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Background: Public health emergencies, such as the Covid-19 pandemic, put great pressure on healthcare workers (HCW) across the world, possibly increasing the risk of experiencing ethically challenging situations (ECS). Whereas experiencing ECS as a HCW in such situations is likely unavoidable, mitigation of their adverse effects (e.g., moral distress) is necessary to reduce the risk of long-term negative consequences. One possible route of mitigation of these effects is via work environmental factors., Objectives: The current study aimed to examine: [1] risk factors associated with ECS among HCW [2], intensity of moral distress associated with ECS across various occupational factors (i.e., profession, degree of exposure to patients with Covid-19), and [3] the impact of work environmental factors on this association, in a sample of HCW during the pandemic., Methods: We employed multiple logistic and linear regression to self-report data from 977 HCWs at four Norwegian hospitals responding to a survey at the fourth wave of the pandemic., Results: About half of HCW in this study had experienced ECS during the pandemic, and levels of moral distress associated with such were higher than in previous studies using similar assessment methods. Younger age, female sex, geographical work area (mid-north of Norway), and profession (nurse) were all associated with higher odds (range of OR: 1.30-2.59) of experiencing ECS, as were direct contact with patients with Covid-19. Among those participants who reported that they had experienced ECS during the pandemic, moral distress levels when recalling those situations were moderate (Mean 5.7 on a 0-10 scale). Men reported somewhat lower intensity of moral distress (partial eta squared; ηp 2  = 0.02). Reporting a manageable workload (ηp 2  = 0.02), and greater opportunity to work according to best practice (ηp 2  = 0.02), were associated with lower levels of moral distress., Conclusions: Our findings suggest that moral distress could potentially be mitigated on an organizational level, particularly by focusing on ensuring a manageable workload, and an ability to work according to best practice. To build sustainable healthcare systems robust enough to withstand future public health emergencies, healthcare organizations should implement measures to facilitate these aspects of HCWs' work environment., (© 2024. The Author(s).)

Objectives: To explore serum cytokine levels over time in patients with chronic low back pain (cLBP) and Modic changes (MCs), difference in change between treatment groups in the Antibiotics in Modic Changes (AIM) study and associations between change in cytokines and low back pain., Methods: Serum concentrations of 39 cytokines were measured at baseline and 1 year from 73 participants in the AIM study; 30 randomized to placebo, 43 to Amoxicillin. Low back pain intensity was measured by numeric rating scale. Change in cytokine levels over time were assessed by paired t-tests. Difference in change in cytokine levels between treatment groups and associations between changes in LBP and cytokine levels were assessed by linear regression models. Networks of cytokine changes in each treatment groups were explored by Pearson's correlations., Results: Five cytokines changed from baseline to 1 year, (mean change, log transformed values with CI) C-X-C motif chemokine ligand (CXCL) 10 (IP-10) (0.11 (0.01-0.20)), CXCL13 (0.61 (0.00-0.12)), C-C motif chemokine ligand (CCL)26 (0.05 (0.01-0.1)), granulocyte macrophage-colony stimulating factor (GM-CSF) (-0.12 (-0.23 to 0.00)) and CXCL11 (0.12 (0.03-0.22)). Treatment group only influenced change in CCL21 (β 0.07 (0.01-0.12)), and IL-6 (β -0.17 (-0.30 to -0.03)). Change in CXCL13 (β 2.43 (0.49-4.38)), CCL27 (β 3.07 (0.46-5.69)), IL-8 (β 1.83 (0.08-3.58)) and CCL19 (β 3.10 (0.86-5.43)) were associated with change in LBP. The correlation networks of cytokine changes demonstrate small differences between treatment groups., Conclusions: Cytokine levels are relatively stable over time in our sample, with little difference between treatment groups. Some cytokines may be associated with LBP intensity. The differences between the correlation networks suggest that long-term Amoxicillin-treatment may have longstanding effects to be further explored., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hand-arm vibration (HAV) is a risk factor for carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE). It is unclear how ergonomic factors influence the relationship between HAV exposure and CTS and UNE., Aims: We aimed to assess the relationship between cumulative HAV exposure and CTS and UNE in workers exposed to HAV from two tools with different ergonomic profiles., Methods: We performed nerve conduction studies (NCSs) of the sensory and motor median and ulnar nerves and recorded symptoms indicating CTS and UNE in workers exposed to HAV from impact wrenches or from rock drills. Exposure was measured as cumulative lifetime exposure. We used linear regression adjusted for age and body mass index to assess linear relationships., Results: Sixty-five workers participated (33 rock drill and 32 impact wrench operators). We found inverse linear associations between cumulative HAV exposure and median nerve sensory conduction velocity in impact wrench operators and ulnar nerve motor conduction velocity in rock drill operators (beta of 0.63 and 0.75). Based on NCS findings and symptoms, seven impact wrench operators had CTS and one UNE, and four rock drill operators had CTS and six UNE., Conclusions: Our findings indicate that ergonomic factors influence the development of CTS and UNE under HAV exposure. The ergonomic profile seems to influence which type of neuropathy workers exposed to HAV will develop. Design of occupational exposure guidelines and future studies should be based on ergonomic profile and exposure characteristics for different tools and not merely HAV., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To develop and externally validate prediction models for incident hand osteoarthritis (OA) in a large population-based cohort of middle aged and older men and women., Design: We included 17,153 men and 18,682 women from a population-based cohort, aged 35-70 years at baseline (1995-1997). Incident hand OA were obtained from diagnostic codes in the Norwegian National Patient Register (1995-2018). We studied whether a range of self-reported and clinically measured predictors could predict hand OA, using the Area Under the receiver-operating Curve (AUC) from logistic regression. External validation of an existing prediction model for male hand OA was tested on discrimination in a sample of men. Bootstrapping was used to avoid overfitting., Results: The model for men showed modest discriminatory ability (AUC = 0.67, 95% CI 0.62-0.71). Adding a genetic risk score did not improve prediction. Similar discrimination was observed in the model for women (AUC = 0.62, 95% CI 0.59-0.64). Prediction was not improved by adding a genetic risk score or hormonal and reproductive factors. Applying external validation, similar results were observed among men in HUNT (The Nord-Trøndelag Health Study) as in the developmental sample (AUC = 0.62, 95% CI 0.57-0.65)., Conclusion: We developed prediction models for incident hand OA in men and women. For women, the model included body mass index (BMI), heavy physical work, high physical activity and perceived poor health. The model showed moderate discrimination. For men, we have shown that a prediction model including BMI, education and information on sleep can predict incident hand OA in several populations with moderate discriminative ability., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: The aims of this study were to determine the rates of surgical complications, reoperations, and readmissions following herniated lumbar disc surgery, and to investigate the impact of sociodemographic factors and comorbidity on the rate of such unfavourable events., Patients and Methods: This was a longitudinal observation study. Data from herniated lumbar disc operations were retrieved from a large medical database using a combination of procedure and diagnosis codes from all public hospitals in Norway from 1999 to 2013. The impact of age, gender, geographical affiliation, education, civil status, income, and comorbidity on unfavourable events were analyzed by logistic regression., Results: Of 34 639 operations, 2.7% (95% confidence interval (CI) 2.6 to 2.9) had a surgical complication, 2.1% (95% CI 2.0 to 2.3) had repeat surgery within 90 days, 2.4% (95% CI 2.2 to 2.5) had a non-surgical readmission within 90 days, and 6.7% (95% CI 6.4 to 6.9) experienced at least one of these unfavourable events. Unfavourable events were found to be associated with advanced age and comorbidity., Conclusion: The results suggest that surgical complications are less frequent than previously suggested. There are limited associations between sociodemographic patient characteristics and unfavourable events. Cite this article: Bone Joint J 2019;101-B:470-477.

