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2.
Ultrasound Obstet Gynecol ; 57(3): 431-439, 2021 03.
Article in English | MEDLINE | ID: mdl-32959909

ABSTRACT

OBJECTIVE: To evaluate the long-term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. METHODS: This was a follow-up study of the Triple P trial, which randomized 80 low-risk women with a short cervix (≤ 30 mm) at 18-22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general-health questionnaire. The main outcome of interest was mean BSID-III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID-III ≤-1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID-III tests. RESULTS: Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow-up data were obtained for 59/77 (77%) children and BSID-III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785-3620 g). In the progesterone vs placebo groups, mean BSID-III cognitive development scores were 101.6 vs 105.0 (MD, -3.4 (95% CI, -9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, -4.9 (95% CI, -11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health-related outcomes. CONCLUSION: In this sample of children born to low-risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health-related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Subject(s)
Neurodevelopmental Disorders/epidemiology , Premature Birth/prevention & control , Prenatal Exposure Delayed Effects/epidemiology , Progesterone/adverse effects , Progestins/adverse effects , Administration, Intravaginal , Adult , Cervical Length Measurement , Cervix Uteri/pathology , Child Development/drug effects , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Mental Status and Dementia Tests , Neurodevelopmental Disorders/chemically induced , Pregnancy , Premature Birth/diagnostic imaging , Prenatal Exposure Delayed Effects/chemically induced , Progesterone/administration & dosage , Progestins/administration & dosage , Treatment Outcome
3.
BMC Med Res Methodol ; 19(1): 227, 2019 12 04.
Article in English | MEDLINE | ID: mdl-31801463

ABSTRACT

BACKGROUND: Goal Attainment Scaling (GAS) is an instrument that is intended to evaluate the effect of an intervention by assessing change in daily life activities on an individual basis. However, GAS has not been validated adequately in an RCT setting. In this paper we propose a conceptual validation plan of GAS in the setting of rare disease drug trials, and describe a hypothetical trial where GAS could be validated. METHODS: We have used the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) taxonomy to deduce which measurement properties of GAS can be evaluated, and how. As individual GAS scores cannot be interpreted outside the context of a RCT, the validation of GAS needs to be done on trial as well as on individual level. RESULTS: The procedure of GAS consists of three steps. For the step of goal selection (step 1) and definition of levels of attainment (step 2), face validity may be assessed by clinical experts. For the evaluation of the goal attainment (step 3), the inter and intra rater reliability can be evaluated on an individual level. Construct validity may be evaluated by comparison with change scores on other instruments measuring in the same domain as particular goals, if available, and by testing hypotheses about differences between groups. A difference in mean GAS scores between a group who received an efficacious intervention and a control group is an indication of well-chosen goals, and corroborates construct validity of GAS on trial level. Responsiveness of GAS cannot be evaluated due to the nature of the construct being assessed. CONCLUSION: GAS may be useful as an instrument to assess functional change as an outcome measure in heterogeneous chronic rare diseases, but it can only be interpreted and validated when used in RCTs with blinded outcome assessment. This proposed theoretical validation plan can be used as a starting point to validate GAS in specific conditions.


Subject(s)
Goals , Outcome Assessment, Health Care , Rare Diseases/therapy , Activities of Daily Living , Clinical Trials as Topic , Humans , Psychometrics , Reproducibility of Results , Research Design
4.
Orphanet J Rare Dis ; 14(1): 31, 2019 02 07.
Article in English | MEDLINE | ID: mdl-30732630

