John Anker Henrik Zwart

• Qu, Kang; Li, Ming-Xi; Yu, Peng; Wu, Bai-Hua; Shi, Miao & Dong, Ming [Show all 72 contributors for this article] (2024). HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study. Scientific Reports. ISSN 2045-2322. 14(1). doi: 10.1038/s41598-024-61628-9.
• Glad, Kristin Alve; Wøien, Hilde; Stensland, Synne; Reitan, Solveig Klæbo; Zwart, John Anker Henrik & Atar, Dan [Show all 8 contributors for this article] (2024). Health care workers’ qualitative descriptions of ethically challenging situations evoking moral distress during Covid-19. Nursing Ethics. ISSN 0969-7330. doi: 10.1177/09697330241257567.
• Rolfsen, Mads Peder; Gammelsrud, Karianne Wiger; Espeland, Ansgar; Bråten, Lars Christian Haugli; Mjønes, Sverre Bugge & Austevoll, Ivar Magne [Show all 15 contributors for this article] (2024). Bacterial growth in patients with low back pain and Modic changes: protocol of a multicentre, case–control biopsy study. BMJ Open. ISSN 2044-6055. 14(5). doi: 10.1136/bmjopen-2023-082244.
• Nievergelt, Caroline M.; Maihofer, Adam X.; Atkinson, Elizabeth G.; Chen, Chia-Yen; Choi, Karmel W. & Coleman, Jonathan R. I. [Show all 235 contributors for this article] (2024). Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. Nature Genetics. ISSN 1061-4036. doi: 10.1038/s41588-024-01707-9.
• Petersen, Anja Sofie; Barloese, Mads; Lund, Nunu; Pedersen, Adam Friis; Søborg, Marie-Louise Kulas & Chalmer, Mona Ameri [Show all 16 contributors for this article] (2023). Cluster headache polygenetic risk and known functional variants of CYP3A4 are not associated with treatment response. European Journal of Neurology. ISSN 1351-5101. 30(5), p. 1425–1434. doi: 10.1111/ene.15736. Show summary

  Background and purpose: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first-line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil. Further, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine. Methods: In, 508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta-analysis of the latest two genome-wide association studies on cluster headache. Results: Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found. Conclusion: The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study.

• Jacobsen, Kaya Kvarme; Børte, Sigrid; Laborie, Lene Bjerke; Kristiansen, Hege; Schäfer, Annette & Martinsen, Amy [Show all 30 contributors for this article] (2023). COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study. Osteoarthritis and Cartilage Open. ISSN 2665-9131. 6(1), p. 1–7. doi: 10.1016/j.ocarto.2023.100424. Full text in Research Archive Show summary

  Objective: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome. Design: We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) 0.01, R2 0.8 and Hardy-Weinberg equilibrium (HWE) P-value 0.0001. Significance level was set at p < 5x10-8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee. Results: Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 ( = -0.43, SE = 0.07, p = 8.4x10-9) and rs6577334 ( = -0.43, SE = 0.08, p = 8.9x10-9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis. Conclusions: This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed.

• Baumann, Monica; Storheim, Kjersti; Stangeland, Helle; Zwart, John Anker Henrik; Wentzel-Larsen, Tore & Skurtveit, Svetlana Ondrasova [Show all 8 contributors for this article] (2023). Childhood trauma and the use of opioids and other prescription analgesics in adolescence and young adulthood. The HUNT study. Pain. ISSN 0304-3959. 165(6), p. 1317–1326. doi: 10.1097/j.pain.0000000000003131. Full text in Research Archive
• Espeland, Ansgar; Kristoffersen, Per Martin; Bråten, Lars Christian Haugli; Grøvle, Lars; Grotle, Margreth & Haugen, Anne Julsrud [Show all 12 contributors for this article] (2023). Longitudinal Relationship Between Reduced Modic Change Edema and Disability and Pain in Patients With Chronic Low Back Pain. Spine. ISSN 0362-2436. 48(24), p. 1699–1708. doi: 10.1097/BRS.0000000000004837. Full text in Research Archive
• Vigeland, Maria Dehli; Flåm, Siri Tennebø; Vigeland, Magnus Dehli; Espeland, Ansgar; Zucknick, Manuela & Wigemyr, Monica [Show all 14 contributors for this article] (2023). Long-Term Use of Amoxicillin Is Associated with Changes in Gene Expression and DNA Methylation in Patients with Low Back Pain and Modic Changes. Antibiotics. ISSN 2079-6382. 12(7). doi: 10.3390/antibiotics12071217. Full text in Research Archive
• Stangeland, Helle; Aakvaag, Helene Flood; Baumann, Monica; Wentzel-Larsen, Tore; Storheim, Kjersti & Zwart, John Anker Henrik [Show all 8 contributors for this article] (2023). Problematic alcohol use in young adults exposed to childhood trauma: The Trøndelag Health (HUNT) Study. Journal of Traumatic Stress. ISSN 0894-9867. 36(5), p. 968–979. doi: 10.1002/jts.22965. Full text in Research Archive
• Winsvold, Bendik Kristoffer Slagsvold; Harder, Aster V. E.; Ran, Caroline; Chalmer, Mona A.; Dalmasso, Maria Carolina & Ferkingstad, Egil [Show all 93 contributors for this article] (2023). Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor. Annals of Neurology. ISSN 0364-5134. 94(4), p. 713–726. doi: 10.1002/ana.26743. Full text in Research Archive
• Baumann, Monica; Zwart, John Anker Henrik; Dyb, Grete Anita; Wentzel-Larsen, Tore; Stangeland, Helle & Storheim, Kjersti [Show all 7 contributors for this article] (2023). Killing pain? A prospective population-based study on trauma exposure in childhood as predictor for frequent use of over-the-counter analgesics in young adulthood. The HUNT study. Psychiatry Research. ISSN 0165-1781. 327, p. 1–8. doi: 10.1016/j.psychres.2023.115400. Full text in Research Archive
• Bråten, Lars Christian Haugli; Gjefsen, Elisabeth; Gervin, Kristina; Pripp, Are Hugo; Skouen, Jan Sture & Schistad, Elina Iordanova [Show all 16 contributors for this article] (2023). Cytokine Patterns as Predictors of Antibiotic Treatment Effect in Chronic Low Back Pain with Modic Changes: Subgroup Analyses of a Randomized Trial (AIM Study). Journal of Pain Research. ISSN 1178-7090. 16, p. 1713–1724. doi: 10.2147/JPR.S406079. Full text in Research Archive
• Bakker, Mark K.; Kanning, Jos P.; Abraham, Gad; Martinsen, Amy; Winsvold, Bendik Kristoffer Slagsvold & Zwart, John Anker Henrik [Show all 22 contributors for this article] (2023). Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity. Stroke. ISSN 0039-2499. 54(3), p. 810–818. doi: 10.1161/STROKEAHA.122.040715. Full text in Research Archive
• Strømme, Sofie Hammernes; Guddal, Maren Hjelle; Fenstad, Anne Marie; Visnes, Håvard; Zwart, John Anker Henrik & Storheim, Kjersti [Show all 7 contributors for this article] (2023). Musculoskeletal pain is not clearly associated with the risk of anterior cruciate ligament reconstruction in adolescents. BMJ Open sport & exercise medicine. ISSN 2055-7647. 9(2). doi: 10.1136/bmjsem-2022-001453.
• Gjefsen, Elisabeth; Gervin, Kristina; Bråten, Lars Christian Haugli; Goll, Guro Løvik; Aass, Hans Christian & Schistad, Elina Iordanova [Show all 13 contributors for this article] (2023). Longitudinal changes of serum cytokines in patients with chronic low back pain and Modic changes. Osteoarthritis and Cartilage. ISSN 1063-4584. 31(4), p. 543–547. doi: 10.1016/j.joca.2023.01.001. Full text in Research Archive
• Baumann-Larsen, Monica; Dyb, Grete Anita; Wentzel-Larsen, Tore; Zwart, John Anker Henrik; Storheim, Kjersti & Stensland, Synne Øien Blixt (2023). Exposure to traumatic events and use of over-the-counter analgesics in adolescents: cross-sectional findings from the Young-HUNT study. BMJ Open. ISSN 2044-6055. 13(3). doi: 10.1136/bmjopen-2022-066058. Full text in Research Archive
• Bondjers, Kristina; Lingaas, Ingebjørg; Stensland, Synne; Atar, Dan; Zwart, John Anker Henrik & Wøien, Hilde [Show all 7 contributors for this article] (2023). “I’ve kept going” – a multisite repeated cross-sectional study of healthcare workers’ pride in personal performance during the COVID-19 pandemic. BMC Health Services Research. ISSN 1472-6963. 23(1). doi: 10.1186/s12913-023-09246-5. Full text in Research Archive
• Heuch, Ingrid; Heuch, Ivar; Hagen, Knut; Storheim, Kjersti & Zwart, John Anker Henrik (2023). Menopausal hormone therapy, oral contraceptives and risk of chronic low back pain: the HUNT Study. BMC Musculoskeletal Disorders. ISSN 1471-2474. 24. doi: 10.1186/s12891-023-06184-5. Full text in Research Archive
• Dhariwal, Achal; Bråten, Lars Christian Haugli; Sturød, Kjersti; Salvadori Da Silva, Gabriela; Bargheet, Ahmed & Åmdal, Heidi Aarø [Show all 11 contributors for this article] (2023). Differential response to prolonged amoxicillin treatment: long-term resilience of the microbiome versus long-lasting perturbations in the gut resistome. Gut microbes. ISSN 1949-0976. 15(1). doi: 10.1080/19490976.2022.2157200.
• Hautakangas, Heidi; Winsvold, Bendik K S; Ruotsalainen, Sanni; Bjornsdottir, Gyda; Harder, Aster V. E. & Kogelman, Lisette J. A. [Show all 50 contributors for this article] (2022). Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles . Nature Genetics. ISSN 1061-4036. 54, p. 152–160. doi: 10.1038/s41588-021-00990-0. Full text in Research Archive
• Mjåset, Christer; Solberg, Tore; Zwart, John Anker Henrik; Småstuen, Milada Cvancarova; Kolstad, Frode & Grotle, Margreth (2022). Anterior surgical treatment for cervical degenerative radiculopathy: a prediction model for non-success. Acta Neurochirurgica. ISSN 0001-6268. p. 1–13. doi: 10.1007/s00701-022-05440-2. Full text in Research Archive
• Schulze, Daniel Gregor; Nilsen, Kristian Bernhard; Clemm, Thomas; Grotle, Margreth; Zwart, John Anker Henrik & Ulvestad, Bente [Show all 7 contributors for this article] (2022). Influence of ergonomic factors on peripheral neuropathy under HAV exposure. Occupational Medicine. ISSN 0962-7480. 73(1), p. 13–18. doi: 10.1093/occmed/kqac118. Full text in Research Archive
• Mishra, Aniket; Malik, Rainer; Hachiya, Tsuyoshi; Jürgenson, Tuuli; Namba, Shinichi & Posner, Daniel C. [Show all 203 contributors for this article] (2022). Stroke genetics informs drug discovery and risk prediction across ancestries. Nature. ISSN 0028-0836. 611(7934). doi: 10.1038/s41586-022-05165-3. Full text in Research Archive
• Bortsov, Andrey V.; Parisien, Marc; Khoury, Samar; Martinsen, Amy; Lie, Marie & Heuch, Ingrid [Show all 10 contributors for this article] (2022). Brain-specific genes contribute to chronic but not to acute back pain. Pain Reports. ISSN 2471-2531. 7(5), p. 1–10. doi: 10.1097/PR9.0000000000001018. Full text in Research Archive
• Hartley, April; Sanderson, Eleanor; Granell, Raquel; Paternoster, Lavinia; Zheng, Jie & Smith, George Davey [Show all 62 contributors for this article] (2022). Using multivariable Mendelian randomization to estimate the causal effect of bone mineral density on osteoarthritis risk, independently of body mass index. International Journal of Epidemiology. ISSN 0300-5771. 51(4), p. 1254–1267. doi: 10.1093/ije/dyab251. Full text in Research Archive
• Kristoffersen, Per Martin; Vetti, Nils; Grøvle, Lars; Brox, Jens Ivar; Bråten, Lars Christian Haugli & Grotle, Margreth [Show all 17 contributors for this article] (2022). Amoxicillin did not Reduce Modic Change Oedema in Patients with Chronic Low Back pain - subgroup Analyses of a Randomised Trial (the AIM study). Spine. ISSN 0362-2436. doi: 10.1097/BRS.0000000000004513. Full text in Research Archive
• Yengo, Loïc; Vedantam, Sailaja; Marouli, Eirini; Sidorenko, Julia; Bartell, Eric & Sakaue, Saori [Show all 628 contributors for this article] (2022). A saturated map of common genetic variants associated with human height. Nature. ISSN 0028-0836. 610, p. 704–712. doi: 10.1038/s41586-022-05275-y. Full text in Research Archive
• Bråten, Lars Christian Haugli; Grøvle, Lars; Wigemyr, Monica; Wilhelmsen, Maja; Gjefsen, Elisabeth & Espeland, Ansgar [Show all 13 contributors for this article] (2022). Minimal important change was on the lower spectrum of previous estimates and responsiveness was sufficient for core outcomes in chronic low back pain. Journal of Clinical Epidemiology. ISSN 0895-4356. 151, p. 75–87. doi: 10.1016/j.jclinepi.2022.07.012. Full text in Research Archive
• Stangeland, Helle; Handal, Marte; Skurtveit, Svetlana Ondrasova; Aakvaag, Helene Flood; Dyb, Grete Anita & Wentzel-Larsen, Tore [Show all 10 contributors for this article] (2022). Killing pain?: a population-based registry study of the use of prescription analgesics, anxiolytics, and hypnotics among all children, adolescents and young adults in Norway from 2004 to 2019. European Child and Adolescent Psychiatry. ISSN 1018-8827. p. 1–12. doi: 10.1007/s00787-022-02066-8. Full text in Research Archive
• Taso, Mirad; Sommernes, Jon Håvard; Bjorland, Siri; Zwart, John Anker Henrik; Engebretsen, Kaia Beck & Sundseth, Jarle Østberg [Show all 9 contributors for this article] (2022). What is success of treatment? Expected outcome scores in cervical radiculopathy patients were much higher than the previously reported cut-off values for success. European spine journal. ISSN 0940-6719. doi: 10.1007/s00586-022-07234-7. Full text in Research Archive
• Dagestad, Magnhild Hammersland; Vetti, Nils; Kristoffersen, Per M; Zwart, John Anker Henrik; Storheim, Kjersti & Bakland, Gunnstein [Show all 12 contributors for this article] (2022). Apparent diffusion coefficient values in Modic changes – interobserver reproducibility and relation to Modic type. BMC Musculoskeletal Disorders. ISSN 1471-2474. 23, p. 1–12. doi: 10.1186/s12891-022-05610-4. Full text in Research Archive Show summary

