanercept, although further investigations would be needed to confirm this. [ABSTRACT FROM AUTHOR]

Introduction: In the Spring of 2020, the world was hit with unparalleled impact by the coronavirus pandemic. Antibiotics were widely used, even without good rationale. The aim of our study was to compare the use of antibiotics in patients with confirmed COVID-19 from three hospitals across Europe (Poland, the Netherlands and Spain) between two subsequent periods in the early days of the pandemic., Method: We analysed data (antibiotics used and variation in the use of antibiotics, patients, admission and disease-related characteristics) from 300 patients admitted in three hospitals (University Hospital in Cracow, University Medical Center in Utrecht and Vall d'Hebron University Hospital in Barcelona) with confirmed infection of SARS-CoV-2 during Q1 2020 and Q4 2020., Results: There was ample variation in terms of patient mix and outcomes across the 3 hospitals. The majority of patients (225 out of 300) in all 3 hospitals received at least 1 antibiotic during the hospitalisation period. A minority of patients (68 out of 300) had their bacterial test results positive during their hospitalisation period. Throughout the 2 study periods, third-generation cephalosporins (ceftriaxone in 170 out of 300 patients) emerged as the most commonly used class of antibiotics. There was an apparent shift towards more rational utilisation of antibiotics, in all three hospitals., Conclusions: Our study shows that during the early stage of COVID-19 pandemic in 2020, antibiotics were frequently used in three European teaching hospitals despite the relatively low incidence of microbiologically confirmed bacterial infections. While in the early days of the COVID-19 pandemic antibiotic prescribing was full of trial and error, we could also confirm a learning curve over time., (© 2024. The Author(s).)

Objective: In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC) <70 years of age. LSS consists of immunohistochemical (IHC) staining for loss of mismatch repair (MMR) protein expression, supplemented with MLH1 methylation analysis if indicated. Test results are evaluated by the treating gynaecologist, who refers eligible patients to a clinical geneticist. We evaluated the implementation of this guideline., Methods: From the nation-wide pathology database we selected all women diagnosed with EC < 70 years of age, treated from 1.6.2016-1.6.2017 in 14 hospitals. We collected data on the results of LSS and follow up of cases with suspected LS., Results: In 183 out of 204 tumours (90%) LSS was performed. In 41 cases (22%) MMR protein expression was lost, in 25 cases due to hypermethylation of the MLH1 promotor. One patient was known with a pathogenic MLH1 variant. The option of genetic counselling was discussed with 12 of the 15 remaining patients, of whom three declined. After counselling by the genetic counsellor nine patients underwent germline testing. In two no pathogenic germline variant was detected, two were diagnosed with a pathogenic PMS2 variant, and five with a pathogenic MSH6 variant, in concordance with the IHC profiles., Conclusion: Coverage of LSS was high (90%), though referral for genetic counselling could be improved. Gynaecologists ought to be aware of the benefits and possible drawbacks of knowing mutational status, and require training in discussing this with their patients., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The disconnectivity hypothesis postulates that partial loss of connecting white matter fibers between brain regions contributes to the development of dementia. Using diffusion MRI to quantify global and tract-specific white matter microstructural integrity, we tested this hypothesis in a longitudinal population-based study., Methods: Global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were obtained in 4,415 people without dementia (mean age 63.9 years, 55.0% women) from the prospective population-based Rotterdam Study with brain MRI between 2005 and 2011. We modeled the association of these diffusion measures with risk of dementia (follow-up until 2016) and with changes on repeated cognitive assessment after on average 5.4 years, adjusting for age, sex, education, macrostructural MRI markers, depressive symptoms, cardiovascular risk factors, and APOE genotype., Results: During a median follow-up of 6.8 years, 101 participants had incident dementia, of whom 83 had clinical Alzheimer disease (AD). Lower global values of FA and higher values of MD were associated with an increased risk of dementia (adjusted hazard ratio [95% confidence interval (CI)] per SD increase for MD 1.79 [1.44-2.23] and FA 0.65 [0.52-0.80]). Similarly, lower global values of FA and higher values of MD related to more cognitive decline in people without dementia (difference in global cognition per SD increase in MD [95% CI] was -0.04 [-0.07 to -0.01]). Associations were most profound in the projection, association, and limbic system tracts., Conclusions: Structural disconnectivity is associated with an increased risk of dementia and more pronounced cognitive decline in the general population., (© 2020 American Academy of Neurology.)

