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Aims: To assess whether lifestyle factors, including sleep pattern, are predictors for the development of functional somatic disorder (FSD)., Methods: A population-based prospective cohort of 9656 men and women aged 18-76 years was established in 2011-2015 and invited for re-examination in 2017-2020, when 5738 participated. Median follow-up period was 65 months. Participants filled in validated questionnaires on lifestyle, sleep pattern and various delimitations of FSD, which were operationalized using two different approaches: bodily distress syndrome (BDS) and functional somatic syndromes (FSS) (i.e. chronic fatigue, chronic widespread pain (CWP), irritable bowel, and multiple chemical sensitivity (MCS)). Baseline lifestyle and sleep pattern in relation to incidence of BDS and FSS (chronic fatigue, CWP, irritable bowel, MCS) was analysed by logistic regressions, adjusted for age, sex and subjective social status., Results: Inferior sleep quality at baseline predicted both incidence of BDS and all FSS delimitations except MCS. Smoking, alcohol intake, and low physical activity, but not diet, were predictors for the development of BDS. No uniform pattern was observed for the FSS. Smoking predicted development of chronic fatigue, CWP and irritable bowel, but not MCS. Alcohol and food quality only influenced the development of chronic fatigue whereas low physical activity only influenced the development of chronic fatigue and CWP., Conclusions: Lifestyle factors and sleep pattern seem to be predictors for some delimitations of FSD, but the importance of the various lifestyle factors is different for the different delimitations. The study shows the importance of analysing the various FSSs separately ., Competing Interests: Declaration of conflicting interestsThe authors have no conflicts of interest to declare.

Aim: To examine trends in all body mass index (BMI) groups in children from 1936 to 2011., Methods: We included 197 694 girls and 201 276 boys from the Copenhagen School Health Records Register, born between 1930 and 1996, with longitudinal weight and height measurements (6-14 years). Using International Obesity Task Force criteria, BMI was classified as underweight, normal-weight, overweight and obesity. Sex- and age-specific prevalences were calculated., Results: From the 1930s, the prevalence of underweight was stable until a small increase occurred from 1950 to 1970s, and thereafter it declined into the early 2000s. Using 7-year-olds as an example, underweight changed from 10% to 7% in girls and from 9% to 6% in boys during the study period. The prevalence of overweight plateaued from 1950 to 1970s and then steeply increased from 1970s onwards and in 1990-2000s 15% girls and 11% boys at 7 years had overweight. The prevalence of obesity particularly increased from 1980s onwards and in 1990-2000s 5% girls and 4% boys at 7 years had obesity. These trends slightly differed by age., Conclusion: Among Danish schoolchildren, the prevalence of underweight was greater than overweight until the 1980s and greater than obesity throughout the period. Thus, monitoring the prevalence of childhood underweight remains an important public health issue., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objectives: Earlier studies on the association between plasma lipid profiles and functional somatic disorders (FSD) are mainly small case control studies hampered by selection bias and do not consider the great overlap between the various FSDs. The aim of the present study was to investigate the associations between various FSDs and plasma lipid profiles (total cholesterol, HDL cholesterol, non-HDL cholesterol and triglycerides) in a large, unselected population., Design: A cross-sectional general population-based study., Setting: The Danish Study of Functional Somatic Disorders (DanFunD) conducted in 2011-2015 in 10 municipalities in the western part of greater Copenhagen, Denmark., Participants: A total of 8,608 men and women aged 18-76 years were included in the analyses. Various delimitations of FSD such as chronic fatigue, chronic widespread pain, irritable bowel, and bodily distress syndrome were measured using validated self-administrated questionnaires. Lipid parameters were measured from fasting plasma samples using colorimetric slide methods with Vitros 4600/5600 Ortho Clinical Diagnostics., Outcome Measures: Logistic regression analyses were used to calculate possible associations between plasma lipids and the various delimitations of FSD. Associations are presented by OR (95% CI) and shown in boxplots., Results: We found a positive association between bodily distress syndrome and triglycerides and non-HDL cholesterol and a negative association with HDL-cholesterol, but no consistent association with total cholesterol. A similar pattern was observed for persons with chronic fatigue, and to some degree for persons with chronic widespread pain, whereas persons with irritable bowel did not show a clear association with the lipid profiles., Conclusion: This is the first major study on plasma lipid profiles and FSD indicating an association between some delimitations of FSD and an unfavorable lipid profile. Due to the cross-sectional design, it cannot be determined whether the findings are consequences or determinants of FSD. Further studies-preferable prospective studies-are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jørgensen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: High occupational physical activity (OPA) seems to increase risk of cardiovascular diseases among men. However, findings are mixed, and it is not known if women are differently affected. Therefore, the aim of this study is to investigate the relationship between OPA and risk for ischaemic heart disease (IHD), and whether it differs across sex., Methods and Results: This prospective cohort study was based on 1399 women and 1706 men, aged 30-61 years, participating in the Danish Monica 1 study in 1982-84, actively employed, without prior IHD and answering an OPA question. The information on incidence of IHD, before and during the 34-years follow-up, was retrieved by individual linkage to the Danish National Patient Registry. Cox proportional hazards models were used to investigate the association between OPA and IHD. Compared to women with sedentary work, women in all other OPA categories had lower hazard ratio (HR) for IHD. Among men, the risk of IHD was 22% higher among those with light OPA, and 42% and 46% higher among those with moderate OPA with some lifting or strenuous work with heavy lifting, respectively, compared to men with sedentary OPA. Compared to women with sedentary work, HR for IHD was higher among men in all OPA categories. There was statistically significant interaction between OPA and sex., Conclusion: Demanding or strenuous OPA seems to be a risk factor for IHD among men, whereas a higher level of OPA seems to protect women from IHD. This emphasizes the importance of taking sex differences into account in studies of health effects of OPA., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification., Methods and Analysis: The InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52-82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance., Ethics and Dissemination: Oral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported., Trial Registration Number: NCT05259046., Competing Interests: Competing interests: FBK, SMT and AL have received funds and tablets for the trial from Kappa Bioscience AS. AL discloses the application of a patent on vitamin K on lung function for prognostic and therapeutic purposes. Aside from this, the authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Major depression (MD) aggregates within families, but how family history of MD confers risk of MD over the life course is unclear. Such knowledge is important to identify and prevent possible depressogenic effects of family environment., Objective: To examine the association between family MD history and risk of MD including association with age, sex, type of kinship, and age of the affected family member., Design, Setting, and Participants: This cohort study included all Danish citizens born from 1960 to 2003 with known parental identity followed up from their 15th birthday until time of MD, censoring, or December 31, 2018. Analysis took place between April 2022 and December 2022., Exposures: Family members with first-time MD using International Classification of Diseases, Eighth Revision codes 296.09, 296.29, 298.09, and 300.49 or 10th Revision codes F32.0-F33.9, family members' age at MD onset, and individuals' age at exposure to family MD., Main Outcomes and Measures: Multivariable Poisson regression was applied to estimate the incidence rate ratio (IRR) with 95% CI of first-time MD., Results: Of 2 903 430 individuals (1 486 574 [51.2%] men), 37 970 men (2.6%) and 70 223 women (5.0%) developed MD during follow-up. For men, exposure to maternal, paternal, or full sibling MD were associated with a 2-times higher risk of MD (IRR, 2.10 [95% CI, 2.02-2.19]; IRR, 2.04 [95% CI, 1.94-2.14]; IRR, 2.08 [95% CI, 1.97-2.19]) and the associated risk increased with number of affected family members. This pattern was similar for women. For men, family members' age at MD onset was not associated with MD. For women, maternal MD onset at 69 years or younger was associated with higher IRRs of MD (age <40 years: IRR, 1.64 [95% CI, 1.28-2.10]; age 40-49 years: IRR, 1.62 [95% CI, 1.27-2.07]; age 50-59 years: IRR, 1.56 [95% CI, 1.22-2.00]; and age 60-69 years: IRR, 1.67 [95% CI, 1.28-2.16]) compared with women with maternal MD onset at 70 years or older. For men, exposure to maternal MD younger than 30 years (age <1 year: IRR, 1.95 [95% CI, 1.70-2.25]; age 1 to <12 years: IRR, 2.31 [95% CI, 2.16-2.47]; age 12 to <19 years: IRR, 2.18 [95% CI, 2.03-2.35]; age 19 to <30 years: IRR, 1.42 [95% CI, 1.32-1.53]) was associated with increased IRRs, while exposure to maternal MD at 30 years or older was associated with a lower IRR (0.77 [95% CI, 0.70-0.85]). The findings were similar across type of kinships and for women., Conclusions and Relevance: In this study, risk of MD was associated with increased numbers of affected family members but did not vary by gender or type of kinship. Exposure to family MD during childhood and adolescence was associated with increased risk.