  Background Modic Changes (MCs) in the vertebral bone marrow were related to back pain in some studies but have uncertain clinical relevance. Diffusion weighted MRI with apparent diffusion coefficient (ADC)-measurements can add information on bone marrow lesions. However, few have studied ADC measurements in MCs. Further studies require reproducible and valid measurements. We expect valid ADC values to be higher in MC type 1 (oedema type) vs type 3 (sclerotic type) vs type 2 (fatty type). Accordingly, the purpose of this study was to evaluate ADC values in MCs for interobserver reproducibility and relation to MC type. Methods We used ADC maps (b 50, 400, 800 s/mm2) from 1.5 T lumbar spine MRI of 90 chronic low back pain patients with MCs in the AIM (Antibiotics In Modic changes)-study. Two radiologists independently measured ADC in fixed-sized regions of interests. Variables were MC-ADC (ADC in MC), MC-ADC% (0% = vertebral body, 100% = cerebrospinal fluid) and MC-ADC-ratio (MC-ADC divided by vertebral body ADC). We calculated mean difference between observers ± limits of agreement (LoA) at separate endplates. The relation between ADC variables and MC type was assessed using linear mixed-effects models and by calculating the area under the receiver operating characteristic curve (AUC). Results The 90 patients (mean age 44 years; 54 women) had 224 MCs Th12-S1 comprising type 1 (n = 111), type 2 (n = 91) and type 3 MC groups (n = 22). All ADC variables had higher predicted mean for type 1 vs 3 vs 2 (p < 0.001 to 0.02): MC-ADC (10− 6 mm2/s) 1201/796/576, MC-ADC% 36/21/14, and MC-ADC-ratio 5.9/4.2/3.1. MC-ADC and MC-ADC% had moderate to high ability to discriminate between the MC type groups (AUC 0.73–0.91). MC-ADC-ratio had low to moderate ability (AUC 0.67–0.85). At L4-S1, widest/narrowest LoA were for MC-ADC 20 ± 407/12 ± 254, MC-ADC% 1.6 ± 18.8/1.4 ± 10.4, and MC-ADC-ratio 0.3 ± 4.3/0.2 ± 3.9. Difference between observers > 50% of their mean value was less frequent for MC-ADC (9% of MCs) vs MC-ADC% and MC-ADC-ratio (17–20%). Conclusions The MC-ADC variable (highest mean ADC in the MC) had best interobserver reproducibility, discriminated between MC type groups, and may be used in further research. ADC values differed between MC types as expected from previously reported MC histology.

