Social position and functional somatic disorders: The DanFunD study.

BACKGROUND AND AIM: It is generally accepted that functional somatic disorders (FSDs) are a product of biological, psychological, and social factors. Social position might be part of this complex, but the literature on this issue is currently heterogeneous and inconsistent. The aim of the present study was - in a population-based cohort - to test the hypothesis that lower social position would be associated with higher a risk of FSD. METHOD: The association between social position and FSD was examined in a cross-sectional study with various measures of social position (education as measured by vocational training; employment; cohabitation; subjective social status) and delimitations of FSD (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, bodily distress syndrome, and symptom profiles). The associations were analyzed using logistic regressions to calculate odds ratios and 95% confidence intervals. Each social measure was analyzed independently and was adjusted for age and sex. RESULTS: Lower levels of vocational training, being unemployed, and living alone were associated with higher risk of FSD, regardless of the FSD delimitation. There was also a significant negative association between subjective evaluated social status and FSD. The associations remained after multiple adjustments, and seemed to be strongest for the more severe FSD-types. CONCLUSIONS: Lower social position is associated with higher risk of FSD, especially the more severe FSD delimitations, which might constitute an especially vulnerable group. However, the mechanisms behind the relations remain unknown.

Decision-Analytic Modeling Studies in Prevention and Treatment of Iodine Deficiency and Thyroid Disorders: A Systematic Overview.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goiter, or other thyroid disorders, and it has economic implications. Our aim was to give an overview of studies applying decision-analytic modeling to evaluate the effectiveness and/or cost-effectiveness of iodine deficiency-related prevention strategies or treatments related to thyroid disorders. Methods: We performed a systematic literature search in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica Database), Tuft's Cost-Effectiveness Analysis Registry, and National Health System Economic Evaluation Database (NHS EED) to identify studies published between 1985 and 2018 comparing different prevention or treatment strategies for iodine deficiency and thyroid disorders by applying a mathematical decision-analytic model. Studies were required to evaluate patient-relevant health outcomes (e.g., remaining life years, quality-adjusted life years [QALYs]). Results: Overall, we found 3950 studies. After removal of duplicates, abstract/title, and full-text screening, 17 studies were included. Eleven studies evaluated screening programs (mainly newborns and pregnant women), five studies focused on treatment approaches (Graves' disease, toxic thyroid adenoma), and one study was about primary prevention (consequences of iodine supplementation on offspring). Most of the studies were conducted within the U.S. health care context (n = 7). Seven studies were based on a Markov state-transition model, nine studies on a decision tree model, and in one study, an initial decision tree and a long-term Markov state-transition model were combined. The analytic time horizon ranged from 1 year to lifetime. QALYs were evaluated as health outcome measure in 15 of the included studies. In all studies, a cost-effectiveness analysis was performed. None of the models reported a formal model validation. In most cases, the authors of the modeling studies concluded that screening is potentially cost-effective or even cost-saving. The recommendations for treatment approaches were rather heterogeneous and depending on the specific research question, population, and setting. Conclusions: Overall, we predominantly identified decision-analytic modeling studies evaluating specific screening programs or treatment approaches; however, there was no model evaluating primary prevention programs on a population basis. Conclusions deriving from these studies, for example, that prevention is cost-saving, need to be carefully interpreted as they rely on many assumptions.

The unifying diagnostic construct of bodily distress syndrome (BDS) was confirmed in the general population.

