Simulation-based team training for healthcare professionals in pediatric departments: study protocol for a nonrandomized controlled trial.

BACKGROUND: Healthcare systems worldwide face challenges related to patient safety, quality of care, and interprofessional collaboration. Simulation-based team training has emerged as a promising approach to address some of these challenges by providing healthcare professionals with a controlled and safe environment to enhance their teamwork and communication skills. The purpose of this study protocol is to describe an intervention using simulation-based team training in pediatric departments. METHODS: Using a parallel-group, non-randomized controlled trial design, a simulation-based team training intervention will be implemented across four pediatric departments in Denmark. Another four pediatric departments will serve as controls. The intervention implies that healthcare professionals engage in simulation-based team training at a higher quantity and frequency than they did previously. Development of the intervention occurred from April 2022 to April 2023. Implementation of the intervention occurs from April 2023 to April 2024. Evaluation of the intervention is planned from April 2024 to April 2025. All simulation activity both before and during the intervention will be registered, making it possible to compare outcomes across time periods (before versus after) and across groups (intervention versus control). To evaluate the effects of the intervention, we will conduct four analyses. Analysis 1 investigates if simulation-based team training is related to sick leave among healthcare professionals. Analysis 2 explores if the simulation intervention has an impact on patient safety culture. Analysis 3 examines if simulation-based team training is associated with the treatment of critically ill newborns. Finally, Analysis 4 conducts a cost-benefit analysis, highlighting the potential return on investment. DISCUSSION: The implemented simulation-based team training intervention can be defined as a complex intervention. Following the Medical Research Council framework and guidelines, the intervention in this project encompasses feasibility assessment, planning of intervention, implementation of intervention, and rigorous data analysis. Furthermore, the project emphasizes practical considerations such as stakeholder collaboration, facilitator training, and equipment management. TRIAL REGISTRATION: Registered as a clinical trial on clinicaltrials.gov, with the identifier NCT06064045.

Treatment intensification without improved HbA1c levels in children and adolescents with Type 1 diabetes mellitus.

AIMS: To examine trends in diabetes treatment in Danish children and adolescents with Type 1 diabetes mellitus, comparing treatment intensity with metabolic outcomes in the population, and to describe the challenges of population-based registries in a clinical setting with rapidly changing treatment methods. METHODS: This observational study is based on the Danish national population registry of childhood diabetes, which includes 99% of children diagnosed with Type 1 diabetes before the age of 15 years. We included 4527 people diagnosed between 2000 and 2012. Self-monitored blood glucose measurements, insulin injections/boluses, treatment method and metabolic control quantifications were analysed and adjusted for the effects of gender and ethnicity, the combined effect of age, visit year and duration, and for the random effects of individual and hospital settings. RESULTS: Treatment was intensified via an increasing number of self-monitored blood glucose measurements and injections/boluses. More than six injections/boluses and an increased number of self-monitored blood glucose measurements were significantly associated with lower metabolic control. No reduction, however, in the overall mean HbA1c concentration was observed between 2005 [66 mmol/mol (8.2%)] and 2012 [65 mmol/mol (8.1%)]. Changed registration practices in 2009 introduced artificial jumps in data. CONCLUSIONS: Intensifying treatment alone does not lead to improved metabolic control in the overall population despite the appearance of lower HbA1c in individuals with a greater number of self-monitored blood glucose measurements and injections/boluses. The contradictory results reflect difficulties in using observational studies to predict results of intervention in the individual. Data collected from population-based registries need to be adjusted continuously to reflect changes in care.

Response to growth hormone treatment and final height in Noonan syndrome in a large cohort of patients in the KIGS database.

BACKGROUND: Noonan syndrome (NS) is an autosomal dominant inherited disease, characterized by a distinctive facial appearance, congenital heart defects, and short stature. Treatment with growth hormone (GH) is an option to enhance height, but long-term effects are still unclear. PATIENTS AND METHODS: A cohort of 402 patients (269 males, 133 females), mean age 9.7 years at start with GH, was studied within the KIGS International growth database with respect to long-term response to GH therapy and final height after GH therapy. RESULTS: At the start of GH therapy median height was -2.61 SDS (Tanner 1966 standards). Seventy-three patients who were followed longitudinally for 3 years had an increment in height SDS (Ht SDS) over the first 3 successive years of 0.54, 0.13 and 0.13, respectively. Twenty-four patients had reached their final height after 4-12 years of GH treatment. Their Ht SDS increased from a median of -3.28 to a median of -2.41 at final height. CONCLUSION: This group of patients with NS showed an early response to GH treatment, with an attenuation of this effect thereafter. At final height the median increment of final height was 0.61 SDS according to Tanner standards and 0.97 SDS according to Noonan standards. No serious side effects were reported.

