Esben Meulengracht Flachs

Attentional and executive impairments in children with spastic cerebral palsy

Aim  Children with cerebral palsy (CP) are reported to have learning and social problems. The aim of the present study was to examine whether children with CP have impairments in attention or executive function.

Cerebral palsy in eastern Denmark: Declining birth prevalence but increasing numbers of unilateral cerebral palsy in birth year period 1986–1998

The Cerebral Palsy Registry in eastern Denmark has been collecting cases using a uniform data sampling procedure since birth year 1979. Children are included by two child neurologists and an obstetrician. Information on pregnancy, birth, neonatal period, impairments and demographic data are registered. The total cerebral palsy birth prevalence has been significantly decreasing since the birth period 1983-1986 with 3.0 per 1000 live births until the period 1995-1998 with 2.1 per 1000 live births. The overall decrease was seen in preterm infants (<31 weeks) as well as in term infants and despite a simultaneous fall in perinatal and early neonatal mortality in the preterm group. Analysing the subtypes of CP we found a significant increase in the numbers as well as the rate of unilateral CP with a simultaneous fall in the numbers as well as the rate of bilateral CP. The explanation of this rise is not obvious. A change from bilateral periventricular lesions to unilateral is a possibility, but no major change in the neonatal handling could be documented. Regarding associated impairments, developmental delay/learning disabilities as well as motor function assessed by ability to walk (unassisted/assisted), both have changed toward higher percentage of children with unassisted walking and in need of special education.

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis

BACKGROUND More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commissions list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field.

Age-Related Macular Degeneration in Patients With Chronic Myeloproliferative Neoplasms

Importance It has been suggested that systemic inflammation increases the risk of age-related macular degeneration (AMD). Given that chronic immune modulation is present in patients with myeloproliferative neoplasms (MPNs), the risk of AMD in these patients may be increased. Objective To compare the risk of AMD in patients with MPNs with the risk of AMD in matched controls from the general population. Design, Setting, and Participants A nationwide population-based cohort study using Danish registers was conducted of all patients in Denmark who received a diagnosis between January 1, 1994, and December 31, 2013, of essential thrombocythemia, polycythemia vera, myelofibrosis, or unclassifiable MPNs. For each patient, 10 age- and sex-matched controls were included. All patients without prior AMD were followed up from the date of diagnosis (or corresponding entry date for the controls) until the first AMD diagnosis, death or emigration, or December 31, 2013, whichever occurred first. Data analysis was performed from April 1, 2015, to October 31, 2016. Main Outcomes and Measures Incidence of AMD recorded in specialized hospital-based care. The rates and absolute risk of AMD were calculated. Using Cox proportional hazards regression models, smoking and risk-time adjusted hazard ratios (HRs) between patients and controls were calculated. In addition, HRs of neovascular AMD after 2006 were calculated since antivascular endothelial growth factor treatment was introduced nationwide at hospitals thereafter. Results A total of 7958 patients with MPNs (4279 women [53.8%] and 3679 men [46.2%]; mean [SD] age at diagnosis, 66.4 [14.3] years) were included in the study. The rate of AMD per 1000 person-years at risk was 5.2 (95% CI, 4.6-5.9) for patients with MPNs (2628 with essential thrombocythemia, 3063 with polycythemia vera, 547 with myelofibrosis, and 1720 with unclassifiable MPNs) and 4.3 (95% CI, 4.1-4.4) for the 77 445 controls, while the 10-year risk of AMD was 2.4% (95% CI, 2.1%-2.8%) for patients with MPNs and 2.3% (95% CI, 2.2%-2.4%) for the controls. The risk of AMD was increased overall for patients with MPNs (adjusted HR, 1.3; 95% CI, 1.1-1.5), with adjusted HRs for the subtypes of 1.2 (95% CI, 1.0-1.6) for essential thrombocythemia, 1.4 (95% CI, 1.2-1.7) for polycythemia vera, 1.7 (95% CI, 0.8-4.0) for myelofibrosis, and 1.5 (95% CI, 1.1-2.1) for unclassifiable MPNs. In addition, patients with MPNs had a higher risk of neovascular AMD (adjusted HR, 1.4; 95% CI, 1.2-1.6). Conclusions and Relevance Our results suggest that patients with MPNs are at increased risk of AMD, supporting the possibility that systemic inflammation is involved in the pathogenesis of AMD.

