Effects of individual and parental educational levels on multimorbidity classes: a register-based longitudinal study in a Danish population.

OBJECTIVES: To assess the effects of individual educational level in adulthood and parental educational level during childhood, as well as combinations of individual and parental educational levels, on multimorbidity classes. DESIGN AND SETTING: In this longitudinal study, we used data from a random sample of the Danish population aged 32-56 years without multimorbidity in 2010 (n=102 818). The study population was followed until 2018. Information on individual and parental educational levels and chronic conditions was obtained from national registers. Multinomial logistic regression analyses were adjusted for sex, age and ethnicity. OUTCOME MEASURE: Seven multimorbidity classes were identified using latent class analysis based on 47 chronic conditions. Persons deceased during follow-up comprised a separate class. RESULTS: We found an independent effect of individual educational level on five multimorbidity groups and death, most pronounced for the multimorbidity group 'Many conditions' (OR=1.89, 95% CI 1.58 to 2.26 for medium and OR=3.22, 95% CI 2.68 to 3.87 for short compared with long educational level) and of parental education on four groups and death, most pronounced for the multimorbidity group 'Many conditions' (OR=1.36, 95% CI 1.07 to 1.73 for medium and OR=1.48, 95% CI 1.15 to 1.89 for short compared with long educational level). Odds of belonging to four multimorbidity classes increased with lower combination of individual and parental educational levels, most pronounced for the multimorbidity group 'Many conditions'. CONCLUSION: As both individual and parental educational levels contribute to the risk of multimorbidity, it is important to address inequality throughout the life course to mitigate multimorbidity. Future studies could adopt a life course approach to investigate the mediating role of behavioural, clinical, environmental and other social factors.

Disparities in postpartum depression screening participation between immigrant and Danish-born women.

BACKGROUND: Qualitative studies suggest that immigrant women experience barriers for postpartum depression (PPD) screening. This study examines the prevalence of participation in PPD screening in the universal home-visiting programme in Denmark, in relation to migrant status and its association with acculturation factors, such as length of residence and age at migration. METHODS: The sample consists of 77 694 births from 72 292 mothers (2015-18) that participated in the programme and were registered in the National Child Health Database. Lack of PPD screening using the Edinburgh Postpartum Depression Scale (EPDS) was examined in relation to migrant group and acculturation factors. We used Poisson regression with cluster robust standard errors to estimate crude and adjusted relative risk. RESULTS: In total, 27.8% of Danish-born women and 54.7% of immigrant women lacked screening. Compared with Danish-born women, immigrant women in all groups were more likely to lack PPD screening (aRR ranging from 1.81 to 1.90). Women with low acculturation were more likely to lack screening. Women who migrated as adults [aRR = 1.27 (95% CI 1.16, 1.38)] and women who had resided in Demark for <5 years [aRR = 1.37 (95% CI 1.28, 1.46)] were more likely to lack screening. CONCLUSIONS: Immigrant women in Denmark, particularly recent immigrants, are at increased risk of not being screened for PPD using the EPDS. This can lead to under-recognition of PPD among immigrant women. More work is needed to understand how health visitors recognize the mental health needs of immigrant women who are not screened, and whether this gap results in reduced use of mental health services.

Using both electromyography and movement disorder assessment improved the classification of children with dyskinetic cerebral palsy.

AIM: Children with dyskinetic cerebral palsy (CP) are often severely affected and effective treatment is difficult, due to different underlying disease mechanisms. Comprehensive systematic movement disorder evaluations were carried out on patients with this disorder. METHODS: Patients born from 1995 to 2007 were identified from the Danish Cerebral Palsy Register and referrals to the neuropaediatric centre, Rigshospitalet, Copenhagen. They were classified by gross motor function, manual functional ability, communication ability, dystonia and spasticity. Electromyography was carried out on the upper and lower limbs. Magnetic resonance imaging scans were revised, and aetiological searches for underlying genetic disorders were performed. RESULTS: We investigated 25 patients with dyskinetic CP at a mean age of 11.7 years. Dystonia, spasticity and rigidity were found in the upper limbs of 21, four and six children, respectively, and in the lower limbs of 18, 18 and three children. The mean total Burke-Fahn-Marsden score for dystonia was 45.02, and the mean Disability Impairment Scale level was 38% for dystonia and 13% for choreoathetosis. Sustained electromyography activity was observed in 20/25 children. Stretching increased electromyography activity more in children with spasticity. There were 10 re-classifications. CONCLUSION: The children had heterogenic characteristics, and 40% were reclassified after systematic movement disorder evaluation.

