Caring for a child with sickle cell disease poses extra demands on parents, both practically and psychologically, which may influence their quality of life. Since families of children with sickle cell disease in the Netherlands usually belong to immigrant communities with a low socio-economic status, there may be an additional strain on caregivers. The aim of the present study was to evaluate the quality of life of caregivers of children with sickle cell disease. The quality of life of female caregivers of sickle cell disease patients, measured with the TNO-AZL Adult Quality of Life questionnaire, was compared to the norm data of healthy Dutch females (n=700) and female caregivers of healthy children with the same socio-economic status and ethnic background (socio-economic status control group). Groups were compared by the Mann-Whitney U test. Point estimates and 95% confidence intervals of the median difference are presented. The results of questionnaires of 54 caregivers of children with sickle cell disease and 28 caregivers of a control group of the same socio-economic status were analyzed. Caregivers of patients with sickle cell disease had a significantly lower quality of life on all subscales compared to the Dutch norm population. Compared to the control group of the same socio-economic status, the quality of life of caregivers of patients with sickle cell disease was significantly lower on the subscales depressive moods, daily activities and vitality. In this first study reporting on the quality of life of caregivers of children with sickle cell disease, we demonstrate a reduced quality of life in these caregivers compared to the healthy Dutch female population and caregivers of healthy children with the same socio-economic status.Key words: sickle cell disease, quality of life, caregivers. Citation

There is no instrument to measure severity of sickle cell disease (SCD) in pediatric patients that is generally accepted. The aim of this study was to develop and validate a severity index for SCD in children. We developed an index consisting of 12 items and tested its validity of the index using data from 92 children. We tested whether different scores were obtained for patients classified by severity both subjectively and objectively by a partially validated existing index. Furthermore, we tested whether the index could differentiate patients classified according to genotype or the number of a-gene deletions and evaluated whether the score on the index was correlated with the average number and days of hospitalizations/year, age and a risk of death score. We explored the effect of three different weighting systems (Score A, B, and C) to summarize these items. All weightings demonstrated a significant difference between the scores of mild, moderate, and severely affected patients, as classified by a subjective rating or with an existing index (P < 0.01). The index clearly differentiated patients by genotype (P < 0.01) or a-gene deletions (P < 0.01). The correlation with hospitalization was moderate. Age and the risk of death score were weakly associated with the pediatric severity index for SCD. This is the first pediatric SCD severity index that was developed and validated using modern clinimetric methodology. The validity and reliability of this index should be further evaluated in a prospective study including a larger cohort, preferably diagnosed at birth. Am. J. Hematol. 85:746-751, 2010. V

SUMMARY:Arterial spin-labeling (ASL) is a relatively new and noninvasive MR imaging technique, used to measure cerebral blood flow (CBF). Scanning time and reproducibility remain important issues in the clinical applicability of ASL. We expected both to benefit from higher field strengths. We describe that when performing ASL at 3T, 20 averages suffice to obtain steady and reproducible CBF values. Scanning time can be as short as 3 minutes.A rterial spin labeling (ASL) is a noninvasive MR imaging technique, used for visualization and quantification of cerebral perfusion. Cerebral blood flow (CBF) values measured by ASL are comparable with CBF values measured by conventional techniques (eg, positron-emission tomography or susceptibility-weighted MR imaging). ASL is based on magnetic labeling of arterial blood water protons, which are used as an endogenous tracer of flow. Magnetic inversion takes place in a plane proximal to the brain. The decay rate of the labeled spins is sufficiently long to visualize perfusion of brain vasculature and microvasculature. Perfusion images are obtained by subtraction of successively acquired labeled and nonlabeled control images. In general, 40 to 60 paired acquisitions are averaged to improve perfusion signal intensity. ASL sequences differ in the way magnetic labeling is applied and are commonly classified as continuous or pulsed ASL (CASL or PASL, respectively). In CASL, continuous adiabatic inversion of spins is applied. In PASL, labeling is performed at once over a wide spatial range. Pseudocontinuous ASL (pCASL) has been introduced recently and uses a series of discrete labeling pulses. 1-8Despite its advantages, scanning time and reproducibility remain important issues in the clinical applicability of ASL. The use of higher-field strengths could overcome these issues because of increased signal-to-noise ratio, prolonged T1-weighted relaxation time of labeled blood, and better spatial and temporal resolution. 7,9 We hypothesized that scanning time of the CASL sequence can be reduced at 3T because fewer averages might suffice to obtain steady and reproducible CBF values. Our primary objective was to assess the number of averages needed to obtain steady and reproducible CBF values with use of 3T CASL.Also, we hypothesized that acquisition-related reproducibility of ASL will improve at higher-field strengths, whereas physiology-related reproducibility will not change. Previous CASL reproducibility studies were performed at 1.5T with test-retest timeframes of at least 1 hour. 4,6,10 Measurement of reproducibility within scans would be more valuable to assess physiologic variations. Our secondary objective was to assess 3T CASL reproducibility within scans (intrascan Ϸ 4 minutes), within sessions (intrasession Ϸ 10 minutes), and between sessions (intersession Ϸ 1 to 3 weeks). TechniqueAfter approval of the local ethics committee and written informed consent from all volunteers, we scanned 10 volunteers (5 men; age range, 25-33 years) without known cerebrovascular disease during 3...

