Migraine and the development of additional psychiatric and pain disorders in the transition from adolescence to adulthood.

INTRODUCTION: The transition from childhood to adolescence and from adolescence to adulthood are vulnerable phases in life. In these phases, late or insufficient treatment of diseases may lead to chronification and favor development of additional disorders. In adolescents, migraine often has a highly negative impact on school performance and everyday life. The hypothesis of the present study was that adolescents with migraine have a higher risk for developing additional disorders such as psychiatric disorders or other pain syndromes in the course of the disease. MATERIALS AND METHODS: In this study, we analyzed health insurance data of 56,597 German adolescents at the age of 15 years in the year 2006. By using the International Classification of Diseases (ICD 10), we determined a group with migraine diagnosis in the year 2006 and a control group without any headache diagnosis in 2006. We then compared both groups regarding the development of additional disorders (based on the ICD 10) during the following 10 years (2007 to 2016). RESULTS: Adolescents with migraine had a 2.1 fold higher risk than persons without migraine diagnosis to develop an additional affective or mood disorder, a 1.8 fold higher risk to obtain neurotic, stress-related and somatoform disorders, a 1.8 fold higher risk to subsequently suffer from behavioral syndromes, a 1.6 higher risk to get back pain and a 1.5 fold higher risk for irritable bowel syndrome during the next 10 years. CONCLUSION: Adolescents with migraine are at risk for developing additional disorders later. Considering and addressing the patient's risks and potential medical and psychosocial problems might improve the long-term outcome significantly.

Comparison of a pediatric practice-based therapy and an interdisciplinary ambulatory treatment in social pediatric centers for migraine in children: a nation-wide randomized-controlled trial in Germany: "moma - modules on migraine activity".

BACKGROUND: Migraine is common in childhood, peaks in adolescents and persists into adulthood in at least 40% of patients. There is need for early interventions to improve the burden of disease and, if possible, reduce chronification. The aim of the project is to compare two types of ambulatory treatment strategies regarding their effect on headache days and quality of life in 6 to 11 year old children with migraine: 1) the routine care in pediatricians' practices (intervention group A) and 2) a structured interdisciplinary multimodal intervention administered at social pediatric centers (intervention group B). METHODS: The study is a nation-wide cluster-randomized study. Based on the postal codes the regions are randomly assigned to the two intervention-strategies. Children with migraine are recruited in the pediatric practices, as common outpatient-care in the German health-care system. Parents rate headache frequency, intensity and acute medication intake at a daily basis via a digital smartphone application specifically designed for the study. Migraine-related disability and quality of life are assessed every 3 months. Study duration is 9 months for every participant: 3 months of baseline at the pediatric practice (both groups); 3 months of intervention at the pediatric practice (intervention group A) or at the social pediatric center (intervention group B), respectively; 3 months of follow-up at the pediatric practice (both groups). DISCUSSION: Results of the planned comparison of routine care in pediatric practices and interdisciplinary social pediatric centers will be relevant for treatment of children with migraine, both for the individual and for the health care system. TRIAL REGISTRATION: The study was approved by the ethics committee at the Ludwig-Maximilians-University Munich (number 18-804) and was retrospectively registered on 27 April 2021 in the WHO approved German Clinical Trials Register (number DRKS00016698 ).

[Decrease in Group B Streptococcal Infections in Neonates: Analysis of Health Insurance Data 2005 to 2017]. / Rückgang von Infektionen durch Streptokokken der Gruppe B bei Neugeborenen: Analyse von Krankenversicherungsdaten 2005 bis 2017.