ABSTRACT

BACKGROUND: Clinical trials in rare diseases are more challenging than trials in frequent diseases. Small numbers of eligible trial participants, often complicated by heterogeneity among rare disease patients, hamper the design and conduct of a 'classical' Randomized Controlled Trial. Therefore, novel designs are developed by statisticians. However, it is important to be aware of possible design aspects that may jeopardize the feasibility of trial conduct. If the burden of participation is considered out of proportion by patients or parents, recruitment may fail or participants may drop out before trial completion. In order to maximize the chance of success of trials in small populations, it is important to know which aspects of trial design are considered important by patients. RESULTS: We have interviewed all ten members of the Patient Think Tank (PTT) of the ASTERIX project, a European research consortium on methodology for clinical trials in small populations. The PTT members are rare disease patient representatives who have completed extensive training in clinical trial methodology. We have analyzed the interviews qualitatively according to Grounded Theory using a thematic analysis, and we structured the topics in four chronologically ordered themes: 1. Involvement in trial design; 2. Opinions on trial design; 3. Trial participation; 4. Phase after the trial. Our main findings are that the PTT-members recommend that patients are involved in trial design from an early stage on, and have influence on the outcomes and measurement instruments that are chosen in the trial, the length of the study, the choice of participants, and the information that is sent to potential participants. Also, according to the PTT-members, patient groups should consider setting up disease registries, placebo groups should be minimized, and more education on clinical trials is advised. CONCLUSIONS: Rare disease patient representatives who have been educated about clinical trial methodology think it is important to involve patient representatives in research at an early stage. They can be of advice in trial design in such a way that the ratio of potential benefit and burden of trial participation as well as the chosen outcome measures and in- and exclusion criteria are optimized.


Subject(s)
Qualitative Research , Rare Diseases , Humans , Patient Participation , Patient Selection , Quality of Life
5.
Stat Methods Med Res ; 28(6): 1893-1910, 2019 06.
Article in English | MEDLINE | ID: mdl-29921167

ABSTRACT

Goal Attainment Scaling is an assessment instrument to evaluate interventions on the basis of individual, patient-specific goals. The attainment of these goals is mapped in a pre-specified way to attainment levels on an ordinal scale, which is common to all goals. This approach is patient-centred and allows one to integrate the outcomes of patients with very heterogeneous symptoms. The latter is of particular importance in clinical trials in rare diseases because it enables larger sample sizes by including a broader patient population. In this paper, we focus on the statistical analysis of Goal Attainment Scaling outcomes for the comparison of two treatments in randomised clinical trials. Building on a general statistical model, we investigate the properties of different hypothesis testing approaches. Additionally, we propose a latent variable approach to generate Goal Attainment Scaling data in a simulation study, to assess the impact of model parameters such as the number of goals per patient and their correlation, the choice of discretisation thresholds and the type of design (parallel group or cross-over). Based on our findings, we give recommendations for the design of clinical trials with a Goal Attainment Scaling endpoint. Furthermore, we discuss an application of Goal Attainment Scaling in a clinical trial in mastocytosis.


Subject(s)
Data Interpretation, Statistical , Endpoint Determination , Patient Care Planning , Randomized Controlled Trials as Topic/methods , Endpoint Determination/statistics & numerical data , Humans , Models, Statistical , Probability , Rare Diseases/therapy , Treatment Outcome
6.
Health Policy ; 122(12): 1287-1294, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30274934

ABSTRACT

In clinical trials, it is relevant to ask patients and/or their caregivers which aspects concerning their disease they consider important to measure when a new intervention is being investigated. Those aspects, useful as outcome measures in a trial, are of pivotal importance for the result of the trial and the subsequent decision-making. In rare diseases the choice of outcome measures may be even more important, due to the small numbers and heterogeneity of the patients that are included. We have developed a tool to involve patients in the determination of outcome measures and the choice of measurement instruments. This tool was developed together with a patient think tank, consisting of a group of rare disease patient representatives, and by interviewing end users. We have road-tested our tool in an ongoing trial, and evaluated it during a focus group meeting. The tool consists of three steps: 1) Preparation, 2) Consultation of patients, 3) Follow-up during which the consultation results are implemented in the trial design. The tool provides guidelines for researchers to include the patient's opinion in the choice of outcome measures in the trial design stage. We describe the development of the POWER-tool (Patient participation in Outcome measure WEighing for Rare diseases), and first experiences of the tool in an ongoing trial.


