Abstract: OBJECTIVES: To study the extent to which otitis media (OM) in childhood is associated with adult hearing thresholds. Furthermore, to study whether the effects of OM on adult hearing thresholds are moderated by age or noise exposure. DESIGN: Population-based cohort study of 32,786 participants who had their hearing tested by pure-tone audiometry in primary school and again at ages ranging from 20 to 56 years. Three thousand sixty-six children were diagnosed with hearing loss; the remaining sample had normal childhood hearing. RESULTS: Compared with participants with normal childhood hearing, those diagnosed with childhood hearing loss caused by otitis media with effusion (n = 1255), chronic suppurative otitis media (CSOM; n = 108), or hearing loss after recurrent acute otitis media (rAOM; n = 613) had significantly increased adult hearing thresholds in the whole frequency range (2 dB/17-20 dB/7-10 dB, respectively). The effects were adjusted for age, sex, and noise exposure. Children diagnosed with hearing loss after rAOM had somewhat improved hearing thresholds as adults. The effects of CSOM and hearing loss after rAOM on adult hearing thresholds were larger in participants tested in middle adulthood (ages 40 to 56 years) than in those tested in young adulthood (ages 20 to 40 years). Eardrum pathology added a marginally increased risk of adult hearing loss (1-3 dB) in children with otitis media with effusion or hearing loss after rAOM. The study could not reveal significant differences in the effect of self-reported noise exposure on adult hearing thresholds between the groups with OM and the group with normal childhood hearing. CONCLUSIONS: This cohort study indicates that CSOM and rAOM in childhood are associated with adult hearing loss, underlining the importance of optimal treatment in these conditions. It appears that ears with a subsequent hearing loss after OM in childhood age at a faster rate than those without; however this should be confirmed by studies with several follow-up tests through adulthood.

Abstract: OBJECTIVE: In addition to hepatocellular cancer, HFE C282Y homozygotes are reported to have increased risk of colorectal cancer and breast cancer. This study was done to further explore the cancer risk in C282Y homozygotes. MATERIAL AND METHODS: We studied cancer incidence in 292 homozygotes and 62,568 others that participated in the HUNT 2 population screening in 1995-1997. Using Cox proportional hazard models, we estimated cancer hazard ratio as a function of C282Y homozygosity and several screening variables including serum transferrin saturation, alcohol consumption and daily smoking. RESULTS: Cancer was diagnosed in 36 homozygotes, five of which had two cancer diagnoses. The overall cancer incidence was not increased in C282Y homozygotes (hazard ratio 1.10 [95% CI 0.60-2.03] in women and 0.94 [95% CI 0.53-1.66] in men). However, homozygous men had increased risk of colorectal cancer (hazard ratio 3.03 [95% CI 1.17-7.82], p = 0.022) and primary liver cancer (hazard ratio 54.0 [95% CI 2.68-1089], p = 0.009). The risk of breast cancer in homozygous women was not increased (hazard ratio 1.13 [95% CI 0.35-3.72]). Adjusted for other variables including C282Y homozygosity, very low and very high serum transferrin saturation were associated with increased overall cancer incidence. CONCLUSIONS: C282Y homozygosity is associated with increased risk of colorectal cancer and hepatocellular cancer in men. In the general population, individuals with a very low or a very high serum transferrin saturation may have increased cancer risk.

Abstract: BACKGROUND AND OBJECTIVE: People with asthma may seek advice about physical activity. However, the benefits of leisure time physical activity on lung function are unclear. We investigated the association between leisure time physical activity and lung function decline in adults with asthma. METHODS: In a population-based cohort study in Norway, we used multiple linear regressions to estimate the annual mean decline in lung function (and 95% CI) in 1329 people with asthma over a mean follow-up of 11.6 years. The durations of light and hard physical activity per week in the last year were collected by questionnaire. Inactive participants did not report any light or hard activity, while active participants reported light or hard activity. RESULTS: The mean decline in forced expiratory volume in 1 s (FEV1 ) was 37 mL/year among inactive participants and 32 mL/year in active participants (difference: -5 mL/year (95% CI: -13 to 3)). The mean decline in forced vital capacity (FVC) was 33 mL/year among inactive participants and 31 mL/year in active participants (difference: -2 mL/year (95% CI: -11 to 7)). The mean decline in FEV1 /FVC ratio was 0.36%/year among inactive participants and 0.22%/year in active participants (difference: -0.14%/year (95% CI: -0.27 to -0.01)). The mean decline in peak expiratory flow (PEF) was 14 mL/year among the inactive participants and 10 mL/year in active participants (difference: -4 mL/year (95% CI: -9 to 1)). CONCLUSION: We observed slightly less decline in lung function in physically active than inactive participants with asthma, particularly for FEV1 , FEV1 /FVC ratio and PEF.

