'It was hell on earth': perspectives of people living with celiac disease on diagnostic delay.

BACKGROUND: Celiac disease (CD) is underdiagnosed and associated with diagnostic delays. This has long-term consequences for the health and well-being of people living with the condition. Little is known about the qualitative configurations of the assessment processes of people living with CD. METHODS: Using a thematic network analysis of 24 in-depth interviews, this study explored the experiences of people living with CD related to their assessment processes leading to being diagnosed. RESULTS: A significant diagnostic delay (up to 26 years) was evident in many interviews. Factors contributing to diagnostic delay included limited knowledge about CD among general practitioners (GP) and in the general population, categorisations of symptoms as 'typical' or 'atypical' and psychosomatic explanations of symptoms. Diagnostic delay resulted in (1) decreased psychological well-being due to severe symptoms, changes in self-perception and self-blame; (2) decreased physiological well-being due to comorbidities; and (3) mistrust in the healthcare system, leading to an increase in informants' responsibility for expediting their assessment processes. This suggested the presence of a neoliberal tendency because informants felt they were primarily responsible for their assessment processes. CONCLUSIONS: We encourage the implementation of initiatives to increase awareness of CD among GPs as well as more consistent and frequent use of the screening guideline due to variations in its clinical presentation. Increased awareness and consistency could reduce variations in assessment processes given GPs' varying knowledge about the condition.

Associations of occupational and leisure-time physical activity with all-cause mortality: an individual participant data meta-analysis.

OBJECTIVE: Health effects of different physical activity domains (ie, during leisure time, work and transport) are generally considered positive. Using Active Worker consortium data, we assessed independent associations of occupational and leisure-time physical activity (OPA and LTPA) with all-cause mortality. DESIGN: Two-stage individual participant data meta-analysis. DATA SOURCE: Published and unpublished cohort study data. ELIGIBILITY CRITERIA: Working participants aged 18-65 years. METHODS: After data harmonisation, we assessed associations of OPA and LTPA with all-cause mortality. In stage 1, we analysed data from each study separately using Cox survival regression, and in stage 2, we pooled individual study findings with random-effects modelling. RESULTS: In 22 studies with up to 590 497 participants from 11 countries, during a mean follow-up of 23.1 (SD: 6.8) years, 99 743 (16%) participants died. Adjusted for LTPA, body mass index, age, smoking and education level, summary (ie, stage 2) hazard ration (HRs) and 95% confidence interval (95% CI) for low, moderate and high OPA among men (n=2 96 134) were 1.01 (0.99 to 1.03), 1.05 (1.01 to 1.10) and 1.12 (1.03 to 1.23), respectively. For women (n=2 94 364), HRs (95% CI) were 0.98 (0.92 to 1.04), 0.96 (0.92 to 1.00) and 0.97 (0.86 to 1.10), respectively. In contrast, higher levels of LTPA were inversely associated with mortality for both genders. For example, for women HR for low, moderate and high compared with sedentary LTPA were 0.85 (0.81 to 0.89), 0.78 (0.74 to 0.81) and 0.75 (0.65 to 0.88), respectively. Effects were attenuated when adjusting for income (although data on income were available from only 9 and 6 studies, for men and women, respectively). CONCLUSION: Our findings indicate that OPA may not result in the same beneficial health effects as LTPA.

Celiac disease and risk of neuropsychiatric disorders: A nationwide cohort study.