Background and Purpose: Headache has been associated with various lifestyle and psychosocial factors, one of which is smoking. The aim of the present study was to investigate whether the association between smoking intensity and headache is likely to be causal., Method: A total of 58 316 participants from the Nord-Trøndelag Health (HUNT) study with information on headache status were genotyped for the rs1051730 C>T single-nucleotide polymorphism (SNP). The SNP was used as an instrument for smoking intensity in a Mendelian randomization analysis. The association between rs1051730 T alleles and headache was estimated by odds ratios with 95% confidence intervals. Additionally, the association between the SNP and migraine or non-migrainous headache versus no headache was investigated. All analyses were adjusted for age and sex., Results: There was no strong evidence that the rs1051730 T allele was associated with headache in ever smokers (odds ratio 0.99, 95% confidence interval 0.95-1.02). Similarly, there was no association between the rs1051730 T allele and migraine or non-migrainous headache versus no headache., Conclusion: The findings from this study do not support that there is a strong causal relationship between smoking intensity and any type of headache. Larger Mendelian randomization studies are required to examine whether higher smoking quantity can lead to a moderate increase in the risk of headache subtypes., (© 2018 EAN.)

Studies involving multivariate pattern analysis (MVPA) of BOLD fMRI data generally attribute the success of the information-theoretic approach to BOLD signal contrast on the fine spatial scale of millimeters facilitating the classification or decoding of perceptual stimuli. However, to date MVPA studies that have actually explored fMRI resolutions at less than 2 mm voxel size are rare and limited to small sets of unnatural stimuli (like visual gratings) as well as specific sub-regions of the brain, notably the primary somatosensory cortices. To investigate what spatial scale best supports high information extraction under more general conditions this study combined naturalistic movie stimuli with high-resolution fMRI at 7 T and linear discriminant analysis (LDA) of global and local BOLD signal patterns. Contrary to predictions, LDA and similar classifiers reached a maximum in classification accuracy (CA) at a smoothed resolution close to 3 mm, well above the 1.2 mm voxel size of the fMRI acquisition. Maximal CAs around 90% were contingent upon global fMRI signal patterns comprising 4 k-16 k of the most reactive voxels distributed sparsely throughout the occipital and ventro-temporal cortices. A Searchlight analysis of local fMRI patterns largely confirmed the global results, but also revealed a small subset of brain regions in early visual cortex showing limited increases in CA with higher resolution. Principal component analysis of the global and local fMRI signal patterns suggested that reproducible neuronal contributions were spatially auto-correlated and smooth, while other components of higher spatial frequency were likely related to physiological noise and responsible for the reduced CA at higher resolution. Systematic differences between experiments and subjects suggested that higher CA was significantly correlated with more consistent behavior revealed by eye tracking. Thus, the optimal resolution of fMRI data for MVPA was mainly limited by physiological noise of high spatial frequency as well as behavioral (in-)consistency., (Copyright © 2017. Published by Elsevier Inc.)

Objective: To investigate whether parity, age at menarche, menopausal status, age at menopause, use of oral contraceptives (OC) or use of hormone replacement therapy (HRT) were associated with total knee replacement (TKR) or total hip replacement (THR) due to primary osteoarthritis., Method: In a prospective cohort study of 30,289 women from the second and third surveys of the Nord-Trøndelag Health Study, data were linked to the Norwegian Arthroplasty Register (NAR) in order to identify TKR or THR due to primary osteoarthritis. Cox proportional hazards models were used to estimate the hazard ratios (HRs)., Results: We observed 430 TKRs and 675 THRs during a mean follow-up time of 8.3 years. Increasing age at menarche was inversely associated with the risk of TKR (P-trend < 0.001). Past users and users of systemic HRT were at higher risk of TKR compared to never users (HR 1.42 (95% confidence interval (CI) 1.06-1.90) and HR 1.40 (95% CI 1.03-1.90), respectively). No association was found between parity, age at menarche, menopausal status, age at menopause, oral contraceptive use or HRT use and THR., Conclusion: We found that increasing age at menarche reduced the risk of TKR. Past users and users of systemic HRT were at higher risk of TKR compared to never users. Parity did not increase the risk of THR or TKR., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal., Method: 55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex., Results: Smoking quantity (no. of cigarettes) was inversely associated with TJR (HR 0.97, 95% CI 0.97-0.98). In the Mendelian randomization analysis, rs1051730 T alleles were associated with reduced risk of TJR among current smokers (HR 0.84, 95% CI 0.76-0.98, per T allele), however we found no evidence of association among former (HR 0.97, 95% CI 0.88-1.07) and never smokers (HR 0.97, 95% CI 0.89-1.06). Neither adjusting for body mass index (BMI), cardiovascular disease (CVD) nor accounting for the competing risk of mortality substantially changed the results., Conclusion: This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Inconsistent results have been obtained with regard to headache comorbidity in multiple sclerosis (MS)., Objective: Investigate the one-year prevalence of migraine and tension-type headache (TTH) in Norwegian MS patients and relate this to clinical parameters., Methods: A questionnaire concerning headache was administered to 756 MS patients and 1090 controls and used to determine the one-year prevalence of migraine and frequent TTH., Results: No significant differences were seen between patients and controls or between patients with different disease course. Less migraine was observed in patients with Expanded Disability Status Scale score (EDSS) ≥4.0., Conclusions: This case-control study does not support an association between migraine or TTH and MS.

Background: There is a predominance of chronic widespread musculoskeletal complaints (WMSC) among women. Previous studies suggest an association between hormonal factors and pain. However, it is not known whether earlier age at menarche is associated with higher prevalence of chronic WMSC. The aim of this study was to investigate the association between age at menarche and chronic WMSC., Methods: Data from a cross-sectional study of inhabitants ≥20 years in Nord-Trøndelag County (Helseundersøkelsen i Nord-Trøndelag -HUNT), conducted in 1995-1997 (HUNT 2) were used. The study population comprised 32,673 women with valid information of age at menarche (exposure) and chronic WMSC (outcome data)., Results: In total, 8986 (27.5%) women reported WMSC. The overall prevalence of WMSC was 29.7% among those with menarche ≤12 years and 26.7% among those with menarche >12 years. The prevalence of chronic WMSC was consistently higher for those with early age at menarche in all age groups. The crude odds ratio for chronic WMSC, when comparing women with age at menarche ≤12 years to women with age at menarche >12 years, was 1.16 (95% CI: 1.10-1.22). The corresponding odds ratio was 1.26 (95% CI: 1.19-1.34) when adjusted for age, education, body mass index (BMI), smoking, alcohol consumption, depression, systolic blood pressure (SBP) and parity., Conclusion: In this cross-sectional study, there was an association between early age at menarche and chronic WMSC later in life, but the difference in absolute risk was low (3%)., (© 2015 European Pain Federation - EFIC®)