The effect of gestational age on major neurodevelopmental disorders in preterm infants.

BACKGROUND: Preterm infants have an increased risk of neurodevelopmental disorders. We established a direct quantitative comparison of the association between the degree of prematurity and three different neurodevelopmental disorders. METHODS: In this cohort study, we combined data from 995,498 children in the Danish Medical Birth Register, from birth years 1997-2013, with information on cerebral palsy, epilepsy, and special educational needs. We estimated the gestational week-specific prevalence and risk for each of the disorders. RESULTS: The risk ratio of cerebral palsy at gestational weeks 21-24, compared to term birth, was more than ten times higher than for the two other disorders. The prevalence of epilepsy and special educational needs declined almost parallel, with 9.2% (4.6%-13.5%) and 12.5% (11.2%-13.7%), respectively, per week of gestation toward term birth. Cerebral palsy did not decline similarly: from gestational weeks 21-24 until week 29 the prevalence declined insignificantly by 0.6% (-11.1%-11.0%) per week; whereas from week 29 until term, the prevalence declined markedly by 36.7% (25.9%-45.9%) per week. CONCLUSIONS: The prevalence and risk of cerebral palsy are affected differently by the degree of prematurity compared with epilepsy and special educational needs, possibly reflecting important differences in cerebral pathophysiology. IMPACT: For each week of gestation toward term birth, there was a clear log-linear decline in the prevalence of early childhood epilepsy and special educational needs. In contrast, the risk of cerebral palsy was high at the earliest gestational age, and the prevalence did not decline significantly until gestational week 29, from where it declined notably by nearly 40% for each week of gestation until term birth. Our results indicate important differences in the pathophysiological processes that associate preterm birth with these three neurodevelopmental disorders.

Declining prevalence of cerebral palsy in children born at term in Denmark.

AIM: To investigate reasons for the declining prevalence of cerebral palsy (CP) in children born at term in Denmark by evaluating obstetric and neonatal factors associated with CP, and their changes over time. METHOD: In this cohort study, we included 987 495 children (504 600 [51.1%] males and 482 895 [48.9%] females) born after 37 completed gestational weeks during birth years 1997 to 2013. Risk ratios of CP for each factor were calculated with log-binominal regression analyses. Significant factors were evaluated concerning their development in prevalence over time. RESULTS: In the antenatal period, there were significant associations with an increased risk of CP and high maternal body mass index (BMI), smoking during pregnancy, nulliparity, male sex, gestational age, and low birthweight. In the study period, fewer females smoked during pregnancy and fewer children were born post-term, dropping from 22.6% to 11.4% and 9.4% to 2.5% respectively. Conversely, the proportion of females with high BMI increased. Most significant risk factors were found in the neonatal period, with an increase in children with diagnosed birth defects and children admitted to neonatal care. INTERPRETATION: Reasons for the declining prevalence of CP appear to be multifactorial and likely include the decline in maternal smoking and children born post-term along with centralization and advances in neonatal treatment.

Parental education, parent-child relations and diagnosed mental disorders in childhood: prospective child cohort study.

