Underlying pathways of social inequality in tooth loss: the mediating role of sugary beverages and diabetes.

BACKGROUND: Previous studies show social inequality in tooth loss, but the underlying pathways are not well understood. The aim was to investigate the mediated proportion of sugary beverages (SBs) and diabetes and the association between educational level and tooth loss, and to investigate whether the indirect effect of SBs and diabetes varied between educational groups in relation to tooth loss. METHODS: Data from 47,109 Danish men and women aged 50 years or older included in the Danish Diet, Cancer and Health Study was combined with data from Danish registers. Using natural effect models, SBs and diabetes were considered as mediators, and tooth loss was defined as having <15 teeth present. RESULTS: In total, 10,648 participants had tooth loss. The analyses showed that 3% (95% confidence interval 2-4%) of the social inequality in tooth loss was mediated through SBs and diabetes. The mediated proportion was mainly due to differential exposure to SBs and diabetes among lower educational groups. CONCLUSIONS: The findings show that SBs and diabetes to a minor degree contribute to tooth-loss inequalities. The explanation indicates that individuals in lower educational groups have higher consumption of SBs and more often suffer from diabetes than higher educational groups.

Clinical assessment as a part of an early warning score-a Danish cluster-randomised, multicentre study of an individual early warning score.

BACKGROUND: The clinical benefit of Early Warning Scores (EWSs) is undocumented. Nursing staff's clinical assessment might improve the prediction of outcome and allow more efficient use of resources. We aimed to investigate whether the combination of clinical assessment and EWS would reduce the number of routine measurements without increasing mortality. METHODS: We did a cluster-randomised, crossover, non-inferiority study at eight hospitals in Denmark. Patients aged 18 years or older, admitted for more than 24 h were included. Admissions to paediatric or obstetric wards were excluded. The participating hospitals were randomly assigned 1:1 to start as either intervention or control with subsequent crossover. Primary outcomes were 30-day all-cause mortality (non-inferiority margin=0·5%) and average number of EWS per day per patient. The intervention was implementation of the Individual EWS (I-EWS), in which nursing staff can adjust the calculated score on the basis of their clinical assessment of the patient. I-EWS was compared with the National Early Warning Score (NEWS). The study is registered at ClinicalTrials.gov, NCT03690128 and is complete. FINDINGS: Unique admissions longer than 24 h were included from Oct 15, 2018 to Sept 30, 2019. Of 90 964 patients assessed, n=46 470 were assigned to the I-EWS group and n=44 494 to the NEWS group. Mortality within 30 days was 4·6% for the I-EWS group, and 4·3% for the NEWS group (adjusted odds ratio 1·05 [95% CI 0·99-1·12], p=0·12). In subgroup analyses I-EWS showed increased 30-day mortality for hospitals that did I-EWS in fall-winter, which was probably due to seasonality, and within patients admitted in a surgical specialty. Overall risk difference was 0·22% (95% CI -0·04 to 0·48) meaning that the non-inferiority criteria were met. The average number of scorings per patient per day was reduced from 3·14 to 3·10 (ie, a relative reduction of 0·64% [95% CI -0·16 to -1·11], p=0·0084) in the I-EWS group. INTERPRETATION: Including clinical assessment in I-EWS was feasible and overall non-inferior to the widely implemented NEWS in terms of all-cause mortality at 30 days, and the number of routine measurements was minimally reduced. However I-EWS should be used with caution in surgical patients. FUNDING: Capital Region Research Foundation, Gangsted Foundation, Candys Foundation, Herlev-Gentofte Hospital Research Foundation, Laerdal Foundation, and The Foundation of Director Boennelycke and wife.

Assessment of assumptions of statistical analysis methods in randomised clinical trials: the what and how.

When analysing and presenting results of randomised clinical trials, trialists rarely report if or how underlying statistical assumptions were validated. To avoid data-driven biased trial results, it should be common practice to prospectively describe the assessments of underlying assumptions. In existing literature, there is no consensus on how trialists should assess and report underlying assumptions for the analyses of randomised clinical trials. With this study, we developed suggestions on how to test and validate underlying assumptions behind logistic regression, linear regression, and Cox regression when analysing results of randomised clinical trials.Two investigators compiled an initial draftbased on a review of the literature. Experienced statisticians and trialists from eight different research centres and trial units then participated in a anonymised consensus process, where we reached agreement on the suggestions presented in this paper.This paper provides detailed suggestions on 1) which underlying statistical assumptions behind logistic regression, multiple linear regression and Cox regression each should be assessed; 2) how these underlying assumptions may be assessed; and 3) what to do if these assumptions are violated.We believe that the validity of randomised clinical trial results will increase if our recommendations for assessing and dealing with violations of the underlying statistical assumptions are followed.