Background: The Neck Disability Index (NDI) is widely used as a self-rated disability score in patients with cervical radiculopathy. The purpose of this study was to evaluate whether the NDI score correlated with other assessments of quality of life and mental health in a specific group of patients with single-level cervical disc disease and corresponding radiculopathy., Methods: One hundred thirty-six patients were included in a prospective, randomized controlled clinical multicenter study on one-level anterior cervical discectomy with arthroplasty (ACDA) versus one-level anterior cervical discectomy with fusion (ACDF). The preoperative data were obtained at hospital admission 1 to 3 days prior to surgery. The NDI score was used as the dependent variable and correlation as well as regression analyses were conducted to assess the relationship with the short form-36, EuroQol-5Dimension-3 level and Hospital Anxiety and Depression Scale., Results: The mean age at inclusion was 44.1 years (SD ±7.0, range 26-59 years), of which 46.3 % were male. Mean NDI score was 48.6 (SD = 12.3, minimum 30 and maximum 88). Simple linear regression analysis demonstrated a significant correlation between NDI and the EuroQol-5Dimension-3 level [R = -0.64, 95 % confidence interval (CI) -30.1- -19.8, p < 0.001] and to a lesser extent between NDI and the short form-36 physical component summary [R = -0.49, 95 % CI (-1.10- -0.58), p < 0.001] and the short form-36 mental component summary [R = -0.25, 95 % CI (-0.47- -0-09), p = 0.004]. Regarding NDI and the Hospital Anxiety and Depression Scale, a significant correlation for depression was found [R = 0.26, 95 % CI (0.21-1.73), p = 0.01]. Multiple linear regression analysis showed a statistically significant and the strongest correlation between NDI and the independent variables in the following order: EuroQol-5Dimension-3 level [R = -0.64, 95 % CI (-23.5- -7.9), p <0.001], short form-36 physical component summary [R = -0.41, 95 % CI (-0.93- -0.23), p = 0.001] and short form-36 mental component summary [R = -0.36, 95 % CI (-0.53- -0.15), p = 0.001]., Conclusion: The results from the present study show that the NDI correlated significantly with a different quality of life and mental health measures among patients with single-level cervical disc disease and corresponding radiculopathy.

Introduction: Chronic migraine (CM) is at the severe end of the clinical migraine spectrum, but its genetic background is unknown. Our study searched for evidence that genetic factors are involved in the chronification process., Methods: We initially selected 144 single-nucleotide polymorphisms (SNPs) from 48 candidate genes, which we tested for association in two stages: The first stage encompassed 262 CM patients, the second investigated 226 patients with high-frequency migraine (HFM). Subsequently, SNPs with p values < 0.05 were forwarded to the replication stage containing 531 patients with CM or HFM., Results: Eight SNPs were significantly associated with CM and HFM in the two-stage phase. None survived replication in the third stage., Discussion: We present the first comprehensive genetic association study for migraine chronification. There were no significant findings. Future studies may benefit from larger, genome-wide data sets or should use other genetic approaches to identify genetic factors involved in migraine chronification., (© International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background and Purpose: During the past decade, several population-based studies have found an inverse association between blood pressure (BP) and headache. However, most of them have a cross-sectional design or lack a validated definition of a headache-free population at baseline. Therefore, additional population-based studies using a clearly defined headache-free population and a prospective design are warranted., Methods: Data from two large epidemiological studies, the Nord-Trondelag Health Survey 1995-1997 (HUNT 2) and 2006-2008 (HUNT 3), were used to evaluate the association between BP (systolic, diastolic and pulse pressure) at baseline and headache (migraine and tension type headache) at follow-up., Results: An inverse relationship was found between all three BP measures at baseline in HUNT 2 and any headache in HUNT 3, more evident for systolic BP [odds ratio (OR) 0.90 per 10 mmHg increase in systolic BP, 95% confidence interval (CI) 0.87-0.93, P < 0.001] and pulse pressure (OR 0.84 per 10 mmHg increase in pulse pressure, 95% CI 0.80-0.89, P < 0.001) than for diastolic BP (OR 0.92 per 10 mmHg increase in diastolic BP, 95% CI 0.87-1.00, P = 0.036). The most robust finding, evident for both sexes, was that increased pulse pressure was linked to decreased prevalence of both migraine and tension type headache., Conclusion: An inverse relationship between BP and subsequent development of headache was confirmed in this large-scale population-based cohort study. Nevertheless, further research is needed to investigate the underlying mechanisms explaining these findings., (© 2014 EAN.)

Background: Epidemiological studies have suggested inverse relationships between blood pressure and prevalence of conditions such as migraine and headache. It is not yet clear whether similar relationships can be established for back pain in particular in prospective studies., Methods: Associations between blood pressure and chronic low back pain were explored in the cross-sectional HUNT 2 survey of a Norwegian county in 1995-1997, including 39,872 individuals who never used antihypertensive medication. A prospective study, comprising 17,209 initially back pain-free individuals and 5740 individuals reporting low back pain, was established by re-examinations in the HUNT 3 survey in 2006-2008. Associations were assessed by logistic regression with respect to systolic, diastolic and pulse pressure, with adjustment for education, work status, physical activity, smoking, body mass and lipid levels., Results: In the cross-sectional study, all three blood pressure measures showed inverse relationships with prevalence of low back pain in both sexes. In the prospective study of disease-free women, baseline pulse pressure and systolic pressure were inversely associated with risk of low back pain [odds ratio (OR) 0.93 per 10 mm Hg increase in pulse pressure, 95% confidence interval (CI) 0.89-0.98, p = 0.007; OR 0.95 per 10 mm Hg increase in systolic pressure, 95% CI 0.92-0.99, p = 0.005]. Results among men were equivocal. No associations were indicated with the occurrence of pain in individuals with low back pain at baseline., Conclusions: Results for low back pain are consistent with the theory of hypertension-associated hypalgesia, predicting diminished pain sensitivity with increasing blood pressure, possibly with modified reactions in people suffering from long-lasting pain., (© 2013 European Pain Federation - EFIC®)

Background: Obesity increases the risk for a number of solid malignant tumours. However, it is not clear whether body mass index (BMI) and height are associated with the risk of primary tumours of the central nervous system (CNS)., Methods: In a large population study (The Nord-Trøndelag Health Study (HUNT Study)) of 74 242 participants in Norway, weight and height were measured. During follow-up, incident CNS tumours were identified by individual linkage to the Norwegian Cancer Registry. Sex- and age-adjusted and multivariable Cox regression analyses were used to evaluate BMI and height in relation to the risk of meningioma, glioma and schwannoma., Results: A total of 138 meningiomas, 148 gliomas and 39 schwannomas occurred during 23.5 years (median, range 0-25) of follow-up. In obese women (BMI ≥ 30 kg m(-2)), meningioma risk was 67% higher (hazard ratio (HR)=1.68, 95% confidence interval (CI): 0.97-2.92, P-trend=0.05) than in the reference group (BMI 20-24.9 kg m(-2)), whereas no association with obesity was observed in males. There was no association of BMI with glioma risk, but there was a negative association of overweight/obesity (BMI ≥ 25 kg m(-2)) with the risk of schwannoma (HR=0.48, 95% CI: 0.23-0.99). However, the schwannoma analysis was based on small numbers. Height was not associated with the risk for any tumour subgroup., Conclusion: These results suggest that BMI is positively associated with meningioma risk in women, and possibly, inversely associated with schwannoma risk.

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-Trøndelag 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., (© 2012 The Author(s) European Journal of Neurology © 2012 EFNS.)

