Increase in Streptococcus pneumoniae serotype 3 associated parapneumonic pleural effusion/empyema after the introduction of PCV13 in Germany.

INTRODUCTION: Pediatric pneumococcal pneumonia complicated by parapneumonic pleural effusion/empyema (PPE/PE) remains a major concern despite general immunization with pneumococcal conjugate vaccines (PCVs). METHODS: In a nationwide pediatric hospital surveillance study in Germany we identified 584 children <18 years of age with bacteriologically confirmed PPE/PE from October 2010 to June 2018. Streptococcus pneumoniae was identified by culture and/or PCR of blood samples and/or pleural fluid and serotyped. RESULTS: S. pneumoniae was identified in 256 of 584 (43.8%) children by culture (n = 122) and/or PCR (n = 207). The following pneumococcal serotypes were detected in 114 children: serotype 3 (42.1%), 1 (25.4%), 7F (12.3%), 19A (7.9%), other PCV13 serotypes (4.4%) and non-PCV13 serotypes (7.9%). Between October 2010 and June 2014 serotype 1 (38.1%) and serotype 3 (25.4%) were most prevalent, whereas between July 2014 and June 2018 serotype 3 (62.7%) and non-PCV13 serotypes (15.7%) were dominant. Compared to children with other pneumococcal serotypes, children with serotype 3 associated PPE/PE were younger (median 3.2 years [IQR 2.1-4.3 years] vs. median 5.6 years [IQR 3.8-8.2 years]; p < 0.001) and more frequently admitted to intensive care (43 [89.6%] vs. 48 [73.8%]; p = 0.04). Seventy-six of 114 (66.7%) children with pneumococcal PPE/PE had been vaccinated with pneumococcal vaccines. Thirty-nine of 76 (51.3%) had received a vaccine covering the serotype detected. Thirty of these 39 breakthrough cases were age-appropriately vaccinated with PCV13 and considered vaccine failures, including 26 children with serotype 3, three children with serotype 19A and one child with serotype 1. CONCLUSION: Following the introduction of PCV13 in general childhood vaccination we observed a strong emergence of serotype 3 associated PPE/PE in the German pediatric population, including a considerable number of younger children with serotype 3 vaccine breakthrough cases and failures. Future PCVs should not only cover newly emerging serotypes, but also include a more effective component against serotype 3.

Three by three weeks of robot-enhanced repetitive gait therapy within a global rehabilitation plan improves gross motor development in children with cerebral palsy - a retrospective cohort study.

AIM: To assess the improvement in gross motor function following three blocks of a three-week, intensive robot-enhanced treadmill therapy (ROBERT-Program). METHOD: retrospective chart review in a before-after interventional trial in children with cerebral palsy attending a university hospital outpatient rehabilitation centre. Patients received three blocks of a three-week, 12 sessions ROBERT-Program over a mean period of 24 months. Outcome measures were block specific and cumulative improvement in GMFM 66, D and E. Longterm GMFM 66 improvements were compared to the individuals' expected increment as derived from previously published GMFM-66 percentiles. 95% confidence intervals (CI) and paired t-test were calculated. RESULTS: 20 children (8 GMFCS Level II; 12 GMFCS Level III, mean age 5.9 years (CI: [5.0; 6.7])) were treated. For each block a significant increase in motor performance in similar size could be observed without deterioration between blocks. The cumulative improvement during 21 months observation period was: 6.5 (CI: [4.8; 8.2]) in GMFM 66, which represents a clinically meaningful effect size of 3.6 (CI: [1.4; 5.8]) above the expected improvement. INTERPRETATION: Progressive clinically meaningful improvement in motor performance for three blocks of ROBERT-Program was observed. Cumulative GMFM 66 improvements exceeded the individuals' age-specific expected course.

Differences in maternal smoking across successive pregnancies - dose-dependent relation to BMI z-score in the offspring: an individual patient data (IPD) meta-analysis.

INTRODUCTION: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. METHODS: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. RESULTS: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses ≥25 cigarettes per day. CONCLUSIONS: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.

No further improvement in pregnancy-related outcomes in the offspring of mothers with pre-gestational diabetes in Bavaria, Germany, between 2001 and 2016.