Pubertal development in Danish children: comparison of recent European and US data.

Two recent epidemiological studies (PROS and NHANES III) from the USA noted earlier sexual maturation in girls, leading to increased attention internationally to the age at onset of puberty. We studied the timing of puberty in a large cohort of healthy Danish children in order to evaluate differences between USA and Denmark, as well as to look for possible secular trends in pubertal development. Healthy Caucasian children from public schools in Denmark participated in the study which was carried out in 1991-1993. A total number of 826 boys and 1,100 girls (aged 6.0-19.9 years) were included, and pubertal stages were assessed by clinical examination according to methods of Tanner. In boys testicular volume was determined using an orchidometer. We found that age at breast development 2 (B2) was 10.88 years, and mean menarcheal age was 13.42 years. Girls with body mass index (BMI) above the median had significantly earlier puberty (age at B2 10.42 years) compared with girls with BMI below the median (age at B2 11.24 years, p < 0.0001). Similarly, menarcheal age was significantly lower in girls with BMI above the median compared with girls with BMI below the median (13.12 vs. 13.70 years, p = 0.0012). In Danish boys we found that age at genital stage 2 (G2) was 11.83 years. Both sexes were significantly taller compared with data from 1964, but timing of pubertal maturation seemed unaltered. Finally, puberty occurred much later in Denmark compared with recent data from USA. We could not detect any downwards secular trend in the timing of puberty in Denmark between 1964 and 1991-1993 as seen in the US. Obesity certainly plays a role in the timing of puberty, but the marked differences between Denmark and USA cannot be attributed exclusively to differences in BMI. A possible role of other factors like genetic polymorphisms, nutrition, physical activity or endocrine disrupting chemicals must therefore also be considered. Therefore, we believe it is crucial to monitor the pubertal development closely in Denmark in the coming decades.

Cushing's disease in childhood as the first manifestation of multiple endocrine neoplasia syndrome type 1.

OBJECTIVE: To describe three cases of Cushing's disease in children with multiple endocrine neoplasia type 1 (MEN1), as clinical manifestations of MEN1 are very rare in childhood. DESIGN AND METHODS: A retrospective review of three cases of Cushing's disease diagnosed between 1997 and 1999. Genetic screening for MEN1 gene mutation was performed in each patient. RESULTS: An ACTH-secreting microadenoma was diagnosed in three children, aged 11-13 years, presenting with growth retardation and weight gain over a period of 3-4 years. All patients had successful transsphenoidal adenomectomies. Primary hyperparathyroidism was subsequently diagnosed in two of the patients, and in the monozygotic twin of one of the patients. A new mutation in the MEN1 gene (Tyr351His) was identified in two of the patients and the affected members of their families. In the third patient a de novo MEN1 gene mutation (Leu444Pro) was found. CONCLUSIONS: MEN1 has to be considered in all children with tumours of the pituitary gland, and in those presenting with primary hyperparathyroidism. The children and their families should be advised to seek genetic counselling. We suggest that careful growth records be kept for children at risk of developing inherited MEN1 and, in the event of a decelerating growth rate, further diagnostic evaluation be undertaken with regards to ACTH-secreting pituitary tumours.

Late relapse of adrenocortical carcinoma in Beckwith-Wiedemann syndrome. Clinical, endocrinological and genetic aspects.

UNLABELLED: We report on a girl with an unusual Beckwith-Wiedemann syndrome (BWS) and hemihypertrophy, who developed an adrenocortical carcinoma with atypical clinical behaviour. At 4 y of age the girls was admitted to hospital with cushingoid features, virilization, increased excretion of steroids and low serum ACTH. A right-sided adrenocortical carcinoma was removed. At age 12.5 y the cushingoid features reappeared together with a tumour in the left thigh. A CT scan of the thorax and abdomen revealed pulmonary metastasis only. Corticosteroid excretion was increased and serum ACTH level suppressed. The femoral and the pulmonary metastases were removed and histology showed adrenocortical carcinoma. Excretion of corticosteroids subsequently normalized. Meningeal and pulmonary metastases with similar histologies appeared one year later with normal hormone values. Twenty-two months after the recurrence the girl died of an intracranial metastasis. Southern blot analysis of the LITI transcript in the KvLQT1 gene in the BWS region on chromosome 11p15 revealed hypomethylation of the maternal allele. CONCLUSION: Adrenocortical carcinoma in childhood may recur years after onset and at rare sites and hormonal levels may be an insufficient indicator of small metastases.

Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in hypochondroplasia.

UNLABELLED: Hypochondroplasia is characterized by a disproportionate short stature with rhizomelic shortening of the limbs. Amino acid substitutions Asn540Lys, Asn540Thr and Ile538Val in the fibroblast growth factor receptor 3 (FGFR3) are considered to cause hypochondroplasia. In this study we examined the FGFR3 gene for the previously described hypochondroplasia mutations and the phenotype of 23 probands with clinically and radiologically diagnosed hypochondroplasia. For the phenotype comparison, the patients were divided into two groups: Group 1: hypochondroplasia with Asn540Lys substitution; Group 2: hypochondroplasia with no mutations identified so far. A three-generation family negative for the known hypochondroplasia mutations was examined with polymorphic markers flanking the FGFR1, FGFR2 and FGFR3 genes. Nine (39%) of 23 probands were found to be heterozygous for the Asn540Lys substitution. The individuals positive for the Asn540Lys substitution were significantly more disproportionate than the individuals without this mutation. In this respect, a genotype-phenotype correlation was found in our patients. However, some individuals belonging to the group without mutations identified so far showed similarly abnormal proportions. Genotyping/haplotyping in the three-generation family with hypochondroplasia showed that FGFR1, FGFR2 and FGFR3 genes were not linked to the hypochondroplasia phenotype in this family, thus further confirming the genetic heterogeneity of hypochondroplasia. CONCLUSION: Individuals with hypochondroplasia heterozygous for the Asn540Lys substitution are significantly more disproportionate than individuals without this mutation. Our study further confirms the clinical and genetic heterogeneity of hypochondroplasia.

Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone.

Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, leptin levels and various hormonal parameters were investigated in a large cohort of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a specific and sensitive RIA was developed that allowed the accurate measurement of low leptin levels in young lean children. With this assay, leptin proved to be a comparatively stable protein under common conditions of blood sampling and storage. Leptin levels increased in girls with age (r = 0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0.0001). An analysis according to pubertal stage showed a steady increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further progression of puberty that was much less pronounced in girls. Although the relative increase of leptin with BMI and percent body fat was the same in both genders, the absolute values at a given BMI or percent body fat were significantly lower in boys in late puberty and in adolescents. In boys, but not in girls, there was an inverse correlation with testosterone concentrations (r = -0.43, P < 0.0001), which explained 10.5% of the variation of leptin levels in a multiple regression model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression line of the form leptin = a*e(b*BMI) and stratifying ranges according to gender and pubertal stage. In conclusion, these data suggest that 1) plasma leptin levels increase in girls and decrease in boys after Tanner stage 2 as the pubertal development proceeds; 2) they show a significant gender difference especially in late puberty and adolescence, even after adjustment for BMI or percent body fat; 3) the lower levels in males may be explained at least in part by a suppressive effect of androgens; 4) reference ranges with BMI as the independent variable should be stratified according to gender and pubertal stage.

Abnormal ultrasonic pattern in contralateral testes in patients with unilateral testicular cancer.

Ultrasound examination and biopsy of the nonaffected testis was performed in 78 men with a unilateral testicular cancer. Each testis was measured in three planes and the volume was calculated using the formula of an ellipsoid. The ultrasonic texture of each testis was given a score ranging from 1 to 5 as follows: 1, very regular; 2, slightly irregular; 3, irregular with small echogenic points; 4, very irregular or with coarse echogenic points; and 5, irregular with demarcated areas raising suspicion of tumor. Biopsies were examined for the presence of tubules with carcinoma in situ (CIS), germinative epithelium, Sertoli cell only, and obliterations; the thickness of tubular membranes and the amount of Leydig cells were registered. The mean ultrasonic testicular volume was 12.88 ml (range 3-24 ml), which was smaller than that previously reported for normal men and larger than that previously reported for infertile men. The ultrasonic testicular volume was inversely correlated to the score. Score 4 was given to 46% of the testes (median score, 4), and the score distribution was different from that reported in normal men (median, 2) and in infertile men (median, 3). In all, 9 testes contained CIS tubules, and 8 of these were given score 4; 1 testis with CIS in only 5% of the tubules was given score 3. The predictive value of score 4 for the testis to contain CIS was 22.2%, and the predictive value of a score different from 4 that the testis would not contain CIS was 97.6%. We conclude that a large percentage of contralateral testes in men with unilateral testicular cancer have an abnormal echotexture and that CIS is most likely found in testes given score 4 by ultrasound.