OBJECTIVES: Bodily distress syndrome (BDS) has been shown to encompass a range of functional somatic syndromes (FSS) such as irritable bowel syndrome (IBS), fibromyalgia (FM), and chronic fatigue syndrome (CFS) in clinical samples. This study aimed to explore symptom clusters and test classification of individuals with illness similar to the BDS criteria in a general population sample. METHODS: A stratified subsample of 1590 individuals from the DanFunD part two cohort was included. Symptoms were assessed with the Research Interview for Functional somatic Disorders, performed by trained physicians. In 44 symptoms pooled from criteria of IBS, FM, CFS, and BDS, symptom clusters were explored with explorative factor analysis. Confirmation of symptom clusters of BDS in the previously described 25- and 30-item BDS checklists was performed with confirmatory factor analysis. Classification of individuals into illness groups was investigated with latent class analysis. RESULTS: Four symptom clusters (cardiopulmonary, gastrointestinal, musculoskeletal, general symptoms/fatigue) corresponding to the BDS subtypes and their corresponding FSS were identified and confirmed. A three-class model including 25 BDS items had the best fit for dividing participants into classes of illness: One class with low probability, one class with medium probability, and one class with high probability of having ≥4 symptoms in all symptom clusters. CONCLUSION: The BDS concept was confirmed in the general population and constitutes a promising approach for improved FSS classification. It is highly clinical relevant being the only diagnostic construct defining the complex multi-organ type.

Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification.

OBJECTIVE: To investigate the impact of mandatory iodine fortification (IF) on the incidence of nosological subtypes of overt thyrotoxicosis and hypothyroidism. DESIGN: We identified and scrutinized all possible new cases of overt thyrotoxicosis and hypothyroidism in an open cohort in Northern Jutland (n = 309 434; 1 January 1997) during the years 2014-2016. Individual medical history was evaluated to verify and detail the incidence of overt thyroid dysfunction and for classification into nosological subtypes. A number of cases were excluded during final verification due to spontaneous normalization of thyroid function, as they had no medical history suggesting a known condition, which could transiently affect thyroid function (subacute/silent thyroiditis, PPTD and iatrogenic thyroid dysfunction). An identical survey was conducted in 1997-2000 prior to mandatory IF of salt (13 µg/g) that was in effect from year 2001. RESULTS: The standardized incidence rate (SIR) of verified overt thyrotoxicosis decreased markedly from 97.5/100 000/year in 1997-2000 to 48.8 in 2014-2016 (SIRR: 0.50 [95% CI: 0.45-0.56]). This was due to a distinct decrease in the SIR of multinodular toxic goitre (SIRR: 0.18 [0.15-0.23]), solitary toxic adenoma (SIRR: 0.26 [0.16-0.43]) and to a lesser degree Graves' disease (SIRR: 0.67 [0.56-0.79]). SIR for overt hypothyroidism was unaltered by 2014-2016 (SIRR: 1.03 [0.87-1.22]). However, age distribution shifted with more young and fewer elderly cases of verified overt hypothyroidism. CONCLUSION: Mandatory IF caused a substantial reduction in SIR of verified overt thyrotoxicosis (especially of nodular origin) while avoiding an increase in SIR of verified overt hypothyroidism.

Predictors of accelerated FEV1 decline in adults with airflow limitation-Findings from the Health2006 cohort.

To investigate predictors of accelerated decline in forced expiratory volume in 1 s (FEV1) in individuals with preexisting airflow limitation (AL). Participants in the Health2006 baseline study aged ≥ 35 with FEV1/ forced vital capacity (FVC) < lower limit of normal (LLN) were invited for a 10-year follow-up. At both examinations, data were obtained on demographics, spirometry, fitness level, allergy, and exhaled nitric oxide. We used multiple regression modeling to predict the annual decline in FEV1, reported as regression coefficients ( R) and 95% confidence intervals (CIs). A total of 123 (43% of those invited) participated in the follow-up examination, where more had exercise-induced dyspnea but fewer had asthma symptoms. Being female ( R = -29.8 ml, CI: -39.7 to -19.8), diagnosed with asthma ( R = -13.7, CI: -20.4 to -7.0) or atopic dermatitis ( R = -29.0, CI: -39.7 to -18.4), and having current asthma symptoms or nightly respiratory symptoms ( R = -22.1, CI: -31.9 to -12.4 and R = -14.3, CI: -19.9 to -8.7, respectively) were significantly associated with a steeper decline in FEV1. Although to a smaller extent, a steeper decline was also predicted by age, baseline FEV1, waist/hip-ratio, and number of pack-years smoked. In individuals with preexisting AL, being female and having ever or current respiratory symptoms were associated with an accelerated annual decline in FEV1.