INTRODUCTION: Previous studies have indicated that patients with celiac disease (CD) may have an increased risk of developing neuropsychiatric disorders. However, large-scale epidemiologic studies on the topic are still scarce. We aimed to examine the association between CD and development of neuropsychiatric disorders during an 18-year follow-up period. METHODS: We conducted a prospective cohort study. All Danish patients with an incident diagnosis of CD (ICD-10 K90.0) from 2000 to 2018 were identified in nationwide registries and compared with birthdate- and sex-matched controls (variable 1:10 ratio) for the development of a neuropsychiatric disease. Individual neuropsychiatric diseases were also examined. The absolute risk was calculated by the cumulative incidence, and the relative risk was estimated in Cox regression models. RESULTS: We identified a cohort of 6329 patients with CD diagnosed from 2000 to 2018 and 63,287 matches at risk for developing incident neuropsychiatric disorders. The cumulative incidence of development of any neuropsychiatric disorder was 3.9%, 14.9%, 24.8%, 35.9% after 1, 5, 10, and 15 years of follow-up, respectively, in patients with CD compared with 1.8%, 9.3%, 18.3%, and 27.0% in controls. Gray's test for equality p < 0.001. The relative risk was HR = 1.58 (95% confidence interval: 1.49-1.68) in CD patients compared with matches. For the individual outcomes, CD was associated with an increased relative risk of developing anxiety, depression, eating disorders, epilepsy, migraine, and stress. We also found indications of an increased relative risk of ADHD, alcoholism, bipolar disorders, and drug abuse, although the associations were less clear. No associations were found between CD and dementia, Parkinson's disease, and schizophrenia. CONCLUSIONS: In this nationwide study including more than 6000 patients with CD, we found an increased risk of development of a neuropsychiatric disorder compared with age- and sex-matched controls. The causes and the clinical relevance of these associations remain to be elucidated.

Association of milk intake with hay fever, asthma, and lung function: a Mendelian randomization analysis.

BACKGROUND: Previous observational studies have indicated a protective effect of drinking milk on asthma and allergy. In Mendelian Randomization, one or more genetic variants are used as unbiased markers of exposure to examine causal effects. We examined the causal effect of milk intake on hay fever, asthma, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) by using the lactase rs4988235 genotype associated with milk intake. METHODS: We performed a Mendelian Randomization study including 363,961 participants from the UK Biobank. RESULTS: Observational analyses showed that self-reported milk-drinkers vs. non-milk drinkers had an increased risk of hay fever: odds ratio (OR) = 1.36 (95% CI 1.32, 1.40, p < 0.001), asthma: OR = 1.33 (95% CI 1.38, 1.29, p < 0.001), yet a higher FEV1: ß = 0.022 (SE = 0.004, p < 0.001) and FVC: ß = 0.026 (SE = 0.005, p < 0.001). In contrast, genetically determined milk-drinking vs. not drinking milk was associated with a lower risk of hay fever: OR = 0.791 (95% CI 0.636, 0.982, p = 0.033), and asthma: OR = 0.587 (95% CI 0.442, 0.779, p = 0.001), and lower FEV1: ß = - 0.154 (standard error, SE = 0.034, p < 0.001) liter, and FVC: ß = - 0.223 (SE = 0.034, p < 0.001) liter in univariable MR analyses. These results were supported by multivariable Mendelian randomization analyses although not statistically significant. CONCLUSIONS: As opposed to observational results, genetic association findings indicate that drinking milk has a protective effect on hay fever and asthma but may also have a negative effect on lung function. The results should be confirmed in other studies before any recommendations can be made.

Examine the public health impacts of functional somatic disorders using the DanFunD study.

Background: Persistent physical symptoms (e.g. pain, fatigue) are prevalent in the population and some persons may develop a functional somatic disorder (FSD). We still need to explore the limits between general bodily sensations and FSD, and great controversies exist as regard delimitation, occurrence, risk factors, prognosis, and costs of FSD in the general population. This is mainly due to the lack of focused, sufficient powered, population-based epidemiological studies. Material and Methods: The DanFunD study is the largest focused population-based study on FSD and has the potential to answer these crucial questions regarding the FSD disorders. DanFunD has its origin in the Copenhagen area of Denmark and was initiated in 2009 by an interdisciplinary team of researchers including basic scientists, clinical researchers, epidemiologists, and public health researchers. A population-based cohort of nearly 10,000 people have filled in detailed questionnaires, gone through a thorough health examination, and a biobank is established. The cohort was re-examined after five years. Results:The prevalence of FSD in the Danish population is about 10-15% and is twice as common in women as in men. Persons with FSD report impaired daily activities and low self-perceived health, which qualifies FSD as a major public health problem. The research plan to unravel the risk factors for FSD employs a bio-psycho-social approach according to a detailed plan. Preliminary results are presented, and work is in progress. Likewise, plans for assessing prognosis and health care costs are provided. Conclusion: We invite researchers in the field to collaborate on this unique data material.