AIMS: To investigate whether there has been further improvement in the risk of adverse outcomes in pregnancies in women with diabetes during 2008-2016 in Bavaria, Germany. METHODS: Using cross-sectional data on all 1716 170 deliveries in Bavarian hospitals between 2001 and 2016, we assessed the risks of stillbirth, early neonatal death, preterm delivery, large for gestational age, malformations, low Apgar score and low umbilical cord pH by maternal group with diabetes (gestational, pre-gestational, or none) separately for 2001-2007 and 2008-2016. We also investigated the associations of specific risk factors such as maternal smoking with respect to early mortality and malformations in each group with diabetes during 2008-2016. RESULTS: No further reduction in the risk for any adverse outcome in mothers with pre-gestational diabetes and their offspring during 2008-2016 was observed. Maternal smoking, multiple delivery and substandard antenatal care were the strongest additional predictors of both early perinatal mortality and malformations for mothers with pre-gestational diabetes. The respective risks were lower and also decreased over time for mothers with gestational diabetes. CONCLUSIONS: No significant improvement has been achieved in the management of pregnancies affected by pre-gestational diabetes during the last decade. The apparent risk reductions in women with gestational diabetes may partly be due to a change in diagnostic criteria over time. Women with pre-gestational diabetes who smoke, carry more than one child, or are not regularly seen during pregnancy, may need particular attention.

Children with migraine: Provocation of headache via pressure to myofascial trigger points in the trapezius muscle? - A prospective controlled observational study.

BACKGROUND: The objective was to evaluate a supposed clinical interdependency of myofascial trigger points and migraine in children. Such interdependency would support an interaction of spinal and trigeminal afferences in the trigemino-cervical complex as a contributing factor in migraine. METHODS: Children ≤18 years with the confirmed diagnosis of migraine were prospectively investigated. Comprehensive data on medical history, clinical neurological and psychological status were gathered. Trigger points in the trapezius muscle were identified by palpation and the threshold of pressure pain at these points was measured. Manual pressure was applied to the trigger points, and the occurrence and duration of induced headache were recorded. At a second consultation (4 weeks after the first), manual pressure with the detected pressure threshold was applied to non-trigger points within the same trapezius muscle (control). Headache and related parameters were again recorded and compared to the results of the first consultation. RESULTS: A total of 13 girls and 13 boys with migraine and a median age of 14.5 (Range 6.3-17.8) years took part in the study. Manual pressure to trigger points in the trapezius muscle led to lasting headache after termination of the manual pressure in 13 patients while no patient experienced headache when manual pressure was applied to non-trigger points at the control visit (p < 0.001). Headache was induced significantly more often in children ≥12 years and those with internalizing behavioural disorder. CONCLUSION: We found an association between trapezius muscle myofascial trigger points and migraine, which might underline the concept of the trigemino-cervical complex, especially in adolescents. SIGNIFICANCE: In children with migraine headache can often be induced by pressure to myofascial trigger points, but not by pressure to non-trigger points in the trapezius muscle. This supports the hypothesis of a trigemino-cervical-complex in the pathophysiology of migraine, which might have implications for innovative therapies in children with migraine.

[Migraine in children and adolescents-brain and muscle? : Another example of why children are not small adults]. / Migräne im Kindes- und Jugendalter ­ Gehirn und Muskel? : Warum Kinder einmal mehr keine kleinen Erwachsenen sind.

Migraine as primary headache is a life-long disease which is relevant for the quality of life and is based on complex genetics. It often starts in childhood with symptoms typical for the specific age. These show different nuances compared to the migraine symptoms in adults, for example, regarding (bilateral/unilateral) localization of the acute migraine headache. Only over the course of years-during adolescence and young adulthood-do the more specific symptoms as defined by the International Classification of Headache Disorders (ICHD 3 beta) develop. In this article we focus on the clinical specifics of children and adolescents with migraine. We elaborately refer to the trigeminocervical complex (TCC) because it forms a conceptual bridge for the understanding of migraine, for psychoeducation, and for therapeutic options. We pragmatically discuss options and limits of treatments.

[Utilization of Physiotherapy Services by Children and Adolescents - Results of the KiGGS- Baseline Survey]. / Inanspruchnahme von Physiotherapie im Kindes- und Jugendalter ­ Ergebnisse aus der KiGGS-Basiserhebung.