Subject(s)
Decision Making , Outcome Assessment, Health Care , Patient Participation/methods , Rare Diseases , Research Design , Caregivers , Clinical Trials as Topic , Focus Groups , Humans
7.
BMC Pediatr ; 18(1): 147, 2018 05 02.
Article in English | MEDLINE | ID: mdl-29720158

ABSTRACT

BACKGROUND: There is increasing evidence that neonatal seizures in term neonates with stroke, asphyxia or brain haemorrhage might be associated with adverse neurodevelopment and development of epilepsy. The extent of this association is not known. The objective of this study was to assess the possible impact of neonatal seizures on these outcomes and if possible calculate a relative risk. METHODS: A systematic review and meta-analysis was performed (study period January 2000-June 2015). PubMed, Medline and Embase were searched for cohort studies evaluating neurodevelopmental outcome at the age of at least 18 months or development of epilepsy in surviving term neonates with or without neonatal seizures. The methodological quality of included studies was assessed and data extractions were performed in a standardized manner by independent reviewers. Pooled Relative Risks (RR) with 95% confidence intervals for adverse outcome were calculated if possible. RESULTS: Out of 1443 eligible studies 48 were selected for full text reading leaving 9 cohort studies for the final analyses (4 studies on stroke, 4 on perinatal asphyxia and one on cerebral hemorrhage). For all cases with stroke or asphyxia combined the pooled risk ratio (RR) for adverse outcome when suffering neonatal seizures was 7.42 (3.84-14.34); for neonates with perinatal asphyxia: 8.41 (4.07-17.39) and for neonates with stroke: 4.95 (1.07-23.0). The pooled RR for development of late onset epilepsy could only be determined for infants suffering from stroke: 1.48 (0.82-2.68). Results were biased and evidence sparse. CONCLUSIONS: The presence of neonatal seizures in term newborns with vascular or hypoxic brain injury may have an impact on or be a predictor of neurodevelopmental outcome. The biased available data yield insufficient evidence about the true size of this association.


Subject(s)
Asphyxia Neonatorum/complications , Cerebral Hemorrhage/complications , Hypoxia, Brain/complications , Neurodevelopmental Disorders/etiology , Seizures/complications , Stroke/complications , Epilepsy/etiology , Humans , Infant, Newborn , Prognosis , Risk Factors
8.
Ultrasound Obstet Gynecol ; 51(5): 621-628, 2018 May.
Article in English | MEDLINE | ID: mdl-29468770

ABSTRACT

OBJECTIVE: A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age. METHODS: This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother. RESULTS: From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation. CONCLUSION: In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Subject(s)
Neurodevelopmental Disorders/epidemiology , Pessaries , Pregnancy, Twin , Premature Birth/prevention & control , Adult , Cervical Length Measurement/statistics & numerical data , Cervix Uteri/diagnostic imaging , Child, Preschool , Female , Follow-Up Studies , Gestational Age , Humans , Infant, Newborn , Male , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/etiology , Pregnancy , Pregnancy Outcome/epidemiology , Premature Birth/epidemiology , Statistics, Nonparametric
10.
Clin Pharmacol Ther ; 103(3): 458-467, 2018 03.
Article in English | MEDLINE | ID: mdl-28555724

ABSTRACT

The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.


Subject(s)
Amoxicillin/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Hypothermia/metabolism , Aging/metabolism , Algorithms , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Birth Weight , Body Temperature , Cohort Studies , Computer Simulation , Female , Gestational Age , Humans , Infant, Newborn , Male , Monte Carlo Method , Prospective Studies , Urodynamics
11.
Ann Nutr Metab ; 70(2): 111-121, 2017.
Article in English | MEDLINE | ID: mdl-28334709

ABSTRACT

INTRODUCTION: In phenylketonuria (PKU), a natural protein-restricted dietary treatment prevents severe cognitive impairment. Nutrient deficiencies may occur due to strict diet. This study is aimed at evaluating the dietary intake and blood concentrations of micronutrients and essential fatty acids (FA), bone mineral density (BMD) and fracture history in patients on long-term dietary treatment. METHODS: Sixty early diagnosed Dutch patients (aged 1-39 years) were included in a multi-center cross-sectional study. Their dietary intake, blood concentrations of micronutrients, FA, fracture history and BMD were assessed. RESULTS: Selenium dietary intake and serum concentrations were low in 14 and 46% of patients, respectively. The serum 25-OH vitamin D2 + D3 concentration was low in 14% of patients while 20% of patients had a low vitamin D intake. Zinc serum concentrations were below normal in 14% of patients, despite adequate intake. Folic acid serum concentrations and intake were elevated. Despite safe total protein and fat intake, arginine plasma concentrations and erythrocyte eicosapentaenoic acid were below reference values in 19 and 6% of patients, respectively. Low BMD (Z-score <-2) was slightly more prevalent in patients, but the lifetime fracture prevalence was comparable to the general population. CONCLUSIONS: Dutch patients with PKU on long-term dietary treatment have a near normal nutrient status. Supplementation of micronutrients of which deficiency may be deleterious (e.g., vitamin D and selenium) should be considered. BMD warrants further investigation.