Pregnant women with psychosocial vulnerabilities should be offered perinatal interventions that include a parenting component to ameliorate the potential negative effects of maternal mental health problems and/or poor social network on parenting. One such intervention program is the Circle of Security-Parenting intervention (COS-P). The COS-P is a manualized video-based intervention that based on attachment theory seek to enhance maternal sensitivity and decrease the risk on insecure and disorganized attachment. We carried out a randomized controlled trial examining the efficacy of a perinatal adapted version of COS-P for women with psychosocial vulnerabilities (e.g. histories of mental health problems and/or poor social networks). Eligible participants (N = 78) were recruited to the study by midwives during regular prenatal sessions. Interventions were delivered individually at home by trained health nurses both pre and post birth. The primary outcome was maternal sensitivity assessed with the Coding Interactive Behavior Manual by blinded coders from video-recordings of mother-infant free play interactions. Secondary outcomes were mother-reported depressive symptoms, parental reflective functioning, parental stress, infant socio-emotional functioning, and maternal wellbeing. All outcomes were assessed at nine months infant age. We did not find an effect of the intervention on the primary outcome of maternal sensitivity (β = -0.08; 95% CI [-0.41, 0.26], p = .66). Neither did we find intervention effects on the secondary outcomes of depressive symptoms, parental reflective functioning, maternal well-being, or infant socio-emotional functioning. We did however find that the intervention decreased parental stress (β = -8.51; 95% CI [-16.6;-0.41], p = .04). The results are discussed in light of existing findings on the effect of COS-P and sample heterogeneity. Furthermore, we discuss the challenges of adapting the COS-P for pregnant women, some without prior experiences with caregiving. Future research with larger at-risk samples examining moderation factors (e.g. adult attachment, depression maternal-fetal attachment) are recommended., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Røhder et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Metformin has pleiotropic effects including anti-inflammatory properties and effects on the gut microbiome. It is primarily used in the older population, where the occurrence of inflammatory bowel disease (IBD) is increasing. The aim of this study was to examine whether metformin protects against development of IBD., Methods: In the setting of a Danish nationwide population-based cohort, we conducted a nested case-control study using a new-user active comparator design. For each patient with IBD, we selected 10 IBD-free individuals matched on age, sex, and duration of follow-up. Conditional logistic regression was used to estimate odds ratios (ORs) of IBD. Adjustment included educational level, other immune-mediated inflammatory diseases, and use of dipeptidyl peptidase (DPP)-4 inhibitors and statins., Results: Among 302,863 IBD-free new users of oral glucose-lowering drugs, we identified 1271 patients who developed IBD and 12,676 matched IBD-free individuals. Mean age at IBD diagnosis was 66 (SD, 11) years. We found no association between ever use of metformin and risk of IBD, Crohn's disease or ulcerative colitis, adjusted OR 0.95 (95% CI 0.78-1.15), 0.87 (95% CI 0.60-1.26), and 1.04 (95% CI 0.83-1.31), respectively. Neither was the cumulative dose of metformin or the treatment duration with metformin associated with risk of IBD., Conclusions: In this population-based study, we report that despite anti-inflammatory effects and a notable impact on the gut microbiome, metformin use is not associated with reduced risk of older onset IBD., (© 2022. Japanese Society of Gastroenterology.)