Aim of the study: The use of physical therapy in German children and adolescents has so far solely been analyzed on the basis of health insurance data, which can neither consider case history nor social factors. Using the KiGGS-baseline survey it is possible to examine the use of physical therapy on the basis of parental reported health problems and social factors. Methodology: Identifiable determinants for the use of physical therapy in the last 12 months in the KiGGS-baseline survey were examined bivariate and multivariate in logistic regression models with mutual adjustment. The following determinants were considered: social factors, somatic disorders and psychological abnormalities. The proportion of the use of physical therapy, which can be explained by these determinants, was estimated using population-attributable risk fraction. Results: The frequency of the use of physical therapy in the last 12 months in the 0 to 17-year-olds in the KiGGS-baseline survey was 6,4% with higher use during infancy and adolescence. The socio-economic status of parents was not associated with the use of physical therapy. A migration background decreased the probability of the use of physical therapy, for example, among children aged 0 to 2 years (ORadjusted: 0,5 [95% CI: 0,2-1,0]). In those with scoliosis, the use of physical therapy was almost twice as frequent in infancy as in adolescence (58,4 vs. 34,4%). A maximum of 15% of all children and adolescents with back pain reported the use of physical therapy. When ADHD was diagnosed at preschool age, the probability of using physical therapy was increased (ORadjusted: 5,1 [95% CI: 1,4-18,6]). The health problems, which were assessed in the KiGGS-baseline survey and considered for this analysis could explain 37% of the use of physical therapy in the 0 to 2-year-olds. In the other age groups, 59 to 62% could be explained. Conclusion: Comparison of the KiGGS-baseline survey with health insurance data shows similar frequencies and patterns of the use of physical therapy and can therefore be used for the analysis of healthcare questions on the use of physical therapy. The data point to potential deficits in treatment in population segments and for some conditions. An examination of these hypotheses based on analyses of health insurance data seems to be reasonable.

[Transition of Adolescents with Chronic Neurologic Disorders into Adult Health Care]. / Transition chronisch neurologisch kranker Jugendlicher in die Erwachsenenmedizin.

BACKGROUND: Transition of care from pediatric to adult services is a complex process. Factors influencing the success of health care transition of adolescents with chronic neurological disorders are poorly understood. METHODS: Young adults with chronic neurological disorders who had been cared for in an Interdisciplinary Pediatric Center participated in this study. Using the Patient Satisfaction Questionnaire Short-form (PSQ-18) we investigated whether satisfaction of these patients with their medical care in adult services was depending on the severity and complexity of their condition. They were assigned to a group of severely disabled patients (group 1; intellectual disability or learning disability plus motor handicap or degree of disability≥80, n=11) or a group 2 of patients with milder impairment (N=39). We used descriptive and t-statistics to compare both groups. RESULTS: Patients of group 1 reported slightly lower satisfaction with their present medical care in adult services (M=3.25; 95%-KI=[2.96-3.55]) compared to patients of group 2 (M=3.59; 95%.KI=[3.37-3.81]; p=0.084). Satisfaction with transition was significantly lower in group 1 (M=2.65; 95% KI=[2.29-3.01]) than in group 2 (M=3.11; 95% KI=[2.89-3.33], p=0.045). The difference of mean values of 0.46 reflects a moderate effect size (Hedges' g=0.68). CONCLUSION: Health care transition of adolescent patients with chronic neurological disorders is significantly more successful in patients with minor impairment compared to patients with severe complex neurological conditions.

[Utilization of Occupational Therapy in Children - Results from the KiGGS Basis Survey]. / Inanspruchnahme von Ergotherapie im Kindesalter - Ergebnisse aus der KiGGS-Basiserhebung.

BACKGROUND: A population-based analysis on use of occupational therapy by child's parentally reported health restrictions and socio-demographic determinants is missing. PATIENTS AND METHODS: The basis KiGGS survey (2003 to 2006) reports on health in 17 641 children aged 0 to 17 years. The use of occupational therapy in the last 12 months could be ticked as other therapies with a free text field to name occupational therapy or others. Health restrictions potentially relevant for the use of occupational therapy and sociodemographic factors were assessed. The proportion of use of occupational therapy explained by the health restrictions was estimated by the population attributable risk fraction. RESULTS: The average use of occupational therapy for 3 to 13-year-olds was 2.4%. There was no association with the socioeconomic status; Children with immigration background used occupational therapy less often (e. g. age group 3 to 6 years: ORadjusted 0.2 [95-% KI: 0.1-1.0]). The proportion of occupational therapy explainable by the health restrictions considered ranged from 45% (3 to 6 years) to 65% (11 to 13 years). DISCUSSION: The lower use of occupational therapy in the KiGGS survey compared to health insurance reports may be explained by the ascertainment method. A lower use of occupational therapy related to immigration background matches lower use for physician visits. CONCLUSION: The causes for the low proportion of explained occupational therapy in young children and the lower use in children with immigration background warrant further research.

Latent class analysis of diagnostic tests for adenovirus, Bordetella pertussis and influenza virus infections in German adults with longer lasting coughs.

Laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. While the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus A and B infections is unclear. A sentinel study into the population-based incidence of longer lasting coughs in adults was done in Rostock (former East Germany) and Krefeld (former West Germany). A total of 971 outpatients who consulted general practitioners or internists were included. Inclusion criteria were coughing for ⩾1 week and no chronic respiratory diseases. We evaluated the performance of polymerase chain reaction (PCR) as well as IgG and IgA serology, applying a latent class model for diagnosing infections with adenovirus, B. pertussis, and influenza virus A and B. The adult outpatients first sought medical attention when they had been coughing for a median of 3 weeks. In this situation, direct detection of infectious agents by PCR had a low sensitivity. Modelling showed that additional serological tests equally improved sensitivity and specificity for diagnosis for adenovirus, B. pertussis and influenza virus A and B infections. The combination of serology and PCR may improve the overall performance of diagnostic tests for B. pertussis and also for adenovirus, and influenza virus A and B infections.

Obtaining a genetic diagnosis in a child with disability: impact on parental quality of life.

Recent progress in genetic testing has facilitated obtaining an etiologic diagnosis in children with developmental delay/intellectual disability (DD/ID) or multiple congenital anomalies (MCA) or both. Little is known about the benefits of diagnostic elucidation for affected families. We studied the impact of a genetic diagnosis on parental quality of life (QoL) using a validated semiquantitative questionnaire in families with a disabled child investigated by array-based comparative genomic hybridization (aCGH). We received completed questionnaires from 95 mothers and 76 fathers of 99 families. We used multivariate analysis for adjustment of potential confounders. Taken all 99 families together, maternal QoL score (percentile rank scale 51.05) was significantly lower than fathers' QoL (61.83, p = 0.01). Maternal QoL score was 20.17 [95% CI (5.49; 34.82)] percentile rank scales higher in mothers of children with diagnostic (n = 34) aCGH as opposed to mothers of children with inconclusive (n = 65) aCGH (Hedges' g = 0.71). Comparison of these QoL scores with retrospectively recalled QoL before aCGH revealed an increase of maternal QoL after diagnostic clarification. Our results indicate a benefit for maternal QoL if a genetic test, here aCGH, succeeds to clarify the etiologic diagnosis in a disabled child.

Impact of 10- and 13-valent pneumococcal conjugate vaccines on incidence of invasive pneumococcal disease in children aged under 16 years in Germany, 2009 to 2012.

We assessed the impact of 10-valent and 13-valent pneumococcal vaccines (PCV10 and PCV13), which were introduced in Germany in 2009, on the incidence of meningitis and non-meningitis invasive pneumococcal disease (IPD) in children aged under 16 years in a population previously vaccinated with a seven-valent vaccine (PCV7). Surveillance of IPD (isolation of Streptococcus pneumonia from a normally sterile body site) is based on data from two independent reporting sources: hospitals and laboratories. IPD incidence was estimated by capture-recapture analysis. Incidence rate ratios (IRRs) were calculated for 2009 and 2012, thus comparing pre- and post-PCV10 and PCV13 data. IPD incidence caused by serotypes included in PCV13 decreased in all age and diagnosis groups. A rise in non-vaccine serotype incidence was seen only in children aged under two years. The overall impact varied by age group and infection site: for meningitis IPD in children aged under 2, 2-4 and 5-15 years, incidence changed by 3% (95% CI: -31 to 52), -60% (95% CI: -81 to -17) and -9% (95% CI: -46 to 53), respectively. A more pronounced incidence reduction was observed for non-meningitis IPD: -30% (95% CI: -46 to -7), -39% (95% CI: -54 to -20) and -83% (95% CI: -89 to -73) in children aged under 2, 2-4 and 5-15 years, respectively. A higher tropism of the additional serotypes for non-meningitis IPD may be a potential explanation. The heterogeneous findings emphasise the need for rigorous surveillance

Alterations in the trapezius muscle in young patients with migraine--a pilot case series with MRI.

BACKGROUND/PURPOSE: Migraine is frequent in young adults and adolescents and often associated with neck muscle tension and pain. Common pathophysiological pathways, such as reciprocal cervico-trigeminal activation, are assumed. Tense areas within the neck muscles can be clinically observed many patients with migraine. The aim of this pilot case study was to visualize these tense areas via magnet resonance imaging (MRI). METHODS: Three young patients with migraine were examined by an experienced investigator. In all three patients tense areas in the trapezius muscles were palpated. These areas were marked by nitroglycerin capsules on the adjacent skin surface. RESULTS: The MRI showed focal signal alterations at the marked locations within the trapezius muscles. CONCLUSION: Visualization of palpable tense areas by MRI may be usefully applied in the future to help elucidate the underlying pathophysiological processes of migraine.

Headache cessation by an educational intervention in grammar schools: a cluster randomized trial.

