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.

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.

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.

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.

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.

Validity of the ECG diagnosis of left ventricular hypertrophy in normotensive and moderately hypertensive men when using the echocardiographic assessment of left ventricular mass index as reference.

The diagnostic validity of ECG criteria for left ventricular hypertrophy (LVH) was assessed in 100 men aged 22-64 (mean 47) years with moderate hypertension (Group 1) and 95 age-matched normotensive men (Group 2) using echocardiographic recordings of LV mass index (MI) as reference. A diagnosis of LVH was made in subjects with LVMI greater than or equal to 125 g/m2. Mean LVMI was 126 +/- 34 g/m2 in Group 1 vs. 100 +/- g/m2 in Group 2 (P less than 0.001), and the prevalence of LVH was 48% and 11% respectively (P less than 0.001). The mean ECG voltage according to Sokolow-Lyon (S-L) was 28 +/- 8 mm in Group 1 and 27 +/- 7 mm in Group 2 (NS); with 19% having LVH in Group 1 and 14% in Group 2 (NS). Using the Cornell criterion Group 1 had on average 15 +/- 6 mm vs. 12 +/- 5 mm in Group 2 (P less than 0.001), but only two Group 1 patients had LVH. In Group 2 a significant negative correlation between age and S-L voltage was found (r = 0.33, P less than 0.001). LVMI was not correlated with any of the two voltage criteria using linear regression analysis whereas multiple regression analysis revealed a weak, but significant correlation between LVMI and S-L voltage in Group 1 (t = 2.06, P = 0.04). No subject had LV strain pattern or LVH according to the Romhilt Estes point score system. In the assessment of possible LVH in normal or moderately hypertensive men less than 65-70 years of age, ECG has limited value.

Correlations between left ventricular mass and systolic blood pressure at rest and during maximal exercise in moderately hypertensive men.

We examined 87 men with moderate hypertension (diastolic blood pressure, DPB, greater than or equal to 95 and less than 110 mmHg) (mean age 45, range 22-64, years) with echocardiography and maximal ergometer bicycle test. Left ventricular mass index (LVMI) was calculated according to the Penn convention. Mean LVMI was 126 (60-210) g/m2. The maximal systolic blood pressure (SBP) during exercise was on average 217 (155-260) mmHg. Linear regression analysis revealed a significant correlation between LVMI and SBP at rest (r = 0.48, P less than 0.001) and during exercise (r = 0.39, P less than 0.001). Multiple regression analysis correcting for differences in age, cumulative work and cholesterol level revealed a significant correlation between LVMI and SBP at rest (t = 4.07, P less than 0.0001) and during exercise (t = 3.25, P = 0.002). Thus in patients with established, moderate hypertension exercise SBP is not more predictable for LVMI than is SBP at rest.

The Dübendorf Study: a population-based investigation on normal values of blood pressure self-measurement.

There is evidence that self-measurement of BP increases precision, reproducibility and prognostic value of BP measurement. However, generally accepted normal values for BP values obtained by self-measurement are still missing. The present study was undertaken to investigate differences between office and self-measured blood pressure; 503 randomly selected inhabitants (265 men and 238 women, age 20-90 years, mean age 46.5 +/- 12.9 years) of the small town of Dübendorf in Switzerland were studied. The subjects were not preselected according their BP levels, only patients taking antihypertensive drugs were excluded. Self-measurement was performed at home by the subjects during 14 days in the morning between 6 and 8 am and in the evening between 6 and 8 pm (mean of 26.7 measurements). Office BP was taken before and after the two week period. Mean office BP (130.0 +/- 16.5/82.1 +/- 11.1 mmHg) was significantly (P < 0.01) higher than mean self-measured BP (123.1 +/- 14.6/77.6 +/- 10.7 mmHg). There was no significant difference between first and second office BP measurement. Morning self-measured BP was lower than evening pressure (delta 4.0/1.4 mmHg, both P < 0.01) and the mean was taken for comparison with office BP.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

Reproducibility of cumulative work, heart rate and blood pressure response during stepwise versus continuous load increment during a maximal bicycle ergometer test.