Influence of educational level on test and treatment for incident hypothyroidism.

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.

Symptoms and biomarkers associated with undiagnosed celiac seropositivity.

BACKGROUND: Studies have indicated that underdiagnosis and diagnostic delay are common in celiac disease. Therefore, it is important to increase our knowledge of what symptoms and biomarkers could identify undiagnosed cases of celiac disease. METHODS: We screened for celiac disease antibodies in stored blood samples from 16,776 participants in eight population-based studies examined during 1976-2012. Undiagnosed celiac seropositivity was defined as celiac disease antibody positivity (IgG-deamidated gliadin peptide above 10.0 U/mL and/or IgA-tissue transglutaminase (TTG) or IgG-TTG above 7.0 U/mL) without a known diagnosis of celiac disease in the National Patient Register. In all studies general health symptoms were recorded by participant-completed questionnaire, including self-perceived health, tiredness, headache and gastrointestinal symptoms. Furthermore, blood samples were drawn for analyses of biomarkers e.g. hemoglobin, blood glucose, cholesterol, liver parameters and vitamins. The participants with undiagnosed celiac seropositivity were matched by sex, age and study with four controls among the celiac disease antibody negative participants. RESULTS: We excluded, five participants with known celiac disease, resulting in a population of 16,771 participants. In this population 1% (169/16,771) had undiagnosed celiac seropositivity. There were no statistically significant differences in symptoms between cases and controls. Undiagnosed celiac seropositivity was associated with low blood cholesterol (< 5 mmol/L) and low hemoglobin (< 7.3 mmol/L for women and < 8.3 mmol/L for men). CONCLUSION: In this general population study, undiagnosed cases of celiac seropositivity did not have more symptoms than controls, confirming the diagnostic difficulties of celiac disease and the low prognostic value of symptoms for a diagnosis of celiac disease. Furthermore, decreased levels of cholesterol and/or hemoglobin in the blood were associated with undiagnosed celiac seropositivity.

Long-term Consequences of Undiagnosed Celiac Seropositivity.

INTRODUCTION: Diagnosed celiac disease (CD) is associated with lymphoproliferative malignancy and gastrointestinal cancer, but little is known about the long-term consequences of undiagnosed CD. We aimed to investigate long-term consequences of undiagnosed CD for mortality and incidence of cancer and other chronic diseases. METHODS: We screened biobank serum samples for immunoglobulin (Ig) A and IgG tissue transglutaminase (TTG) and IgG deamidated gliadin peptide in a study of 8 population-based cohort studies comprising 16,776 participants examined during 1976-2012 and followed with >99% complete follow-up in Danish nationwide registries until December 31, 2017, regarding vital status and incidence of diseases. Undiagnosed CD was defined as antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/mL and/or IgG deamidated gliadin peptide ≥ 10 U/mL) in individuals without a diagnosis of CD recorded in the National Patient Register. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression analyses with age as the underlying time scale. RESULTS: The prevalence of undiagnosed CD was 1.0% with no statistically significant increase over time. Undiagnosed CD was associated with increased risk of cancer overall (HR, 1.57; 95% CI, 1.16-2.11), gastrointestinal cancer (HR, 2.33; 95% CI, 1.35-4.04), cancer of the uterus (HR, 3.95; 95% CI, 1.46-10.69), breast cancer (HR, 1.98; 95% CI, 1.02-3.82), head and neck cancer (HR, 3.12; 95% CI, 1.15-8.43), and cardiovascular disease (HR, 1.37; 95% CI, 1.01-1.85). We found no statistically significant association between undiagnosed CD and mortality (HR, 1.19; 95% CI, 0.87-1.61). DISCUSSION: Undiagnosed CD was associated with increased risk of cardiovascular disease and cancer suggesting that untreated CD has serious long-term health consequences not only affecting the gastrointestinal tract (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/AJG/B566).