• Vigeland, Maria Dehli; Flåm, Siri Tennebø; Vigeland, Magnus Dehli; Espeland, Ansgar; Kristoffersen, Per Martin & Vetti, Nils [Show all 17 contributors for this article] (2022). Correlation between gene expression and MRI STIR signals in patients with chronic low back pain and Modic changes indicates immune involvement. Scientific Reports. ISSN 2045-2322. 12(1), p. 1–12. doi: 10.1038/s41598-021-04189-5. Full text in Research Archive Show summary

  Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. A subgroup of patients has Modic changes (MC), identifiable by MRI as vertebral bone marrow lesions. The cause of such changes and their relationship to pain are not yet understood. We explored the pathobiology of these lesions using profiling of gene expression in blood, coupled with an edema-sensitive MRI technique known as short tau inversion recovery (STIR) imaging. STIR images and total RNA from blood were collected from 96 patients with chronic LBP and MC type I, the most inflammatory MC state. We found the expression of 37 genes significantly associated with STIR signal volume, ten genes with edema abundancy (a constructed combination of STIR signal volume, height, and intensity), and one gene with expression levels significantly associated with maximum STIR signal intensity. Gene sets related to interferon signaling, mitochondrial metabolism and defense response to virus were identified as significantly enriched among the upregulated genes in all three analyses. Our results point to inflammation and immunological defense as important players in MC biology in patients with chronic LBP.

• Gheorghiu, Ana; Brunborg, Cathrine; Johannessen, Tom Børge; Helseth, Eirik; Zwart, John Anker Henrik & Wiedmann, Markus (2022). The impact of body mass index and height on risk for primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves in 1.7 million norwegian women and men: a prospective cohort study. Acta Oncologica. ISSN 0284-186X. 61(1), p. 1–6. doi: 10.1080/0284186X.2021.2009562. Show summary

  Background Primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves comprise a heterogenous group of pathology, dominantly represented by meningioma, nerve sheath tumours (NST) and glioma. Body height and body mass index (BMI) are risk factors for certain brain tumour subgroups, but no other study has specifically assessed height and BMI in relation to primary tumours of the spine and peripheral nerves in women and men. Methods In this prospective population-based cohort study height and weight were measured in 1.7 million adult Norwegian women and men at baseline. Incident cases of primary tumours arising from the spinal cord, spinal meninges, spinal and peripheral nerves during follow-up were identified by linkage to the National Cancer Registry. Tumour risk was assessed by Cox regression analyses in relation to height and BMI. Results During 49 million person-years of follow-up, 857 primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves were identified. Overweight and obesity were not associated with risk for all tumours or any tumour subgroup. Height was positively associated with risk for all tumours (HR per 10 cm increase: 1.30, 95% CI 1.16–1.46). The association between height and tumour risk varied between tumour subgroups: while height was not significantly associated with NST, height increased the risk for meningioma (HR 1.42, 95% CI 1.13–1.78) and glioma (HR 1.56, 95% CI 1.06–2.28). The strongest association between height and tumour risk was found for the glioma subgroup of ependymoma in women (HR 3.38, 95% CI 1.64–6.94). Conclusion This study could not identify overweight and obesity as risk factors for primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves in women or men. Increasing body height was associated with increased tumour risk overall, but not universal for all tumour subgroups. Importance of the study Primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves have received little focus in epidemiologic studies, although the incidence and histo-pathological tumour subgroups differ significantly from primary brain tumours. Risk factors for these tumours have hardly been assessed in previous studies. Height, overweight and obesity are known risk factors for several cancers, including certain brain tumour subgroups, such as meningioma. This is the first study to report the association between height, overweight and obesity and primary tumours of the spinal cord, spinal meninges, spinal and peripheral nerves. This includes tumour subgroups of meningioma, nerve sheath tumour, glioma and the most common spinal glioma subgroup of ependymoma. While overweight and obesity were not associated with either of the tumour subgroups, an association between increasing body height and risk for spinal meningioma and glioma, including ependymoma, was found. Nerve sheath tumour risk was not associated with increasing body height.

• Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Winsvold, Bendik K S; O'Connell, Kevin Sean; Frei, Oleksandr & Shadrin, Alexey [Show all 39 contributors for this article] (2022). Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools. Brain. ISSN 0006-8950. 145(1), p. 142–153. doi: 10.1093/brain/awab267. Full text in Research Archive Show summary

  Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation.

• Mjåset, Christer; Zwart, John Anker Henrik; Kolstad, Frode; Solberg, Tore & Grotle, Margreth (2022). Clinical improvement after surgery for degenerative cervical myelopathy; A comparison of Patient-Reported Outcome Measures during 12-month follow-up. PLOS ONE. ISSN 1932-6203. 17(3), p. 1–14. doi: 10.1371/journal.pone.0264954. Full text in Research Archive Show summary

  Object Although many patients report clinical improvement after surgery due to degenerative cervical myelopathy, the aim of intervention is to stop progression of spinal cord dysfunction. We wanted to provide estimates and assess achievement rates of Minimal Clinically Important Difference (MCID) at 3- and 12-month follow-up for Neck Disability Index (NDI), Numeric Rating Scale for arm pain (NRS-AP) and neck pain (NRS-NP), Euro-Qol (EQ-5D-3L), and European Myelopathy Score (EMS). Methods 614 degenerative cervical myelopathy patients undergoing surgery responded to Patient-Reported Outcome Measures (PROMs) prior to, 3 and 12 months after surgery. External criterion was the Global Perceived Effect Scale (1–7), defining MCID as “slightly better”, “much better” and “completely recovered”. MCID estimates with highest sensitivity and specificity were calculated by Receiver Operating Curves for change and percentage change scores in the whole sample and in anterior and posterior procedural groups. Results The NDI and NRS-NP percentage change scores were the most accurate PROMs with a MCID of 16%. The change score for NDI and percentage change scores for NDI, NRS-AP and NRS-NP were slightly higher in the anterior procedure group compared to the posterior procedure group, while remaining PROM estimates were similar across procedure type. The MCID achievement rates at 12-month follow-up ranged from 51% in EMS to 62% in NRS-NP. Conclusion The NDI and NRS-NP percentage change scores were the most accurate PROMs to measure clinical improvement after surgery for degenerative cervical myelopathy. We recommend using different cut-off estimates for anterior and posterior approach procedures. A MCID achievement rate of 60% or less must be interpreted in the perspective that the main goal of surgery for degenerative cervical myelopathy is to prevent worsening of the condition.

• Heuch, Ingrid; Heuch, Ivar; Hagen, Knut; Storheim, Kjersti & Zwart, John Anker Henrik (2022). Does the risk of chronic low back pain depend on age at menarche or menopause? A population-based cross-sectional and cohort study: the Trøndelag Health Study. BMJ Open. ISSN 2044-6055. 12, p. 1–11. doi: 10.1136/bmjopen-2021-055118. Full text in Research Archive
• Lie, Marie; Pedersen, Linda Margareth; Heuch, Ingrid; Winsvold, Bendik K S; Gjerstad, Johannes & Hasvik, Eivind Olay [Show all 11 contributors for this article] (2022). Low Back Pain With Persistent Radiculopathy; the Clinical Role of Genetic Variants in the Genes SOX5, CCDC26/GSDMC and DCC. Frontiers in Genetics. ISSN 1664-8021. 12. doi: 10.3389/fgene.2021.757632. Full text in Research Archive Show summary

  In a recently published genome-wide association study (GWAS) chronic back pain was associated with three loci; SOX5, CCDC26/GSDMC and DCC. This GWAS was based on a heterogeneous sample of back pain disorders, and it is unknown whether these loci are of clinical relevance for low back pain (LBP) with persistent radiculopathy. Thus, we examine if LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy is associated with the selected single nucleotide polymorphisms (SNPs); SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. In this prospective cohort study, subjects admitted to a secondary health care institution due to an acute episode of LBP with radiculopathy, reported back pain, leg pain, and Oswestry Disability Index (ODI), were genotyped and followed up at 12 months (n = 338). Kruskal-Wallis H test showed no association between the SNPs and back pain, leg pain or ODI. In conclusion, LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy, is not associated with the selected SNPs; SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. This absent or weak association suggests that the SNPs previously associated with chronic back pain are not useful as prognostic biomarkers for LBP with persistent radiculopathy.

• Tanha, Hamzeh M; Martin, Nicholas G; Whitfield, John B; Nyholt, Dale R; Gormley, Padhraig & Anttila, Verneri [Show all 111 contributors for this article] (2021). Association and genetic overlap between clinical chemistry tests and migraine. Cephalalgia. ISSN 0333-1024. 41(11-12), p. 1208–1221. doi: 10.1177/03331024211018131.
• Winsvold, Bendik K S; Kitsos, Ioannis; Thomas, Laurent; Skogholt, Anne Heidi; Gabrielsen, Maiken Elvestad & Zwart, John Anker Henrik [Show all 7 contributors for this article] (2021). Genome-Wide Association Study of 2,093 Cases With Idiopathic Polyneuropathy and 445,256 Controls Identifies First Susceptibility Loci. Frontiers in Neurology. ISSN 1664-2295. 12, p. 1–11. doi: 10.3389/fneur.2021.789093. Full text in Research Archive Show summary

  Background: About one third of patients with chronic polyneuropathy have no obvious underlying etiology and are classified as having idiopathic polyneuropathy. The lack of knowledge about pathomechanisms and predisposing factors limits the development of effective prevention and treatment for these patients. We report the first genome-wide association study (GWAS) of idiopathic polyneuropathy. Methods: Cases with idiopathic polyneuropathy and healthy controls were identified by linkage to hospital records. We performed genome-wide association studies using genetic data from two large population-based health studies, the Trøndelag Health Study (HUNT, 1,147 cases and 62,204 controls) and UK Biobank (UKB, 946 cases and 383,052 controls). In a two-stage analysis design, we first treated HUNT as a discovery cohort and UK Biobank as a replication cohort. Secondly, we combined the two studies in a meta-analysis. Downstream analyses included genetic correlation to other traits and diseases. We specifically examined previously reported risk loci, and genes known to cause hereditary polyneuropathy. Results: No replicable risk loci were identified in the discovery-replication stage, in line with the limited predicted power of this approach. When combined in a meta-analysis, two independent loci reached statistical significance (rs7294354 in B4GALNT3, P-value 4.51 × 10−8) and (rs147738081 near NR5A2, P-value 4.75 × 10−8). Idiopathic polyneuropathy genetically correlated with several anthropometric measures, most pronounced for height, and with several pain-related traits. Conclusions: In this first GWAS of idiopathic polyneuropathy we identify two risk-loci that indicate possible pathogenetic mechanisms. Future collaborative efforts are needed to replicate and expand on these findings.

