Short communication: Persistent socio-economic inequality in frequent headache among Danish adolescents from 1991 to 2014.

BACKGROUND: The association between socio-economic status (SES) and headache among adolescents is an understudied issue, and no study has examined whether such an association changes over time. The aim was to examine trends in socio-economic inequality in frequent headache among 11- to 15-year-olds in Denmark from 1991 to 2014, using occupational social class (OSC) as indicator of SES. METHODS: The study applies data from the Danish part of the international Health Behaviour in School-aged Children (HBSC) study. HBSC includes nationally representative samples of 11-, 13- and 15-year-olds. This study combines data from seven data survey years from 1991 to 2014, participation rate 88.6%, n = 31,102. We report absolute inequality as per cent difference in frequent headache between high and low OSC and relative inequality as odds ratio for frequent headache by OSC. RESULTS: In the entire study population, 10.4% reported frequent headache. There was a significant increase in frequent headache from 8.0% in 1991 to 12.9% in 2014, test for trend, p < 0.0001. This increasing trend was significant in all OSCs. The prevalence of frequent headache was significantly higher in low than high OSC, OR = 1.50 (95% CI: 1.34-1.67). This socio-economic inequality in frequent headache was persistent from 1991 to 2014. CONCLUSION: There was a significant and persistent socio-economic inequality, i.e. increasing prevalence of frequent headache with decreasing OSC. The association between socio-economic position and headache did not significantly change over time, i.e. the statistical interaction between OSC and survey year was insignificant. SIGNIFICANCE: The prevalence of frequent headache among adolescents increases with decreasing SES. This socio-economic inequality has been persistent among adolescents in Denmark from 1991 to 2014. Clinicians should be aware of this social inequality.

Non-specific effects of BCG vaccination on morbidity among children in Greenland: a population-based cohort study.

Background: The potential non-specific effects of BCG (Bacillus Calmette-Guérin) vaccination, with reported reduction of infectious disease morbidity among vaccinated children, in addition to the protective effect against tuberculosis (TB), are highly debated. In Greenland, BCG vaccination was introduced in 1955, but temporarily discontinued from 1991 to 1996 due to nationwide policy changes. Using the transient vaccination stop, we aimed to investigate possible non-specific effects of BCG vaccination by measuring nation-wide hospitalization rates due to infectious diseases other than TB among vaccinated and unvaccinated children. Methods: A retrospective cohort study including all children born in Greenland aged 3 months to 3 years from 1989 to 2004. A personal identification number assigned at birth allowed for follow-up through national registers. Information on hospitalization due to infectious diseases was obtained from the Greenlandic inpatient register using ICD-8 and ICD-10 codes. Participants with notified TB were censored. Incidence rate ratios (IRR) were estimated using Poisson regression. Results: Overall, 19 363 children, hereof 66% BCG-vaccinated, were followed for 44 065 person-years and had 2069 hospitalizations due to infectious diseases. IRRs of hospitalization in BCG-vaccinated as compared with BCG-unvaccinated children were 1.07 [95% confidence interval (CI) 0.96-1.20] for infectious diseases overall, and specifically 1.10 (95% CI 0.98-1.24) for respiratory tract infections. Among BCG-vaccinated children aged 3 to 11 months, the IRR of hospitalization due to infectious diseases was 1.00 (95% CI 0.84-1.19) as compared with BCG-unvaccinated children. Conclusion: Our results do not support the hypothesis that neonatal BCG vaccination reduces morbidity in children caused by infectious diseases other than TB.

The effectiveness of BCG vaccination in preventing Mycobacterium tuberculosis infection and disease in Greenland.

BACKGROUND: The BCG vaccine's ability to prevent Mycobacterium tuberculosis infection (MTI) remains highly debated. In Greenland, BCG vaccination was introduced in 1955, but was temporarily discontinued (1991-1996) due to nationwide policy changes. The study aimed to use the transient stop in BCG vaccination to evaluate the effect of vaccination on MTI prevalence and TB incidence. METHODS: MTI study: A cross-sectional study (2012), comprising East Greenlanders born during 1982-2006, evaluated the effect of BCG vaccination on MTI prevalence; a positive interferon γ release assay defined an MTI case. Associations were estimated using logistic regression. TB study: a cohort study covering the same birth cohorts with follow-up until 2012 evaluated the vaccine's effect on TB incidence. A personal identifier allowed for follow-up in the TB notification system. Associations were estimated using Cox regression. RESULTS: MTI study: Included 953 participants; 81% were BCG-vaccinated; 29% had MTI, 23% among vaccinated and 57% among non-vaccinated. BCG vaccination reduced the odds of MTI, OR 0.52 (95% CI 0.32 to 0.85), p=0.01. Vaccine effectiveness against MTI was 20%. TB study: Included 1697 participants followed for 21,148 person-years. 6% were notified with TB, 4% among vaccinated and 11% among non-vaccinated. BCG vaccination reduced the risk of TB, HR 0.50 (95% CI 0.26 to 0.95), p=0.03, yielding a vaccine effectiveness of 50%. CONCLUSIONS: BCG vaccination was effective in reducing both MTI and TB disease among children and young adults in a TB high-endemic setting in Greenland.