Determinants of airflow limitation in Danish adults - findings from the Health2006 cohort.

Background and aim: Airflow limitation may be found in patients with both asthma and COPD and is often associated with more symptoms and poorer outcome. We aimed to identify factors associated with airflow limitation in a well-characterized, population-based sample of adults. Methods: From the Health2006 cohort, we selected participants aged ≥35 years at enrolment (n=2,959). Airflow limitation was defined as FEV1/FVC < lower limit of normal. Participants with (cases) and without (controls) airflow limitation were compared with regard to self-reported symptoms, medical history, atopy, lung function and exhaled nitric oxide. Between-group differences were analyzed using Chi-square and Mann-Whitney U tests, and effect size was estimated by logistic regression (reported as OR and 95% CI). Results: We identified 313 cases, majority of which were female, reported poor overall health, physically inactivity and experienced respiratory symptoms within the previous year. The presence of airflow limitation was associated with BMI (OR 3.1 for overweight, P<0.001, CI 1.97-4.78), age (OR 2.3, P<0.001 for age 55+, CI 1.7-3.2), tobacco exposure (OR 1.6, P=0.01, CI 1.1-2.32, and OR 1.76, P=0.019, CI 1.2-2.3 for former and current smokers, respectively), sex (OR 1.6 for being female, P=0.002, CI 1.2-2.2), presence of specific IgE to common aeroallergen(s) (OR 1.4, P=0.041, CI 1.2-2.0), and ever being diagnosed with asthma (OR 1.6, P=0.003, CI 1.3-2.0). Conclusion: Apart from tobacco exposure and age, the presence of airflow limitation was associated with being overweight, female, sensitized to common aeroallergens or ever having a diagnosis of asthma.

Prospective Studies Exploring the Possible Impact of an ID3 Polymorphism on Changes in Obesity Measures.

OBJECTIVE: Changes in fat mass depend on adipogenesis and angiogenesis, mechanisms regulated by the inhibitor of differentiation-3 (ID3). Id3 knockout mice showed attenuated increases in BMI and visceral fat mass. We hypothesized that the ID3 missense variant (rs11574-A) would lead to an attenuated increase over time in fat mass, BMI, waist circumference (WC), and waist-hip ratio (WHR) in humans. METHODS: The genotyped study populations included the Obesity Research Group - Genetics (ORGGEN) cohort, a cohort of men with obesity (N = 716) and of randomly selected men (N = 826) from the Danish draft register who were examined at mean ages of 20 and 46 years, and the Inter99 (N = 6,116) and Health2006 (N = 2,761) cohorts, two population-based samples of middle-aged people, followed up after 5 years. RESULTS: In meta-analyses of all data, no association was found between rs11574-A and changes in BMI, WC, WHR, or fat mass. We found an association between rs11574-A and cross-sectional BMI (N = 10,359, ß: -0.16 kg/m2 per allele, 95% CI: -0.30 to -0.01, P = 0.033) and fat mass (N = 4,188, ß: -0.52 kg/m2 per allele, 95% CI: -1.03 to -0.01, P = 0.046). CONCLUSIONS: No consistent impact of the genetic variant on changes in fat mass, BMI, or fat distribution was found in three Danish cohorts.

Individual testosterone decline and future mortality risk in men.

OBJECTIVE: Male aging is characterized by a decline in testosterone (TS) levels with a substantial variability between subjects. However, it is unclear whether differences in age-related changes in TS are associated with general health. We investigated associations between mortality and intra-individual changes in serum levels of total TS, SHBG, free TS and LH during a ten-year period with up to 18 years of registry follow-up. DESIGN: 1167 men aged 30-60 years participating in the Danish Monitoring Trends and Determinants of Cardiovascular Disease (MONICA1) study and who had a follow-up examination ten years later (MONICA10) were included. From MONICA10, the men were followed up to 18 years (mean: 15.2 years) based on the information from national mortality registries via their unique personal ID numbers. METHODS: Cox proportional hazard models were used to investigate the association between intra-individual hormone changes and all-cause, CVD and cancer mortalities. RESULTS: A total of 421 men (36.1%) died during the follow-up period. Men with most pronounced decline in total TS (<10th percentile) had a higher all-cause mortality risk compared to men within the 10th to 90th percentile (hazard ratio (HR): 1.60; 95% confidence interval (CI): 1.08-2.36). No consistent associations were seen in cause-specific mortality analyses. CONCLUSION: Our study showed that higher mortality rates were seen among the men who had the most pronounced age-related decline in TS, independent of their baseline TS levels.