BACKGROUND: In the German guidelines for prophylaxis of group B streptococcal (GBS) early onset sepsis in neonates (EOS), GBS screening of all pregnant women has been recommended, but is not yet included in the Maternity Directives. Aim of the study was to identify temporal trends in incidence of EOS and their association to GBS Screening. METHODS: The analysis based on health insurance data of the statutory health insurance provider Barmer from 2005 to 2017 of 313,385 mother-child pairs. Annual frequency of GBS infections in newborns was determined by ICD-10 P36.0. The frequency of maternal GBS colonization was indicated by ICD-10 B95.1, which was used as surrogate for GBS screening. Temporal trends of the risk of EOS in neonates were assessed in logistic regression models. Pearson's correlation coefficient of EOS incidence and the surrogate marker for maternal GBS colonization was calculated. RESULTS: The risk of EOS in neonates caused by GBS has decreased annually by 9.3%, resulting in an overall decrease in the observation period of 72.0%. There was no statistical significant change in the risk for LOS (Late Onset Sepsis). The decrease of EOS could not be explained by temporal changes in Caesarian section, risk factors or preterm delivery. The 3.5 fold increase in the proportion of mothers with documented positive GBS colonization in the same period correlated inversely with the incidence of EOS (r=- 0.75; p=0.002). CONCLUSION: The decrease of EOS in neonates caused by GBS in Germany and the unchanged risk of LOS in neonates may be explained by the increasing application of the GBS Screening in pregnant women.

Total health insurance costs in children with a migraine diagnosis compared to a control group.

BACKGROUND: Health care costs of migraine constitute a major issue in health economics. Several publications analyzed health care costs for adult migraine patients, based on questionnaires or secondary (health insurance) data. Although migraine often starts already in primary school age, data on migraine related costs in children is scarce. In this paper we aimed to assess the migraine-related health care costs in 6 to 11 year old children in Germany. METHODS: Using claims data of a large German health insurer (BARMER), overall annual health care costs of 6 to 11 year old children with a diagnosis of migraine in 2017 (n = 2597) were compared to a control group of 6 to 11 year old children without a headache diagnosis between 2013 and 2017 (n = 306,926). The association of migraine and costs was modeled by generalized linear regression (Gamma regression) with adjustment for sex, age and comorbidities. RESULTS: Children with migraine caused considerably higher annual per capita health care costs than children without a headache diagnosis (migraine group: € 1018, control group: € 618). Excess costs directly related to migraine amounted to € 115. The remaining excess costs were related to comorbidities, which were more frequent in the migraine group. Mental and behavioural disorders constituted the most expensive comorbidity, accounting for € 105 of the € 400 annual excess costs in the migraine group. CONCLUSION: 6 to 11 year old children with a migraine diagnosis cause significant direct and comorbidity related excess costs in the German health care system.

Do pre-school episodic syndromes predict migraine in primary school children? A retrospective cohort study on health care data.

OBJECTIVE: To assess the relative risk, predictive value and population attributable risk fraction of pre-school episodic syndromes for later migraine in primary school age children. METHODS: This retrospective cohort study used health insurance data on 55,035 children born in 2006 with no diagnosis of migraine up to the age of 5 years. The relative risk, probability and population attributable risk fraction of migraine prompting a physician visit at the age of 6-10 years in children with episodic syndromes included in the International Classification of Headache Disorders (benign paroxysmal torticollis, benign paroxysmal vertigo, cyclic vomiting syndrome, recurrent abdominal symptoms and abdominal migraine) and those not included in the International Classification of Headache Disorders (pavor nocturnus, somnabulism and bruxism) diagnosed up to the age of 5 years were determined. RESULTS: The period prevalence of individual episodic syndromes ranged between 0.01% and 1.40%. For episodic syndromes included in the International Classification of Headache Disorders (recurrent abdominal symptoms and abdominal migraine) and for the episodic syndromes not included in the International Classification of Headache Disorders (somnambulism), the risk for later migraine was increased by factors of 2.08, 21.87 and 3.93, respectively. The proportion of risk for migraine in primary school children explained by any episodic syndromes included in the International Classification of Headache Disorders was 2.18% and for any episodic syndromes not included in the International Classification of Headache Disorders it was 0.59%. CONCLUSION: Several pre-school episodic syndromes are risk factors for migraine in primary school age children. The fraction of migraine in primary school age children explained by prior episodic syndromes, however, is below 3%. A probability to develop primary school age migraine above 50% was only observed for abdominal migraine.