[Body proportions of Danish children. Curves for sitting height ratio, subischial length and arm span]. / Kropsproportioner hos danske børn. Kurver for siddehøjde, siddehøjderatio, subiskial benloengde og armspoend.

No previous Danish growth charts have been published for sitting height, subischial leg length, armspan or the ratio of sitting height to stature. These growth charts are useful in the evaluation of dysproportional growth retardation. Foreign standards have previously been used. However, due to population-specific differences and "the secular trend", the construction of Danish growth charts was found to be appropriate. We examined 1977 children (927 boys and 1050 girls) from the Copenhagen area, aged six to 20 years. Height, sitting height and armspan were measured. Growth charts were constructed using local linear regression and smoothing of residuals. We found sitting height values in Danish children to be comparable to English and Norwegian children. Sitting height values were lower than values of Dutch children, but higher than values of Swiss and Swedish children. The extremities of Danish children were 3-4 cm longer than the extremities of English children, but Dutch children had 2-3 cm longer armspan than the Danish boys and girls. Growth charts for sitting height, sitting height ratio, subischial leg length and armspan are presented. These charts should be useful when evaluating dysproportionality in growth retarded children and when assessing the effect of growth modulating therapy in children.

Automatic needle insertion diminishes pain during growth hormone injection.

Non-compliance in children receiving growth hormone (GH) treatment is often caused by pain on injection and difficulties in administration of GH. It has been suggested that automatic needle insertion diminishes pain perception. We quantitatively measured pain intensity on injection with two prototype pens for GH administration, providing either manual or automatic sc needle insertion, using a combined visual analogue/facial scale and a five-item scale in 18 children. With the automatic pen there was a significantly lower maximum pain score compared with the manual pen (median 28.5 versus 52.0 mm) as well as a lower mean pain score (mean 13.7 versus 23.5 mm). The five-item scale revealed that automatic needle insertion was significantly less painful than manual insertion and 13 patients chose to continue treatment with the automatic pen. In conclusion, pain during GH injection can be significantly diminished by automatic needle insertion, which may improve compliance in long-term GH treatment.

The impact of gender and puberty on reference values for urinary growth hormone excretion: a study of 3 morning urine samples in 517 healthy children and adults.

Some recent studies have indicated that measurement of urinary GH (U-GH) excretion may be a useful tool for the evaluation of GH insufficiency in children with growth disorders, although some investigators are skeptical about the diagnostic value of U-GH. Most current assays are only available for specific laboratories or require time-intensive pretreatments of the specimens. This limits the possibility for many centers to compare their patients' data with others or to establish their own reference ranges for U-GH excretion. Therefore, we investigated the performance of a commercially available kit, which allows direct measurement of U-GH in untreated urine specimens. We established a reference range for the geometric mean of 3 morning urine samples in 446 healthy children and 71 adults. U-GH could be determined in all but 9 of 1526 samples (99.4%). U-GH excretion was significantly dependent on pubertal maturation (P < 0.001) and sex (P < 0.001), whereas age had no significant influence in the prepubertal group (P > 0.3). Peak values occurred in Tanner stages 3 and 4 (369 and 391 pg/h in females; 503 and 882 pg/h in males), corresponding to an age interval of 11-18 yr in boys and 9-15 yr in girls. Short collection periods (< 6 h) were related to low values for U-GH excretion (nanograms per night; P < 0.02). This time effect disappeared if U-GH excretion was expressed as picograms per h. If U-GH was related to creatinine output, there was a decrease in U-GH excretion during prepuberty, a blunting of the pubertal peak, and lower values in adults than in prepubertal children (P < 0.0002). The intraindividual variation in U-GH excretion (picograms per h) ranged from 40-61%, constituting approximately two thirds of the interindividual variation. This variation was not lowered by relating U-GH to creatinine. We conclude that the assay was suitable for measurement of U-GH excretion in virtually all healthy volunteers. Sex and pubertal stage as well as urinary volume and clock times for collection periods should be registered when establishing a reference range for U-GH excretion and applying it for clinical purposes. Our reference values may be useful for further studies of patients with GH disorders.

Ultrasonic texture and volume of testicles in infertile men.

