Effectiveness of alpine climate treatment for children with difficult to treat atopic dermatitis: Results of a pragmatic randomized controlled trial (DAVOS trial).

BACKGROUND: Alpine climate treatment has historically been used in Europe to treat atopic dermatitis (AD), but no randomized trials have been conducted to provide evidence for its effectiveness. OBJECTIVE: To investigate the long-term effectiveness of alpine climate treatment for children with difficult to treat AD. MATERIALS & METHODS: A pragmatic, open, randomized controlled trial was conducted. Children diagnosed with AD that was considered difficult to treat, aged between 8 and 18 years and willing to be treated in Switzerland were randomized to a six-week personalized integrative multidisciplinary treatment period in a clinical setting in the alpine climate (Switzerland) or an outpatient setting in moderate maritime climate (Netherlands). Study assessments were conducted at the Wilhelmina Children's Hospital; an electronic portal was used for the collection of questionnaire data. Primary outcomes were disease activity (SAEASI), quality of life (CDLQI) and catastrophizing thoughts (JUCKKI/JU) 6 months after intervention. Other assessments were immediately and 6 weeks after intervention. Subgroup analyses concerned asthma-related outcomes. Children were randomly assigned to either the intervention or control group using a covariate adaptive randomization method, taking age and asthma diagnosis into account. Children, parents and healthcare professionals involved in treatment were not blinded to group assignment. Data were analysed according to intention-to-treat with linear mixed-effects models for continuous outcomes. The trial is registered at Current Controlled Trials ISCRTN88136485. RESULTS: Between 14 September 2010 and 30 September 2014, 88 children were enrolled in the trial, 84 children were randomized (41 assigned to intervention, 43 to control) of whom 77 completed the intervention (38 of 41 (93%) intervention, 39 of 43 (91%) control) and 74 completed follow-up (38 of 41 (93%) intervention, 36 of 43 (84%) control). Six months after intervention there were no significant differences between the groups on disease activity (SAEASI mean difference -3.4 (95%CI -8.5 to 1.7)), quality of life (CDLQI mean difference -0.3 (95%CI -2.0 to 1.4)) and catastrophizing thoughts (JUCCKI/JU subscale mean difference -0.7 (95%CI -1.4 to -0.0)). Immediately and 6 weeks after intervention, disease activity and quality of life were significantly different in favour of alpine climate treatment. Mean differences on SAEASI were -10.1 (95%CI -14.5 to -5.8) and -8.4 (95%CI -12.2 to -4.6) and on CDLQI -1.9 (95%CI -3.3 to -0.5) and -1.5 (95%CI -2.8 to -0.3) immediately and 6 weeks after the intervention, respectively. There were no long-term differences on asthma-related outcomes. Five serious adverse events occurred during the study period, which were not thought to be related to the treatment. CONCLUSIONS & CLINICAL RELEVANCE: For children with difficult to treat AD, there was no additional long-term benefit of alpine climate treatment, in contrast to the short-term, compared to an outpatient treatment programme in moderate maritime climate, using a personalized integrative multidisciplinary treatment approach.

Cognitive and neurological outcome at the age of 5-8 years of preterm infants with post-hemorrhagic ventricular dilatation requiring neurosurgical intervention.

BACKGROUND: Preterm infants with progressive post-hemorrhagic ventricular dilatation (PHVD) in the absence of associated parenchymal lesions may have a normal neurodevelopmental outcome. OBJECTIVES: To evaluate neurodevelopmental and cognitive outcomes among preterm infants with severe intraventricular hemorrhage (IVH) and PHVD requiring neurosurgical intervention. METHODS: 32 preterm infants were admitted to a neonatal intensive care unit with PHVD requiring neurosurgical intervention, and were seen in the follow-up clinic for standardized cognitive, behavioral and neurological assessments between 5 and 8 years of age. Only preterm infants with a gestational age (GA) of <30 weeks, as well as preterm and full-term infants with PHVD and full-term infants with perinatal asphyxia are seen in our follow-up clinic at this age. There were 23 infants with a GA of <30 weeks in this study population. For these 23, matched controls were available and compared with the IVH group. RESULTS: The majority (59.4%) had no impairments. None of the children with grade III and 8 of the 15 children (53%) with grade IV hemorrhage developed cerebral palsy. More subtle motor problems assessed with the Movement-ABC score were seen in 39% (n = 9); the mean IQ of all children was 93.4, and 29% of the children had an IQ of <85 (-1 SD). Timing of intervention did not have a beneficial effect on outcome. With respect to cognition, no significant differences were found between the IVH and the control group. CONCLUSION: The majority of the children in our population had no impairments. Cerebral palsy was not seen in any of the infants with a grade III hemorrhage.