Importance: Observational studies have indicated that glasses might protect against contracting COVID-19 through reduced airborne and contact transmission., Objective: To investigate the association between wearing one's own glasses with contracting COVID-19 when adjusting for relevant confounders., Design, Setting, and Participants: This cohort study was conducted during the first wave of the COVID-19 pandemic (June to August 2020) in Denmark and Sweden, where personal protective equipment was not recommended for the general population at the time. Employees at Falck, an international rescue corps with different job functions (ambulance, health care, office, and field staff, firefighters, and roadside assistance) participated in the study., Exposures: The main exposure was wearing glasses (also including contact lenses and reading glasses), which was assessed in a questionnaire. Persons wearing glasses were compared with those who did not wear glasses (ie, nonusers). To adjust for potential confounders, information on age, sex, job function, and number of workday contacts were included., Main Outcomes and Measures: The outcome was COVID-19 infection before (positive polymerase chain reaction test) or during the study period (biweekly voluntary tests with a rapid test). The investigated hypothesis was formulated after collecting the data., Results: A total of 1279 employees in Denmark and 841 in Sweden were included (839 [39.6%] female and 1281 [60.4%] male; 20.5% were aged <40 years; 57.0%, 40-60 years, and 22.5%, >60 years). Of these, 829 individuals (64.8%) in Denmark and 619 (73.6%) in Sweden wore glasses. Wearing glasses was inversely associated with COVID-19 infection in the Swedish cohort (odds ratio [OR], 0.61 [95% CI, 0.37-0.99]; P = .047; seroprevalence, 9.3%) but not in the Danish cohort (OR, 1.14 [95% CI, 0.53-2.45]; P = .73; seroprevalence, 2.4%). Adjusting for age, sex, job function, and number of workday contacts in Sweden, wearing glasses no longer was associated with COVID-19 infection (OR, 0.64 [95% CI, 0.37-1.11]; P = .11). When stratifying by job function, a large difference was observed among office staff (OR, 0.20 [95% CI, 0.06-0.70]; P = .01) but not ambulance staff (OR, 0.83 [95% CI, 0.41-1.67]; P = .60) nor health care staff (OR, 0.89 [95% CI, 0.35-2.30]; P = .81)., Conclusions and Relevance: While wearing one's glasses was inversely associated with COVID-19 in Sweden in an unadjusted analysis, an association no longer was identified when adjusting for confounders. These results provide inconclusive findings regarding whether wearing one's own glasses is associated with a decreased risk of COVID-19 infections.

The Animated Triangles Task (AT) is commonly used to measure Theory of Mind (ToM). AT can be scored by clinicians based on participants' verbal responses (AT-verbal) or using a multiple-choice paradigm (AT-MCQ). This study aimed to evaluate the validity of the less time-consuming AT-MCQ. To do this, we examined agreement and correlations between the AT-MCQ and the original AT-verbal scores in 1546 adolescents from a population-based sample. As a supplementary analysis of known-groups validity, we examined if AT-MCQ was as sensitive as AT-verbal in detecting ToM-limitations in 54 adolescents with autism spectrum disorder (ASD), using register-data. The agreement between AT-verbal and AT-MCQ varied markedly across test items. Scores on the two scoring methods were weakly correlated. Both scoring methods weakly detected differences between adolescents with and without ASD in this population-based sample. Most participants had appropriate responses on both AT-MCQ and AT-verbal, which yielded overall acceptable agreement. However, the feasibility of using either scoring methods to measure ToM-limitations in adolescents from the general population is questionable., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: The aim of this study was to examine the risk of new-onset inflammatory bowel disease [IBD] following bariatric surgery., Methods: We conducted a nationwide population-based prospective cohort study of the entire Danish population 18 to 60 years of age, alive, and residing in Denmark, from 1996 to 2018. Bariatric surgery was included as a time-dependent variable, and Cox proportional hazards regression models were used to estimate hazard ratios [HRs] of IBD. We used a model adjusting for age, sex, and birth cohort and a multifactor-adjusted model additionally including educational status and number of obesity-related comorbidities., Results: We followed 3 917 843 individuals of whom 15 347 had a bariatric surgery, for development of new-onset IBD. During 106 420 person-years following bariatric surgery, 100 IBD events occurred [incidence rate 0.940/1000 person-years]. During 55 553 785 person-years without bariatric surgery, 35 294 events of IBD occurred [incidence rate 0.635/1000 person-years]. This corresponded to a multifactor-adjusted hazard ratio [HR] of 1.15 (95% confidence interval[CI], 0.94-1.40) for IBD. Multifactor-adjusted HRs of Crohn's disease [CD] and ulcerative colitis [UC] were 1.85 [95% CI, 1.40-2.44] and 0.81 [95% CI, 0.61-1.08], respectively. Among women, the multifactor-adjusted HR for CD was 2.18 [95% CI, 1.64-2.90]. When limiting the study population to individuals with a diagnosis of overweight/obesity, bariatric surgery remained associated with increased risk of CD, multifactor-adjusted HR 1.59 [95% CI, 1.18-2.13]., Conclusions: This nationwide cohort study shows that bariatric surgery is associated with increased risk of development of new-onset CD, but not of UC. The underlying mechanisms remain elusive., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The incidence of hypothyroidism is not expected to differ by socioeconomic factors. However, the decision to test and initiate treatment may differ. We aimed to examine whether educational level influences the probability of thyroid stimulation hormone (TSH)-measurement and initiation of levothyroxine treatment., Design: Citizens in the greater Copenhagen Area during 2001-2015 were included. Individual-level data on educational level, diagnoses, GP-contact, TSH-measurement and medication were derived from administrative and healthcare registers. The relative risks (RR) between educational levels of annual TSH-measurement and treatment initiation following a TSH-measurement were analysed in Poisson regression models with generalized estimation equations., Results: A TSH-measurement was performed in 19% of 9,390,052 person years. The probability of TSH-measurement was higher with short (RR 1.16 [95% CI 1.15-1.16]) and medium (RR 1.11 [95% CI 1.06-1.12]) compared with long education. Treatment was initiated after 0.8% of 2,049,888 TSH-measurements. For TSH < 5 mIU/L, RR for treatment initiation ranged between 0.47 (95%CI 0.39-0.57) and 0.78 (95%CI 0.67-0.91) for short and medium compared with long education. For TSH 5-10 mIU/L, there was no statistically significant difference. For TSH > 10 mIU/L, RR was 1.07 (95% CI 1.02-1.12) for short and 1.08 (95% CI 1.03-1.13) for medium compared with long education., Conclusion: The probability of TSH-measurement was higher with shorter education, and the probability of treatment initiation with TSH > 10 mIU/L was marginally higher with short-medium education compared with long education. However, the probability of treatment initiation with TSH < 5 mIU/L, that is treatment incongruous with guidelines, was substantially higher in persons with long education., (© 2021 John Wiley & Sons Ltd.)