Understanding pathways to inequalities in child mental health: a counterfactual mediation analysis in two national birth cohorts in the UK and Denmark.

OBJECTIVES: We assessed social inequalities in child mental health problems (MHPs) and how they are mediated by perinatal factors, childhood illness and maternal mental health in two national birth cohorts. DESIGN: Longitudinal cohort study SETTING: We used data from the UK Millennium Cohort Study and the Danish National Birth Cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: We applied causal mediation analysis to longitudinal cohort data. Socioeconomic conditions (SECs) at birth were measured by maternal education. Our outcome was child MHPs measured by the Strength and Difficulty Questionnaire at age 11. We estimated natural direct, indirect and total effects (TEs) of SECs on MHPs. We calculated the proportion mediated (PM) via three blocks of mediators-perinatal factors (smoking/alcohol use during pregnancy, birth weight and gestational age), childhood illness and maternal mental health. RESULTS: At age 11 years, 9% of children in the UK and 3.8% in Denmark had MHPs. Compared with high SECs, children in low SECs had a higher risk of MHPs (relative risk (RR)=4.3, 95% CI 3.3 to 5.5 in the UK, n=13 112; and RR=6.2, 95% CI 4.9 to 7.8 in Denmark, n=35 764). In the UK, perinatal factors mediated 10.2% (95% CI 4.5 to 15.9) of the TE, and adding maternal mental health tripled the PM to 32.2% (95% CI 25.4 to 39.1). In Denmark, perinatal factors mediated 16.5% (95% CI 11.9 to 21.1) of the TE, and including maternal mental health increased the PM to 16.9% (95% CI 11.2 to 22.6). Adding childhood illness made little difference in either country. CONCLUSION: Social inequalities in child mental health are partially explained by perinatal factors in the UK and Denmark. Maternal mental health partially explained inequalities in the UK but not in Denmark.

Adjusting Early Warning Score by clinical assessment: a study protocol for a Danish cluster-randomised, multicentre study of an Individual Early Warning Score (I-EWS).

INTRODUCTION: Track and trigger systems (TTSs) based on vital signs are implemented in hospitals worldwide to identify patients with clinical deterioration. TTSs may provide prognostic information but do not actively include clinical assessment, and their impact on severe adverse events remain uncertain. The demand for prospective, multicentre studies to demonstrate the effectiveness of TTSs has grown the last decade. Individual Early Warning Score (I-EWS) is a newly developed TTS with an aggregated score based on vital signs that can be adjusted according to the clinical assessment of the patient. The objective is to compare I-EWS with the existing National Early Warning Score (NEWS) algorithm regarding clinical outcomes and use of resources. METHOD AND ANALYSIS: In a prospective, multicentre, cluster-randomised, crossover, non-inferiority study. Eight hospitals are randomised to use either NEWS in combination with the Capital Region of Denmark NEWS Override System (CROS) or implement I-EWS for 6.5 months, followed by a crossover. Based on their clinical assessment, the nursing staff can adjust the aggregated score with a maximum of -4 or +6 points. We expect to include 150 000 unique patients. The primary endpoint is all-cause mortality at 30 days. Coprimary endpoint is the average number of times per day a patient is NEWS/I-EWS-scored, and secondary outcomes are all-cause mortality at 48 hours and at 7 days as well as length of stay. ETHICS AND DISSEMINATION: The study was presented for the Regional Ethics committee who decided that no formal approval was needed according to Danish law (J.no. 1701733). The I-EWS study is a large prospective, randomised multicentre study that investigates the effect of integrating a clinical assessment performed by the nursing staff in a TTS, in a head-to-head comparison with the internationally used NEWS with the opportunity to use CROS. TRIAL REGISTRATION NUMBER: NCT03690128.

How do early-life factors explain social inequalities in adolescent mental health? Findings from the UK Millennium Cohort Study.

