Trends in social inequality in breastfeeding duration in Denmark 2002-2019.

AIMS: The aim of the present study was to analyse trends in full breastfeeding for at least 4 months across socioeconomic position in Denmark over a 17-year-long period from 2002 to 2019 using parental education as the indicator of socioeconomic position. METHODS: The study used data on full breastfeeding collected between 2002 and 2019 by community health nurses in the collaboration Child Health Database, n=143,075. Data were linked with five categories of parental education from population registers. Social inequality was calculated as both the relative (odds ratio) and absolute social inequality (slope index of inequality). A trend test was conducted to assess changes in social inequality over time. RESULTS: A social gradient in full breastfeeding was found for the entire study period. The odds ratio for not being fully breastfed for at least 4 months ranged from 3.30 (95% confidence interval 2.83-3.84) to 5.09 (95% confidence interval 4.28-6.06) during the study period for infants of parents with the lowest level of education (primary school) compared with infants of parents with the highest level of education (5+ years of university education). The slope index of inequality was between -38.86 and -48.81 during the entire study period, P=0.80. This indicated that both the relative and absolute social inequality in full breastfeeding to at least 4 months of age was unchanged in the study period from 2002 to 2019. CONCLUSIONS: This study showed a persistent relative and absolute social inequality in full breastfeeding for at least 4 months from 2002 to 2019 in Denmark.

Psychotropic medication among children who experience parental death to cancer.

The psychological consequences of losing a parent to cancer are unclear. We investigated whether experiencing parental death to cancer before 18 years of age increases the risk of psychotropic medication. We used register data of all children born in Denmark between 1 January 1987 and 31 December 2016 (N = 1,488,846). We assessed rate ratios (RRs) with 95% confidence intervals (CIs) for first redeemed prescription of antidepressants, anxiolytics and hypnotics according to parental death status using Poisson multi-state models. We further examined whether the associations differed according to the gender of the deceased parent, child's age at the time of death or the parental length of illness. Cancer-bereaved children had a significantly increased risk of first prescription of psychotropic medication (rate ratio, RR 1.22, 95% confidence interval, CI 1.10-1.34 for males; RR 1.18, 95% CI 1.09-1.28 for females). Associations were strongest if the parent had the same sex as the child and if the parent died within one year of diagnosis. The risk was highest during the first six months after the loss (RR 2.35, 95% confidence interval, CI 1.48-3.73 for males; RR 1.81, 95% CI 1.17-2.80 for females). Children who lose a parent to cancer, particularly in cases when the disease progressed quickly, may need extra psychological support, especially during the first six months after the death.

A novel approach for production of an active N-terminally truncated Ulp1 (SUMO protease 1) catalytic domain from Escherichia coli inclusion bodies.

The SUMO fusion system is widely used to facilitate recombinant expression and production of difficult-to-express proteins. After purification of the recombinant fusion protein, removal of the SUMO-tag is accomplished by the yeast cysteine protease, SUMO protease 1 (Ulp1), which specifically recognizes the tertiary fold of the SUMO domain. At present, the expression of the catalytic domain, residues 403-621, is used for obtaining soluble and biologically active Ulp1. However, we have observed that the soluble and catalytically active Ulp1403-621 inhibits the growth of E. coli host cells. In the current study, we demonstrate an alternative route for producing active Ulp1 catalytic domain from a His-tagged N-terminally truncated variant, residues 416-621, which is expressed in E. coli inclusion bodies and subsequently refolded. Expressing the insoluble Ulp1416-621 variant is advantageous for achieving higher production yields. Approximately 285 mg of recombinant Ulp1416-621 was recovered from inclusion bodies isolated from 1 L of high cell-density E. coli batch fermentation culture. After Ni2+-affinity purification of inactive and denatured Ulp1416-621 in 7.5 M urea, different refolding conditions with varying l-arginine concentration, pH, and temperature were tested. We have successfully refolded the enzyme in 0.25 M l-arginine and 0.5 M Tris-HCl (pH 7) at room temperature. Approximately 80 mg of active Ulp1416-621 catalytic domain can be produced from 1 L of high cell-density E. coli culture. We discuss the applicability of inclusion body-directed expression and considerations for obtaining high expression yields and efficient refolding conditions to reconstitute the active protein fold.