Open dialogue (OD) is a family-oriented approach that has demonstrated good outcomes in treatment of first-episode psychosis. OD focuses on communication as a joint process of constructing meaning among patients, their social networks, and professionals. The current study investigates how 42 participants experienced a training program in OD. The study comprises a cohort with a longitudinal design. Data were collected by means of semi-structured questionnaires and contained quantitative and qualitative data. Descriptive analysis was performed to analyze quantitative data and thematic analysis for qualitative data. Findings show that participants' learning outcomes and confidence with using OD with patients, social networks, and professionals increased significantly throughout the training program. Reflection and role play were essential learning methods. Participants defined themselves as in-progress and considered the training program educational, engaging, and varied. Three main themes arose from the data: Developing an OD Training Program , Competence Development "From Novice to Expert ," and Participation and Commitments . [ Journal of Psychosocial Nursing and Mental Health Services, 59 (5), 38-47.].

Objectives: MTX is the most commonly recommended DMARD for first-line treatment of RA, however, it has been hypothesized to cause lung disease as an adverse effect. We investigated the risk of interstitial lung disease (ILD) and acute and chronic respiratory failure in persons with RA treated with MTX and other medications., Methods: From the Danish National Patient Register (NPR) and the DANBIO register for rheumatic diseases, we retrieved data on 30 512 persons with RA registered in 1997-2015. Information on ILD and respiratory failure was obtained from the NPR. Information on age and sex for all Danish citizens was obtained from the Danish Civil Registration System. MTX and other medication purchases were retrieved from the Danish Prescription Registry. Associations between MTX and lung disease outcomes were analysed in Cox regression models with adjustment for age, calendar time, sex and other medications. Standardized incidence ratios (SIRs) of lung disease were calculated to compare the RA population with the general population., Results: There was no increased risk of lung disease with MTX treatment [one or more purchases compared with no purchases; HR 1.00 (95% CI 0.78, 1.27) for ILD and 0.54 (95% CI 0.43, 0.67) for respiratory failure] at the 5 year follow-up. The SIR was three to four times higher for ILD in MTX-treated persons with RA, but similar to the whole RA population compared with the background population., Conclusion: Persons with RA had an increased risk of ILD compared with the general population, but there was no further increased risk associated with MTX treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pregnancy offers a unique period for initiating preventive parenting interventions. Disturbances in maternal-fetal bonding may indicate suboptimal parenting and a need for intervention. However, more knowledge is needed on the development of maternal-fetal bonding among at-risk groups. The study aim was to examine psychosocial correlates of maternal-fetal bonding among pregnant women identified to be at risk socially and regarding their mental health. The sample consisted of 78 at-risk pregnant women participating in a perinatal intervention study: Godt på Vej Sammen [A Good Start to Life-an Early Cross-sectorial Intervention]. This study was cross-sectional reporting on the baseline characteristics of the participants. In the beginning of the second trimester, participants completed questionnaires assessing maternal-fetal bonding (the Maternal Antenatal Attachment Scale [MAAS]), prenatal parental reflective functioning, adult attachment style, and depressive symptoms. We compared the distribution of MAAS styles with norms from a recent Dutch community sample. In addition, we tested associations between psychosocial variables and the quality and intensity of MAAS scores in regression models and performed Chi-square analyses to assess the association of MAAS styles with psychosocial variables. First, compared to women from a community sample, approximately half of the women in our sample presented lower and suboptimal MAAS scores. Second, insecure avoidant adult attachment style was negatively associated with MAAS intensity, and depressive symptoms were negatively associated with MAAS quality. Third, prenatal parental reflective functioning positively correlated with both quality and intensity of MAAS. Fourth, we found no association between insecure anxious adult attachment style and MAAS scores. Fifth, women with a negative disinterested MAAS style demonstrated the highest avoidant attachment scores, while women with a positively preoccupied MAAS style demonstrated the highest prenatal parental reflective functioning scores. The results suggest that there is a need to differentiate among at-risk pregnant woman and that prenatal screening using the MAAS may help identify those who need preventive parenting interventions and what those interventions should focus on. A main limitation of the study is the lack of a representative group of at-risk pregnant women which limits the generalizability of the study results to all risk groups., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To investigate whether tumour necrosis factor alpha inhibitors (TNFis) are associated with an increased risk of neuroinflammatory diseases among patients with arthritic diseases., Methods: Cohorts of patients with rheumatoid arthritis (RA, n=25 796), psoriatic arthritis (PsA, n=8586) and ankylosing spondylitis (AS, n=9527) who initiated a TNFi treatment year 2000-2017 were identified from nationwide clinical rheumatology registers in Sweden and Denmark. Information on demyelinating disease and inflammatory neuropathy diagnoses was retrieved from prospective linkage to National Patients Register. A Cox proportional hazard model was used to estimate HRs and 95% CI comparing TNFi exposed and non-exposed, by disease and country., Results: Among 111 455 patients with RA, we identified 270 (Sweden) and 51 (Denmark) events (all types of neuroinflammatory diseases combined), corresponding to crude incidence rates (per 1000 person-years) of 0.37 (Sweden) and 0.39 (Denmark) in TNFi-treated patients vs 0.39 (Sweden) and 0.28 (Denmark) in unexposed patients, and an age-sex-calendar-period-adjusted HR (95% CI) of 0.97 (0.72 to 1.33) (Sweden) and 1.45 (0.74 to 2.81) (Denmark) in TNFi exposed compared with non-exposed patients. For a total of 64 065 AS/PsA patients, the corresponding numbers were: 196 and 32 events, crude incidence rates of 0.59 and 0.87 in TNFi-treated patients vs 0.40 and 0.19 in unexposed patients, and HRs of 1.50 (1.07 to 2.11) and 3.41 (1.30 to 8.96), for Sweden and Denmark, respectively. For multiple sclerosis, the patterns of HRs were similar., Conclusions: Use of TNFi in AS/PsA, but not in RA, was associated with increased risk of incident neuroinflammatory disease, though the absolute risk was below one in 1000 patients/year., Competing Interests: Competing interests: MM has received grants from Novartis and Biogen, and has received personal fees from Novartis, Biogen, Merck, Sanofi Genzyme and Teva. FS has received grants and personal fees from Biogen, Merck, Novartis, Sanofi Genzyme and Roche. JA has received grants from Abbvie, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi and UCB. LD has received grants from BMS and has received personal fees from Eli Lilly and Galderma. TIK, BD, EVA, RKJ, EHI, RLC, HL and DVJ have nothing to disclose., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objectives: Studies of the effect of vitamin B12 and folate on the risk of asthma and hay fever have shown inconsistent results that may be biased by reverse causation and confounding. We used a Mendelian randomization approach to examine a potential causal effect of vitamin B12 and folate on hay fever, asthma, and selected biomarkers of allergy by using 11 vitamin B12-associated single-nucleotide polymorphisms (SNPs) and 2 folate-associated SNPs as unconfounded markers., Subjects/methods: We included 162,736 participants from 9 population-based studies including the UK Biobank. Results were combined in instrumental variable and meta-analyses and effects expressed as odds ratios (ORs) or estimates with 95% confidence interval (CI)., Results: Using genetic proxies for B12 and folate, instrumental variable analyses did not show evidence for associations between serum B12 and hay fever: OR = 1.02 (95% CI: 0.98, 1.05), asthma: OR = 0.99 (95% CI: 0.95, 1.04), allergic sensitization: OR = 1.02 (95% CI: 0.74, 1.40), or change in serum IgE: 10.0% (95% CI: -9.6%, 29.6%) per 100 pg/ml B12. Similarly, there was no evidence for association between serum folate and hay fever: OR = 0.74 (95% CI: 0.45, 1.21), asthma: OR = 0.80 (95% CI: 0.43, 1.49), or allergic sensitization: OR = 1.92 (95% CI: 0.11, 33.45), but there was a statistically significant association with change in serum IgE: 2.0% (95% CI: 0.43%, 3.58%) per 0.1 ng/ml serum folate., Conclusions: Our results did not support the hypothesis that levels of vitamin B12 and folate are causally related to hay fever, asthma, or biomarkers of allergy, but we found evidence of a positive association between serum folate and serum total IgE.

