Design and rationale of the NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT).

BACKGROUND: Angina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands. METHODS: The NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered. The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee. CONCLUSION: NL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.

Urea for hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion.

BACKGROUND: Hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) can pose a therapeutic challenge. After fluid restriction, urea is recommended as a second-line treatment by Dutch and European treatment guidelines. Data on this practice are still scarce. We introduced urea for the treatment of SIADH in our hospital and prospectively collected data on its effectiveness and tolerability. METHODS: In hospitalised patients with a serum sodium level ≤ 129 mmol/l due to SIADH, urea in a dosage of 0.25-0.50 g/kg/day was indicated if prescribed fluid restriction had no effect or could not be applied. Measurement of serum sodium was performed at baseline, after the first and second day of urea therapy and at the end of the first inpatient treatment episode (EIT). The primary outcomes were normonatraemia (serum sodium level 135-145 mmol/l) at EIT and discontinuation of urea due to side effects. RESULTS: Thirteen patients were treated with urea over a median of 5 days (range 2-10 days). The median serum sodium level at baseline was 124 mmol/l (IQR 122-128), which increased to 128 mmol/l (IQR 123-130) (p = 0.003) after the first dose of urea and to 130 mmol/l (IQR 127-133) (p = 0.002) after the second dose of urea. Normonatraemia at EIT was observed in 8 (62%) patients. Seven (54%) patients reported distaste. In one of these patients, urea was discontinued because of nausea. Overcorrection was not observed. CONCLUSION: Our data show that urea is an effective treatment for hospitalised patients with SIADH. Distaste was a frequent side effect, but usually did not lead to early treatment discontinuation.

Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14++ monocytes.

AIMS/HYPOTHESIS: In adults, circulating inflammatory mediators and activated CD14(++) monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis of circulating inflammatory mediators, monocyte populations and their function in childhood obesity. METHODS: In lean and obese children aged 6 to 16 years (n = 96), 35 circulating inflammatory mediators including adipokines were measured. Hierarchical cluster analysis of the inflammatory mediator profiles was performed to investigate associations between inflammatory mediator clusters and clinical variables. Whole-blood monocyte phenotyping and functional testing with the toll-like receptor 4 ligand, lipopolysaccharide, were also executed. RESULTS: First, next to leptin, the circulating mediators chemerin, tissue inhibitor of metalloproteinase 1, EGF and TNF receptor 2 were identified as novel inflammatory mediators that are increased in childhood obesity. Second, cluster analysis of the circulating mediators distinguished two obesity clusters, two leanness clusters and one mixed cluster. All clusters showed distinct inflammatory mediator profiles, together with differences in insulin sensitivity and other clinical variables. Third, childhood obesity was associated with increased CD14(++) monocyte numbers and an activated phenotype of the CD14(++) monocyte subsets. CONCLUSIONS/INTERPRETATION: Inflammatory mediator clusters were associated with insulin resistance in obese and lean children. The activation of CD14(++) monocyte subsets, which is associated with increased development of atherosclerosis in obese adults, was also readily detected in obese children. Our results indicate that inflammatory mechanisms linking obesity to its metabolic and cardiovascular complications are already activated in childhood obesity.

Pathways of problem behaviors from childhood to adolescence.

OBJECTIVE: the purpose of this study was to determine the 6-year longitudinal course of psychiatric disorders in children from the general population commencing at age 4 to 11 years. METHOD: three groups of children were selected on the basis of Child Behavior Checklist ratings obtained at 2-year intervals: "persisters," "decreasers," and "increasers." Selected subjects and their parents were clinically interviewed, and DSM-III-R diagnoses were derived. RESULTS: the majority of children whose overall level of psychopathology persisted over time obtained lifetime DSM-III-R diagnoses classified as externalizing: attention-deficit hyperactivity disorder, oppositional disorder, or conduct disorder. The majority of children whose overall level of psychopathology decreased obtained lifetime DSM-III-R diagnoses classified as internalizing: anxiety disorders, major depression, or dysthymic disorder. Children with initial Child Behavior Checklist scores in the normal range whose problem scores increased received lifetime diagnoses that were neither predominantly externalizing or internalizing. CONCLUSIONS: this study showed that the majority of initially disordered children with the poorest outcome showed aggressive or antisocial behaviors, whereas disordered children whose functioning improved had problems reflecting fearful, inhibited, or depressive behavior. The findings also showed that retrospective information on the course of children's problem behaviors should be regarded with caution.