Subject(s)
Bone and Bones/drug effects , Fatty Acids, Essential/administration & dosage , Micronutrients/blood , Phenylketonurias/blood , Phenylketonurias/drug therapy , Adolescent , Adult , Bone Density/drug effects , Bone and Bones/physiology , Child , Child, Preschool , Cross-Sectional Studies , Dietary Proteins/administration & dosage , Dietary Proteins/blood , Erythrocytes/chemistry , Fatty Acids, Essential/blood , Female , Humans , Infant , Male , Micronutrients/administration & dosage , Nutrition Assessment , Nutritional Status , Phenylalanine/administration & dosage , Phenylalanine/blood , Selenium/administration & dosage , Selenium/blood , Vitamin D/administration & dosage , Vitamin D/blood , Young Adult
12.
Child Care Health Dev ; 43(3): 369-384, 2017 05.
Article in English | MEDLINE | ID: mdl-27774638

ABSTRACT

BACKGROUND: High levels of maltreatment are found in children who are identified because their parents visit the emergency department due to partner violence, substance abuse or suicide attempt. However, it is unknown if these children experience psychosocial problems. This study aims to assess their levels of post-traumatic stress, anxiety, depression, behavioural problems and health-related quality of life. METHODS: A cross-sectional study was conducted in six hospitals. All consecutive families of which a parent visited the emergency department due to partner violence, substance abuse or suicide attempt between 1 July 2012 and 1 March 2014 with children aged 1.5-17 years were approached for participation. Parents and children aged 8 years and older filled out questionnaires measuring post-traumatic stress [13-item version of Children's Revised Impact of Event Scale (CRIES-13)], anxiety, depression (Revised Child Anxiety and Depression Scale), behavioural problems [Child Behavior Checklist (CBCL) and Youth Self-Report (YSR)] and health-related quality of life (PedsQL). Scores of participants were compared with reference data obtained in children in similar age ranges from representative Dutch community samples (CRIES-13, Revised Child Anxiety and Depression Scale, PedsQL and CBCL) and to a normed cutoff score (CRIES-13). RESULTS: Of 195 eligible families, 89 (46%) participated in the study. Participating children did not score different from community children, both on child-reported and parent-reported instruments. Standardized mean differences of total sum scores were 0 (CRIES-13 and CBCL 1.5-5), 0.1 (YSR), 0.2 (CBCL 6-18) and -0.3 (PedsQL) and not statistically different from community children. Thirty-five percent of the participating children scored above the cutoff score on the CRIES-13, indicating post-traumatic stress disorder, but this difference was not statistically significant from community children (mean difference 8%; 95% CI -4-22%). CONCLUSIONS: We found no differences in psychosocial problems between children whose parents visited the emergency department due to partner violence, substance abuse or suicide attempt and children from community samples. Because 35% of the children scored in the range of post-traumatic stress disorder, we advise healthcare providers to pay attention to post-traumatic stress symptoms.