Background: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC)., Methods: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI)., Results: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=-0.0012 (95% CI: -0.0019, -0.0006) and FVC: β=-0.0022 (95% CI: -0.0031, -0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m 2 higher BMI., Conclusions: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background Health checks of the general population are widely used to prevent cardiovascular diseases, but are the current clinical guidelines from the European Society of Cardiology (ESC) suitable for screening the general population? Design A cross-sectional, population-based study of 978 men and women aged 40-65 years examined in 2010-2011 was used to estimate the proportion of the general Danish population fulfilling the criteria from the clinical guidelines from the ESC on medical treatment and lifestyle intervention to prevent cardiovascular disease. Methods The ESC criteria for medical treatment and lifestyle intervention were applied to a general population using information on previous cardiovascular diseases, known diabetes, urinalbumin, smoking, total cholesterol, systolic and diabolic blood pressure, low-density lipoprotein cholesterol and a multifactor risk score (SCORE). Results A total of 12.5% fulfilled the criteria for immediate medical treatment to prevent cardiovascular diseases. Furthermore, 30.4% are recommended for medical treatment if an initial lifestyle intervention fails summing to 42.9% eligible for medical treatment. The majority (79%) of persons aged 60-65 years are eligible for medical treatment, while close to half (44.9%) of all persons aged 50-59 years are recommended for medical treatment. Conclusion If ESC's guidelines were followed in Denmark, a conservative estimate shows that medical preventive treatment would involve nearly half the general population aged 40-65 years. The use of these guidelines in screening of the general population can be questioned as realistic and suitable.

Objective: To examine whether mental vulnerability, an enduring personality characteristic, predicts incident hospital-diagnosed ulcer over three decades., Materials and Methods: A population-based cohort study enrolled 3365 subjects with no ulcer history, ages 30-60, in 1982-3. Mental vulnerability, Helicobacter pylori IgG antibodies, socioeconomic status, and sleep duration were determined at baseline; non-steroidal antiinflammatory drug use, smoking, leisure time physical activity, and alcohol consumption both at baseline and in 1993-4. Hospital diagnoses of incident ulcer through 2011 were detected using the Danish National Patient Registry., Results: Ulcers were diagnosed in 166 subjects, including 83 complicated by bleeding or perforation. Age-, gender-, and socioeconomic status-adjusted associations were significant for mental vulnerability (Hazard Ratio (HR) 2.0, 95% Confidence Interval 1.4-2.8), Helicobacter pylori (HR 1.7, CI 1.2-2.3), smoking (HR 2.0, CI 1.3-3.1), heavy drinking (HR 1.6, CI 1.1-2.4), abstinence (HR 1.6, CI 1.1-2.5), non-steroidal antiinflammatory drugs (HR 2.1, CI 1.5-3.0), and sedentary lifestyle (HR 1.9, CI 1.4-2.7). Adjusted for all behavioral mediators, the HR for mental vulnerability was 1.5 (CI 1.0-2.2, p = .04). Mental vulnerability raised risk in Helicobacter pylori seropositive subjects and those exposed to neither Helicobacter pylori nor non-steroidal antiinflammatory drugs; its impact was virtually unchanged when analysis was limited to complicated ulcers., Conclusions: A vulnerable personality raises risk for hospital-diagnosed peptic ulcer, in part because of an association with health risk behaviors. Its impact is seen in 'idiopathic' and Helicobacter pylori-associated ulcers, and in acute surgical cases.