Ultrasound scanning of the testes and surgical biopsy were performed in 95 infertile men to evaluate the use of ultrasound in male infertility. Ultrasonic testicular volume was calculated using three measurements and the formula of an ellipsoid, and the ultrasonic texture was evaluated and given a score from 1 to 5, indicating increasing degrees of irregularity. The median score was 3 (range 1-5), which was higher than previously found in normal men (median score 2; range 1-5; P < 0.0001). The ultrasonic texture score was lower in testes with a uniform pattern of 100% spermatogenic tubules compared with the rest, both for the right (P < 0.001) and for the left (P < 0.0005) testis. Texture score was correlated with the number of obliterated tubules for both testes (P < 0.001). The mean ultrasonic testicular volume of the right testis was 10.30 ml, and that of the left 10.26 ml. Both were smaller compared with the findings in normal men (P < 0.0001). Ultrasonic testicular volume was negatively correlated with texture score (P < 0.001). A positive correlation between ultrasonic volume and sperm count was seen (P < 0.001). Sperm count was negatively correlated with texture score if calculated together with data from 119 men from the general population (P < 0.001). The study shows that ultrasonic volume and texture are valuable parameters in the evaluation of infertile men.

Anthropometry in skeletal dysplasia.

Skeletal dysplasia or osteochondrodysplasia is the designation of more than 200 different disorders, that are characterized by abnormalities of the skeleton, disproportional short stature, and a variety of other problems. The underlying biochemical defect is unknown in the vast majority of skeletal dysplasias, and the diagnosis is based on radiological findings and anthropometric measurements. Despite this fact, the information on body proportions in even the more common forms of skeletal dysplasia is scarce. Patients with achondroplasia are often diagnosed shortly after birth. Linear growth is severely compromised with relatively short extremities. Head circumference is above normal and final height ranges from 115 to 145 cm in males and 112 to 137 cm in females. Individuals with hypochondroplasia may go unnoticed until puberty, at which time the growth problem becomes obvious. Sitting height to height ratio is increased, but the body disproportion may not be apparent until puberty. Final height has been reported between 118 and 165 cm. Spondyloepiphyseal and spondylometaepiphyseal dysplasias are characterized by severe impairment of growth both in trunk and extremities, and therefore the sitting height to height ratio may be normal. Final height is severely reduced and ranges from 94 to 132 cm. It is concluded that anthropometric studies of patients with skeletal dysplasia are needed. More quantitative information on body proportions may assist in the diagnostic procedure and ensure that growth promoting therapy, e.g. growth hormone, does not worsen the disproportion.

Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index.

Serum levels of insulin-like growth factor-I (IGF-I) increase with age and pubertal development. The large variation in circulating IGF-I levels in adolescence makes it difficult to use the IGF-I value of a single child in the assessment of his growth status. In addition, the interference of IGF-binding proteins in many IGF-I assays contributes to this problem. We measured IGF-I in acid-ethanol-extracted serum from 1030 healthy children, adolescents, and adults, employing a RIA that reduces interference of IGF-binding proteins by using monoiodinated Tyr31-[125I]des-(1-3)IGF-I as radioligand. Mean serum IGF-I concentrations increased slowly in prepubertal children from 80-200 micrograms/L with a further steep increase during puberty to approximately 500 micrograms/L. After puberty, a subsequent continuous fall in circulating IGF-I levels was apparent throughout adulthood to a mean of 100 micrograms/L at the age of 80 yr (P < 0.0001). Girls had maximal IGF-I levels at 14.5 yr of age, whereas boys had peak IGF-I levels 1 yr later. This is almost 2 yr later than average peak height velocity. The large variation in serum IGF-I levels during puberty was diminished when data were separated according to sex and Tanner stage of puberty. Interestingly, we found a significant variation with age within the Tanner stages; there was an increase in serum IGF-I concentrations with age in the early pubertal stages and a decrease in the late stages (P < 0.05). Serum IGF-I increased concomitantly with increasing testicular volume. Multiple regression analysis revealed that serum IGF-I levels predicted height velocity in the following year (r = 0.33; P < 0.0001). Body mass index did not correlate significantly with serum IGF-I in prepubertal children in a multiple regression analysis. In conclusion, there was a significant variation in serum IGF-I levels with age within a given Tanner stage of puberty in addition to the well known increase with increasing age or pubertal stage. Accordingly, the effects of sex, age, and puberty on serum IGF-I cannot be separated into simple additive components when studying 1030 children in a cross-sectional design. Thus, the age-, sex-, and puberty-corrected IGF-I values may, in fact, improve the use of serum IGF-I as a diagnostic tool to distinguish between a child with retarded puberty and a GH-deficient individual.