• Mullins, Niamh; Forstner, Andreas J.; O'Connell, Kevin Sean; Coombes, Brandon; Coleman, Jonathan R. I. & Qiao, Zhen [Show all 59 contributors for this article] (2021). Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature Genetics. ISSN 1061-4036. 53, p. 817–829. doi: 10.1038/s41588-021-00857-4.
• Freidin, Maxim B.; Tsepilov, Yakov A.; Stanaway, Ian B.; Meng, Weihua; Hayward, Caroline & Smith, Blair H. [Show all 36 contributors for this article] (2021). Sex- and age-specific genetic analysis of chronic back pain. Pain. ISSN 0304-3959. 162(4), p. 1176–1187. doi: 10.1097/j.pain.0000000000002100. Show summary

  Sex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity, and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively explored. We performed sex- and age-stratified genome-wide association study and single nucleotide polymorphism-by-sex interaction analysis for cBP defined as “Back pain for 3+ months” in 202,077 males and 237,754 females of European ancestry from UK Biobank. Two and 7 nonoverlapping genome-wide significant loci were identified for males and females, respectively. A male-specific locus on chromosome 10 near SPOCK2 gene was replicated in 4 independent cohorts. Four loci demonstrated single nucleotide polymorphism-by-sex interaction, although none of them were formally replicated. Single nucleotide polymorphism-explained heritability was higher in females (0.079 vs 0.067, P = 0.006). There was a high, although not complete, genetic correlation between the sexes (r = 0.838 ± 0.041, different from 1 with P = 7.8E-05). Genetic correlation between the sexes for cBP decreased with age (0.858 ± 0.049 in younger people vs 0.544 ± 0.157 in older people; P = 4.3E-05). There was a stronger genetic correlation of cBP with self-reported diagnosis of intervertebral disk degeneration in males than in females (0.889 vs 0.638; P = 3.7E-06). Thus, the genetic component of cBP in the UK Biobank exhibits a mild sex- and age-dependency. This provides an insight into the possible causes of sex- and age-specificity in epidemiology and pathophysiology of cBP and chronic pain at other anatomical sites.

• Khoury, Samar; Parisien, Marc; Thompson, Scott J.; Vachon-Presseau, Etienne; Roy, Mathieu & Mitchell, Amy [Show all 32 contributors for this article] (2021). Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions. Brain. ISSN 0006-8950. 145(3), p. 1111–1123. doi: 10.1093/brain/awab359. Full text in Research Archive Show summary

  Chronic pain is often present at more than one anatomical location, leading to chronic overlapping pain conditions (COPC). Whether COPC represents a distinct pathophysiology from the occurrence of pain at only one site is unknown. Using genome-wide approaches, we compared genetic determinants of chronic single-site vs. multisite pain in the UK Biobank. We found that different genetic signals underlie chronic single-site and multisite pain with much stronger genetic contributions for the latter. Among 23 loci associated with multisite pain, 9 loci replicated in the HUNT cohort, with the DCC netrin-1 receptor (DCC) as the top gene. Functional genomics identified axonogenesis in brain tissues as the major contributing pathway to chronic multisite pain. Finally, multimodal structural brain imaging analysis showed that DCC is most strongly expressed in subcortical limbic regions and is associated with alterations in the uncinate fasciculus microstructure, suggesting that DCC-dependent axonogenesis may contribute to COPC via cortico-limbic circuits. Keywords: chronic overlapping pain conditions, netrin, uncinate fasciculus

• Harder, Aster V.E.; Winsvold, Bendik K S; Noordam, Raymond; Vijfhuizen, Lisanne S.; Børte, Sigrid & Kogelman, Lisette J.A. [Show all 22 contributors for this article] (2021). Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache. Annals of Neurology. ISSN 0364-5134. 90(2), p. 203–216. doi: 10.1002/ana.26146. Full text in Research Archive Show summary

  Objective Identifying common genetic variants that confer genetic risk for cluster headache. Methods We conducted a case–control study in the Dutch Leiden University Cluster headache neuro-Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord-Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell-derived RNA-sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses. Results An association was found with cluster headache for 4 independent loci (r2 < 0.1) with genomewide significance (p < 5 × 10−8), rs11579212 (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.33–1.72 near RP11-815 M8.1), rs6541998 (OR = 1.53, 95% CI = 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI = 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI = 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the variance of cluster headache. SNPs rs11579212, rs10184573, and rs976357, as proxy SNP for rs2499799 (r2 = 1.0), replicated in the Norwegian sample (p < 0.05). Gene-based mapping yielded ASZ1 as possible fifth locus. RNA-sequencing indicated differential expression of POLR1B and TMEM87B in cluster headache patients. Interpretation This genomewide association study (GWAS) identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders.

• Rahman, Shafiqur; Winsvold, Bendik K S; Chavez, Sergio; Børte, Sigrid; Tsepilov, Vakov & Sharapov, Sodbo Zh [Show all 32 contributors for this article] (2021). Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain. Annals of the Rheumatic Diseases. ISSN 0003-4967. 80(9), p. 1227–1235. doi: 10.1136/annrheumdis-2020-219624. Full text in Research Archive Show summary

  Background and objectives Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%–54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP. Methods Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined. Results Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca 2+ transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP. Conclusions We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

• Boer, Cindy G.; Hatzikotoulas, Konstantinos; Southam, Lorraine; Stefánsdóttir, Lilja; Almeida, Rodrigo Coutinho de & Zhang, Yanfei [Show all 50 contributors for this article] (2021). Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell. ISSN 0092-8674. 184, p. 4784–4818. doi: 10.1016/j.cell.2021.07.038. Full text in Research Archive Show summary

  Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

• Wightman, Douglas P.; Jansen, Iris E.; Savage, Jeanne E.; Shadrin, Alexey; Bahrami, Shahram & Holland, Dominic [Show all 59 contributors for this article] (2021). A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease. Nature Genetics. ISSN 1061-4036. 53, p. 1276–1282. doi: 10.1038/s41588-021-00921-z. Show summary

  Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.

• Gjefsen, Elisabeth; Gervin, Kristina; Goll, Guro Løvik; Bråten, Lars Christian Haugli; Wigemyr, Monica & Aass, Hans Christian Dalsbotten [Show all 13 contributors for this article] (2021). Macrophage migration inhibitory factor: A potential biomarker for chronic low back pain in patients with Modic changes. RMD Open. ISSN 2056-5933. 7(2), p. 1–10. doi: 10.1136/rmdopen-2021-001726. Full text in Research Archive
• Schulze, Daniel Gregor; Nilsen, Kristian Bernhard; Killingmo, Rikke Munk; Zwart, John Anker & Grotle, Margreth (2021). Clinical Utility of the 6-Item CTS, Boston-CTS, and Hand-Diagram for Carpal Tunnel Syndrome. Frontiers in Neurology. ISSN 1664-2295. 12, p. 1–10. doi: 10.3389/fneur.2021.683807. Full text in Research Archive
• Johansen, Tonje Okkenhaug; Sundseth, Jarle Østberg; Fredriksli, Oddrun; Andresen, Hege; Zwart, John-Anker & Kolstad, Frode [Show all 9 contributors for this article] (2021). Effect of Arthroplasty vs Fusion for Patients With Cervical Radiculopathy: A Randomized Clinical Trial. JAMA Network Open. ISSN 2574-3805. 4(8). doi: 10.1001/jamanetworkopen.2021.19606. Full text in Research Archive Show summary