BACKGROUND: Reducing inequalities in adolescent mental health is a public health priority, yet the pathways that link social conditions to mental health outcomes in the early years are unclear. We aimed to evaluate the extent to which early years risk factors explain social inequalities in adolescent mental health in the UK. METHODS: We analysed data from 6509 children captured in the UK Millennium Cohort Study. Mental health was assessed through the socioemotional behavioural problems at age 14 (Strengths and Difficulties Questionnaire). The main exposure was maternal education at birth, used as a measure of childhood socioeconomic conditions (SECs), and used to calculate the relative index of inequality. Using causal mediation analysis, we assessed how perinatal, individual child, family, peer relation and neighbourhood-level factors measured up to age 3-mediated the total effect (TE) of SECs on adolescent socioemotional behavioural problems, estimating the proportion mediated and natural indirect effect (NIE) via each block of mediators, and all mediators together. RESULTS: Children of mothers with no qualification were almost four times as likely to have socioemotional behavioural problems compared with degree plus level (relative risk (RR) 3.82, 95% CI 2.48 to 5.88). Overall, 63.9% (95% CI 50.2% to 77.6%) (NIE RR 1.97, 95% CI 1.63 to 2.37) of the TE (RR 4.40, 95% CI 3.18 to 6.07) of social inequalities on risk of adolescent socioemotional behavioural problems was mediated by early-life factors. CONCLUSIONS: About two-thirds of the social inequality in adolescent mental health was explained by early risk factors measured by age 3, highlighting the importance of public health interventions in this period.

The Mediating Effect of Pupils' Physical Fitness on the Relationship Between Family Socioeconomic Status and Academic Achievement in a Danish School Cohort.

INTRODUCTION: Family socioeconomic status influences pupils' academic achievements, and studies have established positive associations between physical fitness and academic achievements. However, whether physical fitness mediates the relationship remains unknown. OBJECTIVE: We investigated if pupils' physical fitness mediates the pathway between family socioeconomic status and academic achievement using causal inference-based mediation analysis. METHODS: This study included 527 girls and 552 boys between 13 and 15 years of age from the Danish municipality of Aalborg. Physical fitness was measured through VO2max tests in 2010 and demographic data were obtained from nationwide registers. Family socioeconomic status was classified into four levels ranging from 1 to 4, where level 1 represents the lowest and level 4 the highest based on either family income or education. RESULTS: Controlling for sex, ethnicity, age, and parents' cohabitation status, all total effects display higher academic achievement with increased family socioeconomic status. Splitting the effects, the direct effects reveal the existence of other pathways not involving physical fitness. The indirect effects established physical fitness as a mediator showing that pupils from family socioeconomic status levels one, three, and four changes grade by - 0.13 [95% confidence interval (CI) - 0.26, - 0.01], 0.07 (95% CI 0.00, 0.14), and 0.24 (95% CI 0.14, 0.34), respectively, compared to socioeconomic status level two. The corresponding proportions mediated are 18% (95% CI 1, 57), 6% (95 CI 0, 13), and 12% (95% CI 7, 18) when family socioeconomic status is based on education. Classifying family socioeconomic status on income, pupils from family socioeconomic status levels one, three, and four show grade changes of - 0.07 (95% CI - 0.16, 0.02), 0.22 (95% CI 0.13, 0.32), and 0.26 (95% CI 0.15, 0.37), respectively, compared to socioeconomic status level two. The corresponding proportions mediated are 12% (95% CI - 6, 41), 30% (95% CI 16, 54), and 20% (95% CI 12, 32). CONCLUSION: In conclusion, pupils' physical fitness partially mediated the pathway between family socioeconomic status and academic achievement.

Cerebral palsy among children of immigrants in Denmark and the role of socioeconomic status.

BACKGROUND: Children of immigrants in Denmark have excess risk for some of the most well-established risk factors for cerebral palsy (CP). OBJECTIVES: To study differences in risk of CP between children of immigrants and children of Danish-born mothers, and explore whether socioeconomic status drives any potential association. METHODS: A register-based cohort study including 1,274,616 children born in Denmark between 1981 and 2007. Of these, 2807 had a validated CP diagnosis in the Danish CP Register. We estimated the risk of CP as odds ratios (OR) using logistic regression and assessed mediation through socioeconomic status using natural effect models. RESULTS: In children of Danish-born mothers, 2.2/1000 had CP overall and the prevalence was similar for children of immigrants. However, children of immigrants had lower risk of unilateral spastic CP than children of Danish native-born mothers; OR = 0.59 (95% CI:0.38-0.91) for Western and OR = 0.79 (95% CI:0.61-1.03) for Non-Western immigrants. By contrast, the risk of bilateral spastic CP was higher in children of Non-Western immigrants (OR = 1.27 (95% CI:1.05-1.53)), especially from Turkey and Pakistan compared with children of Danish native-born mothers. The mediation analysis revealed an indirect effect (through maternal educational level and household income) with an OR of 1.06 (95% CI:0.99-1.14) for children of Non-Western immigrants. CONCLUSIONS: While children of immigrants had lower risk of unilateral spastic CP than children of Danish-born mothers, the risk of bilateral spastic CP was increased in children of Non-Western immigrants. Socioeconomic status did not appear to be a significant contributor to the increased risk of bilateral spastic CP.