Subject(s)
Child Behavior Disorders/diagnosis , Child of Impaired Parents/psychology , Emergency Service, Hospital , Parents , Spouse Abuse/psychology , Stress Disorders, Post-Traumatic/diagnosis , Substance-Related Disorders/psychology , Suicide, Attempted/psychology , Adolescent , Affective Symptoms , Child , Child Behavior Disorders/psychology , Child, Preschool , Cross-Sectional Studies , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Infant , Male , Netherlands/epidemiology , Psychiatric Status Rating Scales , Quality of Life , Surveys and Questionnaires
13.
Eur J Pediatr ; 172(8): 1105-10, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23640022

ABSTRACT

UNLABELLED: High plasma C-reactive protein (CRP) levels are associated with favorable outcome in adults with acute lung injury (ALI). The association between CRP levels and outcome has not been studied in ALI in children. We performed a historical cohort study in 93 mechanically ventilated children (0-18 years) with ALI. The CRP level within 48 h of disease onset was tested for association with 28-day mortality and ventilator-free days (VFD). Clinical parameters and ventilator settings were evaluated for possible confounding. Fourteen patients died within 28 days. The median (interquartile range) CRP level in nonsurvivors was 126 mg/L (64; 187) compared with 56 mg/L (20; 105) in survivors (p = 0.01). For every 10-mg/L rise in CRP level, the unadjusted odds (95% confidence interval (95% CI)) for mortality increased 8.7% (2.1-15.8%). Cardiovascular organ failure at onset of ALI was the strongest predictor for mortality (odds ratio, 30.5 (6.2-152.5)). After adjustment for cardiovascular organ failure, for every 10-mg/L rise in CRP level, the OR (95% CI) for mortality increased 4.7% (-2.7-12.6%; p = 0.22). Increased CRP levels were associated with a decrease in VFD (ρ = -0.26, p = 0.01). CONCLUSION: increased plasma CRP levels are not associated with favorable outcome in ALI in children. This is in contrast with findings in adults with ALI.


Subject(s)
Acute Lung Injury/blood , C-Reactive Protein/metabolism , Respiration, Artificial , Acute Lung Injury/mortality , Acute Lung Injury/therapy , Adolescent , Biomarkers/blood , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Infant, Newborn , Intensive Care Units, Pediatric , Logistic Models , Male , Odds Ratio , Prognosis , Severity of Illness Index
15.
Clin Pharmacol Ther ; 90(5): 727-31, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21993427

ABSTRACT

Standards for Research in (StaR) Child Health was founded in 2009 to address the paucity and shortcomings of pediatric clinical trials. This initiative involves international experts who are dedicated to developing practical, evidence-based standards to enhance the reliability and relevance of pediatric clinical research. Through a systematic "knowledge to action" plan, StaR Child Health will make efforts to improve and expand the evidence base for child health across the world.


Subject(s)
Clinical Trials as Topic/methods , Guidelines as Topic , Pediatrics , Research Design/standards , Child , Child Welfare , Clinical Trials as Topic/standards , Evidence-Based Medicine , Global Health , Humans , International Cooperation , Pharmaceutical Preparations/administration & dosage
16.
Neuropediatrics ; 42(1): 13-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21500142

ABSTRACT

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of metabolism, most frequently associated with developmental delay and/or epilepsy. Most SCADD patients carry common SCAD-encoding gene ( ACADS) variants or these variants in combination with a rare ACADS mutation, in the Netherlands predominantly the c.1058C>T. Epilepsy in childhood often remains unexplained and patients with epilepsy related to SCADD may remain undiagnosed because studies for SCADD are often not performed. To test this hypothesis and to further estimate the extent of the Dutch SCADD population, we performed a study on blood spot samples in 131 paediatric patients with epilepsy and 909 anonymous newborns and investigated the presence of the 2 common ACADS variants and the rare c.1058C>T mutation. Overall, the 2 common ACADS variants and the rare c.1058C>T mutation were detected in either homozygous or compound heterozygous forms in 9.2% of the epilepsy and 7.5% of the reference group. A birth prevalence of SCADD with a mutation/variant genotype in the Netherlands as high as >1:1,000 was calculated. This is in contrast with the low number of patients diagnosed clinically and supports the hypothesis that SCADD is clinically irrelevant. Furthermore our study does not support an association between SCADD and epilepsy.