BACKGROUND: Mental disorder in childhood is an important public health issue. We aimed to examine the prospective association between parental education at childbirth and diagnosed mental disorders in young children and explore whether this association was mediated or modified by parent-child relations in infancy. METHODS: Prospective cohort study of all newborn was from 2002 to 2010 from 16 municipalities in the capital region of Copenhagen, Denmark, with follow-up until their 8th birthday, N = 40 762. Baseline data included information from national population registers and from health visitors' records at child aged 0 to 10 months. Outcome variable: any mental disorder diagnosed at hospital from age 11 months to 8 years. RESULTS: Low parental education was predictive of diagnosed child mental disorder, adjusted odds ratio (AOR) = 1.83 (95% CI 1.49-2.23). Problematic parent-child relation at age 8-10 months was also predictive of mental disorder, AOR = 2.06 (1.57-2.70) but did not mediate the association between parental education and mental disorder. AOR for mental disorders was 3.24 (2.03-5.16 for the combination vocational training and problematic parent-child relation and 2.49 (1.42-4.38) for the combination primary school and problematic parent-child relation. CONCLUSIONS: Low parental education and problematic parent-child relation were independent risk factors for diagnosed mental disorders in the age span of 11 months to 8 years.

The Danish Multiple Sclerosis Registry.

OBJECTIVES: The Danish Multiple Sclerosis Registry is the oldest operative and nationwide MS registry. We present The Danish Multiple Sclerosis Registry with its history, data collection, scientific contribution, and national and international research collaboration. MATERIALS AND METHODS: Detailed description of data collection, completeness, quality optimizing procedures, funding, and legal, ethical and data protection issues are provided. RESULTS: The total number of registered cases with clinical isolated syndrome and multiple sclerosis since 1956 was by start of May 2020 30,023 of whom 16,515 cases were alive and residing in Denmark, giving a prevalence rate of about 284 per 100,000 population. The mean annual number of new cases receiving an MS diagnosis was 649 per year in the period 2010 to 2019. In total, 7,945 patients (48.1%) are receiving disease modifying therapy at the start of May 2020. CONCLUSIONS: Multiple Sclerosis registers are becoming increasingly important, not only for epidemiological research but also by quantifying the burden of the disease for the patients and society and helping health care providers and regulators in their decisions. The Danish Multiple Sclerosis Registry has served as data source for a number of scientific publications including epidemiological studies on changes in incidence and mortality, cohort studies investigating risk factors for developing MS, comorbidities and socioeconomic outcomes in the MS population, and observational studies on effectiveness of disease modifying treatments outside the narrow realms of randomized clinical trials.

Patterns of multimorbidity and demographic profile of latent classes in a Danish population-A register-based study.

BACKGROUND: Multimorbidity is an increasing public health concern and is associated with a range of further adverse outcomes. Identification of disease patterns as well as characteristics of populations affected by multimorbidity is important for prevention strategies to identify those at risk. AIM: The aim of the study was to identify and describe demographic characteristics of multimorbidity classes in three age groups (16-44 years, 45-64 years, and 65+ years). METHODS: Based on register information on 47 chronic diseases and conditions, we used latent class analysis to identify multimorbidity classes in a random sample of the Danish population (n = 470,794). Information on sociodemographic characteristics (age, sex, region of origin, educational level, employment status, and marital status) was obtained from registers and linked to the study population. Age- and sex-adjusted multinomial logistic regression models were used to examine associations between multimorbidity classes and sociodemographic characteristics. RESULTS: We identified seven classes among individuals in the age groups 45-64 years and 65+ years and five classes in the age group 16-44 years. Overall, the classes were similar in the three age groups, but varied in size, i.e. the class 'No or few diseases' was larger in the younger age group. The class 'Many diseases' (a class with both somatic diseases and mental illnesses) was only seen in individuals aged 45-64 years and 65+ years. There were social inequalities in odds of belonging to the multimorbidity classes compared to the healthier class. These social inequalities varied but were especially strong in the classes named 'Many diseases' and 'Mental illness, epilepsy'. CONCLUSION: The results of the study suggest that there are social inequalities in multimorbidity but that these inequalities are not universal to all types of multimorbidity. This supports that multimorbidity is diverse and should be prevented and treated accordingly.

Study protocol of the Healthy High School study: a school-based intervention to improve well-being among high school students in Denmark.