Introduction: We have successfully utilized a family-based study design to localize several positional candidate preeclampsia susceptibility genes to chromosomes 2q22(ACVR2A,LCT,LRP1B,RND3,GCA),5q (ERAP2) and 13q(TNFSF13B). We now report on our continued positional cloning efforts using an alternative genome-wide association (GWA) mapping strategy in large Caucasian case-control cohorts from Australia and Norway., Objectives: To identify maternal genetic risk loci for preeclampsia., Methods: The unrelated Australian samples (545 cases,547 controls) were genotyped using Illumina BeadChip technology (700K loci) and have been analyzed using PLINK. All unrelated Norwegian samples were genotyped across several Illumina BeadChip substrates and consist of 847 cases (700K loci) and 638 controls. The Norwegian control samples originate from other HUNT studies pertaining to migraine (n=95,700K loci), lung cancer (n=89,370K loci) and normal brain pathology (n=454,2.5M loci). To analyze a concordant set of 2.5-3 million genotypes across all Norwegian samples we are currently using MaCH to impute those loci not directly genotyped. The Norwegian GWA data will be analyzed in SOLAR utilizing empirical kinship estimates to account for any distant relatedness., Results: 1078 Australian samples (538 cases,540 controls) and 648, 175 SNPs passed our quality control metrics. Two SNP associations (rs7579169,p=3.6×10(-7); rs12711941,p=4.3×10(-7)) satisfied our genome-wide significant threshold (p<5.1×10(-7)). These SNPs reside less than 15kb downstream from the 3 terminus of the Inhibin, beta B (INHBB) gene on 2q14.2. Sequencing of the INHBB locus in our patient cohort identified a third intergenic SNP to significantly associate with preeclampsia (rs7576192,p=1.5×10(-7)). These three SNPs confer risk (OR>1.56) and are in strong linkage disequilibrium with each other (r(2)>0.9) but not with any other genotyped SNP ±200kb. The analysis of the Norwegian GWAS is underway., Conclusion: The Australian GWAS has identified a novel preeclampsia risk locus on chromosome 2q. The INHBB gene closest to our SNP associations is a plausible positional candidate susceptibility gene. There is a substantive body of evidence implicating inhibins, activins and other members of the TGF-βsuperfamily to have a role in the development of preeclampsia. The biological connection between ACVR2A and INHBB leads us to speculate that our linkage-based and GWA-based study designs, respectively, have identified a key biological pathway involved in susceptibility to preeclampsia., (Copyright © 2012. Published by Elsevier B.V.)

Background and Purpose: Migrainous infarction (MI), i.e., an ischemic stroke developing during an attack of migraine with aura is rare and the knowledge of its clinical characteristics is limited. Previous case series using the International Classification of Headache Disorders (ICHD) included <10 cases which make conclusions less valid. This study aimed to describe characteristics and outcome of MI in a larger sample., Methods: We analyzed demographic data, risk factors, migraine medication, stroke localization, symptoms, and outcome in a sample of 33 patients with MI according to second edition of the ICHD criteria collected from seven Nordic headache clinics., Results: Amongst 33 patients with MI, there were 20 (61%) women and 13 (39%) men with the median age for stroke of 39 (range 19-76) years. Traditional risk factors for stroke were rare compared with Scandinavian young ischemic stroke populations. During the acute phase, 12 (36%) patients used ergotamines or triptans. Stroke was located in the posterior circulation in 27 (82%) patients and cerebellum was involved in 7 (21%). Except in two patients with brainstem infarctions, the outcome was favorable with total recovery or limited residual symptoms., Conclusions: The prevalence of traditional risk factors was low and the infarctions were predominantly located in posterior circulation territory, supporting theories of migraine specific mechanisms. The outcome was in general favorable., (© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.)

Background: Migraine with aura (MA) has been found to be a risk factor for cardiovascular disease including ischaemic stroke and myocardial infarction. Studies have also reported a higher prevalence of unfavourable cardiovascular risk factors amongst migraineurs, but results have been conflicting as to whether this is restricted to MA or also holds true for migraine without aura (MO). This study aims to examine the relation between headache and cardiovascular risk factors in a large cross-sectional population-based study., Methods: A total of 48,713 subjects (age ≥ 20 years) completed a headache questionnaire and were classified according to the headache status in the Nord-Trøndelag Health Study in Norway 1995-1997 (HUNT 2). Framingham 10-year risk for myocardial infarction and coronary death could be calculated for 44,098 (90.5%) of these. Parameters measured were blood pressure, body mass index, serum total and high-density lipoprotein cholesterol., Results: Compared to controls, Framingham risk score was elevated in non-migraine headache sufferers (OR 1.17, 95% CI 1.10-1.26), migraineurs without aura (OR 1.17, 95% CI 1.04-1.32) and most pronounced amongst migraineurs with aura (OR 1.54, 95% CI 1.21-1.95). Framingham risk score consistently increased with headache frequency. For non-migrainous headache and MO, the increased risk was accounted for by the lifestyle factors smoking, high BMI and low physical activity, whilst such factors did not explain the elevated risk associated with MA., Conclusions: Both MA, MO and non-migrainous headache are associated with an unfavourable cardiovascular risk profile, but different mechanisms seem to underlie the elevated risk in MA than in the other headache types., (© 2010 The Author(s). European Journal of Neurology © 2010 EFNS.)

Background: Age at menarche is associated with cardiovascular events and lifestyle factors such as body mass index (BMI), certain women's diseases like breast cancer and endometriosis and with occurrence of certain physical symptoms during puberty. It is unclear whether age at menarche is an independent determinant of headache., Objectives: The aim of the study was to explore age of menarche in relation to headache prevalence in a large population-based study of both adolescents and adult women (HUNT)., Methods: In the Nord-Trøndelag Health Study in Norway 1995-97 (HUNT 2), a total of 26,636 (57%) of 46,506 invited women responded to questions regarding menarche and headache (Head-HUNT). In the youth part of HUNT 2, 3196 female students were interviewed about their headache complaints and 2766 (87%) responded to questions regarding menarche. All the final analyses were adjusted for age, use of oral contraceptives and BMI, and for adults also for educational level., Results: Headache was more prevalent amongst females with menarche ≤ 12 years, both amongst adolescents (OR=1.3, 95% CI=1.1-1.5) and adults (OR=1.1, 95% CI=1.1-1.2), evident for migraine and non-migrainous headache., Conclusion: Headache, both migraine and non-migrainous headache, was more prevalent amongst both adolescents and adult females with early menarche. Early menarche may increase headache susceptibility, or be a consequence of a common pathogenetic factor, e.g., sensitivity to estrogens., (© 2010 The Author(s). European Journal of Neurology © 2010 EFNS.)