  Surgical treatment for cervical radiculopathy is increasing. Treatment with motion preserving anterior cervical disc arthroplasty was introduced to prevent symptomatic adjacent segment disease, and there is need to evaluate results of this treatment compared with standard anterior cervical discectomy and fusion. Objective To investigate clinical outcomes at 5 years for arthroplasty vs fusion in patients who underwent surgical treatment for cervical radiculopathy. Design, Setting, and Participants This multicenter, single-blinded, randomized clinical trial included patients aged 25 to 60 years with C6 or C7 radiculopathy referred to study sites’ outpatient clinics from 2008 to 2013. Data were analyzed from December 2019 to December 2020. Interventions Patients were randomly assigned to arthroplasty or fusion. Patients were blinded to which treatment they received. The surgical team was blinded until nerve root decompression was completed. Main Outcomes and Measures The primary end point was change in Neck Disability Index (NDI) score. Secondary outcomes were arm and neck pain, measured with numeric rating scales (NRS); quality of life, measured with the EuroQol-5D (EQ-5D); reoperation rates; and adjacent segment disease. Results Among 147 eligible patients, 4 (2.7%) declined to participate and 7 (4.8%) were excluded. A total of 136 patients were randomized (mean [SD] age, 44.1 [7.0] years; 73 (53.7%) women), with 68 patients randomized to arthroplasty and 68 patients randomized to fusion. A total of 114 patients (83.8%) completed the 5-year follow-up. In the arthroplasty group, the mean NDI score was 45.9 (95% CI, 43.3 to 48.4) points at baseline and 22.2 (95% CI, 18.0 to 26.3) points at 5 years follow-up, and in the fusion group, mean NDI score was 51.3 (95% CI, 48.1 to 54.4) points at baseline, and 21.3 (95% CI, 17.0 to 25.6) points at 5 years follow-up. The changes in mean NDI scores between baseline and 5 years were statistically significant for arthroplasty (mean change, 24.8 [95% CI, 19.8 to 29.9] points; P < .001) and fusion (mean change, 29.9 [95% CI, 24.0 to 35.9] points; P < .001), but the change in mean NDI scores was not significantly different between groups (difference, 5.1 [95% CI, −2.6 to 12.7] points; P = .19). There were no significant differences in changes in arm pain (mean [SE] change, 3.5 [0.5] vs 3.1 [0.4]; P = .47), neck pain (mean [SE] change, 3.0 [0.5] vs 3.4 [0.5]; P = .50), EQ-5D (mean [SE] change, 0.39 [0.4] vs 0.45 [0.6]; P = .46), patients requiring reoperation (10 patients [14.7%] vs 8 patients [11.8%]; P = .61), and adjacent segment disease (0 patients vs 1 patient [1.5%]; P = .32) between the arthroplasty and fusion groups. Conclusions and Relevance In this randomized clinical trial, patients treated with arthroplasty and fusion reported similar and substantial clinical improvement at 5 years. Trial Registration ClinicalTrials.gov Identifier: NCT00735176

• Christensen, Jan Olav; Nilsen, Kristian Bernhard; Hopstock, Laila Arnesdatter; Steingrimsdottir, Olöf Anna; Nielsen, Christopher Sivert & Zwart, John-Anker [Show all 7 contributors for this article] (2021). Shift work, low-grade inflammation, and chronic pain: a 7-year prospective study. International Archives of Occupational and Environmental Health. ISSN 0340-0131. 94, p. 1013–1022. doi: 10.1007/s00420-020-01626-2. Full text in Research Archive Show summary

  Objectives We investigated prospective associations of shift work with chronic pain and C‐reactive protein (CRP), an indicator of inflammation. Furthermore, we elucidated CRP as a possible mediator and/or moderator of effects of shift work on pain. Methods Data from a 7 years follow‐up study were analyzed (N = 2323). Shift work and chronic pain of “neck/shoulder”, “arm/hand”, “upper back”, “low back”, “hip/leg/feet”, and “other regions” were measured by questionnaires. “Chronic widespread pain”, “number of chronic pain sites”, and “any chronic pain” were computed. CRP was measured in serum samples. Logistic and Poisson regressions were conducted. Mediation was assessed by casual mediation analyses and moderation by the Relative Excess Risk due to Interaction (RERI). Results Shift work was not associated with any chronic pain variable and no mediation was detected. CRP was associated with low back pain, hip/leg pain, and “number of pain sites”, and also with the combination of shift work and CRP of 1–2.99 mg/L (compared to: no shiftwork and CRP < 1). Additionally, shiftwork and CRP 1–2.99 mg/L was associated with risk of “any chronic pain” (OR: 1.76, 95% CI: 1.12, 2.85), which was not associated with CRP alone. Moderation analyses suggested the risks for “any chronic pain” and “number of pain regions” increased when individuals with elevated CRP worked shifts—beyond what the separate effects of CRP and shift would suggest. Conclusions We found no evidence of shift work in general affecting CRP or chronic pain. However, shift work and elevated CRP combined may influence chronic pain.

• Sargurupremraj, Muralidharan; Suzuki, Hideaki; Jian, Xueqiu; Sarnowski, Chloé; Evans, Tavia E. & Bis, Joshua C. [Show all 50 contributors for this article] (2020). Cerebral small vessel disease genomics and its implications across the lifespan. Nature Communications. ISSN 2041-1723. 11. doi: 10.1038/s41467-020-19111-2. Full text in Research Archive
• Bryois, Julien; Skene, Nathan G.; Hansen, Thomas Folkmann; Kogelman, Lisette J.A.; Watson, Hunna J. & Liu, Zijing [Show all 50 contributors for this article] (2020). Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease. Nature Genetics. ISSN 1061-4036. 52, p. 482–493. doi: 10.1038/s41588-020-0610-9. Full text in Research Archive
• Guo, Yanjun; Rist, Pamela M.; Daghlas, Iyas; Giulianini, Franco; Winsvold, Bendik K S & Zwart, John-Anker [Show all 50 contributors for this article] (2020). A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine. Nature Communications. ISSN 2041-1723. 11. doi: 10.1038/s41467-020-17002-0. Full text in Research Archive
• Johnsen, Marianne Bakke; Magnusson, Karin; Børte, Sigrid; Gabrielsen, Maiken Elvestad; Winsvold, Bendik K S & Skogholt, Anne Heidi [Show all 10 contributors for this article] (2020). Development and validation of a prediction model for incident hand osteoarthritis in the HUNT study. Osteoarthritis and Cartilage. ISSN 1063-4584. 28(7), p. 932–940. doi: 10.1016/j.joca.2020.04.005. Full text in Research Archive
• Kristoffersen, Per M; Bråten, Lars Christian Haugli; Vetti, Nils; Grøvle, Lars; Hellum, Christian & Storheim, Kjersti [Show all 9 contributors for this article] (2020). Oedema on STIR modified the effect of amoxicillin as treatment for chronic low back pain with Modic changes-subgroup analysis of a randomized trial. European Radiology. ISSN 0938-7994. doi: 10.1007/s00330-020-07542-w. Full text in Research Archive
• Bråten, Lars Christian Haugli; Schistad, Ellina Iordanova; Espeland, Ansgar; Kristoffersen, Per M; Haugen, Anne Julsrud & Marchand, Gunn Hege [Show all 15 contributors for this article] (2020). Association of Modic change types and their short tau inversion recovery signals with clinical characteristics : a cross sectional study of chronic low back pain patients in the AIM-study. BMC Musculoskeletal Disorders. ISSN 1471-2474. 21. doi: 10.1186/s12891-020-03381-4. Full text in Research Archive
• Bakker, Mark K.; Spek, Rick A.A. var der; Rheenen, Wouter van; Morel, Sandrine; Bourcier, Romain & Hostettler, Isabel C. [Show all 50 contributors for this article] (2020). Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors. Nature Genetics. ISSN 1061-4036. 52, p. 1303–1313. doi: 10.1038/s41588-020-00725-7. Full text in Research Archive
• Kristoffersen, Espen Saxhaug; Børte, Sigrid; Hagen, Knut; Zwart, John-Anker & Winsvold, Bendik K S (2020). Caesarean section and the association with migraine: a retrospective register-linked HUNT population cohort study. BMJ Open. ISSN 2044-6055. 10. doi: 10.1136/bmjopen-2020-040685. Full text in Research Archive Show summary

  Objectives: To evaluate the association between caesarean section and migraine in a population-based register-linked cohort study. Setting: Data from the population-based Nord-Trøndelag Health Studies (HUNT2 and HUNT3) were linked to information from the Norwegian Medical Birth Registry. Participants: 65 343 participants responded to the headache questions in any of the two HUNT studies. Only those answering the headache questions in HUNT2 or 3 and had information about mode of delivery in the Norwegian Medical Birth Registry (born after 1967) were included. Our final sample consisted of 6592 women and 4602 men, aged 19–41 years. Outcomes: ORs for migraine given caesarean section. Analyses were performed in multivariate logistic regression models. Results: After adjusting for sex, age and fetal growth restriction, delivery by caesarean section was not associated with migraine later in life (OR 0.86, 95% CI 0.64 to 1.15). Delivery by caesarean section was associated with a reduced OR of non-migrainous headache (OR 0.77, 95% CI 0.60 to 0.99). Conclusion: No association was found between caesarean section and migraine in this population-based register-linked study.