BACKGROUND: The prevalence of low well-being, perceived stress and unhealthy behaviours is high among high school students, but few interventions have addressed these problems. The aim of this paper is to present a study protocol of a cluster randomised controlled trial evaluating the Healthy High School (HHS) intervention programme. The intervention programme is designed to improve well-being (primary outcome) by preventing 1) stress and promoting 2) sleep, 3) sense of community, 4) physical activity (PA) and 5) regular and healthy meals among high school students in Denmark. METHODS: The development of the HHS study was guided by the Intervention Mapping protocol. The intervention comprises four components: 1) a teaching material, 2) a smartphone app, 3) a catalogue focusing on environmental changes, and 4) a peer-led innovation workshop aiming at inspiring students to initiate and participate in various movement activities. The HHS study employs a cluster-randomised controlled trial design. Thirty-one high schools across Denmark were randomly allocated to intervention (16 schools) or control (15 schools) groups. The study included all first-year students (~ 16 years of age) (n = 5976 students). Timeline: Intervention: August 2016 - June 2017. Collection of questionnaire data: Baseline (August 2016), 1st follow-up (May 2017) and 2nd follow-up (April 2018). All students were invited to participate in a monthly sub-study about perceived stress using text messages for data collection (September 2016 - June 2017). PA was objectively assessed among a sub-sample of students using accelerometers (Axivity, AX3) in August 2016 and May 2017. PRIMARY OUTCOME MEASURES: Student well-being measured by the Cantril Ladder and the five item World Health Organisation Well-being Index (individual level outcomes). SECONDARY OUTCOME MEASURES: Stress (10-item Perceived Stress Scale), sleep (quantity and quality), PA (hours of moderate-to-vigorous PA per week, hours of daily sedentary time and average daily PA), meal habits (daily intake of breakfast, lunch, snacks and water), and strong sense of community in class and at school, respectively (individual level outcomes). The study encompasses process and effect evaluation as well as health economic analyses. TRIAL REGISTRATION: ISRCTN ISRCTN43284296, 28 April 2017, retrospectively registered.

Continuing decline in the prevalence of cerebral palsy in Denmark for birth years 2008-2013.

AIM: To quantify and analyse the prevalence and clinical features of cerebral palsy (CP) in Denmark for birth years 2008-2013 and compare results with previous periods. METHOD: A nationwide register-based study covering all children with a confirmed diagnosis of CP born in Denmark. Information about CP subtype, aetiology and severity was collected from the Cerebral Palsy Follow-up Program and supplemented from medical files. Data from the Danish Medical Birth Register was included, and the results were compared to previous data from the Danish National Cerebral Palsy Register. Prevalence per 1000 live births and proportions were analysed using the Cochran-Armitage test for trend. RESULTS: The period covered 368,618 live births and 636 children with CP, making the overall prevalence for the period 1.73 per 1000 live births. This was significantly lower than the prevalence of 1.99 for the previous period 1999-2007 (p = 0.004). The decline in prevalence between the two periods was mainly due to a decrease in children with bilateral spastic and dyskinetic CP born after 37 gestational weeks. The decline in prevalence was accompanied by a smaller proportion of children with associated impairment. CONCLUSION: We found a decrease in prevalence and severity in CP among Danish children. The decline was most pronounced in children born after 37 gestational weeks with severe subtypes of CP. National guidelines that recommend induction of labour before the completion of week 42 and therapeutic hypothermia for term neonates with hypoxic-ischaemic encephalopathy, may have contributed to the decline.

Reproductive history of the Danish multiple sclerosis population: A register-based study.