Abstract: BACKGROUND: Long-term illness and work incapacity in young adulthood has consequences for both the individual and for society. The purpose of the study was to investigate the association between adolescent health and receipt of long-term sickness and disability benefits for young adults in their twenties. MATERIAL AND METHOD: An adolescent population of 8949 school students (aged 13-21 years) assessed their own health in the Young-HUNT1 Study (1995-1997). Health was measured by means of a questionnaire enquiring about chronic somatic illnesses, somatic symptoms, symptoms of anxiety and depression, sleep disturbance, poor concentration, self-reported health and smoking, and by measuring height and weight. Information about receipt of long-term benefits was retrieved from the FD-Trygd registry for the period 1998-2008 and defined as receipt of sickness benefit (>180 days/year), medical/vocational rehabilitation benefit and disability pension in the age group 20-29 years. We investigated the relationship between adolescent health and long-term social insurance benefits with logistic regression, adjusted for sex, age, follow-up time, mother's education and family composition. Siblings with different exposure and outcome were investigated to adjust for all familial factors shared by siblings. RESULTS: Each of the health measures was associated with an increased risk of long-term benefit. For example, adolescents who reported one or more somatic illnesses or poor concentration had a 5.4 and 3.4 percentage point higher risk, respectively, of receiving long-term benefits at the age of 20-29 years than adolescents who did not report somatic illness or poor concentration. Moreover the risk increased with an increase in the number of health problems. Sibling analyses supported these associations. INTERPRETATION: Health in adolescence is an indicator of increased vulnerability in the transition to the labour market. Preventing health selection during this transition should be a priority for welfare policy.

Abstract: The aim of this paper was to investigate whether psychosocial functioning in adulthood (e.g., friends support, cohabitation, community connectedness and work satisfaction) could be predicted by mental health, subjective well-being, social relations and behavior problems in adolescence, and whether gender was a moderator in these associations. Data were obtained from a major population-based Norwegian study, the Nord-Trondelag Health Study (HUNT), in which 517 men and 819 women completed an extensive self-report questionnaires at baseline (mean age 14.4 years) and at follow-up (mean age 26.9 years). Community connectedness as well as work satisfaction were predicted by subjective well-being. Cohabitation was predicted by male gender and frequency of meeting friends in adolescence, and friends support was predicted by frequency of meeting friends. Gender had a minor effect as a moderator. Frequency of meeting friends and subjective well-being seemed to be the strongest adolescent predictors of psychosocial functioning in young adulthood. These findings may have implications both for prevention and intervention in adolescence, as well as for future research.

Abstract: PURPOSE: To study if physical activity within the recommended level over time was associated with risk of developing depression after the first myocardial infarction in older adults. METHODS: Men (n = 143) and women (n = 46) who had reached the age of 60 years in 2006-2008 who participated in the Nord-Trondelag Health Study (HUNT1, 1984-1986; HUNT2, 1995-1997; HUNT3, 2006-2008) without any mental illness or cardiovascular disease at baseline in HUNT2 and who experienced their first myocardial infarction before HUNT3 were included. Based on the patterns of physical activity from HUNT1 to HUNT2, the sample was divided into 4 groups: persistently inactive, from active to inactive, from inactive to active, and persistently active. The primary outcome, post-myocardial infarction depression symptoms, was measured with the Hospital, Anxiety and Depression Scale in HUNT3. RESULTS: In HUNT3, 11% of participants had depression. After multivariable adjustment, those who were persistently active had significantly lower odds of being depressed (odds ratio 0.28; 95% confidence interval, 0.08-0.98) compared with those who were persistently inactive. Additionally, a significant test for trend (P = .033) of lowering odds of depression was observed across all 4 categories of physical activity patterns at baseline. CONCLUSIONS: In this small sample of initially healthy adults, we observed a long-term protective effect of regular physical activity on the development of depression following myocardial infarction.