• Lie, Marie; Winsvold, Bendik ; Gjerstad, Johannes; Matre, Dagfinn; Pedersen, Linda Margareth & Heuch, Ingrid [Show all 8 contributors for this article] (2020). The association between selected genetic variants and individual differences in experimental pain. Scandinavian Journal of Pain. ISSN 1877-8860. 21(1), p. 163–173. doi: 10.1515/sjpain-2020-0091. Show summary

  Objectives The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain. Methods In total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test. Results No significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia). Conclusions The selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments.

• Gjefsen, Elisabeth; Bråten, Lars Christian Haugli; Goll, Guro Løvik; Wigemyr, Monica; Bolstad, Nils & Valberg, Morten [Show all 27 contributors for this article] (2020). The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial. BMC Musculoskeletal Disorders. ISSN 1471-2474. 21:698, p. 1–14. doi: 10.1186/s12891-020-03720-5. Full text in Research Archive
• Heuch, Ingrid; Heuch, Ivar; Hagen, Knut; Storheim, Kjersti & Zwart, John-Anker (2020). Associations between the number of children, age at childbirths and prevalence of chronic low back pain: the Nord- Trøndelag Health Study. BMC Public Health. ISSN 1471-2458. 20, p. 1–11. doi: 10.1186/s12889-020-09480-0. Full text in Research Archive Show summary

  Background: Associations between childbirths and subsequent risk of low back pain (LBP) have not been clarified. Changes in sex hormone levels or lumbar posture during pregnancy may have an impact on LBP later in life. The purpose of this study was to explore associations between the number of childbirths, age at childbirths and prevalence of chronic LBP in a general population of women. Methods: Data were obtained from the Norwegian community-based Nord-Trøndelag Health Study, HUNT2 (1995–1997). Women aged 20–69 years indicated whether they suffered from chronic LBP, defined as LBP persisting at least 3 months continuously during last year. Information about LBP was collected from 3936 women who had experienced no childbirths, 3143 women who had delivered one child only and 20,584 women who had delivered 2 or more children. Of these, 7339 women reported chronic LBP. The 595 women who were pregnant when information was collected were considered separately, regardless of previous births, with 80 women reporting chronic LBP. Associations with prevalence of chronic LBP were examined by generalised linear modelling with adjustment for potential confounders in a cross-sectional design. Results: Women who had delivered one child only showed a higher prevalence of chronic LBP than women with no childbirths (prevalence ratio (PR) 1.11; 95% CI: 1.01–1.22). Among women with one or more childbirths, no overall change in prevalence could be demonstrated with an increasing number of children in analyses adjusted for age at first delivery. In women with at least two childbirths, an age less than 20 years at first childbirth was associated with an increased prevalence of chronic LBP (PR 1.36; 95% CI: 1.25–1.49; compared with age 25–29 years). No association was observed between age at last delivery and chronic LBP. The lowest prevalence of chronic LBP was found among women who were currently pregnant (PR 0.80; 95% CI: 0.63–1.00; compared with women with no childbirths). Conclusions: Having experienced at least one childbirth seems to be associated with a higher prevalence of chronic LBP later in life. A young age at first childbirth is also associated with a long-lasting increased prevalence.

• Mjåset, Christer; Zwart, John-Anker; Goedmakers, Caroline M.W.; Smith, Timothy R.; Solberg, Tore & Grotle, Margreth (2020). Criteria for success after surgery for cervical radiculopathy—estimates for a substantial amount of improvement in core outcome measures. The spine journal. ISSN 1529-9430. 20(9), p. 1413–1421. doi: 10.1016/j.spinee.2020.05.549. Full text in Research Archive
• Bråten, Lars Christian Haugli; Grøvle, Lars; Espeland, Ansgar; Pripp, Are Hugo; Grotle, Margreth & Hellum, Christian [Show all 18 contributors for this article] (2020). Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - Secondary analyses of a randomised, placebo-controlled trial (the AIM study). BMC Musculoskeletal Disorders. ISSN 1471-2474. 21, p. 1–11. doi: 10.1186/s12891-020-03422-y. Full text in Research Archive Show summary

  Background: Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. Methods: We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n = 118) or type II (n = 62) were randomised to 3-months oral treatment with 750 mg amoxicillin (n = 89) or placebo (n = 91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0–24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms. Results: None of the four primary potential effect modifiers had strong evidence of modifying the treatment effect. In patients younger than 40 years the difference in mean RMDQ score between the treatment groups was − 4.0 (95%CI, − 6.9 to − 1.2), compared to − 0.5 (95%CI, − 2.3 to 1.3) in patients 40 years or older, both in favour of amoxicillin treatment (exploratory analysis). Conclusions: We did not find evidence for convincing clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes. Our results for younger age in these explorative analyses should not affect clinical treatment decisions without confirmation in future studies.

• Kristoffersen, Espen Saxhaug; Børte, Sigrid; Hagen, Knut; Zwart, John-Anker & Winsvold, Bendik K S (2020). Migraine, obesity and body fat distribution - a population-based study. The Journal of Headache and Pain. ISSN 1129-2369. 21, p. 1–8. doi: 10.1186/s10194-020-01163-w. Full text in Research Archive Show summary

  Background: Obesity has been linked to an increased prevalence of migraine, and to increased migraine attack frequency, but several questions are left unanswered by previous studies. We examined the relationship between obesity and headache in a large, population-based study where we could take into account body fat distribution, migraine subtypes and tension-type headache. Methods: The third population-based Nord-Trøndelag Health Study (HUNT3) included validated headache questionnaires and objective anthropometric measurements. Using a cross-sectional design, our sample consisted of 18,191 women and 14,985 men, aged 19 to 96 years. Of these 4290 (12.9%) had migraine, 4447 (13.4%) had frequent tension-type headache (TTH), and 24,439 were headache-free controls. A total of 5049 individuals with unclassified headache were excluded from the analyses. Using logistic regression, we modeled the association between obesity and headache prevalence, adjusting for relevant confounders. Results: Both total body obesity (TBO) and abdominal obesity (AO) were associated with a higher prevalence of migraine when compared to headache-free controls (OR 1.45 95% CI 1.32–1.59 and OR 1.29 95% CI 1.18–1.41, respectively), in particular for individuals < 50 years of age (OR 1.74 95% CI 1.54–1.98 and OR 1.89 95% CI 1.69–2.11). Similar results were seen for migraine with and without aura. Similar Overall, a weaker associations were as observed between obesity and TTH. There was a dose-response relationship between obesity categories and increased headache frequency in subjects with migraine. TBO was associated with migraine prevalence and attack frequency independent of AO. Conclusion: Both TBO and AO were associated with migraine prevalence and attack frequency. This association was largely limited to individuals < 50 years of age. TBO, rather than AO, may be a better measure of obesity in relation to migraine.

• Guddal, Maren Hjelle; Stensland, Synne; Småstuen, Milada Cvancarova; Johnsen, Marianne Bakke; Heuch, Ingrid & Zwart, John-Anker [Show all 7 contributors for this article] (2020). Obesity in young adulthood: The role of physical activity level, musculoskeletal pain, and psychological distress in adolescence (the hunt-study). International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 17(12), p. 1–14. doi: 10.3390/ijerph17124603. Full text in Research Archive
• Grotle, Margreth; Bråten, Lars Christian Haugli; Brox, Jens Ivar; Espeland, Ansgar; Zolic-Karlsson, Zinajda & Killingmo, Rikke Munk [Show all 14 contributors for this article] (2020). Cost–utility analysis of antibiotic treatment in patients with chronic low back pain and Modic changes: results from a randomised, placebo-controlled trial in Norway (the AIM study) . BMJ Open. ISSN 2044-6055. 10(6), p. 1–10. doi: 10.1136/bmjopen-2019-035461. Full text in Research Archive
• Hagen, Knut; Stovner, Lars Jacob & Zwart, John-Anker (2020). High sensitivity C-reactive protein and risk of migraine in a 11-year follow-up with data from the Nord-Trøndelag health surveys 2006–2008 and 2017–2019. The Journal of Headache and Pain. ISSN 1129-2369. 21. doi: 10.1186/s10194-020-01142-1. Full text in Research Archive Show summary

  Background Several previous studies have reported a cross-sectional association between elevated high sensitivity C-reactive protein (hs-CRP) and migraine. The aim of this population-based follow-up study was to investigate the influence of hs-CRP at baseline on the risk of developing migraine 11 years later. Methods Data from the Nord-Trøndelag Health Study performed in 2006–2008 (baseline) and 2017–2019 were used. A total of 19,574 participants without migraine at baseline were divided into three groups based on hs-CRP levels (< 3 mg/L, 3–9.99 mg/L and 10.00–20 mg/L). Poisson regression was used to evaluate the associations between hs-CRP levels and risk ratios (RRs) of migraine, and precision of the estimates was assessed by 95% confidence interval (CIs). Results In the multi-adjusted model, increased risk of migraine (RR 1.46, 95% CI 1.05–2.04) was found in the highest hs-CRP levels group compared to the lowest group. In the group with the highest hs-CRP levels, a nearly three times higher risk of chronic migraine (RR 2.81, 95% CI 1.12–7.06) was found, whereas no evident relationship was found between high hs-CRP level and risk of developing episodic migraine. Conclusions The main finding in this 11-year follow-up was that hs-CRP levels between 10.00–20.00 mg/L at baseline was associated with increased risk of chronic migraine.