Health status of children with cerebral palsy living in Europe: a multi-centre study.

AIM: The aim of this report is to describe the health status of 8-12-year-old children with cerebral palsy (CP) of all severities in Europe using the Child Health Questionnaire (CHQ). METHOD: A total of 818 children with CP from nine centres in defined geographical areas participated. CP type, gross and fine motor function, additional impairments were classified and family data were obtained. The CHQ was used to measure the parent's perception of their child's physical (PHY) and psychosocial (PSY) health. RESULTS: PHY scores were lower than the reference samples with a median of 46. The severity of gross motor function influenced the CHQ scores significantly in the PHY scale with the lowest scores for children with least gross motor function. There were significant differences between the CP types in PHY with the higher scores for children with unilateral spastic and the lowest scores for children with bilateral spastic and dyskinetic CP type. Fine motor function severity significantly affected both the PHY and PSY scales. The severity of intellectual impairment was significantly associated with CHQ scores in most dimensions with higher scores for higher IQ level in PHY and PSY. Children with seizures during the last year had a significantly lower health compared with children without seizures. The results of the multivariate regression analyses (forward stepwise regression) of CHQ scores on CP subtype, gross and fine motor function, cognitive function, additional impairments, seizures, parental education and employment revealed gross motor function, cognitive level and type of school attended were significant prognostic factors. CONCLUSION: This report is based on the largest sample to date of children with CP. Health status as measured using the CHQ was affected in all children and was highly variable. Gross motor function level correlates with health from the PHY well-being perspective but the PSY and emotional aspects do not appear to follow the same pattern.

Temporal evolution of confined fast-ion velocity distributions measured by collective Thomson scattering in TEXTOR.

Fast ions created in the fusion processes will provide up to 70% of the heating in ITER. To optimize heating and current drive in magnetically confined plasmas insight into fast-ion dynamics is important. First measurements of such dynamics by collective Thomson scattering (CTS) were recently reported [Bindslev, Phys. Rev. Lett. 97, 205005 2006]. Here we extend the discussion of these results which were obtained at the TEXTOR tokamak. The fast ions are generated by neutral-beam injection and ion-cyclotron resonance heating. The CTS system uses 100-150kW of 110-GHz gyrotron probing radiation which scatters off the collective plasma fluctuations driven by the fast-ion motion. The technique measures the projected one-dimensional velocity distribution of confined fast ions in the scattering volume where the probe and receiver beams cross. By shifting the scattering volume a number of scattering locations and different resolved velocity components can be measured. The temporal resolution is 4ms while the spatial resolution is approximately 10cm depending on the scattering geometry. Fast-ion velocity distributions in a variety of scenarios are measured, including the evolution of the velocity distribution after turnoff of the ion heating. These results are in close agreement with numerical simulations.

Fast-ion dynamics in the TEXTOR tokamak measured by collective Thomson scattering.

Here we present the first measurements by collective Thomson scattering of the evolution of fast-ion populations in a magnetically confined fusion plasma. 150 kW and 110 Ghz radiation from a gyrotron were scattered in the TEXTOR tokamak plasma with energetic ions generated by neutral beam injection and ion cyclotron resonance heating. The temporal behavior of the spatially resolved fast-ion velocity distribution is inferred from the received scattered radiation. The fast-ion dynamics at sawteeth and the slowdown after switch off of auxiliary heating is resolved in time. The latter is shown to be in close agreement with modeling results.

Discussion groups with parents of children with cerebral palsy in Europe designed to assist development of a relevant measure of environment.