Subject(s)
Epilepsy/epidemiology , Lipid Metabolism, Inborn Errors/epidemiology , Acyl-CoA Dehydrogenase/deficiency , Acyl-CoA Dehydrogenase/genetics , Adolescent , Butyryl-CoA Dehydrogenase/genetics , Child , Child, Preschool , DNA Mutational Analysis , Female , Humans , Incidence , Infant , Infant, Newborn , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/genetics , Male , Mutation/genetics , Netherlands/epidemiology , Pediatrics
17.
Tijdschr Gerontol Geriatr ; 41(4): 177-86, 2010 Sep.
Article in Dutch | MEDLINE | ID: mdl-20882721

ABSTRACT

BACKGROUND: Of elderly patients (> 70 years) admitted to a general hospital 35% suffer from loss of self-care abilities compared to the level before admission. Risk of loss of self-care ability increases with age up to 65% after tthe age of 90. In addition, for many of these patients the duration of hospitalisation is relatively long. OBJECTIVE It is important to identify in an early stage frail-elderly patients who are at risk of a relatively long hospital stay. We conducted a study of the prevalence at intake (1st of 2nd admission day) of ten clinically relevant, patient-bound risk factors for a long hospital stay among 158 patients (> 60 years), acute and planned admitted to Vlietland Hospital. In addition, the prognostic value of the dichotomous risk factors for length of hospital stay was estimated as indicator of treatment complications. The ten clinically relevant risk factors were home care, history of falling, medication (> 4), weight loss, cognitive level and functioning, self-care, psychiatric symptoms, health status and quality of life. RESULTS: There was a high prevalence of risk factors; 47.5% of the elderly patients had four or more risk factors at intake. Home care and global cognitive deterioration were significant predictors of longer length of hospital stay. Furthermore, acute admission, weight loss, psychiatric symptoms and health status seemed important. The explained variance of the prognostic model was relatively small. CONCLUSION: The findings in this explorative-observational study showed a high prevalence of clinically relevant, patient-bound risk factors in elderly people in a general hospital. Some risk-factors were of prognostic interest for long hospital stay, although the explained variance was relatively small. This indicates that a more comprehensive study should be designed and conducted to include other patient-bound risk factors like co-morbidity, caregiver issues and social environment. Moreover, non-patient-bound factors should be addressed like intrinsic and logistic factors within the hospital, and the quality of recuperation programmes. Understanding of these factors contributes to timely identification of elderly patients, who are at high risk of a long hospital stay. Future policy is to perform specific treatment programmes for elderly patients identified as being patients at risk. Multidisciplinary person-oriented interventions and case management focussed on risk factors and functional recovery will be provided parallel and after hospital treatment period. Comprehensive scientific research on the cost-effectiveness of such a programme has started at the end of 200oo9 in Vlietland Hospital, Schiedam.


Subject(s)
Health Status , Length of Stay/statistics & numerical data , Patient Admission/statistics & numerical data , Self Care , Aged , Aged, 80 and over , Female , Frail Elderly , Hospitalization/statistics & numerical data , Humans , Male , Mental Health , Netherlands , Prevalence , Prognosis , Risk Factors
18.
Arch Dis Child Fetal Neonatal Ed ; 95(5): F369-72, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20530103

ABSTRACT

BACKGROUND: Central blood flow measurements can provide detailed information on the hemodynamic condition of the preterm infant. However, reference values for right and left ventricular output (RVO and LVO) and superior vena cava flow (SVC flow) are only available for infants in the transitional period. The aim of this study was to determine RVO, LVO and SVC after the transitional period in stable preterm infants. METHODS: RVO, LVO and SVC flow were measured with functional echocardiography on days 7 and 14 of life in stable preterm infants less than 32 weeks gestation, with minimal respiratory support and no cardiovascular support. Infants with a clinical suspicion of an infection within 48 h after data collection or a ductal diameter >1.4 mm were excluded from analysis. RESULTS: We performed 111 measurements in 62 preterm infants with a median (range) gestational age of 28 (25-31) weeks and birth weight of 1105 (650-2370) g. 57 measurements were analysed on day 7 and 47 on day 14. The mean (SD) RVO, LVO and SVC flow were 429 (116), 296 (74) and 89 (33) ml/kg/min on day 7 and 433 (81), 300 (79) and 86 (26) ml/kg/min on day 14. There were no significant differences in flows between days 7 and 14 in the paired measurements. CONCLUSION: This study provides central blood flow values in stable preterm infants after the transitional period. The flow variables were shown to remain stable between days 7 and 14.