A nationwide population-based cross-sectional survey of health-related quality of life in patients with myeloproliferative neoplasms in Denmark (MPNhealthSurvey): survey design and characteristics of respondents and nonrespondents

Objective The Department of Hematology, Zealand University Hospital, Denmark, and the National Institute of Public Health, University of Southern Denmark, created the first nationwide, population-based, and the most comprehensive cross-sectional health-related quality of life (HRQoL) survey of patients with myeloproliferative neoplasms (MPNs). In Denmark, all MPN patients are treated in public hospitals and treatments received are free of charge for these patients. Therefore, MPN patients receive the best available treatment to the extent of its suitability for them and if they wish to receive the treatment. The aims of this article are to describe the survey design and the characteristics of respondents and nonrespondents. Material and methods Individuals with MPN diagnoses registered in the Danish National Patient Register (NPR) were invited to participate. The registers of the Danish Civil Registration System and Statistics Denmark provided information regarding demographics. The survey contained 120 questions: validated patient-reported outcome (PRO) questionnaires and additional questions addressing lifestyle. Results A total of 4,704 individuals were registered with MPN diagnoses in the NPR of whom 4,236 were eligible for participation and 2,613 (62%) responded. Overall, the respondents covered the broad spectrum of MPN patients, but patients 70–79 years old, living with someone, of a Danish/Western ethnicity, and with a higher level of education exhibited the highest response rate. Conclusion A nationwide, population-based, and comprehensive HRQoL survey of MPN patients in Denmark was undertaken (MPNhealthSurvey). We believe that the respondents broadly represent the MPN population in Denmark. However, the differences between respondents and nonrespondents have to be taken into consideration when examining PROs from the respondents. The results of the investigation of the respondents’ HRQoL in this survey will follow in future articles.

Illness and social background affect education in young adults with cerebral palsy

tently higher proportions of CP in the Indigenous population. The three jurisdictions in Australia with the largest Indigenous populations are WA, Northern Territory (NT) and Queensland (Qld). As CP registers in NT and Qld are now considered to have a sufficient level of ascertainment, data from the three registers have been combined to compare the occurrence of CP in their Indigenous and non-Indigenous populations. Aim: To compare proportions of live births subsequently described as having CP, the distributions of associated impairments and causes of postneonatal (PNN) CP between Indigenous and non-Indigenous populations in Australia. Method: Data from statutory birth records and CP registers for 1996–2005 birth cohorts in WA, NT and Qld were stratified by Indigenous status and whether the CP was acquired pre/perinatally or postneonatally. Relative risks associated with Indigenous status were estimated and the distributions of causes of PNN CP compared. Results: Indigenous births had a relative risk of 4.9 (95% confidence interval 3.0, 7.9) for PNN CP but only of 1.42 (95% CI 1.2, 1.7) for pre/perinatal CP. Almost half of PNN CP in Indigenous infants resulted from infection, whereas for nonIndigenous infants the most frequent cause was cerebrovascular accident. The impairments of Indigenous CP and of PNN CP tended to be more numerous and more severe. Conclusion: Indigenous children are at significantly greater risk of CP, particularly PNN CP. The predominant cause of PNN CP in non-Indigenous children has shifted to cerebrovascular accident over time; however, infections followed by head injury are still the most frequent causes in Indigenous infants.

Longitudinal associations between organizational change, work-unit social capital, and employee exit from the work unit among public healthcare workers: a mediation analysis

Objectives Organizational changes are associated with higher rates of subsequent employee exit from the workplace, but the mediating role of social capital is unknown. We examined the associations between organizational changes and subsequent employee exit from the work unit and mediation through social capital. Methods Throughout 2013, 14 059 healthcare employees worked in the Capital Region of Denmark. Data on work-unit changes (yes/no) from July‒December 2013 were collected via a survey distributed to all managers (merger, split-up, relocation, change of management, employee layoff, budget cuts). Eight employee-reported items assessing social capital were aggregated into work-unit measures (quartiles: low-high). Data on employee exit from the work unit in 2014 were obtained from company registries. Results We found a somewhat higher rate of employee exit from the work unit after changes versus no changes [hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.01-1.19] and an inverse dose‒response relationship between social capital and employee-exit rates (low versus high: HR 1.65, 95% CI 1.46-1.86). We also showed a higher risk of low social capital in work units exposed to changes [low versus high: odds ratio (OR) 2.04, 95% CI 1.86-2.23]. Accounting for potential mediation through social capital seemed slightly to reduce the association between changes and employee-exit rates (HR 1.07, 95% CI 0.98-1.16 versus HR 1.10). Conclusions Work-unit organizational changes prospectively predict lower work-unit social capital, and lower social capital is associated with higher employee-exit rates. Detection of weak indications of mediation through social capital, if any, were limited by inconsistent associations between changes and employee exit from the work unit.