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

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.

Health-related quality of life in adult dermatitis patients stratified by filaggrin genotype.

BACKGROUND: Information concerning health-related quality of life (HRQoL) and comorbidities of adult dermatitis patients stratified by loss-of-function mutations in the filaggrin gene (FLG) is limited. OBJECTIVE: To investigate HRQoL, skin symptoms and comorbidities in adult FLG mutation carriers. METHODS: This cross-sectional study included patients diagnosed with atopic dermatitis and/or hand eczema (n = 520). Patients completed questionnaires about dermatitis, skin symptoms, HRQoL, and comorbidities, including actinic keratosis, and atopic and mental disorders. RESULTS: FLG mutations (R501X, 2282del4, and R2447X) were identified in 16.9% of patients, and were significantly associated not only with atopic dermatitis, but also independently with skin fissures on the fingers and heels, and self-reported actinic keratosis. Although FLG mutations were significantly associated with reduced HRQoL, as measured by use of the Dermatology Life Quality Index (DLQI), no association with self-reported anxiety or depression was identified. Notably, the highest median DLQI score, reflecting greater impairment, was reported by patients with both FLG mutations and atopic dermatitis. Overall, 19.7% of patients with both atopic dermatitis and FLG mutations reported a 'large or extremely large' impact on their lives; this represents twice the prevalence seen in patients with atopic dermatitis and wild-type FLG (9.6%). CONCLUSION: Patients with both atopic dermatitis and common FLG mutations are more frequently affected by reduced HRQoL.

Abdominal Adiposity Distribution Quantified by Ultrasound Imaging and Incident Hypertension in a General Population.

Abdominal obesity is a major risk factor for hypertension. However, different distributions of abdominal adipose tissue may affect hypertension risk differently. The main purpose of this study was to explore the association of subcutaneous abdominal adipose tissue (SAT) and visceral adipose tissue (VAT) with incident hypertension in a population-based setting. We hypothesized that VAT, rather than SAT, would be associated with incident hypertension. VAT and SAT were determined by ultrasound imagining in 3363 randomly selected Danes (mean age 49 years, 56% women, mean body mass index 25.8 kg/m2). We constructed multiple logistic regression models to compute standardized odds ratios with 95% confidence intervals per SD increase in SAT and VAT. Of the 2119 normotensive participants at baseline, 1432, with mean SAT of 2.8 cm and mean VAT of 5.7 cm, returned 5 years later for a follow-up examination and among them 203 had developed hypertension. In models including both VAT and SAT, the Framingham Hypertension Risk Score variables (age, sex, smoking status, family history of hypertension, and baseline blood pressure) and glycated hemoglobin, odds ratio (95% confidence interval) for incident hypertension for 1 SD increase in VAT and SAT was 1.27 (1.08-1.50, P=0.004) and 0.97 (0.81-1.15, P=0.70), respectively. Adjusting for body mass index instead of SAT attenuated the association between VAT and incident hypertension, but it was still significant (odds ratio, 1.22 [1.01-1.48, P=0.041] for each SD increase in VAT). In conclusion, ultrasound-determined VAT, but not SAT, was associated with incident hypertension in a random sample of Danish adults.

Symptoms and biomarkers associated with celiac disease: evaluation of a population-based screening program in adults.