The effect of early-life and adult socioeconomic position on development of lifestyle-related diseases.

BACKGROUND: Early-life socioeconomic position (SEP) is associated with lifestyle-related diseases in adulthood. However, evidence is lacking on the extent to which adult SEP mediates this association. METHODS: Time to either chronic obstructive pulmonary disease (COPD), cardiovascular disease or diabetes were assessed in the Danish population born between 1961 and 1971 (n = 793 674) from age 30 until 2015. Early-life position was assessed in 1981 (by parental) and again at age 30 (own) by four markers; income, occupation, education-divided into high, middle, low-and a combined score for all markers. Using a counterfactual approach, we estimated the total effect of early-life position on disease onset and the degree to which adult position mediated this effect. RESULTS: Results of the time-to-event analysis showed a gradient of all early-life markers on the risk of developing all lifestyle-related diseases. Notably, comparing those in the lowest to the highest educational position, the hazard of COPD was 130% higher for women [hazard ratio = 2.30(95% confidence interval = 2.20-2.41)] and 114% higher for men [2.14 (2.05-2.25)]. About 67%(63-70%) of the effect of educational position was mediated through adult position for COPD, 55% for cardiovascular disease and 50% for diabetes. For the combined score 44, 29 and 33%, respectively, was mediated. CONCLUSION: About one-tenth to two-thirds of the effect of early-life position is mediated by the position attained in adulthood. The degree mediated depend on the outcome investigated, gender and the social position marker used indicating that alternative pathways may play a key role in developing effective policies targeting early-life behaviours.

Education and Cognitive Aging: Accounting for Selection and Confounding in Linkage of Data From the Danish Registry and Survey of Health, Ageing and Retirement in Europe.

Earlier studies report inconsistent associations between education and cognitive aging. We assessed the association, accounting for selective dropout due to death or dementia, and, in a subsample, accounting for confounding by early-life intelligence. Data from the Danish component of the Survey of Health, Ageing and Retirement in Europe (n = 3,400) were linked to registry data (education records, dementia diagnoses, and mortality) and the Danish Conscription Database (youth intelligence measurements for 854 men). Word recall and verbal fluency were assessed up to 4 times over 10 years (2004-2013) and combined by averaging the z scores. We fitted a joint model linking a time-to-event model for dementia or death to a linear mixed-effects model for cognitive change. Rate of cognitive decline was slower among people with high education compared with low education (ß = 0.112, 95% confidence interval (CI): 0.056, 0.170). Adjusting for youth intelligence did not attenuate the association between education and cognitive decline (crude ß = 0.136, 95% CI: 0.028, 0.244 vs. adjusted ß = 0.145, 95% CI: 0.022, 0.269). The results suggest that higher education may slow cognitive decline in later life. In this sample, results changed little when accounting for selective attrition and confounding by intelligence.

Work-unit social capital and long-term sickness absence: a prospective cohort study of 32 053 hospital employees.