Influenza and risk of later celiac disease: a cohort study of 2.6 million people.

OBJECTIVES: Influenza has been linked to autoimmune conditions, but its relationship to subsequent celiac disease (CD) is unknown. Our primary aim was to determine the risk of CD after influenza. A secondary analysis examined the risk of CD following pandemic influenza vaccination. METHODS: This nationwide register-based cohort study included 2,637,746 Norwegians (born between 1967-2013) followed during 2006-2014 with information on influenza diagnosed in primary or non-primary care, pandemic vaccination (Pandemrix), and subsequent CD. Cox regression yielded hazard ratios adjusted (HR) for socio-demographic characteristics and earlier healthcare use. RESULTS: During 13,011,323 person-years of follow-up 7321 individuals were diagnosed with CD (56/100,000 person-years). There were 351,666 individuals diagnosed with influenza, including 82,980 during the 2009-2010 pandemic, and 969,968 individuals were vaccinated. Compared with participants without influenza, who had a CD incidence of 55/100,000 person-years, those diagnosed with seasonal and pandemic influenza had a rate of 68 and 78, per 100,000 person-years, respectively. The HR for CD was 1.29 (95%CI, 1.21-1.38) after seasonal influenza and 1.29 (95%CI, 1.15-1.44) after pandemic influenza; HRs remained significantly increased one year after exposure, when restricted to laboratory-confirmed influenza, and after multivariate adjustments. The reverse association, i.e., risk of influenza after CD, was not significant (HR 1.05; 95%CI, 0.98-1.12). The HR for CD after pandemic vaccination was 1.08 (95%CI, 1.03-1.14). CONCLUSION: A positive association with influenza diagnosis is consistent with the hypothesis that infections may play a role in CD development. We could neither confirm a causal association with pandemic vaccination, nor refute entirely a small excess risk.

Screening for celiac disease in Danish adults.

OBJECTIVE: The prevalence of celiac disease (CD) as recorded in the Danish National Patient Registry is ∼50/100,000 persons. This is much lower than the reported prevalence of CD in other Nordic countries and underdiagnosis is suspected. Our aim was to estimate the prevalence of CD in a population-based study of Danish adults. METHODS: A total of 2297 adults aged 24-76 years living in the southwestern part of Copenhagen were screened for CD by immunoglobulin (Ig)A and IgG antibodies to transglutaminases and deamidated gliadin. IgA/IgG-positive participants were invited to a clinical evaluation, including biopsies, by a gastroenterologist. RESULTS: Of the invited 56 participants, 40 underwent a full clinical evaluation and 8 persons were diagnosed with CD; 2 of the 16 persons, who did not complete the clinical evaluation, were considered by experts to have probable CD. None of the above 56 participants had a known history of CD or a recorded diagnosis of CD in National Patient Registry. By combining cases of biopsy-proven CD (n = 8), probable CD (n = 2), and registry-recorded CD (n = 1), the prevalence of CD was estimated to be 479/100,000 (11/2297) persons (95% CI: 197-761). CONCLUSION: In this general adult population, the prevalence of CD as estimated by screening and clinical evaluation was 10 times higher than the registry-based prevalence of CD. Of 11 participants diagnosed with CD in our screening study, 10 were unaware of the diagnosis prior to the study. Thus, our study suggests that CD is markedly underdiagnosed in Danish adults.

Impact of ectopic pregnancy for reproductive prognosis in next generation.