Abstract: BACKGROUND: Lowered physical activity levels may partially explain changes in metabolic risk factors in women after menopause. OBJECTIVES: To evaluate the association between physical activity and metabolic risk factors at baseline and after 11 years, as well as the change in that association over time in women who were premenopausal and >/= 40 years at baseline. METHODS: Subjects in a Norwegian population-based health survey answered questionnaires and had body and serum measurements during 1995-1997 (HUNT 2) and in a follow-up study during 2006-2008 (HUNT 3). Repeated-measures analyses were used to estimate the association between physical activity and metabolic factors, adjusting for age, smoking status, education, alcohol intake, and parity. Adjustment for hormonal treatment and medication was made, as appropriate. RESULTS: In women remaining premenopausal, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01) and waist-hip ratio (p < 0.01) and higher high density lipoprotein (HDL) cholesterol in HUNT 3 (p < 0.01). In women that were postmenopausal by the time of follow-up, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01), waist-hip ratio (p < 0.01), triglycerides (p < 0.01), and higher total cholesterol (p < 0.05), HDL cholesterol (p < 0.01), and diastolic blood pressure (p < 0.05) in HUNT 3. The association of total physical activity score with weight and waist-hip ratio was stronger in HUNT 3 than in HUNT 2 (p < 0.01). CONCLUSION: Increased physical activity may reduce the risk of adverse outcomes and use of pharmacological management in women of menopausal age.

Abstract: BACKGROUND AND PURPOSE: Chronic daily headache (CDH) and chronic musculoskeletal complaints (CMSCs) are associated disorders, but whether there is a causal relationship between them is unclear. OBJECTIVE: To determine whether CMSCs are associated with the subsequent development of CDH and vice versa. METHODS: This longitudinal population-based cohort study used data from two consecutive surveys in the Nord-Trondelag Health Study (HUNT 2 and 3) performed in 1995-1997 and 2006-2008. Amongst the 51 383 participants aged >/= 20 years at baseline, 41 766 were eligible approximately 11 years later. Of these, 26 197 (63%) completed the questions regarding headache and CMSCs in HUNT 3. RESULTS: A bidirectional relationship was found between headache and CMSCs. In the multivariate analyses adjusting for known potential confounders, a nearly two fold risk (OR 1.8; 95% CI 1.5-2.3) for developing CDH was found for those with CMSCs at baseline. Vice versa, a similarly elevated risk of CMSCs (OR 1.8; 95% CI 1.2-2.6), and even higher risk of chronic widespread MSCs (OR 2.7; 95% CI 1.6-4.7), was found at follow-up amongst those with CDH at baseline. CONCLUSION: CMSCs predispose to CDH and CDH predisposes to CMSCs 11 years later. This may have relevance to understanding the pathophysiology of these disorders. CMSCs should be treated not only to relieve them but also to prevent the development of CDH, and vice versa.

Abstract: STUDY DESIGN: A population-based, prospective cohort study. OBJECTIVE: To determine whether overweight, obesity, or more generally an elevated body mass index (BMI) increase the probability of experiencing chronic low back pain (LBP) after an 11-year period, both among participants with and without LBP at baseline. SUMMARY OF BACKGROUND DATA: Chronic LBP is a common disabling disorder in modern society. Cross-sectional studies suggest an association between an elevated BMI and LBP, but it is not clear whether this is a causal relationship. METHODS: Data were obtained from the community-based HUNT 2 (1995-1997) and HUNT 3 (2006-2008) studies of an entire Norwegian county. Participants were 8733 men and 10,149 women, aged 30 to 69 years, who did not have chronic LBP at baseline, and 2669 men and 3899 women with LBP at baseline. After 11 years, both groups indicated whether they currently had chronic LBP, defined as pain persisting for at least 3 months continuously during the last year. RESULTS: A significant positive association was found between BMI and risk of LBP among persons without LBP at baseline. The odds ratio for BMI 30 or more versus BMI less than 25 was 1.34 (95% confidence interval [CI], 1.08-1.67) for men and 1.22 (95% CI, 1.03-1.46) for women, in analyses adjusted for age, education, work status, physical activity at work and in leisure time, smoking, blood pressure, and serum lipid levels. A significant positive association was also established between BMI and recurrence of LBP among women. LBP status at baseline had negligible influence on subsequent change in BMI. CONCLUSION: High values of BMI may predispose to chronic LBP 11 years later, both in individuals with and without LBP. The association between BMI and LBP is not explained by an effect of LBP on later change in BMI.