OBJECTIVE: There is a lack of studies investigating social capital at the workplace level in small and relatively homogeneous work-units. The aim of the study was to investigate whether work-unit social capital predicts a lower risk of individual long-term sickness absence among Danish hospital employees followed prospectively for 1 year. METHODS: This study is based on the Well-being in HospitAL Employees cohort. The study sample consisted of 32 053 individuals nested within 2182 work-units in the Capital Region of Denmark. Work-unit social capital was measured with an eight-item scale covering elements of trust, justice and collaboration between employees and leaders. Social capital at the work-unit level was computed as the aggregated mean of individual-level social capital within each work-unit. Data on long-term sickness absence were retrieved from the employers' payroll system and were operationalised as ≥29 consecutive days of sickness absence. We used a 12-point difference in social capital as the metric in our analyses and conducted two-level hierarchical logistic regression analysis. Adjustments were made for sex, age, seniority, occupational group and part-time work at the individual level, and work-unit size, the proportion of female employees and the proportion of part-time work at the work-unit level. RESULTS: The OR for long-term sickness absence associated with a 12-point higher work-unit social capital was 0.73 (95% CI 0.68 to 0.78). Further, we found an association between higher work-unit social capital and lower long-term sickness absence across quartiles of social capital: compared with the lowest quartile, the OR for long-term sickness absence in the highest quartile was 0.51 (95% CI 0.44 to 0.60). CONCLUSION: Our study provides support for work-unit social capital being a protective factor for individual long-term sickness absence among hospital employees in the Capital Region of Denmark.

Occupational Social Class and Personality Traits in Relation to Leisure-Time Physical Activity Level: Cross-Sectional Results From the Copenhagen Aging and Midlife Biobank.

OBJECTIVE: To investigate separate and combined associations of occupational social class and personality traits with late midlife leisure-time physical activity duration and intensity. METHOD: Cross-sectional data from the Copenhagen Aging and Midlife Biobank ( N = 4,649) were analyzed using linear regression models with leisure-time physical activity (metric equivalence) as outcome. RESULTS: Low versus high occupational social class was associated with 4% (95% confidence interval [CI] = [3%, 5%]) greater leisure-time physical activity duration, but 2% (CI = [1%, 3%]) lower intensity. Each 10-unit increase in extraversion was associated with 5% (CI = [2%, 8%]) greater duration. Intensity increased by each 10-unit increase in conscientiousness (6%, CI = [4%, 7%]), openness (3%, CI = [1%, 4%]), neuroticism (3%, CI = [1%, 4%]), and extraversion (5%, CI = [4%, 7%]). Conscientiousness was positively associated with duration in low, but not in high, occupational social class (interaction p value = .002). DISCUSSION: Higher occupational social class was associated with lower leisure-time physical activity duration, but higher intensity. Extraversion was positively associated with duration and intensity. Conscientiousness, openness, and neuroticism were positively associated with intensity. Overall, interactions were not consistent.

A Methodology for Anatomic Ultrasound Image Diagnostic Quality Assessment.

This paper discusses the methods for the assessment of ultrasound image quality based on our experiences with evaluating new methods for anatomic imaging. It presents a methodology to ensure a fair assessment between competing imaging methods using clinically relevant evaluations. The methodology is valuable in the continuing process of method optimization and guided development of new imaging methods. It includes a three phased study plan covering from initial prototype development to clinical assessment. Recommendations to the clinical assessment protocol, software, and statistical analysis are presented. Earlier uses of the methodology has shown that it ensures validity of the assessment, as it separates the influences between developer, investigator, and assessor once a research protocol has been established. This separation reduces confounding influences on the result from the developer to properly reveal the clinical value. This paper exemplifies the methodology using recent studies of synthetic aperture sequential beamforming tissue harmonic imaging.

Education and cause-specific mortality: the mediating role of differential exposure and vulnerability to behavioral risk factors.

BACKGROUND: Differential exposures to behavioral risk factors have been shown to play an important mediating role on the education-mortality relation. However, little is known about the extent to which educational attainment interacts with health behavior, possibly through differential vulnerability. METHODS: In a cohort study of 76,294 participants 30 to 70 years of age, we estimated educational differences in cause-specific mortality from 1980 through 2009 and the mediating role of behavioral risk factors (smoking, alcohol intake, physical activity, and body mass index). With the use of marginal structural models and three-way effect decomposition, we simultaneously regarded the behavioral risk factors as intermediates and clarified the role of their interaction with educational exposure. RESULTS: Rate differences in mortality comparing participants with low to high education were 1,277 (95% confidence interval = 1,062 to 1,492) per 100,000 person-years for men and 746 (598 to 894) per 100,000 person-years for women. Smoking was the strongest mediator for cardiovascular disease, cancer, and respiratory disease mortality when conditioning on sex, age, and cohort. The proportion mediated through smoking was most pronounced in cancer mortality as a combination of the pure indirect effect, owing to differential exposure (men, 42% [25% to 75%]; women, 36% [17% to 74%]) and the mediated interactive effect, owing to differential vulnerability (men, 18% [2% to 35%], women, 26% [8% to 50%]). The mediating effects through body mass index, alcohol intake, or physical activity were partial and varied for the causes of deaths. CONCLUSION: Differential exposure and vulnerability should be addressed simultaneously, as these mechanisms are not mutually exclusive and may operate at the same time.