The impact of an ectopic pregnancy in the next generation is unknown. Our aim was to compare reproductive outcomes in daughters of women with and without ectopic pregnancy. Designed as a historical prospective controlled cohort study with data collected in four Danish registries from 1977-2009, women with ectopic pregnancy during 1977-1982 were age-matched to women without ectopic pregnancy. Daughters of these two cohorts were followed until 2009. We compared 5126 daughters of women with ectopic pregnancy with 19 928 daughters of women without ectopic pregnancy. The daughters of women with ectopic pregnancy had a 1.5-fold (95% confidence interval 1.2-1.9) increased risk of ectopic pregnancy, while for deliveries this was 1.0 (1.0-1.1), for miscarriages 1.1 (1.0-1.2), and for induced abortions 1.3 (1.2-1.4). Daughters of mothers with ectopic pregnancy have a 50% higher risk of ectopic pregnancy than daughters of women without an ectopic pregnancy, but a normal delivery rate.

Improving reproductive long-term prognosis for women with a first ectopic pregnancy. A national controlled follow-up study.

OBJECTIVE: To describe developments in reproductive long-term prognosis in women with a first ectopic pregnancy as compared with two control cohorts. DESIGN: Controlled cohort study. SETTING: Data were collected from four national Danish registries. POPULATION: All Danish women of reproductive age (15-49 years) through the period 1977-2009 and all reproductive outcomes in these women. METHODS: Data were collected from four national Danish registries. Three cohorts of women with a first recorded ectopic pregnancy during the periods 1980-84, 1985-89, and 1990-94, were compared with age-matched controls with a first miscarriage and a first induced abortion and followed for 15 years for all further pregnancy outcomes. MAIN OUTCOME MEASURES: Pregnancy outcomes included deliveries, miscarriages, induced abortions and ectopic pregnancies. RESULTS: The birth rate for women with a first ectopic pregnancy increased significantly through the three cohorts from 85 to 122 deliveries/100 women during the follow-up period. The risk of miscarriages also increased over time, whereas the risk of further ectopic pregnancies remained unchanged at 22-24 events/100 women. Compared to women with a first miscarriage, the rate ratio for deliveries increased from 0.59 (95% CI 0.56-0.63) to 0.71 (95% CI 0.68-0.75) over the time covering the three cohorts. CONCLUSION: The long-term delivery rate among women with a first ectopic pregnancy has improved significantly over time.

A case of alpha-gal syndrome: Recall urticaria and 10 years of measurements of IgE to galactose-α-1,3-galactose.

Alpha-gal IgE level can change rapidly. Reassessment of a patient's alpha-gal IgE level may be helpful in the patient's clinical follow-up. Pruritus related to the site of a previous tick bite strengthens the diagnosis of alpha-gal syndrome.

Serum Concentrations of Inhibin B in Healthy Females and Males Throughout Life.

OBJECTIVE: To describe the natural history of inhibin B throughout life according to sex, age, and pubertal development. METHODS: Based on serum samples from 2707 healthy controls aged 0 to 80 years, sex- and age-specific reference ranges of inhibin B concentrations were constructed. Concentrations were evaluated according to pubertal development and use of oral contraceptives (OCs). Also, measurements from 42 patients with Klinefelter syndrome were included. RESULTS: In both sexes, inhibin B concentrations were high during minipuberty, decreased in childhood, and increased significantly from Tanner stages B1 to B3 (peak: B4) in females and from G1 to G3 (peak: G3) in males. Despite variations in menstruating females, inhibin B concentrations remained relatively constant after puberty, until becoming unmeasurable at menopause. Despite a modest decrease, the inhibin B concentration in males remained relatively high from puberty onwards. At any age, males had highest concentrations. Inhibin B standard deviation (SD) scores were lower in OC-users (median SD score = -0.88) than in non-users (SD score = 0.35), p < 0.001. In patients with Klinefelter syndrome, inhibin B concentrations spanned the reference range until around 15 years of age, where they decreased to subnormal or unmeasurable levels. CONCLUSION: Valuable sex- and age-specific reference data for inhibin B concentrations were provided. In OC-users, decreased concentrations of inhibin B underlined the ovaries as the only place of inhibin B production. In patients with Klinefelter syndrome, the decline in inhibin B concentrations at puberty underlined the shift in regulation of inhibin B production at pubertal onset.