BACKGROUND: A diagnosis of multiple sclerosis (MS) may impact the choice of parenthood. OBJECTIVE: To investigate the number of live births, abortions and ectopic pregnancies among persons with MS. METHODS: From the Danish Multiple Sclerosis Registry, we extracted data from all persons diagnosed with MS from 1960 to 1996 and matched each MS person with four reference persons. We used a negative binomial regression model for the live births and Poisson regression model for abortions and ectopic pregnancies. The total fertility rate (TFR) during 1960-2016 and the annual number of live births in the MS population were analysed. RESULTS: Persons with MS had fewer children than reference persons. Fewer women with MS had elective abortions after diagnosis (incidence rate ratio (IRR) = 0.88; 95% confidence interval (CI) = 0.78-1.00) than reference persons. There was no difference regarding the number of elective abortions, spontaneous abortions or ectopic pregnancies after onset. The TFR was lower for women with MS than for reference persons, and the number of annual live births by MS persons increased during 1960-2016. CONCLUSION: MS seems to considerably impact reproductive choices, especially after clinical diagnosis, resulting in the MS population having fewer children than the general population.

Children with dyskinetic cerebral palsy are severely affected as compared to bilateral spastic cerebral palsy.

AIM: We aimed at describing clinical findings in children with dyskinetic as compared to bilateral spastic cerebral palsy (CP). METHODS: Data were extracted from the Danish nationwide CP register. Participants were born in 1999-2007 and were 5-6 years at ascertainment. RESULTS: The total number of CP cases was 1165 of which 92 had dyskinetic and 540 bilateral spastic CP. Prevalence of dyskinetic CP was 0.16 per 1000 live births. In participants with dyskinetic compared to bilateral spastic CP, there was more frequently an Apgar level less than five at five minutes (22.7% vs. 11.2%) and neonatal seizures (43.5% vs. 28.5%), but less respiratory deficiency, hyperbilirubinaemia and sepsis. Impairment based on gross motor function classification was more severe in dyskinetic CP (level III-V 90.0% vs. 66.0%). In dyskinetic CP, there was a high rate of reduced developmental quotient (68.1%), visual impairment (39.3%) and epilepsy (51.6%). Basal ganglia lesions were more prevalent in dyskinetic compared to bilateral spastic CP (27.7% vs. 12.8%). CONCLUSION: Cases of dyskinetic CP had overlapping clinical features with cases of bilateral spastic CP, but differed significantly in several perinatal risk factors. The children with dyskinetic CP had experienced more peri- or neonatal adverse events, and neurodevelopmental impairment was severe.

Decline in severe spastic cerebral palsy at term in Denmark 1999-2007.

AIM: To analyse trends in prevalence and severity of cerebral palsy (CP) in Denmark in birth years 1999-2007 and compare with previous periods. METHOD: Data has been collected uniformly in the Danish cerebral palsy national register nationwide since 1995. Rates in the time periods 1999-2001, 2002-2004 and 2005-2007 covering 585,393 births were analysed by gestational age and subtypes. RESULTS: Total number of CP cases in the period was 1165. The overall prevalence of CP decreased significantly from 2.1 in 1999-2001 to 1.8 in 2005-2007 per 1000 livebirths (p = 0.022). The decline was only significant for children born at term (p = 0.007) but not for the preterm (p = 0.44). The decline in children born at term was based on a decrease in bilateral spastic CP (n = 117 in years 1999-2001 and n = 59 in 2005-2007). Multidisciplinary obstetric skills training with neonatal resuscitation in Denmark was initiated in 2003 and timely associated with the decrease. The prevalence of unilateral spastic CP the prevalence did not change, but in the two last time periods more children had a right-sided than left-sided unilateral spastic CP. CONCLUSION: The decline in rate of CP seen in 2005-2007 as compared to 1999-2001 was mainly based on fewer cases of severe spastic CP in term infants. We hypothesize that improved neonatal resuscitation in the delivery room may be partly responsible for the decrease. In premature children the decline was not significant in this time period, but has been dramatically decreasing in the years before the time period here analysed.

Treatment escalation leads to fewer relapses compared with switching to another moderately effective therapy.