Neurodevelopmental outcome over time of preterm born children ≤750 g at birth.

BACKGROUND: Extremely low birth weight (ELBW) infants are at risk of cognitive impairment and follow-up is therefore of major importance. The age at which their neurodevelopmental outcome (NDO) can reliably be predicted differs in the literature. AIMS: To describe NDO at 2, 3.5 and 5.5 years in an ELBW cohort. To examine the value of NDO at 2 years corrected age (CA) for prediction of NDO at 3.5 and 5.5 years. STUDY DESIGN: A retrospective cross-sectional and longitudinal cohort study. SUBJECTS: 101 children with a BW≤750 g, born between 1996 and 2005, who survived NICU admission and were included in a follow-up program. OUTCOME MEASURES: NDO, measured with different tests for general development and intelligence, depending on age of assessment and classified as normal (Z-score≥-1), mildly delayed (-2≤Z-score<-1) or severely delayed (Z-score<-2). RESULTS: At 2, 3.5 and 5.5 years 74.3, 82.2 and 76.2% had a normal NDO. A normal NDO at 2 years CA predicted a normal NDO at 3.5 and 5.5 years in 92% and 84% respectively. Of the children with a mildly or severely delayed NDO at 2 years CA the majority showed an improved NDO at 3.5 (69.2%) and 5.5 years (65.4%) respectively. CONCLUSIONS: The majority of the children with a BW≤750 g had a normal NDO at all ages. A normal NDO at 2 years CA is a good predictor for normal outcome at 3.5 and 5.5 years, whereas a delayed NDO at 2 years CA is subject to change with the majority of the children showing a better NDO at 3.5 and 5.5 years.

Postnatal growth of preterm born children ≤ 750g at birth.

BACKGROUND: Extremely low birth weight (ELBW) infants are at risk of impaired postnatal growth. Impaired postnatal growth has been reported to be associated with delayed cognitive and motor development. AIMS: To describe postnatal growth patterns of appropriate and small for gestational age (AGA and SGA) ELBW children in relation to their cognitive and motor outcome at age 5.5. STUDY DESIGN: Retrospective cohort study. SUBJECTS: One hundred one children with a BW ≤ 750g, born between 1996 and 2005 in the University Hospital Utrecht, The Netherlands. OUTCOME MEASURES: Height (Ht), weight (Wt), occipital-frontal circumference (OFC) at birth, 15 months and 2 years corrected age and 3.5 and 5.5 years. Cognitive and motor outcome at 5.5 years of age, classified as normal (Z-score ≥-1), mildly delayed (-2≤Z-score <-1) or severely delayed (Z-score <-2). AGA (Ht, Wt or OFC at birth ≥-2 SDS) infants were compared with SGA (Ht, Wt or OFC at birth <-2 SDS) infants. RESULTS: Between birth and 5.5 years catch-up growth in Ht, weight for height (Wt/Ht), Wt and OFC was seen in 72.2%, 55.2%, 28.6% and 68.9% respectively of the SGA infants. For AGA infants we found substantial catch-down growth in Ht (15.4%) and Wt (33.8%). Cognitive and motor outcome was normal in 76.2% and 41.6% of the 101 children. A significantly higher percentage of normal cognitive outcome was found in AGA infants with Wt growth remaining at ≥-2 SDS compared to AGA infants with catch-down growth (83% vs 63%). Next, SGA infants who caught-up in OFC had a higher prevalence of normal cognitive outcome compared to SGA infants who did not catch-up in OFC. Furthermore, a higher percentage of severely delayed motor outcome was found in SGA infants without catch-up growth in Wt compared to SGA infants who caught-up in Wt (61.5% vs 32.2%). CONCLUSIONS: Catch-up growth in Ht, Wt/Ht and OFC occurred in the majority of the SGA infants with a BW ≤ 750 g, but was less common in Wt. AGA children who remained their Wt at ≥-2 SDS have a better cognitive and motor developmental outcome at 5.5 years of age. Catch-up growth in OFC was associated with a better cognitive outcome at 5.5 years of age.