OBJECTIVES: To identify possible early predictors (symptoms and biomarkers) of celiac disease, compare symptoms before and after screening, and evaluate the diagnostic efficacy of serologic screening for celiac disease in an adult Danish population. METHODS: This cross-sectional population-based study was based on the 5-year follow-up of the Health2006 cohort, where 2297 individuals were screened for celiac disease; 56 were antibody positive and thus invited to clinical evaluation. Eight were diagnosed with biopsy-verified celiac disease. A follow-up questionnaire was sent to antibody-positive individuals 19 months after the clinical evaluation to obtain information on their symptoms and their experience with participation in the screening. RESULTS: Before screening, participants subsequently diagnosed with celiac disease did not differ from the rest of the population with respect to symptoms, but had significantly lower total cholesterol. Tissue transglutaminase IgA antibodies with a cut-off of 10 U/ml had a positive predictive value of 88%. The majority of participants were satisfied with their participation in the screening program. Individuals with celiac disease were generally satisfied with having been diagnosed and 71% felt better on a gluten-free diet. CONCLUSION: There were no differences in the prevalence of symptoms between participants with and without screening-detected celiac disease, confirming that risk stratification in a general population by symptoms is difficult. The majority of participants diagnosed with celiac disease felt better on a gluten-free diet despite not reporting abdominal symptoms before diagnosis and participants in the clinical evaluation were generally satisfied with participation in the screening program.

Association of indoor air pollution with rhinitis symptoms, atopy and nitric oxide levels in exhaled air.

BACKGROUND: Exposure to particulate matter (PM) outdoors can induce airway inflammation and exacerbation of asthma in adults. However, there is limited knowledge about the effects of exposure to indoor PM. The aim of this study was to investigate the association of exposure to indoor sources of PM with rhinitis symptoms, atopy and nitric oxide in exhaled air (FeNO) as a measure of airway inflammation. METHODS: We conducted a population-based cross-sectional study of 3,471 persons aged 18-69 years. Exposure to indoor sources of PM and prevalence of rhinitis symptoms were assessed by a self-administered questionnaire. Atopy was defined as at least 1 positive test (≥0.35 kU/l) for serum-specific IgE against grass, birch, cat or Dermatophagoides pteronyssinus. Regression analyses were used to adjust for confounders. RESULTS: Self-reported exposure to the use of woodstoves, candles or gas kitchen cookers was not significantly associated with either increased prevalence of rhinitis symptoms or atopy or increased levels of FeNO. The prevalence of atopy and allergic rhinitis and the levels of FeNO were significantly decreased among current and previous smokers. Exposure to environmental tobacco smoke (ETS) for 0.5-5 h, but not above 5 h, was significantly associated with a slightly increased prevalence of rhinitis symptoms. CONCLUSION: Self-reported exposure to the use of woodstoves, candles or gas cookers was not significantly associated with an increased risk of rhinitis symptoms or atopy, nor increased FeNO. Self-reported exposure to ETS was associated with a slightly higher prevalence of self-reported rhinitis symptoms without any clear dose-response relationship.

Lifestyle and genetic determinants of folate and vitamin B12 levels in a general adult population.

Danish legislation regarding food fortification has been very restrictive resulting in few fortified food items on the Danish market. Folate and vitamin B12 deficiency is thought to be common due to inadequate intakes but little is known about the actual prevalence of low serum folate and vitamin B12 in the general population. The aim of the present study was to evaluate the folate and vitamin B12 status of Danish adults and to investigate associations between vitamin status and distinct lifestyle and genetic factors. The study included a random sample of 6784 individuals aged 30-60 years. Information on lifestyle factors was obtained by questionnaires and blood samples were analysed for serum folate and vitamin B12 concentrations and several genetic polymorphisms. The overall prevalence of low serum folate ( < 6.8 nmol/l) was 31.4 %. Low serum folate was more common among men than women and the prevalence was lower with increasing age. Low serum folate was associated with smoking, low alcohol intake, high coffee intake, unhealthy diet, and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR)-C677T polymorphism. The overall prevalence of low serum vitamin B12 ( < 148 pmol/l) was 4.7 %. Low serum vitamin B12 was significantly associated with female sex, high coffee intake, low folate status, and the TT genotype of the MTHFR-C677T polymorphism. In conclusion, low serum folate was present in almost a third of the adult population in the present study and was associated with several lifestyle factors whereas low serum concentrations of vitamin B12 were less common and only found to be associated with a few lifestyle factors.