Objectives: To examine the relationship between recurrent headache disorders (i.e., migraine and tension-type headache) and lifestyle factors (overweight, low physical activity, and smoking) in an unselected population study among adolescents., Methods: In this cross-sectional study from Norway, a total of 5,847 students were interviewed about headache complaints and completed a comprehensive questionnaire including items concerning physical activity and smoking. In addition, they underwent a clinical examination with height and weight measurements. Adolescents with high physical activity who were not current smokers and not overweight were classified as having a good lifestyle status. These students were compared to those with 1 or more of the negative lifestyle factors present in regard to headache diagnosis and headache frequency., Results: In adjusted multivariate analyses, recurrent headache was associated with overweight (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.2-1.6, p < 0.0001), low physical activity (OR = 1.2, 95% CI 1.1-1.4, p = 0.002), and smoking (OR = 1.5, 95% CI 1.3-1.7, p < 0.0001). The prevalence of OR increased with more than 1 negative lifestyle factor present, evident for headache diagnoses and frequency., Conclusion: The results from the present study show that overweight, smoking, or low physical activity are independently and in combination associated with recurrent headache among adolescents. The associations observed and the additive effect of these negative lifestyle factors on the prevalence of recurrent headache indicates possible targets for preventive measures.

Background: Little is known about the cost of neurological disorders in Norway., Objectives: To estimate the cost of disorders of the brain, including the main psychiatric, neurological and neurosurgical conditions in Norway., Methods: Most of the data are extrapolations from a large European cost study that collected the best available epidemiological and health economical evidence for the year 2004. Some epidemiological data are available from Norway, but very little on costs., Results: Brain disorders seemed to affect 1.5 million Norwegians in 2004, and the total cost amounted to 5.8 billion Euros. The most prevalent disorders are anxiety disorders and migraine, and the most costly are affective disorders, addiction and dementia. Migraine is the most costly of the purely neurological conditions, followed by stroke, epilepsy and Parkinson's disease. The indirect costs account for more than half of the total costs., Discussion: Although the different brain disorders are very dissimilar in appearance, from health economic and public health perspectives, it is relevant to view them as a whole, since many of them share important pathophysiological mechanisms. This means that new insights into one disorder can have relevance for many other disorders., Conclusion: As a result of the high impact on individuals and society, more resources should be allocated to treatment and research into brain disorders.

It is a general belief that patients with medication overuse headache (MOH) need withdrawal of acute headache medication before they respond to prophylactic medication. In this 1-year open-labelled, multicentre study intention-to-treat analyses were performed on 56 patients with MOH. These were randomly assigned to receive prophylactic treatment from the start without detoxification, undergo a standard out-patient detoxification programme without prophylactic treatment from the start, or no specific treatment (5-month follow-up). The primary outcome measure, change in headache days per month, did not differ significantly between groups. However, the prophylaxis group had the greatest decrease in headache days compared with baseline, and also a significantly more pronounced reduction in total headache index (headache days/month x headache intensity x headache hours) at months 3 (P = 0.003) and 12 (P = 0.017) compared with the withdrawal group. At month 12, 53% of patients in the prophylaxis group had > or = 50% reduction in monthly headache days compared with 25% in the withdrawal group (P = 0.081). Early introduction of preventive treatment without a previous detoxification programme reduced total headache suffering more effectively compared with abrupt withdrawal. (ClinicalTrials.gov number, NCT00159588).

The aim of this study was to evaluate, using a prospective and a cross-sectional design, the relationship between level of physical activity and migraine and non-migraine headache. In the prospective part, 22,397 participants, not likely to have headache, answered questions about physical activity at baseline (1984-1986) and responded to a headache questionnaire at follow-up. In the cross-sectional part (1995-1997), 46,648 participants answered questions about headache and physical activity. Physically inactive individuals at baseline were more likely than active individuals to have non-migraine headache 11 years later (odds ratio 1.14, 95% confidence interval 1.02, 1.28). In the cross-sectional analyses, low physical activity was associated with higher prevalence of migraine and non-migraine headache. In both headache groups, there was a strong linear trend (P < 0.001) of higher prevalence of 'low physical activity' with increasing headache frequency. The result may indicate that physical inactivity among headache-free individuals is a risk factor for non-migraine headache and that individuals with headache are less physically active than those without headache.

Background: Many antihypertensive drugs are also used as migraine prophylactics, but the relationship between blood pressure and headache is not been well understood. The objective of the present study was to explore the association between blood pressure and headache prevalence, and the effect of antihypertensive medication on this relationship, using both cross-sectional and prospective data from a large population., Methods: We used data from two large epidemiologic studies, the Nord-Trøndelag Health Survey 1984-1986 (HUNT-1) and 1995-97 (HUNT-2), to evaluate the association between blood pressure (systolic, diastolic, mean arterial, and pulse pressure) and migraine and nonmigrainous headache., Results: Increasing systolic blood pressure was associated with decreasing prevalence of having nonmigrainous headache or migraine. The most consistent and robust finding, however, was that increasing pulse pressure was linked to decreased prevalence of both nonmigrainous headache and migraine, evident for both sexes in the prospective and cross-sectional analyses. In subjects using antihypertensive medication, this finding was less clear., Conclusion: Both increased systolic blood pressure and pulse pressure are related to arterial stiffness and may decrease headache prevalence through modulation of the baroreflex arch, which in turn generates hypoalgesia. This is due to a phenomenon called hypertension-associated hypalgesia. Stimulation of the baroreflex arch in response to increased blood pressure is assumed to inhibit pain transmission at both spinal and supraspinal levels, possibly because of an interaction of the centers modulating nociception and cardiovascular reflexes in the brainstem.

Although arterial spin labeling (ASL) MRI has been successfully applied to measure gray matter (GM) perfusion in vivo, accurate detection of white matter (WM) perfusion has proven difficult. Reported literature values are not consistent with each other or with perfusion measured with other modalities. In this work, the cause of these inconsistencies is investigated. The results suggest that WM perfusion values are substantially affected by the limited image resolution and by signal losses caused by the long transit times in WM, which significantly affect the label. From gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) bolus-tracking experiments (N=6), it is estimated that the transit time can be several seconds long in deep WM. Furthermore, simulations show that even at a spatial resolution of 7 microl voxel size, contamination by the GM signals can exceed 40% of the actual WM signal. From 10-min long flow-sensitive alternating inversion recovery ASL (FAIR-ASL) measurements at 3T in normal subjects (N=7), using highly sensitive detectors, it is shown that single-voxel (7 mul) deep WM perfusion values have an signal-to-noise ratio (SNR) less than 1. The poor sensitivity and heterogeneous transit time limit the applicability of ASL for measurement of perfusion in WM.

Associations between headache, including migraine, and gastrointestinal (GI) symptoms were studied in a large questionnaire-based cross-sectional study (the Head-HUNT Study). The headache questionnaire was completed by 43,782 individuals, who answered all the questions concerning nausea, reflux symptoms, diarrhoea and constipation. In the multivariate analyses, adjusting for age, sex, educational level, medication use, depression and anxiety, a higher prevalence of headache was found in individuals with much reflux [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.2, 2.6], diarrhoea (OR 2.4, 95% CI 2.1, 2.8), constipation (OR 2.1, 95% CI 1.9, 2.4) and nausea (OR 3.2, 95% CI 2.6, 3.8) compared with those without such complaints. All the GI symptoms investigated seemed to be approximately as common among persons with non-migrainous headache as among migraine sufferers, but the association between headache and GI complaints increased markedly with increasing headache frequency. This may suggest that headache sufferers generally are predisposed to GI complaints.