BACKGROUND: An instrument to measure environmental factors relevant to physically impaired children is being developed in a European context. Preliminary work in England had identified some potentially important themes. Further inquiry was needed to identify issues important in other European countries. OBJECTIVE: To inform the content of a questionnaire relevant to the environment of children with cerebral palsy (CP) living in Europe. DESIGN: A qualitative study using discussion groups. PARTICIPANTS: Parents of 28 children with CP from five countries; Denmark, France, Italy, Ireland and Sweden. One discussion group was held in each country with an average of seven parents per group. RESULTS: The four themes identified in the preliminary work done in England were strongly confirmed across Europe - namely: Mobility, Transport, Support by and to parents, and Attitudes of individuals and institutions towards children. Two new themes identified in the discussion groups were Bureaucracy and Access to information about rights and entitlements. CONCLUSIONS: The environmental factors that cause concern to parents of children with CP are similar across Europe. A prototype environmental questionnaire has been developed based on these findings. The environmental questionnaire is in use in a study in nine European centres.

The Danish Cerebral Palsy Registry. A registry on a specific impairment.

Cerebral palsy (CP) is the commonest disabling impairment in childhood, with a prevalence of 2-3 per 1000 live births. The Danish Cerebral Palsy Registry is a research registry that contains cases of CP from birth year 1925 and has estimated the birth prevalence since 1950. Data on children with CP are collected from paediatric departments and one special institution for disabled children. The children are included by a child neurologist and an obstetrician, and information on pregnancy, birth, neonatal period, impairments and demographic data on the child and mother are registered in a standard form. The uptake area is eastern Denmark, covering about 50% of the population, but the rest of Denmark is planned to be included from 2001. The Registry is large, well established and validated, and the definitions and collection procedures have not changed through several decades. It therefore has great research potential. Birth prevalence is estimated continuously, and changes over time are analysed and correlated with pre- and perinatal conditions. A correlation between increased survival of preterm babies and an increased prevalence was found previously, and a decreased prevalence in very preterm infants was later associated with less use of mechanical ventilation. A study correlating CP and maternal infection is ongoing. Collaboration between 14 European CP registries allows the true differences in prevalence between different countries to be studied. Linkage to other individually based registries in Denmark will allow the social consequences of CP to be described.

Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms.

UNLABELLED: Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. CONCLUSIONS: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition.

Long-term application of extracorporeal photochemotherapy in severe atopic dermatitis.

BACKGROUND: Extracorporeal photochemotherapy (ECP) using UVA irradiation of enriched leukocytes in the presence of methoxsalen as a photoactivatable substrate has been employed for the treatment of several immunologically mediated disorders. OBJECTIVE: Our purpose was to determine the efficacy and safety of long-term ECP in the treatment of severe atopic dermatitis. METHODS: Fourteen patients with severe recalcitrant atopic dermatitis were treated with ECP in an open clinical trial at 2-week intervals. Disease activity was scored before each ECP cycle by means of a standardized protocol. RESULTS: A complete clinical remission was achieved in 4 patients (29%). Five patients (36%) experienced a substantial response with reduction of skin inflammation by at least 75%, whereas in one patient (7%) disease activity was reduced by more than 50%. Four patients were withdrawn from the study for unresponsiveness. No clinical signs of immunosuppression or other severe adverse events became evident. CONCLUSION: Long-term ECP may have significant beneficial effects on the course of atopic dermatitis and should therefore be considered as a treatment modality for patients suffering from severe and otherwise refractory atopic skin disease.

[Pustular dermatitis after administration of a too highly concentrated dithranol ointment in seborrhea]. / Pustulöse Dermatitis nach Anwendung einer zu hoch konzentrierten magistralen Dithranolzubereitung bei seborrhoischem Ekzem.

Seborrhoic dermatitis is an erythematosquamous condition of unknown etiology with a prevalence of approximately 2.5%. Frequently difficult to treat, it may respond to the application of low doses of dithranol, a substance which can induce a pustular dermatitis as an adverse side effect depending on the applied concentration and individual susceptibility. We describe a pustular dermatitis after the application of a preparation containing dithranol at an erroneously high concentration in a 30-year-old patient with seborrhoic dermatitis.

Thyroid function during and after cardiopulmonary bypass in children.