Objectives: Researchers are increasingly using routine clinical data for care evaluations and feedback to patients and clinicians. The quality of these evaluations depends on the quality and completeness of the input data., Study Design and Setting: We assessed the performance of an electronic health record (EHR)-based data mining algorithm, using the example of the smoking status in a cardiovascular population. As a reference standard, we used the questionnaire from the Utrecht Cardiovascular Cohort (UCC). To assess diagnostic accuracy, we calculated sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV)., Results: We analyzed 1,661 patients included in the UCC to January 18, 2019. Of those, 14% (n = 238) had missing information on smoking status in the UCC questionnaire. Data mining provided information on smoking status in 99% of the 1,661 participants. Diagnostic accuracy for current smoking was sensitivity 88%, specificity 92%, NPV 98%, and PPV 63%. From false positives, 85% reported they had quit smoking at the time of the UCC., Conclusion: Data mining showed great potential in retrieving information on smoking (a near complete yield). Its diagnostic performance is good for negative smoking statuses. The implications of misclassification with data mining are dependent on the application of the data., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice.

Purpose: To determine longitudinally the rate of change in diffusion-tensor imaging (DTI) parameters of white matter microstructure with aging and to investigate whether cardiovascular risk factors influence this longitudinal change., Materials and Methods: This prospective population-based cohort study was approved by a dedicated ethics committee overseen by the national government, and all participants gave written informed consent. Community-dwelling participants without dementia were examined by using a research-dedicated 1.5-T magnetic resonance (MR) imager on two separate visits that were, on average, 2.0 years apart. Among 810 persons who were eligible for imaging at baseline, longitudinal imaging data were available for 501 persons (mean age, 69.9 years; age range, 64.1-91.1 years). Changes in normal-appearing white matter DTI characteristics in the tract centers were analyzed globally to investigate diffuse patterns of change and then locally by using voxelwise multilinear regression. The influence of cardiovascular risk factors was assessed by treating them as additional determinants in both analyses., Results: Over the 2.0-year follow-up interval, global fractional anisotropy (FA) decreased by 0.0042 (P < .001), while mean diffusivity (MD) increased by 8.1 × 10(-6) mm(2)/sec (P < .001). Voxelwise analysis of the brain white matter skeleton showed an average decrease of 0.0082 (Pmean = .002) in FA in 57% of skeleton voxels. The sensorimotor pathway, however, showed an increase of 0.0078 (Pmean = .009) in FA. MD increased by 10.8 × 10(-6)mm(2)/sec (Pmean < .001) on average in 79% of white matter skeleton voxels. Additionally, white matter degeneration was more pronounced in older persons. Cardiovascular risk factors were generally not associated with longitudinal changes in white matter microstructure., Conclusion: Longitudinal diffusion analysis indicates widespread microstructural deterioration of the normal-appearing white matter in normal aging, with relative sparing of sensorimotor fibers., ((©) RSNA, 2015 Online supplemental material is available for this article.)

Background: Loss of brain white matter microstructure is presumed to be an early sign of neurodegenerative disease. Yet, little is known on microstructural changes of various white matter tracts with normal aging., Methods: In 4532 nondemented elderly persons, we studied age-related changes in tract-specific diffusion characteristics for 25 tracts using probabilistic tractography. We studied how diffusion differs across tracts with aging, whether this depends on macrostructural white matter changes, and whether cardiovascular risk factors affect microstructure., Results: With increasing age, loss of microstructural organization occurred in association, commissural and limbic tracts. White matter lesions and atrophy each partially explained this loss. We observed worse microstructure with severe hypertension, current smoking and diabetes mellitus, independent from age and macrostructural white matter changes., Conclusions: Microstructure of white matter tracts changes with age, and may mark neurodegeneration more sensitively than white matter lesion load and atrophy. Cardiovascular factors relate to loss in microstructural organization., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether the presence of cerebral microbleeds, which present as focal lesions on imaging, is associated with a diffuse loss of white matter microstructural integrity in the brain., Methods: In the prospective, population-based Rotterdam Scan Study, a total of 4,493 participants underwent brain MRI to determine microbleed status. With diffusion tensor imaging, global fractional anisotropy (FA) and mean diffusivity (MD) were measured in normal-appearing white matter. Multiple linear regression models, adjusted for age, sex, cardiovascular risk factors, white matter lesions, and infarcts, were applied to investigate the independent association between microbleeds and organization of brain white matter. Analyses were repeated after stratification by APOE ε4 carriership., Results: Presence of microbleeds was related to a lower mean FA and higher mean MD, in a dose-dependent manner, and was already apparent for a single microbleed (standardized FA: -0.13, 95% confidence interval -0.21 to -0.05; MD: 0.12, 95% confidence interval 0.05 to 0.19). For lobar microbleeds, alterations in diffusion tensor imaging measurements were solely driven by APOE ε4 carriers., Conclusions: Presence of microbleeds relates to poorer microstructural integrity of brain white matter, even after adjusting for cardiovascular risk and other markers of cerebral small-vessel disease. Our data suggest that microbleeds reflect diffuse brain pathology, even when only a single microbleed is present.