Short report: persistent social inequality in poor self-rated health among adolescents in Denmark 1991-2014.

The aim was to examine trends in social inequality in poor self-rated health (SRH) among adolescents in Denmark 1991-2014. The analysis included 18 996 11-15-year-old school children from the cross-sectional Health Behaviour in School-aged Children studies in 1991, 2002, 2006, 2010 and 2014. Across the five surveys, the prevalence of poor SRH was 14.2%, remaining almost unchanged from 1991 to 2014. The proportion with poor SRH was 12.2% in high, 14.3% in middle and 17.6% in low occupational social class. This social inequality in poor SRH was persistent during the entire study period, both in terms of absolute and relative social inequality.

Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses.

The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection.

Parental involvement and association with adolescents' fruit and vegetable intake at follow-up: Process evaluation results from the multi-component school-based Boost intervention.

BACKGROUND: Based on the assumption of parental influence on adolescent behavior, multicomponent school-based dietary interventions often include a parental component. The effect of this intervention component is seldom reported and the evidence is inconsistent. We conducted a systematic process evaluation of the parental component and examined whether the leveal of parental involvement in a large multi-component intervention: the Boost study was associated with adolescents' fruit and vegetable (FV) intake at follow-up. METHODS: The Boost study was targeting FV intake among 1,175 Danish 7th graders (≈13- year-olds) in the school year 2010/11. The study included a school component: free FV in class and curricular activities; a local community component: fact sheets for sports- and youth clubs; and a parental component: presentation of Boost at a parent-school meeting, 6 newsletters to parents, 3 guided student-parent curricular activities, and a student-parent Boost event. STUDY POPULATION: Students whose parent replied to the follow-up survey (n = 347). DATA: Questionnaire data from students, parents and teachers at 20 intervention schools. Process evaluation measures: dose delivered, dose received, appreciation and level of parental involvement. Parental involvement was trichotomized into: low/no (0-2 points), medium (3 points) and high (4-6 points). The association between level of parental involvement and self-reported FV intake (24-h recall), was analyzed using multilevel regression analyses. RESULTS: The Boost study was presented at a parent-school meeting at all intervention schools. The dose delivered was low to moderate for the three other parental elements. Most parents appreciated the intervention and talked with their child about Boost (83.5 %). High, medium and low parental involvement was found among 30.5 %, 29.6 % and 39.4 % of the students respectively. Parental involvement was highest among women. More men agreed that the parental newsletters provided new information. Students with a medium and high level of parental involvement ate 47.5 and 95.2 g more FV per day compared to students with low level/no parental involvement (p = 0.02). CONCLUSIONS: Students with a high level of parental involvement ate significantly more FV at follow-up compared to students with a low level/no parental involvement. Parental involvement in interventions may improve adolescents' FV intake if challenges of implementation can be overcome. TRIAL REGISTRATION: ISRCTN11666034 . Registered 06/01/2012. Retrospectively registered.

Fast-food intake and perceived and objective measures of the local fast-food environment in adolescents.