BACKGROUND: Patients with multiple sclerosis who experience disease breakthrough often switch disease-modifying therapy (DMT). OBJECTIVE: To compare treatment effectiveness of switch to highly effective DMT (heDMT) with switch to moderately effective DMT (meDMT) for patients who switch due to disease breakthrough defined as at least one relapse within 12 months of their treatment switch. METHODS: We retrieved data from The Danish Multiple Sclerosis Registry on all relapsing-remitting MS patients with expanded disability status scale (EDSS) less than 6 who experienced disease breakthrough. We used propensity score matching to compare annualized relapse rates (ARRs), time to first confirmed relapse, time to first confirmed EDSS worsening and time to first confirmed EDSS improvement. RESULTS: Each matched group comprised 404 patients. Median follow-up time was 3.2 years [interquartile range (IQR) 1.7-5.8]. ARRs were 0.22 (0.19-0.27) with heDMT and 0.32 (IQR 0.28-0.37) with meDMT; relapse rate ratio was 0.70 (95% CI 0.56-0.86; p = 0.001). Escalation to heDMT reduced the hazard of reaching a first relapse (HR 0.65; 95% CI 0.53-0.80; p < 0.001). We found no evidence of delayed disability worsening (HR 0.83; 95% CI 0.62-1.10; p = 0.20) and weak evidence of disability improvement (HR 1.33; 95% CI 1.00-1.76; p = 0.05) with heDMT. CONCLUSION: Switching to heDMT is associated with reduced ARR and delay of first relapse compared with switching to meDMT. Patients on DMT who experience relapses should escalate therapy to heDMT.

"To survey or to register" is that the question for estimating population incidence of injuries?

BACKGROUND: Measuring the true incidence of injury or medically attended injury is challenging. Population surveys, despite problems with recall and selection bias, remain the only source of information for injury incidence calculation in many countries. Emergency department (ED) registry based data provide an alternative source.The aim of this study is to compare the yearly incidence of hospital treated Home and Leisure Injuries (HLI), and Road Traffic Injuries (RTI) estimated by survey-based and register-based methods and combine information from both sources in to a comprehensive injury burden pyramide. METHODS: Data from Luxemburg's European Health Examination Survey (EHES-LUX), European Health Interview Survey (EHIS) and ED surveillance system Injury Data Base (IDB) collected in 2013, were used. EHES-LUX data on 1529 residents 25-64 years old, were collected between February 2013-January 2015. EHIS data on 4004 other residents aged 15+ years old, were collected between February and December 2014. Participants reported last year's injuries at home, leisure and traffic and treatment received. Two-sided exact binomial tests were used to compare incidences from registry with the incidences of each survey by age group and prevention domain. Data from surveys and register were combined to build an RTI and HLI burden pyramide for the 25-64 years old. This project was part of the European Union project BRIDGE-Health (BRidging Information and Data Generation for Evidence-based Health Policy and Research). RESULTS: Among 25-64 years old the incidence of hospital treated injuries per thousand population was 60.1 (95% CI: 59.2-60.9) according to IDB, 62.1 (95% CI: 50.6-75.4) according to EHES-LUX and 53.2 (95% CI: 45.0-62.4) according to EHIS. The incidence of hospital admissions was 3.7 (95% CI: 3.5-4.0) per thousand population from IDB-Luxembourg, 12.4 (95% CI: 7.5-19.3) from EHES-LUX and 18.0 (95% CI: 13.3-23.8) from EHIS. For 15+ years-old incidence of hospital treated HLI was 62.8 (95% CI: 62.1-63.5) per thousand population according to IDB whereas the corresponding EHIS estimate was lower at 46.9 (95% CI: 40.4-54.0). About half of HLI and RTI of the 25-64 years old were treated in hospital. CONCLUSION: The overall incidence estimate of hospital treated injuries from both methods does not differ for the 25-64 years old. Surveys overestimate the number of hospital admissions, probably due to memory bias. For people aged 15+ years, the survey estimate is lower than the register estimate for hospital treated HLI injuries, probably due to selection and recall biases. ED based registry data is to be preferred as single source for estimating the incidence of hospital treated injuries in all age groups.

Mental health among children of mothers with multiple sclerosis: A Danish cohort and register-based study.