Objective: To identify factors predicting the long term course of complicated grief, depression, and suicide ideation in a community based sample of relatives bereaved through suicide., Design: Longitudinal cohort study. Included in the multilevel regression models were sociodemographic and personality features, mental health history, records of received help, long term complicated grief, depression, and suicide ideation., Setting: Community based sample located in the northern part of the Netherlands., Participants: 153 first degree relatives and spouses of 74 people who had committed suicide., Main Outcome Measures: Complicated grief, depression, and suicide ideation assessed at 2.5 months, 13 months and 96-120 months (8-10 years) by means of self report questionnaires., Results: Complicated grief, depression, and suicide ideation were mutually associated in relatives and spouses of people who had committed suicide. A history of attempted suicide was associated with long term suicide ideation (odds ratio 5.5, 95% confidence interval 1.8 to 16.7; P=0.003). Depression was more likely to be predicted by female sex and low mastery, whereas complicated grief was more likely to be predicted by the trauma of losing a child. The risk of both complicated grief and depression decreased over time; for complicated grief the change corresponded with a Cohen's d effect size of 0.36 at 13 months and 0.89 at 96-120 months; for depression these figures were 0.28 at 13 months and 0.94 at 96-120 months. The long term course of bereavement was not affected by family based cognitive behavioural therapy, support from a general practitioner, and/or mental healthcare. Mutual support was associated with an increased risk of complicated grief: B regression coefficient=6.4 (95% confidence interval 1.8 to 11.0; P=0.006). Throughout this long term study, selection bias might have affected some outcomes., Conclusion: In relatives bereaved by suicide, suicide ideation is associated with an increased risk of long term complicated grief and depression. The risk of complicated grief and depression decreases over time. Although mutual support is associated with an increased risk of complicated grief, we could not draw conclusions about a causal relation.

Two styles of river flood management can be distinguished: dike reinforcement and the more sustainable 'Room for River' option. This paper investigates public adherences to these two management styles and whether their adherence correlates with their Visions of Nature. The focus is especially on people's image of the appropriate human/nature relationship, i.e. Mastery over nature, Stewardship of nature, Partnership of nature or Participation in nature. Other variables that are part of the analysis are the respondents' sense of place, safety perception and background variables. The results of a written survey among riverside residents in France, Germany and the Netherlands (N = 1811) show high adherences to the Room for River style and a rejection of dike reinforcement. A regression analysis shows that adherence to the Room for River style correlates with adherence to the image of Stewardship, while adherence to dike reinforcement is predicted by Mastery over nature. Thus, according to the public a policy shift from dike reinforcement to a more sustainable style is seen as a fundamental one, connected to a change in environmental ethics., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Relatives who are bereaved by suicide likely consult their GP when they feel the need for professional help. GPs may play a key role in establishing who is at risk for adverse consequences of the loss as they are familiar with relatives' possible psychiatric vulnerabilities. The availability of evidence-based services for relatives of suicide victims is limited. Successful implementation of services needs analysis of key factors considered critical in the achievement of changes. We investigated GPs' management of help requests of relatives bereaved by suicide and examined determinants of GPs willingness to refer for evidence-based follow-up care., Methods: A cross-sectional survey among 488 GPs in the northern part of The Netherlands., Results: A 44% response was achieved (n = 214) during the last 3 years, 38 (18%) were exposed to suicide, 21 (10%) to help requests without being exposed to suicide and 52 (24%) to both suicide and help requests. Out of 106 requests, 69 (65%) were handled by the GP; 60 (57%) were either directly or additionally referred, principally for mental health care. Suicide exposure and female gender were associated with the doctor's perception that follow-up care following a loss through suicide is useful. The perception that help is useful increased the likelihood of GPs' referral for evidence-based follow-up care., Conclusions: GPs support the availability of evidence-based follow-up care for relatives of suicide victims. To modify GPs' key role in referring relatives for it, GPs should be well informed of its usefulness and to whom.