Age- and sex-specific first health care use for migraine in 2016 in children and adolescents from prospectively collected health insurance data in Germany.

BACKGROUND: Migraine in children and adolescents is associated with significant disability and a high risk of persistence into adulthood. OBJECTIVE: Data on migraine incidence in children and adolescents are few and relatively coarse. To tailor interventions starting shortly after disease onset, detailed information on age- and sex-specific incidence of migraine in children and adolescents is needed. METHODS: We used health care data prospectively collected by the BARMER statutory health insurance, representing ∼11% of the German population. The incidence of migraine diagnoses (International Classification of Diseases (ICD)-10 code G43) in the year 2016 was assessed in subjects aged 0-19 years, who had been continuously insured with the BARMER between 2005 and 2016 or during their entire lifespan. RESULTS: Data from ∼1.2 million children and adolescents were available. The incidence of migraine diagnoses steadily increased with age, reaching ∼1% per year around the age of 10 for both sexes, and 3.49% per year in females and 1.72% per year in males at the age of 19. Incidences in males and females were similar up to the age of 13 and higher in females from there on. The proportion of incident migraine diagnoses specified as "definite" versus "probable" migraine increased with age. CONCLUSION: The present study provides a representative estimation of the first documented health care use for migraine in children and adolescents in Germany within 1-year age bins, separately for boys and girls. These data will be helpful for tailoring early healthcare interventions to reduce disability and prevent migraine chronification.

Glucocorticoid receptors α and ß are modulated sex specifically in human placentas of intrauterine growth restriction (IUGR).

PURPOSE: The objective of this study was to analyze the expression of the glucocorticoid receptor (GR) subtypes GRα and GRß in placentas affected by intrauterine growth restriction (IUGR). METHODS: We analyzed the sex-specific placental expression of GRα and GRß in 23 IUGR and 40 control placentas using immunohistochemistry and immunofluorescence. The GR gene, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1), mRNA production in trophoblast-like cell line BeWo after stimulation with prednisolone was analyzed using quantitative polymerase chain reaction (qPCR) and on the protein level using western blot analysis. RESULTS: GR subtypes showed a sex-specific upregulation in placentas from IUGR compared to control placentas. An increased expression of GRα was detectable in female placental tissue, whereas GRß was increased in males. CONCLUSION: Our data support previous findings suggesting that the glucocorticoid metabolism plays a role in the pathophysiology of IUGR. Furthermore, the data suggest that the underlying molecular mechanisms differ between male and female cases.

Late-pregnancy dysglycemia in obese pregnancies after negative testing for gestational diabetes and risk of future childhood overweight: An interim analysis from a longitudinal mother-child cohort study.