BACKGROUND: Multiple sclerosis is associated with an increased risk of developing physical, cognitive, and mental health problems. Current studies have demonstrated variating outcomes of parental multiple sclerosis mental health problems and their children's mental health development. OBJECTIVE: The purpose of this study was to investigate whether maternal multiple sclerosis is associated with the mental health status of their child. METHODS: Data from the Danish National Birth Cohort (DNBC) were merged with information from the Danish Multiple Sclerosis Registry. Two proxies, total difficulties score and prediction of any psychiatric diagnosis based on the strengths and difficulties questionnaire, were used to measure the mental health status of the children. The two groups were compared using Mann-Whitney and logistic regression analyses. RESULTS: For the total difficulties score the control and exposed group consisted of respectively n = 42,016 and n = 40, and for the prediction of any psychiatric diagnosis respectively n = 16,829 and n = 17. We found no statistically significant association between maternal multiple sclerosis and mental health status on neither of the proxies. CONCLUSION: Maternal multiple sclerosis did not show any association with the mental health status of their children at age eleven. On the contrary, other studies conclude that there is an association between maternal multiple sclerosis and the child's mental health status, one especially mediated by the maternal mental health status.

Incidence of MS has increased markedly over six decades in Denmark particularly with late onset and in women.

OBJECTIVE: To describe the pattern of development of incidence of multiple sclerosis (MS) over 60 years in Denmark with age-period-cohort analyses and seasonality of birth. METHODS: Data on virtually all patients with onset of MS have since 1950 been prospectively recorded and kept in the Danish Multiple Sclerosis Registry with multiple sources of notification. Annualized incidence rates per 100,000 were directly standardized to the European Standard Population. RESULTS: We have registered 19,536 cases with clinical onset of confirmed MS in Denmark from 1950 to 2009. From the 1950-1959 to the 2000-2009 onset period, incidence more than doubled in women, with an increase from 5.91 (95% confidence interval [CI]: 5.60-6.24) to 12.33 (95% CI: 11.91-12.75) per 100,000 per year compared with a modest 24% increase in men from 4.52 (95% CI: 4.24-4.81) to 6.08 (95% CI: 5.79-6.38). With age at onset of 50 years and older, incidence increased with a factor 4.30 in women and 2.72 in men. The female/male sex ratio increased over time and with year of birth. Age-period-cohort analysis revealed a significant birth cohort effect in addition to the age and period effect. We found no statistically significant seasonality of births. CONCLUSION: The incidence of MS has doubled in women, most pronounced with late onset, and has only modestly increased in men. Lifestyle changes in the female population that could include fewer childbirths, increased occurrence of obesity, and increased cigarette consumption may have a role.

Effect Evaluation of a Randomized Trial to Reduce Infectious Illness and Illness-related Absenteeism Among Schoolchildren: The Hi Five Study.

BACKGROUND: Previous school-based hand hygiene interventions have reported to successfully reduce infectious illness among schoolchildren. But few studies have tested the effect in large populations with adequate statistical power and analyses. The aim of this study was to evaluate whether a school-based multicomponent intervention to improve handwashing among schoolchildren, the Hi Five study, succeeded in reducing infectious illness and illness-related absenteeism in schools. METHODS: The Hi Five study was a three-armed cluster-randomized controlled trial involving 43 randomly selected Danish schools; two intervention arms involving 14 schools each, and 15 control schools. Infectious illness days, infectious illness episodes and illness-related absenteeism were estimated in multilevel regressions, based on available cases of text messages answered by parents and based on questionnaire data reported by schoolchildren, respectively. RESULTS: At follow-up, children in the intervention schools did not differ from the control schools in number of illness days [odds ratio (OR)I-arm I: 0.91 (0.77-1.07) and ORI-arm II: 0.94 (0.79-1.12)] and illness episodes [ORI-arm I: 0.95 (0.81-1.11) and ORI-arm II: 0.98 (0.84-1.16)] or in reporting illness-related absenteeism [ORI-arm I: 1.09 (0.83-1.43) & ORI-arm II: 1.06 (0.81-1.40)]. CONCLUSIONS: The multicomponent Hi Five intervention achieved no difference in the number of illness days, illness episodes or illness-related absenteeism among children in intervention schools compared with control schools. It is noteworthy that one of the main components in the intervention, a mandatory daily handwashing before lunch, was only implemented by 1 of 3 of teachers in intervention schools.