In patients with diabetes mellitus (DM), there are changes in vascular reactivity and nerve conduction that may be relevant for migraine pathophysiology. However, previous studies on the relationship between headache and DM have shown conflicting results. The aim of the present study was to investigate a possible association between headache and DM in a large population-based cross-sectional study. Associations were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence OR of migraine was lower amongst persons with DM compared with those without DM, the OR being 0.4 (95% CI: 0.2-0.9) for type 1 and 0.7 (95% CI: 0.5-0.9) for type 2 DM. Furthermore, OR of headache were lower amongst those with duration of DM > or = 13 years compared with those who had got DM the last 3 years, OR 0.6 (95% CI: 0.4-0.9). The analyses revealed no clear associations between non-migrainous headache and DM. The reason for the inverse relationship between migraine and DM is unknown, but might be related to pathophysiological abnormalities in patients with DM that protect against migraine.

It is unclear how effort translates into brain function. In this study we endeavored to identify the activity in a working memory task that is related to the allocation of mental resources. Such activity, if present, would be a likely candidate to explain how effort works in terms of brain function. Eleven healthy participants performed a Sternberg task with a memory-set of one, three, or five consonants in an fMRI study. Probe stimuli were either one consonant or one digit. We expected digits to be processed automatically and consonants to require working memory. Because the probe type was unpredictable and subjects had to respond as fast as possible, we expected subjects to allocate mental resources on the basis of the memory-set size, not the probe type. Accordingly, we anticipated that activity in regions involved in effort would be a function of the size of the memory-set, but independent of the type of probe. We found that the reaction-time for digits increased in line with our expectation of automatic processing and the reaction time for letters increased in line with our expectation of controlled processing. fMRI revealed that activity in the right ventral-prefrontal cortex changed as a function of effort. The ventral anterior cingulate cortex and hypothalamus showed reduced activity as a function of effort. Activity in regions regarded as pivotal for working memory (among others, the left dorsolateral prefrontal cortex, anterior cingulate cortex) appeared to be predominantly related to information processing and not involved in effort.

The number of epidemiological headache studies is rapidly increasing, and has accentuated the need to improve the quality of the way studies are performed and how results are interpreted. The aims of this review were to summarize the main findings from the Head-HUNT study, to describe strengths and limitations of the Head-HUNT approach and to discuss the significance of some of our findings. Head-HUNT included a large sample size of 51,383 participants that gave the opportunity to make analyses also of relatively rare conditions. The wide range of health-related information made it possible to adjust for many potential confounding variables. Blood samples for future genetic headache studies are available for a non-selected large group of individuals. The data show that among several factors that have been evaluated, age and gender were the two most clearly related to migraine, whereas analgesic overuse and the presence of some comorbid conditions were most strongly associated with the prevalence of chronic headache. Interesting relationships to blood pressure and thyroid-stimulating hormone levels were also found. Methodological problems in headache epidemiological studies are discussed and, in particular, problems with causal inferences. Despite the limitations of the head-HUNT study, we believe that the results so far have provided clues to causes and preventive factors of headache that should be explored in other populations and in prospective studies.

This study, which is a part of the initiative 'Lifting The Burden: The Global Campaign to Reduce the Burden of Headache Worldwide', assesses and presents all existing evidence of the world prevalence and burden of headache disorders. Population-based studies applying International Headache Society criteria for migraine and tension-type headache, and also studies on headache in general and 'chronic daily headache', have been included. Globally, the percentages of the adult population with an active headache disorder are 46% for headache in general, 11% for migraine, 42% for tension-type headache and 3% for chronic daily headache. Our calculations indicate that the disability attributable to tension-type headache is larger worldwide than that due to migraine. On the World Health Organization's ranking of causes of disability, this would bring headache disorders into the 10 most disabling conditions for the two genders, and into the five most disabling for women.

In MRI of human brain, the respiratory cycle can induce B0-field fluctuations through motion of the chest and fluctuations in local oxygen concentration. The associated NMR frequency changes can affect the MRI data in various ways and lead to temporal signal fluctuations, and image artifacts such as ghosting and blurring. Since the size of the effect scales with magnetic field strength, artifacts become particularly problematic at fields above 3.0T. Furthermore, the spatial dependence of the B0-field fluctuations complicates their correction. In this work, a new method is presented that allows compensation of field fluctuations by modulating the B0 shims in real time. In this method, a reference scan is acquired to measure the spatial distribution of the B0 effect related to chest motion. During the actual scan, this information is then used, together with chest motion data, to apply compensating B0 shims in real time. The method can be combined with any type of scan without modifications to the pulse sequence. Real-time B0 shimming is demonstrated to substantially improve the phase stability of EPI data and the image quality of multishot gradient-echo (GRE) MRI at 7T., (Copyright (c) 2007 Wiley-Liss, Inc.)

Conflicting evidence exists whether hormone replacement therapy (HRT) is a risk factor for headache. The aim of the study was to examine the prevalence of headache and migraine amongst postmenopausal women using HRT. In the Nord-Trøndelag Health Study 1995-97 (HUNT 2), 18,323 (62%) out of 29,679 women aged 40 years or more responded to headache questions (Head-HUNT). Amongst the 6007 postmenopausal women, 5507 (92%) responded to questions regarding use of HRT (2375 used or had used it) and questions related to headache (2407 had complaints). There was a significant association between headache and present use of HRT, both with local [odds ratio (OR) = 1.4, 95% confidence intervals (CI) 1.1-1.7] and systemic (OR = 1.6, 95% CI 1.4-1.9) application. This was found for non-migrainous headache (OR = 1.3, 95% CI 1.1-1.5) and migraine (OR = 1.6, 95% CI 1.4-1.9). Both migraine and non-migrainous headache were more probably amongst users of postmenopausal HRT than amongst those who had never used HRT. Whether HRT caused headache or was used partly because of headache cannot be determined in this cross-sectional study.

Blink reflex R2 amplitude was investigated in seven patients with cervicogenic headache (CEH), 12 patients with chronic tension-type headache, 23 patients with migraine (10 with aura) and 17 headache-free controls. Standard electrical stimulation of the supraorbital nerve was applied and the response was recorded from the ipsilateral and the contralateral orbicularis oculi muscles. Low R2 amplitude was found in CEH patients compared with control subjects. Headache is unilateral in CEH and the ipsilateral and contralateral responses after stimulation on the painful side were most depressed. R2 amplitude was not significantly affected in migraine and tension headache patients. The results suggest that lower brainstem excitability is reduced in CEH. A state of hypoactivity may be present in caudal trigeminal nucleus neurons on the symptomatic side.

The aim of this large, cross-sectional, population-based study was to examine the association between sick leave and headache. Between 1995 and 1997, all 92 566 adults in Nord-Trøndelag County in Norway were invited to participate in a health survey. Out of 73 327 invited individuals <67 years old, a total of 38 192 (52%) responded to questions about headache, work situation and sick leave during the past year. Associations between sick leave, headache and migraine included were assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with 95% confidence intervals (CIs). There was an increasing prevalence of sick leave with increasing frequency of migraine and non-migrainous headache. The prevalence of sick leave >8 weeks during the past year was more than three times higher among individuals with headache >14 days per month (20%) compared with those without headache (6%). The results may indicate that better treatment of individuals with chronic headache may have beneficial economic implications.