Protocol for the combined cardiometabolic deep phenotyping and registry-based 20-year follow-up study of the Inter99 cohort.

INTRODUCTION: The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50-80 years old Inter99 participants. METHODS AND ANALYSIS: The Inter99 cohort comprises individuals aged 30-60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999. Age-stratified and sex-stratified random subgroups were invited to participate in either a lifestyle intervention (N=13 016) or questionnaires (N=5264), while the rest served as a reference population (N=43 021). Of the 13 016 individuals assigned to the lifestyle intervention group, 6784 (52%) accepted participation in a baseline health examination in 1999, including screening for cardiovascular risk factors and prediabetic conditions. In total, 6004 eligible participants, who participated in the baseline examination, will be invited to participate in the deep phenotyping 20-year follow-up clinical examination including measurements of anthropometry, blood pressure, arterial stiffness, cardiometabolic biomarkers, coronary artery calcification, heart rate variability, heart rhythm, liver stiffness, fundus characteristics, muscle strength and mass, as well as health and lifestyle questionnaires. In a subsample, 10-day monitoring of diet, physical activity and continuous glucose measurements will be performed. Fasting blood, urine and faecal samples to be stored in a biobank. The established database will form the basis of multiple analyses. A main purpose is to investigate whether low birth weight independent of genetics, lifestyle and glucose tolerance predicts later common T2D cardiometabolic comorbidities. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethics Committee, Capital Region, Denmark (H-20076231) and by the Danish Data Protection Agency through the Capital Region of Denmark's registration system (P-2020-1074). Informed consent will be obtained before examinations. Findings will be disseminated in peer-reviewed journals, at conferences and via presentations to stakeholders, including patients and public health policymakers. TRIAL REGISTRATION NUMBER: NCT05166447.

Should workers be physically active after work? Associations of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels-An individual participant data meta-analysis.

BACKGROUND: There is insufficient evidence to provide recommendations for leisure-time physical activity among workers across various occupational physical activity levels. This study aimed to assess the association of leisure-time physical activity with cardiovascular and all-cause mortality across occupational physical activity levels. METHODS: This study utilized individual participant data from 21 cohort studies, comprising both published and unpublished data. Eligibility criteria included individual-level data on leisure-time and occupational physical activity (categorized as sedentary, low, moderate, and high) along with data on all-cause and/or cardiovascular mortality. A 2-stage individual participant data meta-analysis was conducted, with separate analysis of each study using Cox proportional hazards models (Stage 1). These results were combined using random-effects models (Stage 2). RESULTS: Higher leisure-time physical activity levels were associated with lower all-cause and cardiovascular mortality risk across most occupational physical activity levels, for both males and females. Among males with sedentary work, high compared to sedentary leisure-time physical activity was associated with lower all-cause (hazard ratios (HR) = 0.77, 95% Confidence interval(95%CI): 0.70-0.85) and cardiovascular mortality (HR = 0.76, 95%CI: 0.66-0.87) risk. Among males with high levels of occupational physical activity, high compared to sedentary leisure-time physical activity was associated with lower all-cause (HR = 0.84, 95%CI: 0.74-0.97) and cardiovascular mortality (HR = 0.79, 95%CI: 0.60-1.04) risk, while HRs for low and moderate levels of leisure-time physical activity ranged between 0.87 and 0.97 and were not statistically significant. Among females, most effects were similar but more imprecise, especially in the higher occupational physical activity levels. CONCLUSION: Higher levels of leisure-time physical activity were generally associated with lower mortality risks. However, results for workers with moderate and high occupational physical activity levels, especially women, were more imprecise. Our findings suggests that workers may benefit from engaging in high levels of leisure-time physical activity, irrespective of their level of occupational physical activity.