The reproducibility of physical capacity expressed as cumulative work (CW) and work pulse (WP) as well as haemodynamic response to maximal exercise was evaluated by two different principles for increasing work load during a maximal bicycle ergometer exercise test: (i) stepwise increment (SI) of 50 Watts (W) every fourth minute; (ii) continuous increment (CI) of 10 W at the end of every minute, both with a starting load of 50 W. Forty apparently healthy men aged 29-69 (mean 47) years performed two tests with a mean interval of 17 (3-43) days. Group A: 10 men who did SI twice; group B: 10 who repeated CI; group C: 10 men who performed SI and CI alternatively; group D: 10 men who did SI in the morning vs afternoon. Error % (percentage of the absolute difference of the mean of two values) was 3.9 for CW in group A vs 7.8 in group B (p less than 0.05). The error % of heart rates at submaximal work levels were lower with SI than CI. Mean CW in group C was 182.3 +/- 65.1 kJ for CI and 154.8 +/- 48.8 kJ for SI (p less than 0.01), whereas the mean exercise time was 1206 +/- 297 s and 1089 +/- 197 s respectively (p less than 0.01). Group D subjects achieved 142.7 +/- 49.4 kJ in the morning and 134.4 +/- 48.8 kJ in the afternoon (p less than 0.05). No significant differences were noted for WP in groups A-D. A better reproducibility for CW was found for SI, whereas both tests had similar reproducibility for heart rate and blood pressure response during maximal exercise.

Blood pressure response during maximal exercise in apparently healthy men and women.

The blood pressure (BP) response during a maximal ergometer bicycle test was studied in 190 apparently healthy subjects (95 men and 95 women) aged 21-70 years. The starting load was 50 W and was increased by 50 W every 4 min until exhaustion. Mean physical performance expressed as cumulative work was 2276 +/- 789 W in men and 1109 +/- 276 W in women (P less than 0.0001). The maximum heart rate was similar in men and women and declined significantly with age (r = -0.78, P less than 0.001 for men and r = -0.64, P less than 0.0001 for women). The mean maximal systolic blood pressure (MSBP) was 193 +/- 23 mmHg in men and 171 +/- 21 mmHg in women (P less than 0.0001). Men aged greater than or equal to 50 years had a MSBP of 201 +/- 22 mmHg, compared to 188 +/- 22 mmHg in those aged less than 50 years (P less than 0.01). Women aged greater than or equal to 60 years had a MSBP of 190 +/- 21 mmHg compared to 166 +/- 19 mmHg in their younger counterparts (P less than 0.001). The diastolic BP showed a similar modest increase at all ages and in both sexes. SBP is dependent on age and gender and this must be taken into consideration when assessing a normal response in individual patients.

Influence of age on physical performance, heart rate and systolic blood pressure response during exercise in apparently healthy women.

In order to assess normal physical performance in women, a near-maximal ergometer bicycle test was performed in 95 healthy non-athletic women aged 24-65 years (mean 44 years). The starting load was 50 W and the load was increased by 50 W every 4 min until exhaustion. Physical performance was expressed as cumulative work in Watts (W). All subjects had normal two-dimensional, M-Mode and Doppler echocardiographic findings. Physical performance was similar in the age groups 24-29, 30-39 and 40-49 years. Mean cumulative work among subjects less than 50 years was 1208 (600-1800) W vs. 947 (500-1600) W (p less than 0.001) in those greater than or equal to 50 years. Physical performance was similar in the age groups 50-59 and 60-65 years (NS). An inverse correlation between maximal heart rate and age was found (r = 0.64, p less than 0.001). Systolic blood pressure increased more during exercise in the subjects greater than or equal to 50 years (p less than 0.001 vs. those aged less than 50 years). M-Mode echocardiographic measurements at rest were similar in all age groups. These findings may be related to reduction in beta-sympathetic stimulation during exercise in women greater than or equal to 50 years of age.

Prevalence of tricuspid and pulmonary regurgitation diagnosed by Doppler in apparently healthy women. Possible influence on their physical performance?

Ninety-five apparently healthy, non-athletic women aged 24-65 (mean 44) years were screened by Doppler echocardiography for the presence of tricuspid and pulmonary regurgitation (TR and PR). An Irex Meridian system was used. TR was diagnosed in the presence of a pansystolic regurgitant jet into the right atrium with a maximal velocity of greater than 1.5 m s-1. Regurgitant flow throughout diastole was diagnostic for PR. Right-sided regurgitation was found in 43 women (Group 1), 22 with TR, 12 with PR, and nine with combined TR and PR. The remaining 52 women were studied as a control group (Group 2). Group 1 had a significantly larger heart size on X-ray (P less than 0.025) and left ventricular end systolic diameter assessed from M-mode echocardiography (P less than 0.05) than did Group 2. The possible clinical significance of the valvular regurgitation was assessed by using a standardized symptom-limited exercise test on an ergometer bicycle. In Group 1, the mean cumulative work achieved was 7008 (+/- 1630) kpm, and in Group 2 6363 (+/- 1633) kpm (P less than 0.05). TR and PR occurring in otherwise healthy women does not seem to impair physical exercise performance.

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.

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.

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.