Subject(s)
Coronary Circulation/physiology , Infant, Premature/physiology , Birth Weight , Cardiac Output/physiology , Echocardiography, Doppler, Color/methods , Echocardiography, Doppler, Pulsed/methods , Gestational Age , Hemodynamics/physiology , Humans , Infant, Newborn , Prospective Studies , Reference Values , Vena Cava, Superior/physiology , Ventricular Function, Left/physiology , Ventricular Function, Right/physiology
19.
Ned Tijdschr Geneeskd ; 153: A1310, 2009.
Article in Dutch | MEDLINE | ID: mdl-19900330

ABSTRACT

Accumulating evidence shows that children are not simply little adults, and adapting adult evidence on medical care to children can result in ineffective or even unsafe medical care. The growing number of trials in children reflects this imperative to create a child-specific evidence base. Motivated by the increased focus on clinical research in children and the stark deficiencies in knowledge about the best ways to deal with methodological and practical challenges of research in children, the STaR Child Health initiative was created. It aims to enhance the design, conduct, and reporting of trials in children. The initiative brings together an international group of leading methodologists, clinicians, regulators, funders, and decision-makers to systematically identify what is known, create a research agenda where gaps exist and translate information into practical guidance for end-users. It is critical that funders, researchers, and editors work together for improved conduct and reporting of trials in the next 5-10 years to ensure that the investment in this area will produce the most reliable and relevant results. The first StaR Child Health summit will take place in Amsterdam on the 26th and 27th of October.


Subject(s)
Evidence-Based Medicine , Off-Label Use , Pediatrics/standards , Pharmaceutical Preparations/standards , Research/organization & administration , Child , Dose-Response Relationship, Drug , Humans , Netherlands , Practice Guidelines as Topic
20.
J Thromb Haemost ; 7(6): 930-7, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19548904

ABSTRACT

BACKGROUND: A severe and challenging complication in the treatment of hemophilia A is the development of inhibiting antibodies (inhibitors) directed towards factor VIII (FVIII). Inhibitors aggravate bleeding complications, disabilities and costs. The etiology of inhibitor development is incompletely understood. OBJECTIVES: In a large cohort study in patients with mild/moderate hemophilia A we evaluated the role of genotype and intensive FVIII exposure in inhibitor development. PATIENTS/METHODS: Longitudinal clinical data from 138 mild/moderate hemophilia A patients were retrospectively collected from 1 January 1980 to 1 January 2008 and analyzed by multivariate analysis using Poisson regression. RESULTS: Genotyping demonstrated the Arg593Cys missense mutation in 52 (38%) patients; the remaining 86 patients had 26 other missense mutations. Sixty-three (46%) patients received intensive FVIII concentrate administration, 41 of them for surgery. Ten patients (7%) developed inhibitors, eight of them carrying the Arg593Cys mutation. Compared with the other patients, those with the Arg593Cys mutation had a 10-fold increased risk of developing inhibitors (RR 10; 95% CI, 0.9-119).The other two inhibitor patients had the newly detected mutations Pro1761Gln and Glu2228Asp. In both these patients and in five patients with genotype Arg593Cys, inhibitors developed after intensive peri-operative use of FVIII concentrate (RR 186; 95% CI, 25-1403). In five of the 10 inhibitor patients FVIII was administered by continuous infusion during surgery (RR 13; 95% CI, 1.9-86). CONCLUSION: The Arg593Cys genotype and intensive peri-operative use of FVIII, especially when administered by continuous infusion, are associated with an increased risk for inhibitor development in mild/moderate hemophilia A.


Subject(s)
Arginine/genetics , Autoantibodies/immunology , Cysteine/genetics , Factor VIII/therapeutic use , Hemophilia A/drug therapy , Mutation , Adolescent , Adult , Factor VIII/immunology , Hemophilia A/genetics , Humans , Longitudinal Studies , Middle Aged , Perioperative Care , Retrospective Studies , Risk Factors , Severity of Illness Index , Young Adult
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