OBJECTIVE: We examined associations between fast-food intake and perceived and objective fast-food outlet exposure. DESIGN: Information from the Health Behaviours in School-aged Children Study was linked to fast-food outlets in seventy-five school neighbourhoods. We used multivariate multilevel logistic regression analyses to examine associations between at least weekly fast-food intake and perceived and objective fast-food outlet measures. SUBJECTS: Data represent 4642 adolescents (aged 11-15 years) in Denmark. RESULTS: Boys reporting two or more fast-food outlets had 34% higher odds consuming fast food at least weekly. We detected higher odds of at least weekly fast-food intake among 15-year-old 9th graders (ORall=1.74; 95% CI 1.40, 2.18; ORboys=2.20; 95% CI 1.66, 2.91; ORgirls=1.41; 95% CI 1.03, 1.92), Danish speakers (ORall=2.32; 95% CI 1.68, 3.19; ORboys=2.58; 95% CI 1.69, 3.93; ORgirls=2.37; 95% CI 1.46, 3.84) and those travelling 15 min or less to school (ORall=1.21; 95% CI 1.00, 1.46; ORgirls=1.44; 95% CI 1.08, 1.93) compared with 11-year-old 5th graders, non-Danish speakers and those with longer travel times. Boys from middle- (OR=1.28; 95% CI 1.00, 1.65) and girls from low-income families (OR=1.46; 95% CI 1.05, 2.04) had higher odds of at least weekly fast-food intake compared with those from high-income backgrounds. Girls attending schools with canteens (OR=1.47; 95% CI 1.00, 2.15) had higher odds of at least weekly fast-food intake than girls at schools without canteens. CONCLUSIONS: The present study demonstrates that perceived food outlets may impact fast-food intake in boys while proximity impacts intake in girls. Public health planning could target food environments that emphasize a better understanding of how adolescents use local resources.

Fever during pregnancy and motor development in children: a study within the Danish National Birth Cohort.

AIM: The aim of this study was to examine how fever during pregnancy is associated with motor development in the child. METHOD: This cohort study was based on data from females and their children, from the Danish National Birth Cohort, who took part in an 18-month and/or 7-year follow-up study. Information regarding fever (number of episodes, temperature, duration, and pregnancy week) was obtained around gestation week 12 and at the end of pregnancy. Assessments of motor development in early childhood were based on the ages at which the motor milestones 'sitting unsupported' (n=44,256) and 'walking unassisted' (n=53,959) were attained. The Developmental Coordination Disorder Questionnaire 2007 (DCDQ'07) was used to identify children with indication of developmental coordination disorder (DCD) at age 7 years (n=29,401). Any associations between the exposure to fever during pregnancy and motor development were estimated using Cox regression and logistic regression analyses. RESULTS: Fever during pregnancy was reported by 15,234 (28.0%) participants in the 18-month follow-up and by 7965 (26.9%) participants in the 7-year follow-up. Adjusted analyses showed no association between prenatal exposure to fever and either 'sitting unsupported' or 'walking unassisted'. The proportion of children with indication of DCD was 3.1%. The odds ratio of indication of DCD if children were exposed to fever in utero was 1.29 (95% CI 1.12-1.49). However, no dose-response association was found. INTERPRETATION: We found a significant association between maternal fever during pregnancy and DCD in children at age 7 years. The lack of a dose-response association might suggest that this association is explained by the underlying causes of the fever.

Implementation of strategies to increase adolescents' access to fruit and vegetables at school: process evaluation findings from the Boost study.

BACKGROUND: Access to fruit and vegetables (FV) is associated with adolescents' FV consumption. However, little is known about implementation of strategies to increase access to FV at schools. We examined the implementation of two environmental components designed to increase access to FV at Danish schools. METHODS: We used data from 20 intervention schools involved in the school-based multicomponent Boost trial targeting 13-year-olds' FV consumption. The environmental components at school included daily provision of free FV and promotion of a pleasant eating environment. Questionnaire data was collected by the end of the nine-month intervention period among 1,121 pupils (95%), from all school principals (n = 20) and half way through the intervention period and by the end of the intervention among 114 teachers (44%). The implementation of the components was examined descriptively using the following process evaluation measures; fidelity, dose delivered, dose received and reach. Schools with stable high implementation levels over time were characterised by context, intervention appreciation and implementation of other components. RESULTS: For all process evaluation measures, the level of implementation varied by schools, classes and over time. Dose received: 45% of pupils (school range: 13-72%, class range: 7-77%) ate the provided FV daily; 68% of pupils (school range: 40-93%, class range: 24-100%) reported that time was allocated to eating FV in class. Reach: The intake of FV provided did not differ by SEP nor gender, but more girls and low SEP pupils enjoyed eating FV together. Dose delivered: The proportion of teachers offering FV at a daily basis decreased over time, while the proportion of teachers cutting up FV increased over time. Schools in which high proportions of teachers offered FV daily throughout the intervention period were characterized by being: small; having a low proportion of low SEP pupils; having a school food policy; high teacher- and pupil intervention appreciation; having fewer teachers who cut up FV; and having high implementation of educational components. CONCLUSIONS: The appliance of different approaches and levels of analyses to describe data provided comprehension and knowledge of the implementation process. This knowledge is crucial for the interpretation of intervention effect. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11666034.

