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: OBJECTIVE: In a mortality follow-up of the HUNT Study, serum TSH within the reference range was positively associated with the risk of coronary death in women. We now aimed to confirm the association of high serum TSH with the risk of coronary heart disease, using hospital-based diagnoses of myocardial infarction. DESIGN: Prospective population-based study with linkage to hospital information on myocardial infarction and to the national Cause of Death Registry. PARTICIPANTS: A total of 26, 707 people without previously known thyroid or cardiovascular disease or diabetes at baseline. MEASUREMENTS: Hazard ratios (HR) of coronary death and HRs of hospitalization with a first-time acute myocardial infarction, by baseline thyroid function. RESULTS: During 12, years of follow-up, 960 (3.6%) participants had been hospitalized with first-time myocardial infarction and 558 (2.1%) had died from coronary heart disease. High TSH within the reference range was associated with increased risk of coronary death in women (P(trend) 0.005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0.50-1.4 mU/l. However, thyroid function was not associated with the risk of being hospitalized with myocardial infarction. CONCLUSIONS: High serum TSH was associated with increased mortality from coronary heart disease in women, but we found no association of thyroid function with the risk of being hospitalized with myocardial infarction. Thus, the morbidity finding does not confirm the suggestion that low thyroid function within the clinically normal range is associated with increased risk of coronary heart disease.

Abstract: BACKGROUND: Earlier studies have revealed a high prevalence of dementia among nursing home patients. We conducted a descriptive study of dementia and neuropsychiatric symptoms among patients in nursing homes in Nord-Trondelag County, Norway. MATERIAL AND METHODS: 704 nursing home patients were included and studied with the Norwegian versions of the clinical demential rating scale (CDR) and the neuropsychiatric inventory (NPI). RESULTS: The study indicated that 575 patients (82%) had dementia. Of these, 430 patients (75%) had at least one clinically significant neuropsychiatric syndrome in addition, most commonly delusions, apathy or irritability. The neuropsychiatric symptoms could be grouped in four categories: psychosis, apathy, affective symptoms and agitation. INTERPRETATION: The findings are comparable with earlier studies of Norwegian nursing home patients. The high prevalence of dementia and neuropsychiatric symptoms is of significance for the clinical practice, running and planning of nursing homes.

Abstract: Abstract Objective: To explore the effect of ever having tried to conceive for more than 12 months on levels of anxiety and depressive symptoms and to investigate if symptom levels of anxiety and depression in infertile women who remain childless, or go on to have children, respectively, differ from symptom levels in mothers without reports of infertility. Methods: Analyses were based on information from 12 584 Norwegian women aged 19-45 years who participated in the North-Trondelag Health Study from 1995 to 1997 and data from the Medical Birth Registry of Norway. Anxiety and depressive symptoms were measured by the Hospital Anxiety and Depression Scale. Results: Having tried to conceive for more than 12 months (ever) was weakly associated with higher levels of depressive symptoms. In the categorical analyses, women with resolved infertility had higher levels of anxiety symptoms (B = 0.25 (95% confidence interval (CI) = 0.04-0.47)) and voluntarily childfree had lower levels of depressive symptoms (B = -0.05 (95% CI = -0.50 to -0.21)) than mothers without infertility. However, women with current primary or current secondary infertility had levels of anxiety and depression not significantly different from mothers without infertility. Conclusion: At the population level, and from a longitudinal perspective, unresolved infertility is less burdensome than findings from studies on women seeking help for infertility would suggest.

Abstract: BACKGROUND: There is little knowledge about how factors early in life affect the development of migraine and tension-type headache. We aimed to examine whether growth restriction in utero is associated with development of migraine and frequent tension-type headache in adults. METHODS: The population-based Nord-Trondelag Health Study (HUNT 3) contained a validated headache questionnaire, which differentiated between migraine and tension-type headache. These data were linked to information on weight and gestational age at birth from the Norwegian Medical Birth Registry. In total 4557 females and 2789 males, aged 19-41 years, were included in this registry-based study. Participants were categorized as appropriate for gestational age (AGA, 10th-90th percentile), small for gestational age (SGA, 3rd-10th percentile) or very small for gestational age (VSGA, < 3rd percentile). Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI) for migraine and tension-type headache, with exposure being growth restriction at birth. RESULTS: The effect of growth restriction on migraine was modified by sex, with a significant association in males (p<0.001), but not in females (p = 0.20). In particular, males born VSGA were at increased risk of developing migraine (OR 2.73, 95% CI 1.63-4.58, p<0.001), with an intermediate risk among those born SGA (OR 1.50, 95% CI 0.96-2.35, p = 0.08) compared to those born AGA. There was no significant association between growth restriction and frequent TTH (p = 0.051). CONCLUSION: Growth restriction was associated with increased risk of migraine in adulthood among males, but not among females. This suggests that migraine might, in part, be influenced by early life events, and that males seem to be particularly vulnerable.