• Taso, Mirad; Sommernes, Jon Håvard; Kolstad, Frode; Sundseth, Jarle Østberg; Bjorland, Siri & Pripp, Are Hugo [Show all 8 contributors for this article] (2020). A randomised controlled trial comparing the effectiveness of surgical and nonsurgical treatment for cervical radiculopathy. BMC Musculoskeletal Disorders. ISSN 1471-2474. 21(1), p. 1–9. doi: 10.1186/s12891-020-3188-6. Full text in Research Archive
• Hagen, Knut; Stovner, Lars Jacob & Zwart, John-Anker (2020). Time trends of major headache diagnoses and predictive factors. Data from three Nord-Trøndelag health surveys. The Journal of Headache and Pain. ISSN 1129-2369. 21. doi: 10.1186/s10194-020-01095-5. Full text in Research Archive Show summary

  Aims The primary aim of this study was to investigate time trends of major headache diagnoses using cross-sectional data from two population-based health surveys. In addition, we aimed to perform a longitudinal assessment of baseline characteristics and subsequent risk for having headache at 22-years’ follow-up among those participating in three health surveys. Methods Data from the Nord-Trøndelag Health Study (HUNT) performed in 1995–1997 (HUNT2), 2006–2008 (HUNT3) and 2017–2019 (HUNT4) were used. The 1-year prevalence time trends of major headache diagnoses were estimated among 41,460 participants in HUNT4 and among 39,697 participants in HUNT3, two surveys with identical headache questions. 16,118 persons participated in all three surveys, and among these, a Poisson regression was used to evaluate health-related baseline information in HUNT2 and the risk ratios (RRs) with 95% confidence interval (CIs) of consistently reporting headache during follow-up. Results Compared with the 1-year prevalence in HUNT3, a higher proportion of participants in HUNT4 had tension-type headache (20.7% vs. 15.9%, p < 0.001), whereas a lower 1-year prevalence was found for migraine (11.1% vs. 12.0%, p < 0.001) and medication overuse headache (MOH) (0.3% vs. 1.0%, p < 0.001). Participants in the age group 20–39 years at baseline nearly three times increased risk (RR = 2.8, 95% CI 2.5–3.1) of reporting headache in HUNT2, HUNT3 and HUNT4 than persons aged 50 years or more. Female sex, occurrence of chronic musculoskeletal complaints and high score of depression or anxiety at baseline doubled the risk of having headache in all three surveys. Conclusions The 1-year prevalence of migraine and MOH was lower in HUNT4 than in HUNT3. Young age, female sex, and occurrence of musculoskeletal complaints and high score of anxiety and/or depression were all associated with substantially increased risk of reporting headache in all three surveys.

• Børte, Sigrid; Zwart, John-Anker; Skogholt, Anne Heidi; Gabrielsen, Maiken Elvestad; Thomas, Laurent & Fritsche, Lars [Show all 18 contributors for this article] (2020). Mitochondrial genome-wide association study of migraine – the HUNT Study . Cephalalgia. ISSN 0333-1024. 40(6), p. 625–634. doi: 10.1177/0333102420906835. Full text in Research Archive
• Kogelman, Lisette J.A.; Esserlind, Ann-Louise; Christensen, Anne Francke; Awasthi, Swapnil; Ripke, Stephan & Ingason, Andres [Show all 16 contributors for this article] (2019). Migraine polygenic risk score associates with efficacy of migraine-specific drugs. Neurology: Genetics. ISSN 2376-7839. 5(6). doi: 10.1212/NXG.0000000000000364.
• Schulze, Daniel Gregor; Nordby, Karl-Christian; Småstuen, Milada Cvancarova; Clemm, Thomas; Grotle, Margreth & Zwart, John-Anker [Show all 7 contributors for this article] (2019). Impact of technical variations on the ring-finger test for carpal tunnelsyndrome. Clinical Neurophysiology Practice (CNP). ISSN 2467-981X. 5, p. 23–29. doi: 10.1016/j.cnp.2019.11.005. Full text in Research Archive Show summary

  Objective To assess if recording the sensory latencies of the median and ulnar nerves one-by-one (consecutive) or at the same time (simultaneous) in the ring-finger test for carpal tunnel syndrome (CTS) will show equivalent results or if it will lead to a different clinical classification of patients. Methods We assessed the limits of agreement between the simultaneous and the consecutive method based on the median- ulnar sensory latency difference derived by both methods in 80 subjects and compared the number of minimal CTS cases identified by the two methods. Results Limits of agreement ranged from −0.23 to 0.29 ms. A significantly higher proportion of subjects with minimal CTS (only detectable by using the comparison test) was found using the simultaneous method (n = 8 and 2, respectively; p = 0.03). Conclusion The two methods have a poor to moderate agreement as indicated by the range of the limits of agreement (0.5 ms).

• Grotle, Margreth; Småstuen, Milada Cvancarova; Fjeld, Olaf Randall; Grøvle, Lars; Helgeland, Jon & Storheim, Kjersti [Show all 8 contributors for this article] (2019). Lumbar spine surgery across 15 years: Trends, complications and reoperations in a longitudinal observational study from Norway. BMJ Open. ISSN 2044-6055. 9(8). doi: 10.1136/bmjopen-2018-028743. Full text in Research Archive Show summary

  Background Studies from different Western countries have reported a rapid increase in spinal surgery rates, an increase that exceeds by far the growing incidence rates of spinal disorders in the general population. There are few studies covering all lumbar spine surgery and no previous studies from Norway. Objectives The purpose of this study was to investigate trends in all lumbar spine surgery in Norway over 15 years, including length of hospital stay, and rates of complications and reoperations. Design A longitudinal observational study over 15 years using hospital patient administrative data and sociodemographic data from the National Registry in Norway. Setting and participants Patients aged ≥18 years discharged from Norwegian public hospitals between 1999 and 2013. Outcome measures Annual rates of simple (microsurgical discectomy, decompression) and complex surgical procedures (fusion, disc prosthesis) in the lumbar spine. Results The rate of lumbar spine surgery increased by 54%, from 78 (95% CI (75 to 80)) to 120 (107 to 113) per 100 000, from 1999 to 2013. More men had simple surgery whereas more women had complex surgery. Among elderly people over 75 years, lumbar surgery increased by a factor of five during the 15-year period. The rates of complications were low, but increased from 0.7% in 1999 to 2.4% in 2013. Conclusions There was a substantial increase in lumbar spine surgery in Norway from 1999 to 2013, similar to trends in other Western world countries. The rise in lumbar surgery among elderly people represents a significant workload and challenge for health services, given our aging population. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial.

• Bråten, Lars Christian Haugli; Rolfsen, Mads Peder; Espeland, Ansgar; Wigemyr, Monica; Assmus, Jörg & Froholdt, Anne [Show all 28 contributors for this article] (2019). Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial. The BMJ. ISSN 1756-1833. 367. doi: 10.1136/bmj.l5654. Full text in Research Archive Show summary

  Objective To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). Design Double blind, parallel group, placebo controlled, multicentre trial. Setting Hospital outpatient clinics at six hospitals in Norway. Participants 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. Interventions Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. Main outcome measures The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. Results In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was −1.6 (95% confidence interval −3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was −2.3 (−4.2 to−0.4, P=0.02) for patients with type 1 Modic changes and −0.1 (−2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. Conclusions In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes.

• Guddal, Maren Hjelle; Stensland, Synne; Småstuen, Milada Cvancarova; Johnsen, Marianne Bakke; Zwart, John-Anker & Storheim, Kjersti (2019). Physical activity and sport participation among adolescents: Associations with mental health in different age groups. Results from the Young-HUNT study: A cross-sectional survey. BMJ Open. ISSN 2044-6055. 9(9). doi: 10.1136/bmjopen-2018-028555. Full text in Research Archive
• Heuch, Ingrid; Heuch, Ivar; Hagen, Knut; Sørgjerd, Elin Pettersen; Åsvold, Bjørn Olav & Zwart, John-Anker (2019). Does diabetes influence the probability of experiencing chronic low back pain? A population-based cohort study: the Nord-Trøndelag Health Study. BMJ Open. ISSN 2044-6055. 9(9), p. 1–7. doi: 10.1136/bmjopen-2019-031692. Full text in Research Archive Show summary

  Objective: Low back pain (LBP) is a major problem in modern society and it is important to study possible risk factors for this disorder. People with diabetes are often affected by LBP, but whether diabetes represents a risk factor for LBP has not been studied in detail. The aim of this study was to explore the association between diabetes and subsequent risk of chronic LBP. Design: An 11-year follow-up study. Setting: The Nord-Trøndelag Health Study (HUNT2; 1995–1997) and HUNT3 (2006–2008) surveys of Nord-Trøndelag County in Norway. Main outcome measure: Chronic LBP, defined as LBP persisting at least 3 months continuously during the last year. Participants: A total of 18 972 persons without chronic LBP at baseline in HUNT2, and 6802 persons who reported chronic LBP at baseline in HUNT2. Methods: Associations between diabetes and risk of chronic LBP among individuals aged 30–69 years were examined by generalised linear modelling. Results: Men without chronic LBP at baseline showed a significant association between diabetes and risk of chronic LBP (relative risk (RR) 1.43, 95% CI 1.04 to 1.96, p=0.043). In women, no association was found (RR 1.01, 95% CI 0.69 to 1.48, p=0.98). No association could be established between diabetes and recurrence or persistence of chronic LBP after 11 years in either sex. Conclusions: Men with a diagnosis of diabetes may have a higher risk of subsequently experiencing chronic LBP.