BACKGROUND: Maternal pre-conception obesity is a strong risk factor for childhood overweight. However, prenatal mechanisms and their effects in susceptible gestational periods that contribute to this risk are not well understood. We aimed to assess the impact of late-pregnancy dysglycemia in obese pregnancies with negative testing for gestational diabetes mellitus (GDM) on long-term mother-child outcomes. METHODS AND FINDINGS: The prospective cohort study Programming of Enhanced Adiposity Risk in Childhood-Early Screening (PEACHES) (n = 1,671) enrolled obese and normal weight mothers from August 2010 to December 2015 with trimester-specific data on glucose metabolism including GDM status at the end of the second trimester and maternal glycated hemoglobin (HbA1c) at delivery as a marker for late-pregnancy dysglycemia (HbA1c ≥ 5.7% [39 mmol/mol]). We assessed offspring short- and long-term outcomes up to 4 years, and maternal glucose metabolism 3.5 years postpartum. Multivariable linear and log-binomial regression with effects presented as mean increments (Δ) or relative risks (RRs) with 95% confidence intervals (CIs) were used to examine the association between late-pregnancy dysglycemia and outcomes. Linear mixed-effects models were used to study the longitudinal development of offspring body mass index (BMI) z-scores. The contribution of late-pregnancy dysglycemia to the association between maternal pre-conception obesity and offspring BMI was estimated using mediation analysis. In all, 898 mother-child pairs were included in this unplanned interim analysis. Among obese mothers with negative testing for GDM (n = 448), those with late-pregnancy dysglycemia (n = 135, 30.1%) had higher proportions of excessive total gestational weight gain (GWG), excessive third-trimester GWG, and offspring with large-for-gestational-age birth weight than those without. Besides higher birth weight (Δ 192 g, 95% CI 100-284) and cord-blood C-peptide concentration (Δ 0.10 ng/ml, 95% CI 0.02-0.17), offspring of these women had greater weight gain during early childhood (Δ BMI z-score per year 0.18, 95% CI 0.06-0.30, n = 262) and higher BMI z-score at 4 years (Δ 0.58, 95% CI 0.18-0.99, n = 43) than offspring of the obese, GDM-negative mothers with normal HbA1c values at delivery. Late-pregnancy dysglycemia in GDM-negative mothers accounted for about one-quarter of the association of maternal obesity with offspring BMI at age 4 years (n = 151). In contrast, childhood BMI z-scores were not affected by a diagnosis of GDM in obese pregnancies (GDM-positive: 0.58, 95% CI 0.36-0.79, versus GDM-negative: 0.62, 95% CI 0.44-0.79). One mechanism triggering late-pregnancy dysglycemia in obese, GDM-negative mothers was related to excessive third-trimester weight gain (RR 1.72, 95% CI 1.12-2.65). Furthermore, in the maternal population, we found a 4-fold (RR 4.01, 95% CI 1.97-8.17) increased risk of future prediabetes or diabetes if obese, GDM-negative women had a high versus normal HbA1c at delivery (absolute risk: 43.2% versus 10.5%). There is a potential for misclassification bias as the predominantly used GDM test procedure changed over the enrollment period. Further studies are required to validate the findings and elucidate the possible third-trimester factors contributing to future mother-child health status. CONCLUSIONS: Findings from this interim analysis suggest that offspring of obese mothers treated because of a diagnosis of GDM appeared to have a better BMI outcome in childhood than those of obese mothers who-following negative GDM testing-remained untreated in the last trimester and developed dysglycemia. Late-pregnancy dysglycemia related to uncontrolled weight gain may contribute to the development of child overweight and maternal diabetes. Our data suggest that negative GDM testing in obese pregnancies is not an "all-clear signal" and should not lead to reduced attention and risk awareness of physicians and obese women. Effective strategies are needed to maintain third-trimester glycemic and weight gain control among otherwise healthy obese pregnant women.

Incidence trends of parapneumonic pleural effusions/empyema in children 2009 to 2018 from health insurance data: Only temporal reduction after the introduction of PCV13.