Abstract: Few studies have investigated the association between serum 25-hydroxyvitamin D (25[OH]D), vitamin D supplement and asthma control among adults. We aimed to examine whether low levels of serum 25(OH)D or not taking vitamin D supplement were associated with an increased risk of poorly controlled asthma among Norwegian adults with asthma. We used a definition of asthma control adapted from the Global Initiative for Asthma. We first examined cross-sectional associations between serum 25(OH)D (n=806) or vitamin D supplement (n=1179) and poorly controlled asthma. Next, among those with well controlled asthma at baseline, we examined prospective associations between serum 25(OH)D (n=147) or vitamin D supplement (n=208) and poorly controlled asthma at follow-up, approximately 11 years later. We estimated risk ratios (RR) and 95% confidence intervals (CI) with Poisson regression. The adjusted RR for poorly controlled asthma was 1.00 (95% CI, 0.89-1.13) for adults with serum 25(OH)D<50nmol/L in cross-sectional and 1.50 (95% CI, 0.46-4.95) in prospective analyses. The adjusted RR for poorly controlled asthma was 1.17 (95% CI 1.00-1.37) for non-users of vitamin D supplement in cross-sectional and 1.66 (95% CI 0.49-5.67) in prospective analyses. Our study did not show strong evidence that among adults with asthma, having a low serum 25(OH)D or being a non-user of vitamin D supplement was associated with an increased risk of poorly controlled asthma. Some point estimates indicated an increased risk, however our estimates were generally imprecise and further evidence is needed.

Abstract: PURPOSE: The underlying goal of the study was to examine gender-specific effects of leisure-time physical activity on the development of symptoms of anxiety. METHODS: The second wave of a prospective cohort survey (HUNT 2) was conducted during 1995-1997 in the county of Nord-Trondelag, Norway, with a follow-up in 2006-2008 (HUNT 3). The sample consisted of 12,796 women and 11,195 men with an age range of 19-85 years. A binomial model with a log-link function and generalized linear model analysis with gamma distribution was used to assess the association between physical activity and anxiety symptoms (Hospital Anxiety and Depression Scale anxiety subscale, HADS-A). RESULTS: A total of 1,211 (9.5 %) women and 650 (5.8 %) men developed HADS-defined anxiety (>/=8 on the HADS-A scale). Men who scored in the middle tertile of the calculated physical activity index developed significantly fewer cases of HADS-defined anxiety compared with men in the lowest tertile (p

Abstract: BACKGROUND: Sedentary behaviour is a potential risk factor for chronic-ill health and mortality, that is, independent of health-enhancing physical activity. Few studies have investigated the risk of mortality associated with multiple contexts of sedentary behaviour. OBJECTIVE: To examine the prospective associations of total sitting time, TV-viewing time and occupational sitting with mortality from all causes and cardiometabolic diseases. METHODS: Data from 50 817 adults aged >/=20 years from the Nord-Trondelag Health Study 3 (HUNT3) in 2006-2008 were linked to the Norwegian Cause of Death Registry up to 31 December 2010. Cox proportional hazards models examined all-cause and cardiometabolic disease-related mortality associated with total sitting time, TV-viewing and occupational sitting, adjusting for multiple potential confounders including physical activity. RESULTS: After mean follow-up of 3.3 years (137 315.8 person-years), 1068 deaths were recorded of which 388 were related to cardiometabolic diseases. HRs for all-cause mortality associated with total sitting time were 1.12 (95% CI 0.89 to 1.42), 1.18 (95% CI 0.90 to 1.57) and 1.65 (95% CI 1.24 to 2.21) for total sitting time 4-<7, 7-<10 and >/=10 h/day, respectively, relative to <4 h/day after adjusting for confounders (p-trend=0.001). A similar pattern of associations was observed between total sitting time and mortality from cardiometabolic diseases, but TV-viewing time and occupational sitting showed no or borderline significant associations with all-cause or cardiometabolic disease-related mortality over the same follow-up period. CONCLUSIONS: Total sitting time is associated with all-cause and cardiometabolic disease-related mortality in the short term. However, prolonged sitting in specific contexts (ie, watching TV, at work) do not adversely impact health in the same timeframe. These findings suggest that adults should be encouraged to sit less throughout the day to reduce their daily total sitting time.