The present review of epidemiologic studies on migraine and headache in Europe is part of a larger initiative by the European Brain Council to estimate the costs incurred because of brain disorders. Summarizing the data on 1-year prevalence, the proportion of adults in Europe reporting headache was 51%, migraine 14%, and 'chronic headache' (i.e. > or =15 days/month or 'daily') 4%. Generally, migraine, and to a lesser degree headache, are most prevalent during the most productive years of adulthood, from age 20 to 50 years. Several European studies document the negative influence of headache disorders on the quality of life, and health-economic studies indicate that 15% of adults were absent from work during the last year because of headache. Very few studies have been performed in Eastern Europe, and there are also surprisingly little data on tension-type headache from any country. Although the methodology and the quality of the published studies vary considerably, making direct comparisons between different countries difficult, the present review clearly demonstrates that headache disorders are extremely prevalent and have a vast impact on public health. The data collected should be used as arguments to increase resources to headache research and care for headache patients all over the continent.

Objective: To examine the prevalence of headache and migraine among women using oral contraceptives (OCs) in a large, cross-sectional population-based study., Methods: In the Nord-Trøndelag Health Study in Norway 1995-1997 (HUNT 2), 27,700 (60%) out of 46,506 invited women responded to headache questions (Head-HUNT). Among 14,353 premenopausal women, 13,944 (97%) responded to questions regarding use of contraceptives., Results: There was a significant association between headache and reported use of estrogen-containing OCs in premenopausal women, both for migraine (OR = 1.4, 95% CI = 1.2 to 1.7) and for non-migrainous headache (OR = 1.2, 95% CI = 1.0 to 1.4). A significant dose relationship between headache and the amount of estrogen in the OCs could not be demonstrated. No significant association between headache and OCs containing only gestagen was found., Conclusion: Headache, especially migraine, was more likely among premenopausal women using oral contraceptives containing estrogen.

Some data indicate that migraine with aura (MA) is more strongly associated with anxiety disorder and depression than migraine without aura (MoA), but the evidence is not conclusive. In the Nord-Trøndelag Health study 1995-1997, a total of 49 205 (75% of the participants) subjects gave valid answers to both HADS (Hospital Anxiety and Depression Scale) and a validated headache questionnaire. Associations between anxiety disorder/depression and MA/MoA were evaluated by multiple logistic regression analysis. Depression (DEP) [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.2, 2.6] and depression with comorbid anxiety disorder (COM) (OR 1.6; 95% CI 1.2, 2.1) were more likely in women having MA than in those with MoA. No stronger association was found for pure anxiety disorder (ANX) in MA vs. MoA (OR 0.9; 95% CI 0.7, 1.5). Among men, we found no difference in prevalence of depression and anxiety disorders between MA and MoA. This is a new finding that might have relevance for both research and clinical treatment.

Objective: The main purpose of the present prospective study was to evaluate the course of migraine and non-migrainous headache during pregnancy and to estimate the occurrence of self-reported transient focal neurological symptoms., Material and Methods: In total 1631 (77%) pregnant women completed the study and were followed-up during pregnancy. The first questionnaire (Q1) was sent together with the appointment letter and delivered at the time of ultrasound screening. The second questionnaire (Q2), to be filled in during pregnancy, was delivered at the time of birth. Q1 and Q2 covered questions about headache, transient neurological symptoms, and other background and demographic data. Subjects reporting transient sensory, motor or visual disturbances were also interviewed by phone in order to achieve a more precise description of the symptoms., Results: A total of 58% subjects with migraine reported not having migraine or no headache at all during pregnancy. Among individuals with non-migrainous headache 25% reported not having any headaches, while 1.9% of the subjects without headache experienced headache attacks during pregnancy that fulfilled the criteria for migraine. Individuals without headache or with non-migrainous headache reported significantly less sensory, motor and visual disturbances during pregnancy compared with migraine subjects. More than 60% of those with possible aura phenomenon were migraine patients, while symptoms of peripheral or non-neurological origin were more common among headache free or those with non-migrainous headache., Conclusion: Transient neurological symptoms were less common among individuals without or with non-migrainous headache compared with migraine. This may indicate that there is an increased susceptibility of unknown cause for these symptoms among migraine patients during pregnancy.

As clinic-based studies show an association between headache and both high and low levels of haemoglobin, we analysed this relationship in a population-based cross-sectional study (the HUNT Study). A total of 2385 women aged 20-55 years responded to a headache questionnaire and gave blood samples for measuring haemoglobin and ferritin. In the multivariate analyses, adjusting for age and education, there was a linear trend of decreasing prevalence of headache (P = 0.02) and migraine (P = 0.01) with decreasing haemoglobin. In particular, migraine was less likely among women with low haemoglobin (values < 11.5 g/dl) (odds ratio 0.4, confidence interval 0.2, 0.9). There was no correlation between headache prevalence and ferritin. The present findings may be relevant for the headache reported in polycythaemia and chronic altitude sickness., (Copyright 2004 Blackwell Publishing Ltd)

Objectives: To examine the prevalence of chronic headache (> or =15 days/month) associated with analgesic overuse in relation to age and gender and the association between analgesic overuse and chronic pain (i.e., migraine, nonmigrainous headache, neck and low-back pain)., Methods: In the Nord-Trøndelag Health Study 1995 to 1997 (HUNT-2), a total of 51,383 subjects responded to headache questions (Head-HUNT), of which 51,050 completed questions related to musculoskeletal symptoms and 49,064 questions regarding the use of analgesics., Results: The prevalence of chronic headache associated with analgesic use daily or almost daily for > or =1 month was 1% (1.3% for women and 0.7% for men) and for analgesic overuse duration of > or =3 months 0.9% (1.2% for women and 0.6% for men). Chronic headache was more than seven times more likely among those with analgesic overuse (> or =1 month) than those without (odds ratio [OR] = 7.5, 95% CI: 6.6 to 8.5). Upon analysis of the different chronic pain subgroups separately, the association with analgesic overuse was strongest for chronic migraine (OR = 10.3, 95% CI: 8.1 to 13.0), intermediate for chronic nonmigrainous headache (OR = 6.2, 95% CI: 5.3 to 7.2), and weakest for chronic neck (OR = 2.6, 95% CI: 2.3 to 2.9) and chronic low-back (OR = 3.0, 95% CI: 2.7 to 3.3) pain. The association became stronger with increasing duration of analgesic use for all groups and was most evident among those with headache, especially those with migraine., Conclusions: Chronic headache associated with analgesic overuse is prevalent and especially chronic migraine is more strongly associated with frequent intake of analgesics than other common pain conditions like chronic neck and chronic low-back pain.

The aim of this study was to examine the prevalence of headache and primary headache disorders like migraine and tension-type headaches among adolescents, and to explore the differences in headache prevalence and frequency by gender and age. This cross-sectional study was conducted in Nord-Trøndelag county, Norway, during the years 1995-97. In total, 8984 (88%) out of 10 202 invited adolescents aged 12-19 years participated in the youth part of the Nord-Trøndelag Health Study [Helseundersøkelsen i Nord-Trøndelag (HUNT)]. The total study population in this study consisted of 8255 individuals after exclusion of invalid questionnaires and students outside the target range of 13-18 years of age. The students completed a comprehensive questionnaire, and one of the questions was whether the students had experienced any headaches during the last 12 months. In addition, 5847 of these students were also subject to an interview in which they were asked whether they had experienced recurring headaches during the last year and, if so, were they classified as migraine (MI), tension-type headache (TTH) or non-classifiable headache. In the total questionnaire-based population, 76.8% reported having had headaches during the last 12 months (69.4% boys and 84.2% girls). Among those who also were interviewed, 29.1% reported having recurrent headaches (21.0% boys and 36.5% girls). The overall 1-year prevalence of migraine was 7%, of tension-type headache 18%, and of non-classifiable headache 4.8%. Higher prevalence rates were found for girls in all age groups and for all headache categories. The overall frequency of recurrent headaches did not vary significantly with age, but girls had significantly more frequent headaches than boys. We concluded that headache in general, and recurrent primary headache disorders like migraine and tension-type headaches, are common somatic complaints among Norwegian adolescents, especially among girls.