The role of curriculum dose for the promotion of fruit and vegetable intake among adolescents: results from the Boost intervention.

BACKGROUND: Multi-component interventions combining educational and environmental strategies have proved effective in increasing children and adolescents' fruit and vegetable intake. However such interventions are complex and difficult to implement and several studies report poor implementation. There is a need for knowledge on the role of dose for behaviour change and for assessment of intervention dose to avoid conclusions that intervention components which are not implemented are ineffective. This study aimed to examine 1) the association between dose of a class curriculum and adolescents' fruit and vegetable intake in a school-based multi-component intervention, 2) if gender and socioeconomic position modify this association. METHODS: We carried out secondary analysis of data from intervention schools in the cluster-randomized Boost study targeting 13-year-olds' fruit and vegetable intake. Teacher- and student data on curriculum dose delivered and received were aggregated to the school-level and class-level (only possible for student data). We analysed the association between curriculum dose and students' (n 995) self-reported fruit and vegetable intake (24-h recall questionnaire) after finalization of the intervention using multi-level analyses. Potential moderation was examined by analyses stratified by gender and socioeconomic position. RESULTS: Average dose received at class-level was significantly associated with students' fruit and vegetable intake (10 g (CI: 0.06, 20.33) per curricular activity received). In stratified analyses the association remained significant among boys only (14 g (CI: 2.84, 26.76) per curricular activity received). The average dose delivered and received at the school-level was not significantly associated with students' intake. CONCLUSIONS: We found a dose-response relationship between number of curricular activities received and adolescents' fruit and vegetable intake. The results indicate that curriculum dose received only mattered for promotion of fruit and vegetable intake among boys. Future studies should explore this gender difference in larger samples to guide the planning of school-based curricular interventions with regards to the optimal number of curricular activities required to promote behavioural change in subgroups with low fruit and vegetable intake at baseline. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11666034.

Low Level of Well-being in Young People With Physical-Mental Multimorbidity: A Population-Based Study.

PURPOSE: We aimed to examine whether wellbeing, health behavior, and youth life among young people (YP) with co-occurrence of physical-mental conditions, that is, multimorbidity differ from YP with exclusively physical or mental conditions. METHODS: The population included 3,671 YP reported as having a physical or/and mental condition from a Danish nationwide school-based survey (aged 14-26 years). Wellbeing was measured by the five-item World Health Organization Well-Being Index and life satisfaction by the Cantril Ladder. YP's health behavior and youth life were evaluated in seven domains: home, education, activities/friends, drugs, sleep, sexuality, and self-harm/suicidal thoughts, in accordance with the Home, Education and employment, Eating, Activities, Drugs, Sexuality, Suicide and depression, and Safety acronym. We performed descriptive statistics and multilevel logistic regression analysis. RESULTS: A total of 52% of YP with physical-mental multimorbidity reported a low level of wellbeing, compared to 27% of YP with physical conditions and 44% with mental conditions. YP with multimorbidity had significantly higher odds of reporting poor life satisfaction, compared to YP with exclusively physical or mental conditions. YP with multimorbidity had significantly higher odds for psychosocial challenges and health risk behavior, compared to YP with physical conditions, along with increased odds for loneliness (23.3%), self-harm (63.1%), and suicidal thoughts (54.2%), compared to YP with mental conditions. DISCUSSION: YP with physical-mental multimorbidity had higher odds for challenges and low wellbeing and life satisfaction. This is an especially vulnerable group and systematic screening for multimorbidity and psychosocial wellbeing is needed in all healthcare settings.