Serum concentrations of type I and III procollagen propeptides in healthy children and girls with central precocious puberty during treatment with gonadotropin-releasing hormone analog and cyproterone acetate.

Serum levels of type I and III procollagen propeptides (s-PICP and s-PIIINP) were measured in 466 healthy school children and in 23 girls with central precocious puberty (CPP) during GnRH analog and cyproterone acetate therapy, using two commercially available RIAs. In normal children, s-PICP and s-PIIINP changed significantly with age and pubertal development stages. For s-PIIINP, a peak was seen at 12 yr for girls and 13 yr for boys; no peak could be discerned for s-PICP. The prepubertal (Tanner stage 1) s-PICP value (mean +/- SD) for girls was 374 +/- 132 micrograms/L, the midpubertal value (stage 3) was 442 +/- 135 micrograms/L, and the postpubertal value (stage 5) was 203 +/- 103 micrograms/L. The mean s-PIIINP levels for girls were 9.1 +/- 2.4, 15.0 +/- 4.3, and 6.8 +/- 3.1 micrograms/L, respectively. For boys, levels were 362 +/- 119, 544 +/- 138, and 359 +/- 256 micrograms/L for s-PICP and 8.5 +/- 2.2, 14.5 +/- 5.0, and 8.6 +/- 3.8 micrograms/L for s-PIIINP (P < 0.001 for both propeptides in both boys and girls). There was, however, a large variation in normal values for both propeptides within the age groups and pubertal stages. There was a significant correlation of s-PICP and s-PIIINP levels to height velocity in girls (r = 0.35; P < 0.001 and r = 0.33; P < 0.001, respectively), while in boys, only s-PIIINP showed significant correlation to height velocity (r = 0.40; P < 0.001). In untreated girls with CPP, serum levels of s-PIIINP were elevated [PIIINP SD score (SDS), 2.13]. Levels of s-PICP were normal (PICP SDS, 0.39). Levels of both propeptides decreased within 2 months after initiation of therapy and remained below initial values (P < 0.01). The decrease in s-PIIINP after 2 months of therapy showed a significant correlation with the fall in height velocity SDS for chronological age after 6 months of therapy (r = 0.64; P < 0.01). We conclude that s-PIIINP and, to a lesser degree, s-PICP reflect growth in normal children, but due to the large variation, both propeptides seem unsuitable as markers for screening of growth disorders in children.

[Clinical assessment of acute ankle injuries in relation to the need of radiography]. / Klinisk vurdering af akutte ankelskader med henblik på behov for røntgenundersøgelse.

The object of the present investigation was to attempt to assess the value of some selected individual aspect of the clinical examination of patients with acute ankle injuries with tenderness, swelling or haematoma in the neighbourhood of the lateral malleolus. An attempt was made to investigate whether it was possible to differentiate the group of patients in whom radiographic examination of the ankle was necessary and whether this could be done with sufficient certainty on the basis of the clinical parameters examined. The results are presented in the form of calculation of the diagnostic frequencies. Absence of tenderness over the posterolateral edge of the lateral malleolus was found to be the clinical finding which could be employed to exclude fracture with greatest certainty, as the true negative diagnostic frequency was found to be 97.33 (90.70-99.68). This certainty is of the same magnitude as the certainty of previously selected criteria but the examination appears to be simpler and more objective.

Coxsackie B3 virus encephalitis in a patient with agammaglobulinaemia.

A 19-month-old boy with agammaglobulinaemia contracted a Coxsackie B3 virus infection which caused meningoencephalitis. His neurological status deteriorated over the following 4 years and he died aged 6 years. Treatment with gammaglobulin i.m. and IgG-Fab2 fragments i.v. was not effective. Enterovirus can cause life-threatening infections in immunodeficient patients.

Adrenocortical insufficiency associated with Epstein-Barr virus infection in a patient with the Wiskott-Aldrich syndrome.

A 10-year-old boy with the Wiskott-Aldrich syndrome developed adrenocortical insufficiency including typical clinical findings, low s-Na, high s-K, high p-ACTH (640 ng/l), low p-aldosterone (33-39 pmol/l), high p-renin (2300-4200 mIU/l) as well as an abnormal response to an ACTH-stimulation test. The adrenocortical insufficiency developed concomitantly with the occurrence of infectious mononucleosis diagnosed clinically and serologically. Adrenalitis caused by Epstein-Barr virus is suggested as the causative factor.