Summary This study analyzed the mortality and causes of death in sickle cell disease patients in the Netherlands, to provide a baseline for monitoring the effect of the recently introduced neonatal screening programme and to indicate areas of improvement in the care for these patients. All children (<18 years) diagnosed with sickle cell disease in a tertiary hospital from 1985 to 2007 were included. Vital status was determined up to March 2008. A total of 298 children were included: 189 (63%) patients had HbSS, 17 (6%) HbSβ0 thalassaemia, 72 (24%) HbSC and 20 (7%) HbSβ+ thalassaemia. Twelve patients (4%) died during a total follow‐up of 3896 patient years. All known deaths were sickle cell disease‐related. Meningitis/sepsis (n = 4; 33%), stroke (n = 3; 25%) and death during a visit to the country of origin (n = 3; 25%) were the most common causes of death. The overall mortality rate was 0·27 deaths/100 patient years [95% confidence interval (CI): 0·15–0·43]. The estimated survival at the age of 18 years was 97·3% (95% CI: 95–99%). This report confirms that the burden of mortality in sickle cell disease is increasingly shifting to adults. It is recommended that compliance to antibiotic prophylaxis, thorough counselling and support for patients travelling abroad and specialized peri‐operative care should receive continuous attention.

Background and Purpose-Cerebral infarction is an important complication of sickle cell disease (SCD) and occurs in one third of the patients with SCD. The risk of infarction is commonly attributed to the hyperemia that is associated with anemia and reduces the cerebral vascular reserve. We measured regional cerebral blood flow (rCBF) by continuous arterial spin labeling MRI, which is a noninvasive method that does not require ionizing radiation. The purpose of this study was to examine rCBF in children with SCD and compare it with rCBF in healthy children. Methods-rCBF was measured at 3-T continuous arterial spin labeling MRI in 24 neurological normal patients with SCD and in 12 healthy children matched for ethnicity and age (mean age in both groups 13 years). rCBF was calculated for 6 vascular territories (left and right anterior, middle and posterior cerebral artery). Asymmetry in rCBF was evaluated by measuring differences in flow between left and right hemispheres. The definition of asymmetry (Ͼ11.7 mL/100 g/min) was based on a repeatability study performed in 6 healthy adults. Results-The rCBF was of similar magnitude in patients with SCD and control subjects in the frontal, middle, and posterior territories. The majority of patients with SCD (58%) demonstrated a left-right asymmetry of rCBF in one or more vascular territories, whereas none of the control subjects did. Conclusion-In contrast to previous studies, we found no difference in cerebral blood flow between patients and control subjects. We did observe an asymmetry in rCBF in the majority of patients with SCD that was not present in healthy control subjects. (Stroke. 2009;40:795-800.)