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

We aimed to examine the effect of a large population-based multifactorial screening and lifestyle intervention programme on 10-year incidence of diabetes. In a randomised trial of the general Danish population initiated in 1999-2001 59,616 men and women aged 30-60years were assigned to a five year screening and lifestyle counselling programme (n=11,629) or control group (n=47,987) and followed for ten years in nationwide registers. Intention to treat was applied and risk of diabetes was modeled by Cox regression and expressed as hazard ratios (HRs). We found that 1692 individuals had diabetes at baseline. Among 57,924 individuals without diabetes at baseline, 1267 emigrated, 2593 died and 3369 (Intervention group=684, Control group=2685) developed diabetes. We saw no significant difference in diabetes incidence between the groups after 10-year follow-up (Grey's test: p=0.22). In the first year of follow-up, incidence of diabetes was significantly higher in the intervention group than the control group (HR=1.68, 95%CI 1.29 to 2.29). We observed no difference in incidence of diabetes between the groups in the follow-up intervals from 1 to 6years or after 6-10years (HR=0.94, 0.83 to 1.06; HR=1.03, 0.91 to 1.17). Inviting the general population to participate in a repeated screening and lifestyle counselling programme over five years did not result in lower incidence of diabetes after 10years of follow-up. As expected, significantly more individuals were diagnosed with diabetes in the intervention group during the first year, but this was not followed by a decrease in the following years., Trials Registration: Clinical trials NCT00289237., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Prospective relationships between sedentary behaviour and cardiorespiratory and metabolic markers need to be better delineated in adults with different physical activity levels. We examined the separate and combined relationships of work and leisure time sitting and moderate to vigorous physical activity (MVPA) with cardiorespiratory fitness and cardiometabolic risk factors., Methods: A total of 2308 adults from the Health2006 cohort were followed for five years. Work sitting, leisure time sitting and MVPA were self-reported and cardiorespiratory fitness (Vo2max) was estimated by a submaximal step test. Cardiometabolic risk factors included body mass index, waist circumference, systolic and diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol and insulin levels. Prospective associations with each sitting domain alone and in combination with MVPA level were investigated by multiple linear regression analyses, as were the reverse associations with weight status (body mass index and waist circumference)., Results: Baseline leisure time sitting predicted increased insulin (p < 0.05) and decreased estimated Vo2max (p < 0.05), whereas work sitting predicted decreased waist circumference (p < 0.05) and increased estimated Vo2max (p < 0.01) over the five-year study. Low baseline leisure time sitting, but not work sitting, predicted increased estimated Vo2max regardless of the MVPA level. Weight status predicted increased leisure time sitting (p < 0.01), but leisure time sitting did not predict weight., Conclusions: These findings emphasize sedentary behaviour during leisure time, rather than at work, as a risk behaviour in relation to cardiorespiratory and metabolic health. For cardiorespiratory fitness, it may be important not only to promote MVPA, but also to discourage sedentary behaviour during leisure time., (© The European Society of Cardiology 2015.)

Aims: Our aim was to investigate whether there is social inequality in access to invasive examination and treatment, and whether access explains social inequality in case fatality in a nationwide sample of patients admitted for the first time with unstable angina or non-ST-elevation myocardial infarction (NSTEMI) in Denmark., Methods and Results: All patients admitted for the first time with NSTEMI (n=16,625) or unstable angina (n=8,800) from 2001 to 2009 in Denmark were included. We measured time from admission to coronary angiography (CAG), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The outcomes were 30-day and one-year case fatality. We found social inequality in access to CAG and one-year case fatality for both NSTEMI and unstable angina patients, but the time waited for CAG did not explain the social inequality in case fatality., Conclusions: Despite nominal equal access to health care, social inequality in case fatality after NSTEMI and unstable angina exists in Denmark. The patients with the shortest education waited longer for angio-graphy; however, this did not seem to explain inequality in case fatality. This register-based study was approved by the Danish Data Protection Agency (Approval number 2010-41-5263). Register-based studies do not need approval by a medical ethics committee in Denmark.

Background: Lower case fatality and increased use of evidence-based invasive management incl. coronary angiography (CAG) have been reported for patients admitted with acute myocardial infarction (AMI) in the last 25 years. This article seeks to investigate whether these advances have benefitted patients in all socio-economic groups and how this has impacted on inequality in case fatality., Methods: Forty three thousand eight hundred and forty three patients admitted with AMI in the period from 2001 to 2009 were included. Socio-economic position was measured using individual information on education. Age-standardized cumulative incidence of CAG within 1, 3 and 30 days along with age-standardized case fatality within 30 and 365 days were estimated. Cox regression models were used to model the relative inequality over time., Results: Use of CAG within 1, 3 and 30 days increased for all educational groups over time and the inequality in CAG within 1 and 3 days seen in the beginning of the time frame was eliminated. Case fatality decreased in all educational groups and the relative inequality in 30 days case fatality decreased for women but not 365 days case fatality. No change was seen for inequality in case fatality for men., Conclusion: Increased use of CAG within the evidence based time frame was observed along with a decrease in inequality. However, a reduction in inequality was only observed for short term case fatality, and only for women. These results suggest that inequality in case fatality is not primarily driven by inequality in invasive management of AMI., (© The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Objective: Built environmental attributes have been studied in relation to domestic time spent sedentary. An indoor behaviour has thus been linked to an outdoor setting. Yet, attributes of the actual domestic environment may also influence the time spent sedentary at home. Therefore, the aim was to examine if housing characteristics were cross-sectionally and prospectively related to leisure-time sitting in adults., Methods: In the Danish Health2006 cohort, 2308 adults were followed for 5 years. At baseline, subjects self-reported housing characteristics (habitat type, habitat surface area and household size), moderate-to-vigorous physical activity (MVPA) and socio-demographic factors. Leisure-time sitting was self-reported at baseline and 5-year follow-up. Multiple linear regression was used to assess cross-sectional and prospective associations., Results: At baseline habitat surface area and household size were inversely associated with leisure-time sitting (p<0.01). Living in an apartment was associated with higher leisure-time sitting compared to living in a house (p<0.01). Household size was a predictor of 5-year leisure-time sitting (p<0.01), after adjustment for confounders and the other housing characteristics., Conclusions: Habitat type, habitat surface area and household size were associated with leisure-time sitting in adults, while especially household size was a predictor of leisure-time sitting five years later. The findings highlight the importance of home-environmental attributes when targeting a reduction in sedentary behaviours., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood., Methods and Results: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day., Conclusions: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate., (© 2015 American Heart Association, Inc.)