Parental Illness and Life Satisfaction among Young People: A Cross-Sectional Study of the Importance of School Factors.

BACKGROUND: The aim of this study was to examine the relationship between parental illness and life satisfaction among Danish adolescents and the potential modifying effect of positive school experiences. Moreover, we describe the use of student counsellor services among adolescents with and without ill parents. METHODS: Data included 9565 adolescents primarily aged 13-19 years, who participated in the cross-sectional Well-being Despite Study. Multilevel logistic regression models including joint effect analyses were performed. RESULTS: Parental illness was strongly associated with life satisfaction. Negative school experiences were more frequent among adolescents with ill parents and strongly associated with low life satisfaction for all students. However, joint effect analyses did not show effect modification by school-related variables. The odds ratio of having talked to a student counsellor was highest for adolescents with multiple ill parents, compared to no ill parents. CONCLUSIONS: Parental illness is a strong predictor of low life satisfaction among adolescents; the impact depends on number of ill parents, whether parental illness is physical or mental, and their level of impairment. Positive school experiences were less frequent in adolescents of ill parents and did not counteract the effect of parental illness on life satisfaction.

Identifying and Characterizing Children of Parents with a Serious Illness Using Survey and Register Data.

PURPOSE: To estimate the prevalence and characterize children and adolescents aged 0-21 years with a physically or mentally ill parent based on registers. Further, to explore the use of register and survey data to identify parental serious illness. METHODS: The study is based on: 1) a 20% register sample of children and adolescents aged 0-21 in 2014; and 2) survey data from the Danish Youth Profile 2014 including 63,437 youth education students linked to registers. In registers, parental physical illness comprised hospital diagnoses included in the Charlson Comorbidity Index, and parental mental illness encompassed all mental diagnosis in the registers. Information about socioeconomic and demographic characteristics and use of health care services was retrieved from national registers. In the survey, students were asked if they had experienced serious illness of a parent. RESULTS: In the register sample of 0-21-year-olds, 25.3% had a parent with a physical or mental diagnosis, the prevalence increasing with age of the child. Compared to children without parental illness, children with an ill parent more frequently had unemployed parents, lower parental educational level, and a chronic medical condition. Analyses of the discrepancies between register and survey data revealed that 9% of the adolescents were identified as having an ill parent in both data sources and 64.1% had no identified ill parents. Moreover, a higher frequency of parental primary health care service use was seen for adolescents with an ill parent, across identification method, indicating that both methods identify adolescents with an ill parent. CONCLUSION: The social inequality and elevated frequency of health problems among children and adolescents with an ill parent, underline the vulnerability of this population. Parental illness can be identified from both parental hospital diagnoses as well as self-reported by adolescents, however the two methods detect different populations. Both methods have several limitations and would benefit from further refinement and validation.

Why Do Some Adolescents Manage Despite Parental Illness? Identifying Promotive Factors.