Abstract: AIM: To prospectively examine whether depressive symptoms increase the risk of diabetes and a diabetic foot ulcer. METHODS: The Nord-Trondelag Health Study (HUNT) is a community-based longitudinal study. The Hospital Anxiety and Depression Scale (HADS-D subscale) assessed depressive symptoms. We followed individuals with complete HADS-D data from HUNT2 (1995-97) and assessed whether they reported diabetes with or without a history of diabetic foot ulcer (DFU) in HUNT3 (2006-08) (n=36,031). Logistic regression was used to investigate the effect of depressive symptoms on subsequent development of diabetes and of DFU. RESULTS: Unadjusted odds for reporting diabetes at follow-up was higher among individuals who reported a HADS-D score>/=8 at baseline (OR 1.30 95% CI, 1.07-1.57) than among those reporting a lower score. After adjusting for age, gender and BMI, this association was no longer significant. The odds of developing a DFU was almost two-fold (OR=1.95 95% CI, 1.02-3.74) for those reporting a HADS-D score of 8-10, and 3-fold (OR=3.06 95% CI, 1.24-7.54) for HADS-D scores>/=11, compared to HADS-D scores

Abstract: BACKGROUND: Lifestyle risk behaviours are responsible for a large proportion of disease burden and premature mortality worldwide. Risk behaviours tend to cluster in populations. We developed a new lifestyle risk index by including emerging risk factors (sleep, sitting time, and social participation) and examine unique risk combinations and their associations with all-cause and cardio-metabolic mortality. METHODS: Data are from a large population-based cohort study in a Norway, the Nord-Trondelag Health Study (HUNT), with an average follow-up time of 14.1 years. Baseline data from 1995-97 were linked to the Norwegian Causes of Death Registry. The analytic sample comprised 36 911 adults aged 20-69 years. Cox regression models were first fitted for seven risk factors (poor diet, excessive alcohol consumption, current smoking, physical inactivity, excessive sitting, too much/too little sleep, and poor social participation) separately and then adjusted for socio-demographic covariates. Based on these results, a lifestyle risk index was developed. Finally, we explored common combinations of the risk factors in relation to all-cause and cardio-metabolic mortality outcomes. RESULTS: All single risk factors, except for diet, were significantly associated with both mortality outcomes, and were therefore selected to form a lifestyle risk index. Risk of mortality increased as the index score increased. The hazard ratio for all-cause mortality increased from 1.37 (1.15-1.62) to 6.15 (3.56-10.63) as the number of index risk factors increased from one to six respectively. Among the most common risk factor combinations the association with mortality was particularly strong when smoking and/or social participation were included. CONCLUSIONS: This study adds to previous research on multiple risk behaviours by incorporating emerging risk factors. Findings regarding social participation and prolonged sitting suggest new components of healthy lifestyles and potential new directions for population health interventions.

Abstract: Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.

Abstract: The association between serum 25-hydroxyvitamin D (25(OH)D) level and lung function changes in the general population remains unclear.We conducted cross-sectional (n=1220) and follow-up (n=869) studies to investigate the interrelationship of serum 25(OH)D, smoking and lung function changes in a random sample of adults from the Nord-Trondelag Health (HUNT) Study, Norway.Lung function was measured using spirometry and included forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC ratio. Multiple linear and logistic regression models estimated the adjusted difference in lung function measures or lung function decline, adjusted odds ratios for impaired lung function or development of impaired lung function and 95% confidence intervals.40% of adults had serum 25(OH)D levels