Background & Aims: There is controversy over whether psychological stress contributes to development of peptic ulcers. We collected data on features of life stress and ulcer risk factors from a defined population in Denmark and compared these with findings of confirmed ulcers during the next 11-12 years., Methods: We collected blood samples and psychological, social, behavioral, and medical data in 1982-1983 from a population-based sample of 3379 Danish adults without a history of ulcer participating in the World Health Organization's MONICA study. A 0- to 10-point stress index scale was used to measure stress on the basis of concrete life stressors and perceived distress. Surviving eligible participants were reinterviewed in 1987-1988 (n = 2809) and 1993-1994 (n = 2410). Ulcer was diagnosed only for patients with a distinct breach in the mucosa. All diagnoses were confirmed by review of radiologic and endoscopic reports. Additional cases of ulcer were detected in a search of all 3379 subjects in the Danish National Patient Register., Results: Seventy-six subjects were diagnosed with ulcer. On the basis of the stress index scale, ulcer incidence was significantly higher among subjects in the highest tertile of stress scores (3.5%) than the lowest tertile (1.6%) (adjusted odds ratio, 2.2; 95% confidence interval [CI], 1.2-3.9; P < .01). The per-point odds ratio for the stress index (1.19; 95% CI, 1.09-1.31; P < .001) was unaffected after adjusting for the presence of immunoglobulin G antibodies against Helicobacter pylori in stored sera, alcohol consumption, or sleep duration but lower after adjusting for socioeconomic status (1.17; 95% CI, 1.07-1.29; P < .001) and still lower after further adjustments for smoking, use of nonsteroidal anti-inflammatory drugs, and lack of exercise (1.11; 95% CI, 1.01-1.23; P = .04). The risk for ulcer related to stress was similar among subjects who were H pylori seropositive, those who were H pylori seronegative, and those exposed to neither H pylori nor nonsteroidal anti-inflammatory drugs. On multivariable analysis, stress, socioeconomic status, smoking, H pylori infection, and use of nonsteroidal anti-inflammatory drugs were independent predictors of ulcer., Conclusions: In a prospective study of a population-based Danish cohort, psychological stress increased the incidence of peptic ulcer, in part by influencing health risk behaviors. Stress had similar effects on ulcers associated with H pylori infection and those unrelated to either H pylori or use of nonsteroidal anti-inflammatory drugs., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Concerns that general health checks, including screening for risk factors to ischemic heart disease (IHD), have negative psychological consequences seem widely unfounded; however, previous studies are only based on self-reports from participants., Aim: To investigate if risk factor screening in healthy adults leads to mental distress in the study population, independent of participation., Methods: The Inter99 study (1999 - 2006) was a randomised intervention in the general population, aiming to prevent IHD by a healthier lifestyle. We included the whole study population, independent of participation (n = 60,915). We merged data with information on the use of psychotropic medication and/or hospitalisation due to psychiatric diagnoses, as retrieved from national registers in Denmark, 4 years before and 5 years after the study began. We conducted analyses using generalised estimating equations., Results: There was no significant difference between the intervention and control groups in their use of antipsychotics, hypnotics/sedatives, antidepressants or anxiolytics. As regards admission to the hospital with mental disorders, no significant difference was seen. These findings were true based on a yearly basis, and when investigating both short-term and a long-term effects of the intervention. There was no interaction with socioeconomic status. Of the 918 persons with a psychiatric diagnosis before the study start, 303 (33%) were re-admitted in the intervention period. Pre-screening of psychological status did not influence the psychological impact of screening., Conclusions: This large, randomised intervention study supports that screening for risk factors to IHD does not increase mental distress, not even in the mentally or socioeconomically most vulnerable persons. This study included the whole Inter99 study population not only study participants., (© 2014 the Nordic Societies of Public Health.)

Objectives: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach., Design: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress., Participants: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA)., Primary Outcome Measures: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis., Results: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers., Conclusions: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Sedentary behavior is increasingly recognized as a risk factor for cardiovascular and metabolic morbidity and mortality. Recent studies suggest that sitting during work and leisure time may affect markers of cardiometabolic health, differently. However, little is known about associations' between sitting time and cardiorespiratory and muscular fitness among adults. The aim of the present study was to examine associations between work- and leisure-time sitting, and key markers of cardiorespiratory and muscular fitness among working adults., Methods: Working adults (N=2544) aged 18-69 from Health2006, a Danish population-based study, were included in this cross-sectional study. Sitting time during work and leisure time along with sociodemographic and behavioral covariates, including physical activity, were self-reported. Participants underwent a health examination with assessment of cardiorespiratory fitness (step test estimated VO 2Max, systolic and diastolic blood pressure) and muscular fitness (handgrip strength, lower limb extension power). Associations were explored by linear regression. Results Leisure-time sitting time was significantly (P<0.05) and inversely associated with VO 2Max, systolic blood pressure and handgrip strength among adults <50 years. There were no significant associations between sitting time at work and any of the markers of cardiorespiratory and muscular fitness., Conclusion: Work- and leisure-time sitting were differentially associated with cardiorespiratory and muscular fitness among working adults. This suggests that the domain in which sitting time is accrued should be considered when further investigating the relationship between sedentary behaviors and various healthy outcomes. In particular, caution should be exercised when labeling occupational sitting a danger per se for health.

Objective: To investigate the effect of systematic screening for risk factors for ischaemic heart disease followed by repeated lifestyle counselling on the 10 year development of ischaemic heart disease at a population level., Design: Randomised controlled community based trial., Setting: Suburbs of Copenhagen, Denmark., Participants: 59,616 people aged 30-60 years randomised with different age and sex randomisation ratios to an intervention group (n = 11,629) and a control group (n = 47,987)., Intervention: The intervention group was invited for screening, risk assessment, and lifestyle counselling up to four times over a five year period. All participants with an unhealthy lifestyle had individually tailored lifestyle counselling at all visits (at baseline and after one and three years); those at high risk of ischaemic heart disease, according to predefined criteria, were furthermore offered six sessions of group based lifestyle counselling on smoking cessation, diet, and physical activity. After five years all were invited for a final counselling session. Participants were referred to their general practitioner for medical treatment, if relevant. The control group was not invited for screening., Main Outcome Measures: The primary outcome measure was incidence of ischaemic heart disease in the intervention group compared with the control group. Secondary outcome measures were stroke, combined events (ischaemic heart disease, stroke, or both), and mortality., Results: 6091 (52.4%) people in the intervention group participated at baseline. Among 5978 people eligible at five year follow-up (59 died and 54 emigrated), 4028 (67.4%) attended. A total of 3163 people died in the 10 year follow-up period. Among 58,308 without a history of ischaemic heart disease at baseline, 2782 developed ischaemic heart disease. Among 58,940 without a history of stroke at baseline, 1726 developed stroke. No significant difference was seen between the intervention and control groups in the primary end point (hazard ratio for ischaemic heart disease 1.03, 95% confidence interval 0.94 to 1.13) or in the secondary endpoints (stroke 0.98, 0.87 to 1.11; combined endpoint 1.01, 0.93 to 1.09; total mortality 1.00, 0.91 to 1.09)., Conclusion: A community based, individually tailored intervention programme with screening for risk of ischaemic heart disease and repeated lifestyle intervention over five years had no effect on ischaemic heart disease, stroke, or mortality at the population level after 10 years.Trial registration Clinical trials NCT00289237., (© Jørgensen et al 2014.)