BACKGROUND: Recently, emergence of a higher proportion of serotype 3 in children with parapneumonic pleural effusion/empyema (PPE/PE) were observed in Germany despite general immunization with 13-valent pneumococcal conjugate vaccine (PCV13) since 2009. The impact of PCV13 on the overall incidence of PPE/PE in children is unclear. METHODS: Annual incidence of PPE/PE in children were determined using secondary health care data for 2009-2018, provided by the Barmer statutory health insurer, serving about 11% of the German population. Temporal trends of the annual incidence were modelled applying generalized additive models. RESULTS: Overall incidence of PPE/PE in children ( ≤18 years) in the ten-year observation period was 18.17 per 100,000. The 0-1 year olds showed the highest incidence (43.09 per 100 000). PPE/PE incidence decreased from 2009 until 2013 (nadir 2013 was 15.36; 95% CI: 13.41-17.31). Since 2013, the data show an annual increase. The nadir of incidence for the 2-5 year olds (15.85; 95% CI: 11.27-20.43) and the 6-18 year olds (12.29; 95% CI: 10.23-14.36) was also in 2013, whereas for the 0-1 year olds it was found in 2014 (32.66; 95% CI: 23.79-41.54). The GAM across all age groups showed a nearly U-shaped curve between time and incidence of PPE/PE by calendar year (p-non-linear = 0.0017). The model confirms the nadir in the year 2013. DISCUSSION: We found a nonlinear temporal trend of PPE/PE incidence in children with a decrease from 2009 to 2013 and a subsequent increase until 2018. The former might be explained by a quasi elimination of serotype 1, the latter by an increase in the proportion of serotype 3 as demonstrated in German surveillance data of pediatric PPE/PE cases generated during the same observation period.

Age and sex specific incidence for depression from early childhood to adolescence: A 13-year longitudinal analysis of German health insurance data.

BACKGROUND: Epidemiological studies indicate a disproportionate increase of depression incidence among adolescent girls, compared with boys. Since results regarding the age of onset of this sex difference are heterogeneous, this study aimed to investigate this difference on a large and representative sample. A second investigation sought to clarify whether there is a relevant sex difference in prepubertal onset of depression regarding the further course. METHODS: Health insurance data of 6-18-year-old Barmer insured patients, representing a 7.9% sample of the German population born in 1999 (N = 61.199), were analyzed. The incidence of depression episodes (ICD-10 F32.x) was evaluated. Subsequently, the absolute and relative risk of a depression diagnosis (F32.x/F33.x) in early/late adolescence was analyzed based on the diagnosis of depression in primary school age in unstratified and stratified univariate analyses performed in SAS. RESULTS: From 13 years of age, we found a significantly higher incidence of depressive disorders in girls than in boys. More than a fifth of the children with a depression diagnoses in primary school age had a depression relapse in early or late adolescence (early: 23.2%; 95% CI 19.6-26.9/late: 22.9%; 95% CI 19.3-26.5). Boys with depression in primary school age have a significantly higher relative risk for a depression relapse in late adolescence than girls (boys RR 4.2, 95% CI 3.3-5.2, girls RR: 2.1, 95% CI 1.7-2.7). LIMITATIONS: The analysis is based on administrative data. Low sensitivity for depression in primary care setting and low service utilization leads to an underestimation of the incidence. CONCLUSIONS: During puberty the risk for a first depressive episode increases more steeply in girls than in boys. Childhood depression has a high risk of relapse for both sexes, but is much more pronounced for boys.

Sex-specific epigenetic gene activation profiles are differentially modulated in human placentas affected by intrauterine growth restriction.

BACKGROUND: The purpose of this study was to investigate the sex specific expression of histone protein modifications responsible for rapid gene expression in IUGR placentas. PATIENTS AND METHODS: We screened for fetal sex-specific expression of the histone proteins H3K4me3 and H3K9ac in 23 IUGR and 40 control placentas via immunohistochemistry. The trophoblast-like cell line BeWo was used in order to analyze a potential effect of stimulation with prednisolone on H3K4me3 and H3K9ac in vitro. Calculating regression models with additional adjustment for potential confounders were used. RESULTS: A significantly decreased level of H3K4me3 was detectable in female syncytiotrophoblasts, whereas H3K9ac was reduced predominantly in male extravillous throphoblast (EVT). No association to the gestational age existed. CONCLUSION: Our data showed a reduced expression of the histone proteins H3K4me3 (female) and H3K9ac (male) in IUGR, furthermore elevated cortisol levels may lead to a sex-specific down-regulation of histone proteins in IUGR placentas.

Mechanical Ventilation Guided by Electrical Impedance Tomography in Children With Acute Lung Injury.