Cohort profile: the Social Inequality in Cancer (SIC) cohort study.

The Social Inequality in Cancer (SIC) cohort study was established to determine pathways through which socioeconomic position affects morbidity and mortality, in particular common subtypes of cancer. Data from seven well-established cohort studies from Denmark were pooled. Combining these cohorts provided a unique opportunity to generate a large study population with long follow-up and sufficient statistical power to develop and apply new methods for quantification of the two basic mechanisms underlying social inequalities in cancer-mediation and interaction. The SIC cohort included 83 006 participants aged 20-98 years at baseline. A wide range of behavioural and biological risk factors such as smoking, physical inactivity, alcohol intake, hormone replacement therapy, body mass index, blood pressure and serum cholesterol were assessed by self-administered questionnaires, physical examinations and blood samples. All participants were followed up in nationwide demographic and healthcare registries. For those interested in collaboration, further details can be obtained by contacting the Steering Committee at the Department of Public Health, University of Copenhagen, at inan@sund.ku.dk.

Adherence to preventive statin therapy according to socioeconomic position.

AIM: To explore whether long-term adherence to preventive statin therapy depends on socioeconomic position (SEP). METHODS: A cohort of individuals without established cardiovascular disease (CVD) or diabetes initiating preventive statin therapy during 2002-2005 was followed in the individual-level Danish registries for 4 years or until censoring events (death, emigration, CVD or diabetes). Only individuals aged 40-84 years for whom information was available on the SEP indicators, education and income were included (N = 76,038). Two different aspects of poor adherence were applied as outcome measures: (1) Proportion of days covered (PDC) with medication below 80 %, assuming a daily dose of one tablet (continuity); (2) Discontinuation defined as a gap between two consecutive prescriptions exceeding 365 days (persistence). Stratum-specific logistic regression analyses were applied to estimate the odds ratio (OR) for PDC <80 % across SEP, adjusting for age and hypertension. Hazard ratio (HR) for discontinuation was estimated by Cox regression analyses. RESULTS: Adjusting mutually for income and education, the OR for PDC <80 % decreased with increasing income. Comparing the highest income quintile with the lowest, the OR were 0.64 (95 % Confidence Interval 0.64-0.65) and 0.73 (0.73-0.74) in men aged 40-64 and 65-84 years, respectively; in women, the figures were 0.79 (0.79-0.79) and 0.95 (0.94-0.95), respectively. While observed increases in adherence with longer education in unadjusted analyses were attenuated after adjustment for income among men, the potential inverse relationship between length of education and adherence was enhanced among women. Applying discontinuation as outcome, analogous differences were demonstrated. CONCLUSION: Adherence to preventive statin therapy in Denmark decreases with decreasing income-especially in men aged 40-64 years.

Education and risk of coronary heart disease: assessment of mediation by behavioral risk factors using the additive hazards model.

Educational-related gradients in coronary heart disease (CHD) and mediation by behavioral risk factors are plausible given previous research; however this has not been comprehensively addressed in absolute measures. Questionnaire data on health behavior of 69,513 participants, 52 % women, from seven Danish cohort studies were linked to registry data on education and incidence of CHD. Mediation by smoking, low physical activity, and body mass index (BMI) on the association between education and CHD were estimated by applying newly proposed methods for mediation based on the additive hazards model, and compared with results from the Cox proportional hazards model. Short (vs. long) education was associated with 277 (95 % CI: 219, 336) additional cases of CHD per 100,000 person-years at risk among women, and 461 (95 % CI: 368, 555) additional cases among men. Of these additional cases 17 (95 % CI: 12, 22) for women and 37 (95 % CI: 28, 46) for men could be ascribed to the pathway through smoking. Further, 39 (95 % CI: 30, 49) cases for women and 94 (95 % CI: 79, 110) cases for men could be ascribed to the pathway through BMI. The effects of low physical activity were negligible. Using contemporary methods, the additive hazards model, for mediation we indicated the absolute numbers of CHD cases prevented when modifying smoking and BMI. This study confirms previous claims based on the Cox proportional hazards model that behavioral risk factors partially mediates the effect of education on CHD, and the results seems not to be particularly model dependent.