Background: The workplace is a main setting for prolonged sitting for some occupational groups. Convincing evidence has recently accumulated on the detrimental cardio-metabolic health effects of leisure-time sitting. Yet, much less is known about occupational sitting, and the potential health risk attached compared to leisure-time sitting., Objective: To explore the separate and joint associations of occupational and leisure-time sitting with cardio-metabolic risk factors in working adults., Methods: All working adults (N = 2544) from the Health2006, a Danish population-based study, were included in this cross-sectional study. Participants reported hours of sitting during work, during leisure-time along with socio-demographic and behavioral characteristics, including physical activity. Cardio-metabolic risk factors (waist circumference, body mass index, body fat percentage, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, insulin, hemoglobin A1c and plasma glucose) were measured. Associations were explored by linear regression for leisure-time, occupational, and overall sitting time., Results: Statistically significant (p<.05) detrimental associations of leisure-time sitting were observed with all cardio-metabolic risk factors, except hemoglobin A1c and plasma glucose. Similarly, occupational sitting time was significantly detrimentally associated with HDL cholesterol, triglycerides, and insulin. For categories of sitting time, a joint adverse association of sitting much during both work-time and leisure-time was observed., Conclusion: The associations of occupational sitting time with cardio-metabolic risk factors were fewer and weaker compared to leisure-time sitting. Yet, the joint associations of occupational and leisure-time sitting with cardio-metabolic risk factors were higher than the separate. Our findings amplify the need for further focus in this area prior to making assumptions about equivalent health risks across sedentary behaviors. To our knowledge, this is the first study to contrast the deleterious associations of prolonged occupational and leisure-time sitting, both separately and jointly.

Background: Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. Little is known about potential effects of SCIT on the risk of other chronic immune-related diseases. Over the years, a few casuistic reports have caused concern that SCIT might act as a trigger of autoimmune disease., Objective: We aimed to investigate the association of SCIT with the incidence of autoimmune disease and ischemic heart disease (IHD), as well as all-cause mortality., Methods: All Danish citizens without other known diseases were linked and followed through central registries on medications and hospital admissions. Persons receiving SCIT and persons receiving conventional allergy treatment (CAT; nasal steroids or oral antihistamines) were compared with regard to mortality and development of autoimmune diseases, acute myocardial infarction (AMI), and IHD. Cox regression (survival analysis) with age as the underlying time scale was used to estimate relative risks (hazard ratios [HRs] with 95% CIs) associated with SCIT compared with CAT adjusted for age, sex, vocational status, and income., Results: During the 10-year study period (1997-2006), a total of 18,841 and 428,484 persons were followed in the SCIT and CAT groups, respectively. Receiving SCIT was associated with lower mortality (HR, 0.71; 95% CI, 0.62-0.81) and lower incidence of AMI (HR, 0.70; 95% CI, 0.52-0.93), IHD (HR, 0.88; 95% CI, 0.73-1.05), and autoimmune disease (HR, 0.86; 95% CI, 0.74-0.99)., Conclusion: In this registry-based observational study, receiving SCIT compared with CAT was associated with lower risk of autoimmune disease and AMI, as well as decreased all-cause mortality., (Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Summary: We evaluated the Women's Health Initiative (WHI) hip fracture risk score in 15,648 postmenopausal Danish nurses. The algorithm was well calibrated for Denmark. However, the sensitivity was poor at common decision making thresholds. Obtaining sensitivity better than 80% led to a low specificity of 61.4%., Introduction: A new score based on data from the WHI has been designed to predict 5-year risk of hip fracture in postmenopausal women. The performance of the algorithm has not been validated in populations with different lifestyle characteristics and ethnicity. The aim of this study was to test the clinical performance of the algorithm in a large Danish cohort of postmenopausal Caucasian women against hip fracture., Methods: The Danish Nurse Cohort is a prospective risk factor and hormone therapy (HT) study established in 1993. Participants in the present analysis were 15,648 postmenopausal nurses. The calibration and diagnostic performance of the WHI algorithm was evaluated using fracture events captured in the Danish National Hospital Registry., Results: During 5 years of follow-up, 122 participants suffered a hip fracture (1.8/1,000 person years). The WHI algorithm predicted that 107 hip fractures would occur, indicating an underestimation of the number of fractures by 12%. To obtain sensitivity better than 80%, the cut-off value for 5-year risk was set to 0.5%, which was accompanied by a low positive predictive value of 1.9% and a low specificity of 61.4%. The algorithm predicted too many fractures in HT-users (12 observed, 22 expected) and too few in non HT-users (107 observed, 81 expected)., Conclusions: While the WHI algorithm was well calibrated on the Danish population, the clinical utility of the WHI algorithm in Danish postmenopausal women was limited by poor sensitivity at common decision-making thresholds and suboptimal in non-HT-users.

Aim: To assess the risk of myocardial infarction (MI) as a result of hormone therapy (HT), with focus on the influence of age, duration of HT, various regimens and routes, progestagen type, and oestrogen dose., Methods and Results: All healthy Danish women (n = 698,098, aged 51-69) were followed during 1995-2001. On the basis of a central prescription registry, daily updated national capture on HT was determined. National Registers identified 4947 MI incidents. Poisson regression analyses estimated rate ratios (RRs). Overall, we found no increased risk [RR 1.03 (95% CI: 0.95-1.11)] of MI with the current HT compared with women who never used HT; age-stratified RR among women aged 51-54, 55-59, 60-64, and 65-69 years were 1.24 (1.02-1.51), 0.96 (0.82-1.12), 1.11 (0.97-1.27), and 0.92 (0.80-1.06), respectively. An increasing risk with longer duration was found for younger women, which was not observed with older age groups. In all age groups, the highest risk of MI was found with continuous HT regimen. No increased risk was found with unopposed oestrogen, cyclic combined therapy, or tibolone. Significantly lower risk was found with dermal route than oral unopposed oestrogen therapy (P = 0.04). No associations were found with progestagen type or oestrogen dose., Conclusion: In a National cohort study, we found that HT regimen and route of application could modify the influence of HT on the risk of MI.