OBJECTIVES: To provide proof-of-concept for a protocol applying a strategy of personalized mechanical ventilation in children with acute respiratory distress syndrome. Positive end-expiratory pressure and inspiratory pressure settings were optimized using real-time electrical impedance tomography aiming to maximize lung recruitment while minimizing lung overdistension. DESIGN: Prospective interventional trial. SETTING: Two PICUs. PATIENTS: Eight children with early acute respiratory distress syndrome (< 72 hr). INTERVENTIONS: On 3 consecutive days, electrical impedance tomography-guided positive end-expiratory pressure titration was performed by using regional compliance analysis. The Acute Respiratory Distress Network high/low positive end-expiratory pressure tables were used as patient's safety guardrails. Driving pressure was maintained constant. Algorithm includes the following: 1) recruitment of atelectasis: increasing positive end-expiratory pressure in steps of 4 mbar; 2) reduction of overdistension: decreasing positive end-expiratory pressure in steps of 2 mbar until electrical impedance tomography shows collapse; and 3) maintaining current positive end-expiratory pressure and check regional compliance every hour. In case of derecruitment start at step 1. MEASUREMENTS AND MAIN RESULTS: Lung areas classified by electrical impedance tomography as collapsed or overdistended were changed on average by -9.1% (95% CI, -13.7 to -4.4; p < 0.001) during titration. Collapse was changed by -9.9% (95% CI, -15.3 to -4.5; p < 0.001), while overdistension did not increase significantly (0.8%; 95% CI, -2.9 to 4.5; p = 0.650). A mean increase of the positive end-expiratory pressure level (1.4 mbar; 95% CI, 0.6-2.2; p = 0.008) occurred after titration. Global respiratory system compliance and gas exchange improved (global respiratory system compliance: 1.3 mL/mbar, 95% CI [-0.3 to 3.0], p = 0.026; Pao2: 17.6 mm Hg, 95% CI [7.8-27.5], p = 0.0039; and Pao2/Fio2 ratio: 55.2 mm Hg, 95% CI [27.3-83.2], p < 0.001, all values are change in pre vs post). CONCLUSIONS: Electrical impedance tomography-guided positive end-expiratory pressure titration reduced regional lung collapse without significant increase of overdistension, while improving global compliance and gas exchange in children with acute respiratory distress syndrome.

Risk of traffic accidents after onset of vestibular disease assessed with a surrogate marker.

OBJECTIVES: To determine if the risk of traffic accidents increases after disease onset in patients with acute vestibular disorders. That could provide a valid rationale for guidelines on driving restrictions. METHODS: 5,260,054 patient data (> 18 years of age) from a statutory health insurer were used to identify traffic injuries in incident cases of Menière's disease (MD) and vestibular neuritis (VN) in 2010-2013. Incident diagnoses were defined as the absence of such diagnoses in the preceding 5 years. Comparators were insured individuals with no such diagnoses throughout 2005-2017. The surrogate for traffic injuries were whiplash injuries coded in ICD-10 as diagnosis of sprain of ligaments of the cervical spine without structural changes. RESULTS: We identified 4509 incident patients with Menière's disease and 25,448 with vestibular neuritis and 5,102,655 controls with no such diagnoses throughout the observation period. The incidence of traffic injuries was increased for both vestibular disorders prior to the time point of diagnosis-MD 0.72 [0.47; 0.97] and VN 0.66 [0.56; 0.76] compared to controls (0.46 [0.46; 0.47]). The temporal course of incidence in whiplash injuries showed no increase and was 0.64 [0.41; 0.88] for MD at diagnosis and 0.73 [0.48; 0.98] after diagnosis, for VN it was 0.81 [0.70; 0.92] at diagnosis and 0.65 [0.55; 0.74] after diagnosis. CONCLUSIONS: Although these data were not originally collected to address the research question, they provide a valid body of evidence. There is no rationale for driving restrictions, which substantially interfere with the individuals' quality of life, in patients with incident MD and VN.