In order to study the feasibility of new sensorily stimulating material for elderly demented men, their behaviour was observed while the material was handed over to them. The newly developed materials consisted of five different constructions, i.e. a mirrorbox, a simple hand-operated stroboscope, a spring-operated ball for ringing a bell, two rotating wooden cogwheels, and a box having a sandpaper bottom of different grains causing a tactile contrast. In their verbal and nonverbal responses the demented men showed clear signs of interest in the constructions and the materials. The seven participating men showed much interest in materials made of wood and metal, and in the working of the constructions. The different constructions and materials could be combined into one complete 'snoezelproduct'.

Objective: To assess the value of alpha-atrial natriuretic peptide (alpha-ANP), second messenger cyclic guanosine monophosphate (cGMP,) and endothelin as markers of myocardial depression in septic shock., Design: Prospective observational study., Setting: Medical intensive care unit (ICU) of a university hospital., Patients: Fourteen consecutive patients with septic shock and arterial and pulmonary artery catheters in place., Measurements and Main Results: Hemodynamic variables and plasma levels of alpha-ANP, cGMP, and endothelin were measured every 6 hrs for 3 days after admission. Eight patients died from shock in the ICU. The nadir left ventricular stroke work index (LVSWI) was below 35 g/m2 in all patients, and the median peak circulating alpha-ANP (n < 68 pg/mL) was 276 pg/mL (range, 79-1056), the median peak cGMP (n < 2.1 ng/mL) was 8.1 ng/mL (range, 3.2-29.7), and the median peak endothelin (n < 5.3 pg/mL) was 15.5 pg/mL (range, 8.5-33.9), supranormal in all patients. Outcome groups differed in the course of cardiac index and LVSWI, which were lower in nonsurvivors despite similar filling pressures and more intensive inotropic treatment (p < .01). The course of alpha-ANP, cGMP, and endothelin plasma levels also differed between groups, with higher levels in nonsurvivors (p < .05). As for pooled data, the mean daily or nadir LVSWI inversely related to mean daily or peak alpha-ANP, cGMP, and endothelin levels, respectively (p < .05). The area under the receiver operating characteristic curve for myocardial depression (LVSWI < 35 g/m2) was for alpha-ANP and endothelin 0.77, and for cGMP 0.85 (p < .01). The optimum cutoff values for alpha-ANP, cGMP, and endothelin were 172 pg/mL, 4.5 ng/mL, and 10.0 pg/mL, respectively. The sensitivity for myocardial depression of alpha-ANP, cGMP, and endothelin was 68%, 77%, and 72%, and the specificity was 82%, 93%, and 69%, respectively., Conclusions: Circulating alpha-ANP, endothelin, and, particularly, cGMP may be markers of the myocardial depression of human septic shock, which is associated with mortality.

Background: The application of a heparin dosing nomogram in the treatment of patients with venous thromboembolism resulted in improvement of heparin therapy in clinical research settings. In 1992 a heparin nomogram was introduced in our hospital, which is a community hospital where anticoagulant therapy is supervised by the attending physicians. We studied whether comparable improvements were achieved in such a non-surveyed clinical setting., Methods: Patients were identified from computerized discharge records, and classified into a pre-nomogram (discharged in 1990 or 1991) and a nomogram patient group (discharged in 1993 or 1994). The use of the nomogram was encouraged but the application remained on a voluntary basis. Since the definition of the target APTT range was different in the pre-nomogram period as compared to the nomogram period, a formal analysis of pre- and post-nomogram results was not considered justified., Results: The APTT ratio, six hours after the start of heparin treatment, was below the predefined lower limit in 72% of 127 patients in the pre-nomogram group and in 13% of 127 patients in the nomogram group. During 1043 days heparin therapy in the nomogram group the morning APTT ratio was subtherapeutic in 8%. In 58% of all APTT results the physician responded according to the nomogram. The subsequent APTT was in the target range in 64% of the cases compared to 31% if the adjustement was not performed according to the nomogram (P<.0001). Major bleeding episodes occurred in 3.1% in the pre-nomogram period and in 0.7% in the nomogram period., Conclusion: The present study shows that the introduction of a heparin dosing nomogram in a non-research clinical setting results in more adequate heparin anticoagulation with low risks of bleeding.