Is the high-risk strategy to prevent cardiovascular disease equitable? A pharmacoepidemiological cohort study.

BACKGROUND: Statins are increasingly prescribed to prevent cardiovascular disease (CVD) in asymptomatic individuals. Yet, it is unknown whether those at higher CVD risk - i.e. individuals in lower socio-economic position (SEP) - are adequately reached by this high-risk strategy. We aimed to examine whether the Danish implementation of the strategy to prevent cardiovascular disease (CVD) by initiating statin (HMG-CoA reductase inhibitor) therapy in high-risk individuals is equitable across socioeconomic groups. DESIGN: Cohort study. SETTING AND PARTICIPANTS: Applying individual-level nationwide register information on socio-demographics, dispensed prescription drugs and hospital discharges, all Danish citizens aged 20+ without previous register-markers of CVD, diabetes or statin therapy were followed during 2002-2006 for first occurrence of myocardial infarction (MI) and a dispensed statin prescription (N = 3.3 mill). MAIN OUTCOME MEASURES: Stratified by gender, 5-year age-groups and socioeconomic position (SEP), incidence of MI was applied as a proxy for statin need. Need-standardized statin incidence rates were calculated, applying MI incidence rate ratios (IRR) as need-weights to adjust for unequal needs across SEP.Horizontal equity in initiating statin therapy was tested by means of Poisson regression analysis. Applying the need-standardized statin parameters and the lowest SEP-group as reference, a need-standardized statin IRR > 1 translates into horizontal inequity favouring the higher SEP-groups. RESULTS: MI incidence decreased with increasing SEP without a parallel trend in incidence of statin therapy. According to the regression analyses, the need-standardized statin incidence increased in men aged 40-64 by 17%, IRR 1.17 (95% CI: 1.14-1.19) with each increase in income quintile. In women the proportion was 23%, IRR 1.23 (1.16-1.29). An analogous pattern was seen applying education as SEP indicator and among subjects aged 65-84. CONCLUSION: The high-risk strategy to prevent CVD by initiating statin therapy seems to be inequitable, reaching primarily high-risk subjects in lower risk SEP-groups.

Significant regional differences in Denmark in outcome after cochlear implants in children.

INTRODUCTION: The objectives of the present study were to study regional differences in outcome for a paediatric cochlear implant (CI) population after the introduction of universal neonatal hearing screening (UNHS) and bilateral implantation in Denmark. MATERIAL AND METHODS: Data relate to 94 subjects. A test battery consisting of eight different tests/assessments was performed in order to report the level of audition, speech, language and self-esteem. For data analyses of any associations between the regions, Fisher's exact test was used. Potential rater variability within either of the centres was assessed using logistic regression models. RESULTS: The levels of audition were comparable between the group from West Denmark (West) and the group from East Denmark (East). In contrast, all tests of speech and language revealed a statistically significant difference between East and West. In all tests, West subjects scored significantly lower than East subjects. West children received more hours of speech therapy, more learning support assistance, and more parents used signing. Furthermore, the parents from West were significantly less involved in the auditory rehabilitation of their children than parents from East. CONCLUSION: The results were remarkable and call for a thorough evaluation of both the quality and organization of the paediatric CI population with particular concern for the paediatric CI population of West Denmark. FUNDING: The Oticon foundation financially supported this study. Trial registration was not relevant as the study is designed as a prospective case series. TRIAL REGISTRATION: not relevant.

Direct and indirect effects in a survival context.

A cornerstone of epidemiologic research is to understand the causal pathways from an exposure to an outcome. Mediation analysis based on counterfactuals is an important tool when addressing such questions. However, none of the existing techniques for formal mediation analysis can be applied to survival data. This is a severe shortcoming, as many epidemiologic questions can be addressed only with censored survival data. A solution has been to use a number of Cox models (with and without the potential mediator), but this approach does not allow a causal interpretation and is not mathematically consistent. In this paper, we propose a simple measure of mediation in a survival setting. The measure is based on counterfactuals, and measures the natural direct and indirect effects. The method allows a causal interpretation of the mediated effect (in terms of additional cases per unit of time) and is mathematically consistent. The technique is illustrated by analyzing socioeconomic status, work environment, and long-term sickness absence. A detailed implementation guide is included in an online eAppendix (http://links.lww.com/EDE/A476).