BACKGROUND: The aim of the study was to elucidate the changes in thyroid function during and after cardiopulmonary bypass (CPB) in children. METHODS: Triiodothronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined preoperatively, at specific times throughout CPB, and serially up to 48 h postoperatively, in 10 children (median age 35, range 23-68 months) undergoing elective surgery for congenital heart disease. RESULTS: T3 decreased from 2.01 +/- 0.08 preoperatively to 0.94 +/- 0.10 nmol/l 24 h postoperatively (P < 0.05). T4 levels followed a pattern similar to changes in T3. FT4 increased from 17.4 +/- 0.7 preoperatively to 30.0 +/- 0.4 pmol/l after 30 min of CPB (P < 0.05). TSH decreased from 2.44 +/- 0.43 preoperatively to 0.93 +/- 0.21 24 h postoperatively (P < 0.05). CONCLUSION: T3, T4 and TSH are significantly depressed after open heart surgery in children.

[Catheter treatment of congenital heart defects. Arterial septal defects and open ductus arteriosus]. / Kateterbasert behandling av medfødte hjertefeil. Atrieseptumdefekter og åpen ductus arteriosus.

The results of new methods for catheter treatment of congenital heart defects are presented. Between 1989 and 1996 closure of a patent ductus arteriosus was performed in 66 instances on 63 patients, eight of which were with coils. Three patients were treated twice, one with an additional umbrella, two with coils. The overall complete closure rate for umbrellas was 75%, after two ducts, which were initially totally occluded, recanalized. In six more patients the procedure was either aborted or indication was not present. All six ducts treated with coils as the first procedure were completely closed. One of two patients who had residual leak after previous umbrella treatment achieved complete closure after subsequent coil implantation. Closure of atrial septal defects in the oval fossa was performed using the Amplatzer septal occluder in seven children. Complete closure was achieved in all of them. There have been no complications, in particular there have been no cases of embolization in any of the groups. The results seem to indicate that coil occlusion of a persistently patent duct may be at least as good as the umbrella in terms of complete closure. So far both methods have been safe, but experience with coils is limited. The closure of atrial septal defects shows encouraging results. We will continue to offer this treatment as an alternative to open heart surgery in carefully selected patients.

Release of soluble tumour necrosis factor alpha receptors during and after paediatric cardiopulmonary bypass. Correlation with haemodynamic and clinical variables.

The release of cytokines during cardiopulmonary bypass (CPB) may contribute to haemodynamic alternations encountered after open heart surgery. Regulatory mechanisms exist and include soluble cytokine receptors. We have measured blood levels of tumour necrosis factor (TNF) and its soluble receptor (TNFsr) during and after open heart surgery in children. Correlation analysis to haemodynamic and clinical variables was performed. Using immunoassays the authors registered a significant increase in plasma levels of TNFsr with peak levels 2 h post-operatively at a level of 1702 +/- 170 pg/ml. The concentration of TNFsr remained significantly elevated until 48 h postoperatively but TNF was not significantly elevated. An inverse correlation existed between peak TNFsr and mean arterial pressure (rho = -0.827, P < 0.05), between TNFsr and cardiac index (rho = -0.8, P < 0.05), between TNFsr and left ventricular stroke work index (rho = -0.983, P < 0.01), between TNFsr and weight (rho = -0.85, P < 0.05) and between TNFsr and body surface area (rho = -0.867, P < 0.05). The authors demonstrate that the smallest children experienced the highest TNFsr concentration post-operatively. Furthermore cardiac performance, expressed as cardiac index and left ventricular stroke work index, correlated inversely to peak TNFsr level post-operatively.

Release of interleukin 6 and activation of complement during and after paediatric cardiopulmonary bypass. Effect of autotransfusion of shed mediastinal blood and ultrafiltration.

Interleukin-6 (IL-6) and the complement activation products C3bc and terminal complement complex (TCC) were measured in three groups of children undergoing open heart surgery. One group was treated with intraoperative extracorporeal ultrafiltration and postoperative autotransfusion of shed mediastinal blood, one group was subjected to autotransfusion only and in one group none of these procedures were performed. No differences between the groups were observed concerning the degree of complement activation. Peak and total accumulated level of IL-6 was significantly higher in the group subjected to ultrafiltration and autotransfusion compared to the group treated conventionally with no interventions. IL-6 may be a sensitive marker of maneuvres increasing the inflammatory load during and after open heart surgery in children.

Ultrafiltration after cardiopulmonary bypass in children: effects on hemodynamics, cytokines and complement.