Osteoporosis and bone fractures in patients with celiac disease: A nationwide cohort study.

Celiac disease (CD) is an autoimmune disease caused by an abnormal immune response triggered by ingestion of gluten. Treatment of CD is a lifelong gluten-free diet. Both diagnosed and undiagnosed CD has been found to be associated with reduced bone mineral density, which can lead to an increased risk of fractures. We therefore aimed to investigate the association of CD and the risk of fractures and osteoporosis in Denmark in a nationwide registry-based study. We identified all patients with CD (ICD-10 code K90.0) between 2000 and 2018 and included those with at least two contacts with a CD diagnosis. In total, 9397 CD patients and 93,964 randomly selected age- and sex-matched (1:10) references from the general population were identified. The overall hazard ratio (HR) of developing osteoporosis in CD patients compared with matches was 5.39 (95 % confidence interval (CI): 4.89, 5.95), however when excluding events of osteoporosis occurring within 12 months from the date of diagnosis the overall HR was reduced to 3.87 (95 % CI: 3.44, 4.33). The HR for major osteoporotic fractures was 1.37 (95 % CI: 1.25, 1.51) and for any fractures 1.27 (95 % CI: 1.18, 1.36). For osteoporosis, major osteoporotic fractures, and any fracture prior to diagnosis of CD the odds ratios comparing CD patients with matches were 4.32 (95 % CI: 3.64, 4.68), 1.29 (95 % CI: 1.21, 1.37) and 1.34 (95 % CI: 1.27, 1.41), respectively. Thus, this study showed an increased risk of osteoporosis and bone fractures among individuals with CD, both before and after diagnosis of CD. These results underline that the risk of osteoporosis should be considered in the clinical management of patients with CD and that early diagnosis and treatment could be important.

Prospective relationship between occupational physical activity and risk of ischaemic heart disease: are men and women differently affected?

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.

In the Danish Monica I study among 1399 women and 1706 men, we investigated whether high physical activity at work was associated with higher risk of ischaemic heart disease and whether this association was different among men and women. The association between occupational physical activity and ischaemic heart disease was different among men and women. High physical activity at work was associated with around 45% higher risk of ischaemic heart disease in men, but with around 65% lower risk in women. The underlying mechanisms for this difference, e.g. differences in exposure and physiology, should be further investigated in future studies.

The association of vitamin K status with lung function and disease in a general population.

Introduction: Matrix Gla protein (MGP) is an inhibitor of lung tissue calcification. The plasma level of dephosphorylated-uncarboxylated MGP (dp-ucMGP) is a biomarker of vitamin K status. The present study assessed whether lower vitamin K status (reflected by higher dp-ucMGP) was associated with lung function and lung disease/symptoms. Methods: A general population sample of 4092 individuals, aged 24 to 77 years, underwent a health examination including questionnaires, spirometry and measurements of plasma dp-ucMGP. Associations of dp-ucMGP with lung function and self-reported disease/symptoms were estimated using regression models adjusted for age, sex and height. Associations were expressed as ß-estimates or odds ratios (ORs) per doubling in dp-ucMGP. Results: Lower vitamin K status (higher dp-ucMGP) was associated with lower forced expiratory volume in 1 s (FEV1) (98 mL; 95% CI: 54-141 mL) and lower forced vital capacity (FVC) (136 mL; 95% CI: 85-187 mL). Dp-ucMGP was not associated with the FEV1/FVC ratio (0.0 percentage points higher than the expected value; 95% CI: -1.0-1.0). Furthermore, lower vitamin K status was associated with COPD (OR 2.24, 95% CI: 1.53-3.27), wheezing (OR 1.81, 95% CI: 1.44-2.28) and asthma (OR 1.44, 95% CI: 1.12-1.83). Conclusion: Lower vitamin K status was associated with lower ventilatory capacity (lower FEV1 and FVC), and with higher risk of self-reported asthma, COPD and wheezing. Vitamin K status was not associated with airflow obstruction (FEV1/FVC ratio).