One-third of the new paediatric patients with sickle cell disease in The Netherlands are immigrants and do not benefit from neonatal screening Peters, M.; Fijnvandraat, C.J.; van den Tweel, X.W.; Garre, F.G.; Giordano, P.C.; van Wouwe, J.P.; Pereira, R.R.; Verkerk, P.H. Published in:Archives of disease in childhood DOI: 10.1136/adc.2009.165290 Link to publication Citation for published version (APA): Peters, M., Fijnvandraat, C. J., van den Tweel, X. W., Garre, F. G., Giordano, P. C., van Wouwe, J. P., ... Verkerk, P. H. (2010). One-third of the new paediatric patients with sickle cell disease in The Netherlands are immigrants and do not benefit from neonatal screening. Archives of disease in childhood, 95(10), 822-825. https://doi.org/10.1136/adc.2009.165290 General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Results The prevalence of SCD in children living in The Netherlands on 1 January 2003 was 1:5152 (95% CI 1:4513 to 1:6015). In the next 4 years, the annual incidence was 1:2011 (95% CI 1:1743 to 1:2376). Nearly one-third (27%) of the children newly diagnosed as having SCD immigrated to The Netherlands after birth and would, therefore, be missed by the neonatal screening programme. Approximately 60% of all children with SCD were not reported by paediatricians. Conclusion The number of children with SCD in The Netherlands is much higher than previously estimated, and the majority of these children seem not to be reviewed regularly by a paediatrician. Children born abroad (27% of new cases) do not benefi t from neonatal screening and are at high risk of life-threatening complications before SCD is diagnosed. As this introduces disparities in healthcare, the initiation of adequate measures should be considered.In 2007, a national neonatal screening programme for sickle cell disease (SCD) was launched in The Netherlands, prompted by the increase of the population at risk from 0.5 to 1.7 million people over the last two decades. 1 SCD is an inherited disorder of haemoglobin with its highest incidence in people of African ancestry and an increasing prevalence in Europe. 2 Presently, SCD is the most common genetic disorder in the UK and is increasingly common in The Netherlands, with a carrier incidence of 0.4%. 3-5 SCD is characterised by chronic haemolytic anaemia...

No underlying pathology could be detected in 64% of 208 children presenting with recurrent respiratory tract infections in general pediatric practice. Asthma/preschool wheezing and adenoid hypertrophy were commonly diagnosed. None of the children had a severe primary immunodeficiency or severe pulmonary illness such as cystic fibrosis. Our findings can guide pediatricians in their diagnostic approach of children with respiratory tract infections.

Background: The clinical picture in sickle cell disease (SCD) is highly heterogeneous. Knowledge of the determinants of a severe disease course will help us to unravel the pathophysiological mechanisms underlying the disease process and provide novel targets for therapeutic interventions. To generate this knowledge well designed etiological studies are needed, using a valid outcome measure for disease severity. Objective: The aim of this systematic review is to identify all indices used to discriminate SCD patients by their current disease severity and to evaluate the methodological foundations of the indices and utility for clinical research. Method: We performed a systematic search in MEDLINE (Pubmed) (1966- February 2006) using the search terms: anaemia, sickle cell/ [MeSH]; health status indicators/ [MeSH]; severity; severe and clinical spectrum. Reference lists of relevant studies and reviews were screened to identify additional articles. Information was extracted in duplicate by two independent reviewers (XT, KF). Results: The Medline search yielded 1346 abstracts from which we selected 91 articles. Reference tracking resulted in 20 additional articles. After evaluation of the full text of these 111 articles, 28 articles (27 in English) were included in the review. These 28 indices contained 50 different items, including age at diagnosis, symptoms, findings at physical examination, laboratory values, organ damage, treatments and socio-economic consequences. The five most frequently used items were painful vaso-occlusive crises (86% of the indices), central nervous system abnormalities (59%), aseptic/avascular necrosis of the bone (52% of the indices), acute chest syndrome (48% of the indices) and leg ulcers (48% of the indices). Many indices (37%) were calculated by adding up scores on individual items without making a difference in the weight of the constituent items. In indices that did differentiate between items by allocating scores differentially, the rationale for weighing of the items was not explained. There were no scores that clearly distinguished devastating complications from complications that leave no sequelae. Most severity indices (89%) were not validated. Conclusion: In order to increase our understanding of the pathofysiology of SCD and identify potential targets for new therapeutic interventions, we need to identify the determinants of a severe phenotype. For this purpose, consensus on the concept of severity in SCD and an instrument or index to measure it are necessary. This review reveals that there is no consensus on a definition of SCD severity and an index to measure it. Given the current state, efforts should be made to reach international consensus on a definition of SCD severity and a core set of items to measure this concept should be developed.