Problem behavior in international adoptees: III. Diagnosis of child psychiatric disorders.

This study is a clinical extension of two previous epidemiological studies on problem behavior in international adoptees. In depth pictures were obtained by clinical interviews of 132 14-year-old international adoptees and their parents. Children were selected on the basis of previously obtained Child Behavior Checklist (CBCL) scores. Clinical severity ratings and DSM-III-R diagnoses were obtained. The correlations of r = 0.63 and r = 0.45 between clinical severity ratings and CBCL problem and competence scores, respectively, indicated that the results from the authors' extensive epidemiological survey and the clinical evaluation, which took place more than 10 months later, converged. The results showed that the CBCL may be used in epidemiological studies to obtain an estimate of the prevalence of psychiatric disorders in children. The 28% prevalence rate of psychiatric disorders in this sample of 14-year-old international adoptees (22% rate for girls, 36% for boys) was somewhat higher than for general population samples reported in comparable studies. Conduct disorders were elevated in the sample. The behavior of disordered adopted children was characterized by antisocial behaviors, poor relationships, and problems of affect.

The history and current status of child and adolescent psychiatric day-treatment programs in The Netherlands.

Although its history in Netherlands is a short one, day treatment for children and adolescents is in great demand and an increase in the number of centers throughout the country has been planned. It serves as both a primary and a secondary treatment modality. While the theoretical frames of reference among day units vary, psychoanalytic and systems thinking are the leading orientations. All day units operate with a multidisciplinary staff who work intensively and therapeutically with the children and their families. The day unit at Sophia Children's Hospital in Rotterdam is described as an example of an existing program.

Psychosocial aspects of childhood cancer: a review of the literature.

The literature concerning the psychosocial aspects of childhood cancer is reviewed. The emphasis of the literature is on the impact of the disease on the child and family and depicts the life-situation when faced with childhood cancer and responses to the disease. The literature strongly indicates that families experience serious difficulties and are a population at risk of developing psychosocial problems. The approach of studying the child with cancer and family is discussed and suggestions are made for future research.

Quantitative criteria for attention and activity in child psychiatric patients.

The aim was to find empirically justified criteria for attention and activity. Patients with various disorders and controls were observed during psychiatric examinations. Measures of attention increased with age, were lower in patients than controls, were correlated with each other and related to the quality of task performance. Activity measures decreased with age, were higher in patients, were correlated among each other and concerned motility as well as talking initiatives. Criteria from other studies and the DSM-III were critically examined. Inattention was not associated with hyperactivity, except in mentally retarded children. Inattention was common in many diagnostic categories.

The prevalence of nocturnal enuresis: do DSM III criteria need to be changed? A brief research report.

In this study the prevalence of nocturnal enuresis defined according to the DSM III criteria was determined in a random sample of 2070 children aged from 4 to 16 years. Nocturnal enuresis declines in prevalence with age and is more frequent in boys than in girls. Moreover, the decline in prevalence with age was found to take place earlier in girls than in boys. It is therefore argued that the DSM III age limit for enuresis should be raised to 8 years for boys.

Mental health in Dutch children: (II). The prevalence of psychiatric disorder and relationship between measures.

This study concerns the second, more clinically oriented, part of our epidemiological project. The prevalence of child psychiatric disorders in random samples of 8- and 11-year-old children is assessed by using standardized parent- and child-interviews. The relationships between different measures of child psychopathology are determined. Furthermore, additional validity measures of the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) developed by Achenbach, are provided. Of the 153 8- and 11-year-old children selected through a two-stage sampling procedure, 116 (76%) children and their parents were intensively clinically assessed. The correlation between CBCL and direct child assessment is .42, whereas the correlation between the TRF and direct child assessment is .28. The correlation between TRF and CBCL is .26. The implications of the low correlation between raters who saw children is different situations are emphasized. The weight given to reports from different sources varies with the kind of problem the child exhibits. It is concluded that more research is needed to investigate the relative value of different types of data for different conditions. Seven percent of the 8- and 11-year-olds were judged severely disordered, whereas for 26% the clinicians judged the child to be moderately or severely disordered. The high prevalence rates found in our study compared with others is partly attributed to the arbitrary nature of clinical judgement. ANOVAs and discriminant function analysis were performed to obtain those CBCL items that showed the best discrimination between children who were clinically judged disordered and children from the normative comparison group. Many items found to be good discriminators of clinical status in this study were among the best discriminators of referral status in the earlier reported part of the study. A number of family and social factors were found to be associated with psychiatric disorder. These findings support those in other studies.