Night work and hypertensive disorders of pregnancy: a national register-based cohort study

Objective The aim of this study was to investigate whether night work expressed by number and duration of night shifts, number of consecutive night shifts, and number of quick returns during the first 20 weeks of pregnancy is a risk factor for hypertensive disorders of pregnancy (HDP). Methods The study population comprised Danish workers in public administration and hospitals who gave birth between 2007 and 2013. Exposure was assessed objectively through payroll data. Information on the outcome was retrieved from the National Patient Register. We performed logistic regression on the risk for HDP according to night work adjusted for age, body mass index (BMI), parity, socioeconomic status, and sickness absence prior to pregnancy. Results Among 18 724 workers, 60% had at least one night shift during the first 20 weeks of pregnancy. The prevalence of HDP was 3.7%. Among night workers, the risk of HDP grew with increasing number of consecutive night shifts [odds ratio (OR) 1.41, 95% confidence interval (CI) 1.01-1.98) and of quick returns after night shifts (OR 1.28, 95% CI 0.87-1.95). Among obese women (body mass index ≥30 kg/m 2), those who worked long night shifts and longer spells of consecutive night shifts, and had the highest number of quick returns after night shifts, had a 4-5 fold increased risk of HDP compared to day workers. Conclusion Working consecutive night shifts and quick returns after night shifts during the first 20 pregnancy weeks was associated with an increased risk of HDP, particularly among obese women.

Job-exposure matrices addressing lifestyle to be applied in register-based occupational health studies

Objectives Information about lifestyle factors in register-based occupational health studies is often not available. The objective of this study was therefore to develop gender, age and calendar-time specific job-exposure matrices (JEMs) addressing five selected lifestyle characteristics across job groups as a tool for lifestyle adjustment in register-based studies. Methods We combined and harmonised questionnaire and interview data on lifestyle from several Danish surveys in the time period 1981–2013 for 264 054 employees registered with a DISCO-88 code (the Danish version of International Standard Classification of Occupations (ISCO)-88) in a nationwide register-based Danish Occupational Cohort. We modelled the probability of specified lifestyles in mixed models for each level of the four-digit DISCO code with age and sex as fixed effects and assessed variation in terms of intraclass correlation coefficients (ICCs) and exposure-level percentile ratios across jobs for six different time periods from 1981 through 2013. Results The ICCs were overall low (0.26%–7.05%) as the within-job group variation was large relative to the between job group variation, but across jobs the calendar period-specific ratios between highest and lowest predicted levels were ranging from 1.2 to 6.9, and for the 95%/1% and the 75%/5% percentile ratios ranges were 1.1–2.8 and 1.1–1.6, respectively, thus indicating substantial contrast for some lifestyle exposures and some occupations. Conclusions The lifestyle JEMs may prove a useful tool for control of lifestyle-related confounding in register-based occupational health studies where lacking information on individual lifestyle factors may compromise internal validity.

Physical work demands and psychosocial working conditions as predictors of musculoskeletal pain: a cohort study comparing self-reported and job exposure matrix measurements

Objectives Determining exposure to occupational factors by workers’ job titles is extensively used in epidemiological research. However, the correspondence of findings regarding associations to health between job exposure matrices (JEMs) and individual-level exposure data is largely unknown. We set out to examine the prospective associations of physical work demands and psychosocial working conditions with musculoskeletal pain, comparing JEMs with individual-level self-reported exposures. Methods We analysed data of 8132 participants from the Work Environment and Health in Denmark cohort study. Using random intercept multilevel modelling, we constructed age-specific and sex-specific JEMs estimating predicted exposures in job groups. We analysed associations between working conditions (individual and JEM level) at baseline and musculoskeletal pain at follow-up using multilevel modelling stratified by sex, adjusting for age, education and baseline pain. Results Any consistent associations present in the individual-level analysis were also found in the JEM-level analysis. Higher pain levels at follow-up was seen for employees with higher baseline physical work demands, women exposed to violence and men with lower decision authority, whether measured at the individual or JEM level. Higher JEM-level quantitative demands were associated with less pain, but no association was seen at the individual level. Conclusions We found predominately comparable prospective associations between working conditions and pain, whether using JEMs or individual level exposures, with the exception of quantitative demands. The results suggest that, with few notable exceptions, findings obtained using JEMs may be comparable with those obtained when using self-reported exposures.