Failure to Predict High-risk Kawasaki Disease Patients in a Population-based Study Cohort in Germany.

BACKGROUND: Diverse scores on high-risk Kawasaki disease (KD) patients have proven a good prognostic validity in the Japanese population. However, data on non-Japanese have been inconclusive. Do the Kobayashi, Egami and Sano scores or application of up-to-date statistical methods (Random Forest) predict response to standard intravenous immunoglobulin (IVIG) therapy and the risk of persistent coronary artery aneurysm (CAA) in patients with KD in a mainly Caucasian population in Germany? METHODS: Data on 442 children (German population-based survey, 2013 and 2014) were used to assess the prognostic validity of the Kobayashi, Egami and Sano scores for being refractory to IVIG treatment and for predicting the risk of persistent CAA. Additionally, an up-to-date statistical approach (Random Forest) was applied to identify a potentially more valid score. RESULTS: A total of 301 children were eligible for assessment of their response to IVIG treatment. Among those, 177 children were followed-up for 1 year to identify persistent CAA. Although all scores were significantly associated with being refractory to IVIG (relative risk range between 2.32 and 3.73), the prognostic properties were low (likelihood ratio positive: 1.83-4.57; sensitivity in the range of 0.28-0.53). None of the scores was a significant predictor of CAA 1 year after acute illness. Application of statistical analysis such as Random Forest did not yield a more valid score. CONCLUSIONS: None of the available scores appears to be appropriate for identifying high-risk Caucasian children with KD who might need intensified therapy.

Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients.

Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist. Seasonal variations of 25-(OH)-D serum concentrations were modelled by sinusoidal regression and seasonal variability in the prevalence of relapse by cubic regression. The mean 25-(OH)-D serum concentration was 24.8ng/ml (range 8.3-140ng/ml) with peak levels of 32.2ng/ml in July/August and nadir in January/February (17.2ng/ml). The lowest modelled prevalence of relapse was in September/October (28%) and the highest modelled prevalence in March/April (47%). The nadir of 25-(OH)-D serum concentrations preceded the peak in prevalence of relapses by two months. In summary, seasonal variation of 25-(OH)-D serum levels were inversely associated with clinical disease activity in MS patients. Future studies should investigate whether vitamin D supplementation in MS patients may decrease the seasonal risk for MS relapses.

Reduction of Portion Size and Eating Rate Is Associated with BMI-SDS Reduction in Overweight and Obese Children and Adolescents: Results on Eating and Nutrition Behaviour from the Observational KgAS Study.

OBJECTIVE: Treatment of paediatric obesity focuses on changes of nutrition and eating behaviour and physical activity. The evaluation of the patient education programme by KgAS was utilised to analyse the association of changes of portion size, eating rate and dietary habits with BMI-SDS reductions. METHODS: Patients (n = 297) were examined at the beginning and at the end of treatment and after 1-year follow-up at different out-patient centres. Their parents completed questionnaires including estimation of children's portion size, eating rate and frequency of food intake. Associations of 1- and 2-year changes in BMI-SDS and behaviour were calculated for patients with complete data in BMI-SDS, portion size, eating rate, frequency of green, yellow and red food intake (n = 131) by multiple linear regression models. RESULTS: Significant changes were found in the desired direction for BMI-SDS, portion size, eating rate and the intake of unfavourable red food items both after 1 and 2 years as well as for the consumption of favourable green food items after 1 year. Significant positive associations with BMI-SDS reduction after 1 and 2 years were detected for portion size (Cohen's f2 0.13 and 0.09) and eating rate (Cohen's f2 0.20 and 0.10), respectively. CONCLUSION: Reduced portion sizes and eating rates are associated with BMI-SDS reduction after 1 and 2 years. These findings suggest to focus on appropriate portion sizes and reduced eating rates in patient education programmes.