PURPOSE: This study aimed to examine the association between social support, leisure time, school experience, and well-being among adolescents with an ill parent. Moreover, we explored the cumulative effect of promotive factors in relation to well-being. METHODS: The population included a subsample of 676 students reporting serious or chronic parental illness, selected from a nationwide Danish survey, the Well-being Despite Study. Well-being was measured by the five-item World Health Organization Well-Being Index. Social support included support from parents, siblings, and friends. A positive school experience encompassed trust in teachers, classroom community, and overall judgment of the school. Leisure time included frequency of activities and having enough time for friends and oneself. We performed multilevel logistic regression analyses using SAS 9.4. RESULTS: Social support, a positive school experience, and leisure time were positively associated with well-being. For instance, for boys and girls who felt they had enough time to themselves, the odds ratio of moderate to high well-being was 3.7 (95% confidence interval [CI]: 1.8-7.7) and 2.9 (95% CI: 1.9-4.3) respectively, compared with boys and girls who did not. Cumulative analyses showed increasing odds of moderate to high well-being with increasing number of promotive factors, the odds ratio being 39.7 (CI 95%: 11.6-136.2) among adolescents with 10 promotive factors compared with adolescents with 0-5 promotive factors. CONCLUSIONS: Social support, a positive school experience, and satisfying leisure time may be important promotive factors, and the results point toward a more ecological approach to improve well-being among adolescents with ill parents.

Curricular activities and change in determinants of fruit and vegetable intake among adolescents: Results from the Boost intervention.

Knowledge of the association between implementation of different intervention components and the determinants they are tailored to change may contribute to evaluating the effects and working mechanisms of multi-component interventions. This study examined 1) the effect of a Danish multi-component school-based intervention (2010 - 2011) on key determinants of adolescents' fruit and vegetable intake and 2) if dose of curricular activities was positively associated with change in these determinants. Using multi-level linear and logistic regression analyses stratified by gender and socioeconomic position, we analyzed survey data from the cluster-randomized Boost study targeting Danish 13-year-olds' fruit and vegetable intake. We examined 1) differences in knowledge of recommendations, taste preferences and situational norms between students from 20 intervention (n = 991) and 20 control (n = 915) schools at follow-up; and 2) associations between curriculum dose received and delivered (student and teacher data aggregated to school- and class-level) and these determinants among students at intervention schools only. At follow-up, more students from intervention than control schools knew the recommendation for vegetable intake (OR 1.56, CI:1.18, 2.06) and number of fruits liked (taste preferences) increased by 0.22 (CI:0.04, 0.41). At class-level, curriculum dose received was positively associated with proportion of students knowing the recommendation for vegetable intake (OR 1.06, CI:1.002, 1.13). In stratified analyses, this association was only significant among students from high social class (OR 1.17, CI:1.04, 1.31). The Boost intervention succeeded in improving students' taste preferences for fruit and knowledge of recommendation for vegetable intake, but only the latter determinant was positively associated with curriculum dose. Trial registration: ISRCTN11666034.

Reduced IFNλ4 activity is associated with improved HCV clearance and reduced expression of interferon-stimulated genes.

Hepatitis C virus (HCV) infections are the major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide. Both spontaneous and treatment-induced clearance of HCV depend on genetic variation within the interferon-lambda locus, but until now no clear causal relationship has been established. Here we demonstrate that an amino-acid substitution in the IFNλ4 protein changing a proline at position 70 to a serine (P70S) substantially alters its antiviral activity. Patients harbouring the impaired IFNλ4-S70 variant display lower interferon-stimulated gene (ISG) expression levels, better treatment response rates and better spontaneous clearance rates, compared with patients coding for the fully active IFNλ4-P70 variant. Altogether, these data provide evidence supporting a role for the active IFNλ4 protein as the driver of high hepatic ISG expression as well as the cause of poor HCV clearance.

[Patient safety in a health technology assessment perspective]. / Patientsikkerhed i medicinsk teknologivurderingsperspektiv.

The Danish Act of Patient Safety entered into force in 2004. This paper studies the consequences of the Act for the health care system and its users by a literature evaluation and an interview study with key persons. Despite the substantial resources spent on the reporting system, no evidence is found that the Act has an improved effect on patient safety. One of the biggest barriers for reporting adverse events is a lack of follow-up and feedback. Research into the patient's role on preventing adverse events is limited. The possibilities created by the Act should be utilized to their full potential.