OBJECTIVES: The purpose of the study was to evaluate the clinical and hemodynamic effect of intraoperative extracorporeal ultrafiltration (UF) and its potential in reducing the plasma concentration of circulating cytokines and complement activation products following open heart surgery in children. METHODS: Eighteen children with congenital heart disease were prospectively randomized into a control group (n = 9) and a group who underwent UF (n = 9). Serial plasma samples for measurements of circulating cytokines (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF), and its soluble receptor (sTNF receptor)), and complement factors (C3 activation products (C3a and C3bc) and terminal complement complex (TCC)) were obtained before, during and up to 48 h after cardiopulmonary bypass (CPB). A pulmonary artery thermodilution catheter was introduced preoperatively for hemodynamic monitoring. RESULTS: Postoperative hemodynamics were similar in both groups. Plasma levels of IL-6, sTNF receptors, C3a, C3bc and TCC increased significantly perioperatively (P < 0.01) in both groups. TNF was detected transiently in 16 patients perioperatively and in 4 of the 9 ultrafiltrate samples in concentrations similar to the plasma levels. Complement activating products were not detected in the ultrafiltration samples except for small amounts of C3a in two cases. Compared to the control group the plasma levels of C3a, C3bc and TCC were unaffected by the ultrafiltration procedure. The level of IL-6 and sTNF receptors increased significantly after 15 min of UF but there was no significant difference between the two groups postoperatively. CONCLUSIONS: In this study no clinical or hemodynamic effect was registered after UF. TNF and C3a were occasionally detected in the ultrafiltrate but we were unable to demonstrate reduction of these or any of the other markers tested in the group subjected to ultrafiltration.

Release of interleukin-8 and calprotectin during and after paediatric cardiopulmonary bypass with and without ultrafiltration.

Release of calprotectin and interleukin-8 (IL-8), changes in leukocyte counts and subsets and influence of extracorporeal ultrafiltration were evaluated during and after cardiopulmonary bypass (CPB) in 18 children undergoing open-heart surgery for congenital heart anomalies. Ultrafiltration was used in nine cases and nine were controls. Calprotectin concentration rose after start of CPB, peaking 48 hours postoperatively, with no significant intergroup difference. Positive correlation was found between duration of CPB and calprotectin (peak level and accumulated total). Circulating IL-8 was detected in all patients perioperatively, peaking at wound closure in the ultrafiltration group and at termination of bypass in the controls. CPB duration correlated significantly to peak level and accumulated total of IL-8. Seven of nine ultrafiltrate samples contained IL-8 at levels similar to the plasma concentration. Changes in white cell counts were mainly attributable to neutrophils. The two subgroups did not differ significantly in neutrophil counts. Neutropenia found after 10 minutes of CPB was replaced by neutrophilia, with maximal values postoperatively. Calprotectin and IL-8 thus were released into the circulation during CPB in children. Ultrafiltration did not affect the plasma concentrations of these substances, and only IL-8 was detected in the ultrafiltrate.

Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems during and after open heart surgery in children.

Activation of the fibrinolytic, coagulation and plasma kallikrein-kinin systems may be responsible for some of the coagulation disorders and inflammatory sequelae seen after extracorporeal circulation. The activation pattern of these systems was studied in 10 children undergoing open heart surgery with extracorporeal circulation. Blood samples were drawn serially before, during and up to 48 h after surgery. The heparin injection induced a significant elevation of plasmin (PL) (p < 0.05) which stayed elevated during extracorporeal circulation. Antiplasmin (AP) values were reduced at wound closure, while the levels were significantly elevated 48 h postoperatively (p < 0.05). alpha 2-antiplasmin-plasmin (APP) increased significantly perioperatively peaking 10 min after the initiation of cardiopulmonary bypass (p < 0.05). The coagulation markers thrombin-antithrombin (TAT) and the prothrombin fragment F1 & 2 increased significantly, peaking at wound closure and at termination of bypass respectively (p < 0.05). Plasma kallikrein (KK) values increased significantly with subsequent decreased levels of prekallikrein (PKK) and kallikrein inhibitor (KKI) after heparin injection. The KK level stayed elevated during cardiopulmonary bypass (CPB). The proenzyme functional inhibition index (PFI index), defined as the sum of deviations from the control values for proenzyme and functional inhibition values of the coagulation, fibrinolytic and plasma kallikrein-kinin systems, correlated significantly to the duration of cardiopulmonary bypass (p < 0.05). We conclude that open heart surgery in children activates the fibrinolytic, coagulation and plasma kallikrein-kinin systems.