BACKGROUND AND PURPOSE: Headache is a common health problem in adolescents. There are a number of risk factors for headache in adolescents that are amenable to intervention. The aim of the study was to assess the effectiveness of a low-level headache prevention programme in the classroom setting to prevent these risk factors. METHODS: In all, 1674 students in 8th-10th grade at 12 grammar schools in greater Munich, Germany, were cluster randomized into intervention and control groups. A standardized 60-min prevention lesson focusing on preventable risk factors for headache (physical inactivity, coffee consumption, alcohol consumption and smoking) and providing instructions on stress management and neck and shoulder muscle relaxation exercises was given in a classroom setting. Seven months later, students were reassessed. The main outcome parameter was headache cessation. Logistic regression models with random effects for cluster and adjustment for baseline risk factors were calculated. RESULTS: Nine hundred students (intervention group N = 450, control group N = 450) with headache at baseline and complete data for headache and confounders were included in the analysis. Headache cessation was observed in 9.78% of the control group compared with 16.22% in the intervention group (number needed to treat = 16). Accounting for cluster effects and confounders, the probability of headache cessation in the intervention group was 1.77 (95% confidence interval = [1.08; 2.90]) higher than in the control group. The effect was most pronounced in adolescents with tension-type headache: odds ratio = 2.11 (95% confidence interval = [1.15; 3.80]). CONCLUSION: Our study demonstrates the effectiveness of a one-time, classroom-based headache prevention programme.

[Modifiable risk factors for primary headache. A systematic review]. / Potenziell vermeidbare Risikofaktoren für primäre Kopfschmerzen. Ein systematischer Review.

BACKGROUND: Strategies to prevent primary headaches could be very beneficial, especially given that primary headaches can lead to the development of chronic headache. In order to establish headache prevention strategies, the modifiable risk factors for primary headaches need to be identified. MATERIAL AND METHODS: A systematic literature search on the risk factors for primary headaches was conducted independently by two persons using the databases MEDLINE and Embase. Further inclusion criteria were observational studies in adult general populations or case-control studies, where the effect sizes were reported as odds ratios or where the odds ratios could be calculated from the given data. RESULTS: In all, 24 studies were included in the analysis. There was a large amount of heterogeneity among the studies concerning headache acquisition, headache classification, and risk factors for headache development. Independent of headache trigger and definition of headache, the association between headache and the risk factor "stress" was very high: The meta-analysis shows an overall effect of 2.26 (odds ratio; 95 %-CI = [1.79; 2.85]). Studies evaluating neck and shoulder pain also report a strong association with headache; however, these results could not be summarized in a meta-analysis. Equally, the overall effects of smoking and coffee consumption on headaches could not be verified because the effect sizes were rather small and predominantly noticeable only at higher doses. CONCLUSION: A strong association between headache and the risk factors stress and neck and shoulder pain was confirmed. The effect sizes of smoking and coffee consumption on headaches were rather small.

Prediction of excessive gestational weight gain from week-specific cutoff values: a cohort study.

OBJECTIVE: To assess the prognostic validity of the Institute of Medicine/National Research Council (IOM/NRC) week-specific cutoff values for inadequate or excessive total gestational weight gain (GWG) by 4-week intervals. STUDY DESIGN: We merged data from two German cohorts (LMU cohort (all maternal-weight categories) and PEACHES cohort (obese women)) to provide information on GWG for 749 women (365 normal weight, 199 overweight and 185 obese). We calculated the prognostic values for suboptimal and excessive GWG according to the IOM/NRC cutoff values. RESULT: The positive predictive values for excessive total GWG for those who experienced excessive GWG early in pregnancy was 70.1% (95% confidence interval (CI) 60.5; 78.6) as of week 12/1 to 16/0 in normal-weight women, 89.5% (95% CI 75.2; 97.1) and 95.2 (76.2; 99.9) 95.2% (95% CI 76.2; 99.9) as of week 8/1 to 12/0 for overweight and obese women, respectively. In absence of excessive GWG as of week 12/1 to 16/0, normal-weight women had 77.5% (95% CI 77.1; 83.1) probability of not experiencing excessive total GWG (negative predictive value). In overweight and obese women, the negative predictive value was considerably lower up to week 24/1 to 28/0 (60.0% (95% CI 48.8; 70.5) in week 20/1 to 24/0 and 50.6% (95% CI 39.3; 61.9) in week 24/1 to 28/0). Most women with inadequate GWG in the first and second trimester had adequate total final GWG (positive predictive value for total inadequate GWG <50% up to week 16/1 to 20/0 in all groups). CONCLUSION: As women with excessive weight gain can be identified with high confidence if the GWG exceeds the IOM/NRC week-specific cutoff values, interventions may be initiated early in pregnancy.