Abstract: BACKGROUND: Sedentary behaviour is a potential risk factor for chronic-ill health and mortality, that is, independent of health-enhancing physical activity. Few studies have investigated the risk of mortality associated with multiple contexts of sedentary behaviour. OBJECTIVE: To examine the prospective associations of total sitting time, TV-viewing time and occupational sitting with mortality from all causes and cardiometabolic diseases. METHODS: Data from 50,817 adults aged >/=20 years from the Nord-Trondelag Health Study 3 (HUNT3) in 2006-2008 were linked to the Norwegian Cause of Death Registry up to 31 December 2010. Cox proportional hazards models examined all-cause and cardiometabolic disease-related mortality associated with total sitting time, TV-viewing and occupational sitting, adjusting for multiple potential confounders including physical activity. RESULTS: After mean follow-up of 3.3 years (137,315.8 person-years), 1068 deaths were recorded of which 388 were related to cardiometabolic diseases. HRs for all-cause mortality associated with total sitting time were 1.12 (95% CI 0.89 to 1.42), 1.18 (95% CI 0.90 to 1.57) and 1.65 (95% CI 1.24 to 2.21) for total sitting time 4-

Abstract: AIMS: The aim of this study was to test whether the association between self-rated health and mortality differs between educational groups in Norway, and to examine whether health problems and health-related behaviour can explain any of these differences within a previously unexplored contextual setting. METHODS: The study used data from the Nord-Trondelag Health Study 84-86 (HUNT) with a 20-year follow up. The analyses were performed for respondents between 25-101 years at baseline (n = 56,788). The association between self-rated health and mortality was tested using Cox regression. RESULTS: The results indicate that although self-rated health is associated with mortality there is no difference in the association between self-rated health and mortality between educational groups. Introducing health-related variables did not have an impact on the result. CONCLUSIONS: Given the small educational differences in the association between self-rated health and mortality, this supports the reliability of self-reported health as a measurement for objective health.

Abstract: BACKGROUND: Recent studies have shown that high levels of free thyroxine (FT4), even without leading to hyperthyroidism, are associated with a procoagulant state. OBJECTIVES: The aim of our study was to determine whether high levels of thyroid hormones are associated with an increased risk of venous thrombosis. PATIENTS/METHODS: From a prospective nested case-cohort design within the second Nord-Trondelag Health Study (HUNT2) cohort (1995-1997; 66,140 subjects), all patients with venous thrombosis during follow-up (n=515) and 1476 randomly selected age-stratified and sex-stratified controls were included. Relative and absolute risks for venous thrombosis were calculated for different cut-off levels of thyroid hormones on the basis of percentiles in the controls and different times between blood sampling and thombosis. RESULTS: In subjects with an FT4 level above the 98th percentile (17.3 pmol L(-1)), the odds ratio (OR) was 2.5 (95% confidence interval [CI] 1.3-5.0) as compared with subjects with levels below this percentile. For venous thrombosis within 1 year from blood sampling, this relative risk was more pronounced, with an OR of 4.8 (95% CI 1.7-14.0). Within 0.5 years, the association was even stronger, with an OR of 9.9 (95% CI 2.9-34.0, adjusted for age, sex, and body mass index). For thyroid-stimulating hormone, the relationship was inverse and less pronounced. The absolute risk within 6 months in the population for FT4 levels above the 98th percentile was 6.1 per 1000 person-years (95% CI 1.7-15.7). CONCLUSIONS: Levels of FT4 at the upper end of the normal range are a strong risk factor for venous thrombosis. The risk increased with higher levels of thyroxine and shorter time between blood sampling and thrombosis. Further studies on the effect of clinical hyperthyroidism are warranted.

Abstract: BACKGROUND: In adolescents the temporal directionality to the asthma and adiposity association remains unclear. Asthma may be a consequence of obesity; however, asthma may increase adiposity. OBJECTIVES: This study aimed to assess the associations between (i) baseline weight status and subsequent asthma and (ii) baseline asthma and subsequent weight status after 4 and 11 years of follow-up (N = 1543 and N = 1596, respectively) using data from three, sequentially enrolled population-based surveys of Norwegians aged 12-30 years from 1995 to 2008. METHODS: Weight status was defined as general (body mass index) or abdominal (waist circumference) underweight, normal weight, overweight or obesity. Self-report physician-diagnosed asthma defined asthma status. RESULTS: Over the longitudinal 11-year follow-up, baseline generally overweight or abdominally obese adolescents had increased risk of asthma. Likewise, baseline asthmatics had increased risk of general overweight or abdominal obesity. After sex stratification, these associations were stronger in males. Generally (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.32, 2.73) or abdominally (OR 1.66; 95% CI 1.13, 2.44) overweight males were at increased risk of asthma. Baseline asthmatic males were also at increased risk of general (OR 2.14; 95% CI 1.54, 2.98) and abdominal (OR 1.77; 95% CI 1.27, 2.47) overweight. CONCLUSIONS: Among Norwegian adolescents, a bidirectional association of asthma and adiposity was observed in males. Each baseline condition increased the risk of the other condition over time. No association was observed in females.