The objective was to assess the placebo response in randomized clinical trials of analgesics in the treatment of migraine attacks. We included placebo-controlled studies that used the criteria of the International Headache Society for the diagnosis of migraine and headache response as the primary efficacy parameter. In the 11 studies that qualified for inclusion, headache response occurred after placebo treatment in 7-50% of the migraineurs with an average placebo response rate of 30% (95% confidence interval (CI) 23-36). Two hours after treatment with placebo an average of 9% (95% CI 7-12, range 7-17%) of the patients were found to be pain free. In conclusion, the average headache response rate to placebo was 30% in randomized clinical trials of analgesics in migraine with a tremendous variation among studies. Placebo response rates vary with the choice of primary efficacy measure as well as patient characteristics and study design.

Objective: To examine the relation between analgesic use at baseline and the subsequent risk of chronic pain (> or =15 days/month) and the risk of analgesic overuse., Methods: In total, 32, 067 adults reported the use of analgesics in 1984 to 1986 and at follow-up 11 years later (1995 to 1997). The risk ratios (RR) of chronic pain and RR of analgesic overuse in the different diagnostic groups (i.e., migraine, nonmigrainous headache, neck pain, and low-back pain) were estimated in relation to analgesic consumption at baseline., Results: Individuals who reported use of analgesics daily or weekly at baseline showed significant increased risk for having chronic pain at follow-up. The risk was most evident for chronic migraine (RR = 13.3, 95% CI: 9.3 to 19.1), intermediate for chronic nonmigrainous headaches (RR = 6.2, 95% CI: 5.0 to 7.7), and lowest for chronic neck (RR = 2.4, 95% CI: 2.0 to 2.8) or chronic low-back (RR = 2.3, 95% CI: 2.0 to 2.8) pain. Among subjects with chronic pain associated with analgesic overuse, the RR was 37.6 (95% CI: 21.3 to 66.4) for chronic migraine, 14.4 (95% CI: 10.4 to 19.9) for chronic nonmigrainous headaches, 7.1 for chronic neck pain (95% CI: 5.5 to 9.2), and 6.4 for chronic low-back pain (95% CI: 4.9 to 8.4). The RR for chronic headache (migraine and nonmigrainous headache combined) associated with analgesic overuse was 19.6 (95% CI: 14.8 to 25.9) compared with 3.1 (95% CI: 2.4 to 4.2) for those without overuse., Conclusion: Overuse of analgesics strongly predicts chronic pain and chronic pain associated with analgesic overuse 11 years later, especially among those with chronic migraine.

Background: Among the techniques used to induce and control gene expression, a non-invasive, physical approach based on local heat in combination with a heat-sensitive promoter represents a promising alternative but requires accurate temperature control in vivo. MRI-guided focused ultrasound (MRI-FUS) with real-time feedback control allows automatic execution of a predefined temperature-time trajectory. The purpose of this study was to demonstrate temporal and spatial control of transgene expression based on a well-defined local hyperthermia generated by MRI-FUS., Methods: Expression of the green fluorescent protein (GFP) marker gene was used. Two cell lines were derived from C6 glioma cells. The GFP expression of the first one is under the control of the CMV promoter, whereas it is under the control of the HSP70 promoter in the second one and thus inducible by heat. Subcutaneous tumours were generated by injection in immuno-deficient mice and rats. Tumours were subjected to temperatures varying from 42 to 50 degrees C for 3 to 25 min controlled by MRI-FUS and analyzed 24 h after the heat-shock. Endogenous HSP70 expression and C6 cell distribution were also analyzed., Results: The results demonstrate strong expression at 50 degrees C applied during a short time period (3 min) without affecting cell viability. Induced expression was also clearly shown for temperature in the range 44-48 degrees C but not at 42 degrees C., Conclusions: Heating with MRI-FUS allows a tight and non-invasive control of transgene expression in a tumour., (Copyright 2002 John Wiley & Sons, Ltd.)

The aim of this study was to evaluate the validity of the headache diagnoses (migraine and tension-type headache) obtained from short interviews by nurses, where the subjects were asked to identify their headache(s) based on recognition of typical headache descriptions. All students in junior high schools and high schools aged 12-19 years in Nord-Trøndelag county, Norway, were invited to participate in the youth part of the Nord-Trøndelag Health Study ('Helseundersøkelsen i Nord-Trøndelag'-HUNT), 1995-1997. In this cross-sectional study a total of 8984 students (88%) completed a comprehensive questionnaire with different health-related items. Of these, 6149 were also interviewed by nurses about their headache complaints by giving them two alternative headache descriptions in accordance with either migraine or tension-type headache (Head-HUNT-Youth). The headache diagnoses obtained from nurse interviews were validated in a stratified random sample enriched with headache subjects from the interviewed population. Out of 159 invited individuals, 112 (70%) participated in extensive semistructured interviews by neurologists. The overall chance-corrected agreement (kappa) was 0.76 (confidence interval (CI) 0.66-0.86), which is considered good. For migraine, the positive and negative predictive values were 89% and 90%, respectively, and the chance-corrected agreement (kappa) was 0.72 (CI 0.58-0.87). For tension-type headache, positive and negative predictive values were 83% and 91%, respectively, and chance-corrected agreement (kappa) was 0.74 (CI 0.62-0.87). There was good agreement between the headache diagnoses obtained from the short interviews by nurses and the extensive interviews by neurologists. Short interviews based on recognition of typical headache descriptions seem to be an alternative and efficient way to identify migraine and tension-type headache sufferers among adolescents. The method can be useful in epidemiological research, e.g. in estimation of headache prevalence.

The aim of this large cross-sectional population-based study was to examine the association between migraine, non-migrainous headache and headache frequency with depression, and anxiety disorders. From 1995 to 1997, all 92 566 inhabitants aged 20 years and above in Nord-Trøndelag County in Norway were invited to participate in the Nord-Trøndelag Health Study ('Helseundersøkelsen i Nord-Trøndelag' = HUNT-2). A total of 64 560 participated, whereof 51 383 subjects (80%) completed a headache questionnaire that was included. Of these 51 383 individuals, 47 257 (92%) completed the depression subscale items and 43 478 (85%), the anxiety subscale items of the Hospital Anxiety and Depression Scale (HADS). Associations were assessed in multivariate analyses, estimating prevalence odds ratios (OR) with 95% confidence intervals (CI). Depression and anxiety disorders as measured by HADS, were significantly associated with migraine (OR = 2.7, 95% CI 2.3-3.2; OR = 3.2, 95% CI 2.8-3.6) and non-migrainous headache (OR = 2.2, 95% CI 2.0-2.5; OR = 2.7, 95% CI 2.4-3.0) when compared with headache-free individuals. The association was stronger for anxiety disorders than for depression. The ORs for depression and anxiety disorders amongst both migraine and non-migrainous sufferers increased with increasing headache frequency. Depression and anxiety disorders are associated with both migraine and non-migrainous headache, and this association seems more dependent on headache frequency than diagnostic category.