Comorbidity in multiple sclerosis is associated with diagnostic delays and increased mortality.

OBJECTIVE: To investigate the effect of chronic comorbidity on the time of diagnosis of multiple sclerosis (MS) and on mortality in MS. METHODS: We conducted a population-based, nationwide cohort study including all incident MS cases in Denmark with first MS symptom between 1980 and 2005. To investigate the time of diagnosis, we compared individuals with and without chronic comorbidity using multinomial logistic regression. To investigate mortality, we used Cox regression with time-dependent covariates, following study participants from clinical MS onset until endpoint (death) or to the end of the study, censuring at emigration. RESULTS: We identified 8,947 individuals with clinical onset of MS between 1980 and 2005. In the study of time of diagnosis, we found statistically significant odds ratios for longer diagnostic delays with cerebrovascular comorbidity (2.01 [1.44-2.80]; <0.0005), cardiovascular comorbidity (4.04 [2.78-5.87]; <0.0005), lung comorbidity (1.93 [1.42-2.62]; <0.0005), diabetes comorbidity (1.78 [1.04-3.06]; 0.035), and cancer comorbidity (2.10 [1.20-3.67]; 0.009). In the mortality study, we found higher hazard ratios with psychiatric comorbidity (2.42 [1.67-3.01]; <0.0005), cerebrovascular comorbidity (2.47 [2.05-2.79]; <0.0005), cardiovascular comorbidity (1.68 [1.39-2.03]; <0.0005), lung comorbidity (1.23 [1.01-1.50]; 0.036), diabetes comorbidity (1.39 [1.05-1.85]; 0.021), cancer comorbidity (3.51 [2.94-4.19]; <0.0005), and Parkinson disease comorbidity (2.85 [1.34-6.06]; 0.007). CONCLUSIONS: An increased awareness of both the necessity of neurologic evaluation of new neurologic symptoms in persons with preexisting chronic disease and of optimum treatment of comorbidity in MS is critical.

Excess mortality among patients with multiple sclerosis in Denmark has dropped significantly over the past six decades: a population based study.

BACKGROUND: Lifetime expectancy in multiple sclerosis (MS) is reduced. Few studies have had sufficient follow-up or sufficient number of patients to assess if survival has improved with time. However, a recent meta-analysis found no time-dependent change in MS excess mortality across studies over recent decades. OBJECTIVE: To investigate whether short-term all-cause excess mortality in patients with MS in the total Danish population has changed over the last six decades. PATIENTS AND METHODS: We included all patients with MS recorded in the nationwide Danish MS Registry with definite or probable MS and onset from 1950 through 1999. The Danish Civil Registration System provided date of death for all deceased patients with follow-up in 2015, and Statistics Denmark supplied specific population mortality. We calculated excess number of death per 1000 person-years (EDR) and standardised mortality ratio (SMR). RESULTS: We included 18 847 patients among whom 6102 had died as opposed to 2492 expected deaths. EDR was 10.63 (95% CI 10.19 to 11.09) and a SMR was 2.45 (95% CI 2.39 to 2.51). The 15-year EDR dropped gradually from 11.29 (95% CI 9.95 to 12.73) in the 1950-1959 onset cohort to 2.56 (95% CI 1.98 to 3.18) in the 1990-1999 onset cohort, and SMR dropped from 4.48 (95% CI 4.06 to 4.92) to 1.80 (95% CI 1.62 to 1.99). CONCLUSION: The decline in short-term excess mortality in MS started decades before disease-modifying treatment of MS became available, before use of MRI became widespread, and before the McDonald diagnostic criteria were introduced. A change in the MS cohorts with fewer malignant cases may be a significant contributor.