• Fjeld, Olaf Randall; Grotle, Margreth; Matre, Dagfinn; Pedersen, Linda Margareth; Lie, Marie & Småstuen, Milada Cvancarova [Show all 11 contributors for this article] (2019). Predicting the outcome of persistent sciatica using conditioned pain modulation: 1-year results from a prospective cohort study. Scandinavian Journal of Pain. ISSN 1877-8860. 20(1), p. 69–75. doi: 10.1515/sjpain-2019-0112. Show summary

  Background and aims Recovery in patients hospitalised with severe sciatica is unpredictable. Prognostic tools to aid clinicians in the early identification of patients at risk of developing chronic sciatic pain are warranted. Conditioned pain modulation (CPM) is a psychophysical measure of the endogenous pain modulatory pathways. Several studies have suggested CPM as a potentially important predictive biomarker for the development of chronic pain. The aim of the study was to determine whether CPM effect in patients still suffering from leg pain 6 weeks after hospital discharge for severe sciatica is associated with persistent leg pain at 12 months. A potential association would suggest that measuring CPM effect could be a valuable prognostic tool in the hospital management of sciatica. Methods A prospective cohort study in which CPM effect was measured 6 weeks after hospital discharge following an acute admission with sciatica as the main complaint. The impact of CPM effect on the outcome was analysed using logistic regression. The outcome measured was self-reported leg pain score of ≥1 in the past week on a 0-10 numeric rating scale (NRS) at 12 months post discharge. Results A total of 111 patients completed the entire study, 51 of whom received non-randomised surgical treatment. Crude and confounder adjusted analyses showed no significant association between CPM effect and leg-pain measured at 12 months, crude Odds Ratio 0.87, 95% CI 0.7-1.1, p = 0.23. Conclusions Our results suggest that CPM assessment has limited prognostic value for the long-term outcome in severe sciatica when measured 6 weeks after hospital discharge. Implications The present study adds important knowledge concerning the limited clinical use of late CPM testing in sciatica patients. The heterogeneity in patients, the wide range of treatments received and a generally favourable outcome are factors that may affect CPM's clinical value as a prognostic factor for severe sciatica.

• Wang, Heming; Lane, Jacqueline M.; Jones, Samuel E.; Dashti, Hassan S.; Ollila, Hanna M. & Wood, Andrew R. [Show all 45 contributors for this article] (2019). Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes. Nature Communications. ISSN 2041-1723. 10, p. 1–12. doi: 10.1038/s41467-019-11456-7. Full text in Research Archive

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• Mjåset, Christer; Zwart, John Anker Henrik; Goedmakers, Caroline M.W.; Smith, Timothy R.; Solberg, Tore & Grotle, Margreth (2024). Corrigendum to ‘Criteria for success after surgery for cervical radiculopathy—estimates for a substantial amount of improvement in core outcome measures’ by Christer Mjåset et al’ [The Spine Journal 20/9 (2020) 1413-1421, (S1529943020307701), (10.1016/j.spinee.2020.05.549)]. The spine journal. ISSN 1529-9430. doi: 10.1016/j.spinee.2024.02.024.
• Mjåset, Christer; Solberg, Tore; Zwart, John Anker Henrik; Småstuen, Milada Cvancarova; Kolstad, Frode & Grotle, Margreth (2024). Correction to: Anterior surgical treatment for cervical degenerative radiculopathy: a prediction model for non-success (Acta Neurochirurgica, (2022), 165, 1, (145-157), 10.1007/s00701-022-05440-2). Acta Neurochirurgica. ISSN 0001-6268. 166(1). doi: 10.1007/s00701-024-06045-7.
• Mishra, Aniket; Malik, Rainer; Hachiya, Tsuyoshi; Jürgenson, Tuuli; Namba, Shinichi & Posner, Daniel C. [Show all 57 contributors for this article] (2022). Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries. Nature. ISSN 0028-0836. doi: 10.1038/s41586-022-05492-5. Show summary

  In the version of this article initially published, the name of the PRECISE4Q Consortium was misspelled as “PRECISEQ” and has now been amended in the HTML and PDF versions of the article. Further, data in the first column of Supplementary Table 55 were mistakenly shifted and have been corrected in the file accompanying the HTML version of the article

• Mishra, Aniket; Malik, Rainer; Hachiya, Tsuyoshi; Jürgenson, Tuuli; Namba, Shinichi & Posner, Daniel C. [Show all 187 contributors for this article] (2022). Erratum: Publisher Correction: Stroke genetics informs drug discovery and risk prediction across ancestries (Nature (2022) 611 7934 (115-123)). Nature. ISSN 0028-0836. 612(7938). doi: 10.1038/s41586-022-05492-5.
• Wightman, Douglas P.; Jansen, Iris E.; Savage, Jeanne E.; Shadrin, Alexey; Bahrami, Shahram & Holland, Dominic [Show all 114 contributors for this article] (2022). Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease (Nature Genetics, (2021), 53, 9, (1276-1282), 10.1038/s41588-021-00921-z). Nature Genetics. ISSN 1061-4036. 54(7). doi: 10.1038/s41588-022-01126-8.
• Wøien, Hilde; Rosseland, Leiv Arne; Bondjers, Kristina; Lingaas, Ingebjørg; Dyb, Grete Anita & Zwart, John Anker Henrik [Show all 7 contributors for this article] (2022). Stress reactions and health problems in hospital personel during the Covid-19 pandemic; a longitudinal, multicenter study.
• Bakker, Mark K.; van der Spek, Rick A. A.; Van Rheenen, Wouter; Morel, Sandrine; Bourcier, Romain & Hostettler, Isabel C. [Show all 94 contributors for this article] (2021). Author Correction: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors (Nature Genetics, (2020), 52, 12, (1303-1313), 10.1038/s41588-020-00725-7). Nature Genetics. ISSN 1061-4036. 53(2). doi: 10.1038/s41588-020-00760-4.
• Nygaard, Gro Owren; Schikora-Rustad, Stine; Lie, Ingeborg Haugesag; Aase, Audun; Leiknes, Ingvild Jullum & König, Marton [Show all 15 contributors for this article] (2021). Humoral immune response to the influenza vaccine in multiple sclerosis patients treated with cladribine or rituximab.
• Wightman, Douglas P.; Jansen, Iris E.; Savage, Jeanne E.; Shadrin, Alexey A.; Bahrami, Shahram & Holland, Dominic [Show all 114 contributors for this article] (2021). Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease (Nature Genetics, (2021), 53, 9, (1276-1282), 10.1038/s41588-021-00921-z). Nature Genetics. ISSN 1061-4036. doi: 10.1038/s41588-021-00977-x.
• Bondjers, Kristina; Stensland, Synne; Zwart, John Anker Henrik; Rosseland, Leiv Arne; Wøien, Hilde & Atar, Dan [Show all 11 contributors for this article] (2021). Hvordan gikk det? Støtte og stolthet gjennom pandemien - rapport fra en longitudinell studie av 2000 sykehuspersonell.
• Bondjers, Kristina; Stensland, Synne; Zwart, John Anker Henrik; Rosseland, Leiv Arne; Wøien, Hilde & Atar, Dan [Show all 11 contributors for this article] (2021). Hvordan gikk det? Støtte og stolthet gjennom pandemien - rapport fra en longitudinell studie av 2000 sykehuspersonell.
• Bondjers, Kristina; Stensland, Synne; Zwart, John Anker Henrik; Rosseland, Leiv Arne; Wøien, Hilde & Atar, Dan [Show all 11 contributors for this article] (2021). Psychological impact of the Covid-19 pandemic on healthcare workers.
• Stensland, Synne; Bondjers, Kristina; Zwart, John Anker Henrik; Rosseland, Leiv Arne; Wøien, Hilde & Atar, Dan [Show all 11 contributors for this article] (2021). Did hospital personnel receive adequate help and support to reduce work-related stress during the Covid-19 pandemic? The Norwegian Study of Hospital Personnel.
• Bondjers, Kristina; Lingaas, Ingebjørg; Stensland, Synne; Wøien, Hilde; Muller, Ashley Elizabeth & Atar, Dan [Show all 8 contributors for this article] (2021). Is it all bad? - sense of accomplishment among health-care workers during the Covid-19 pandemic.
• Johnsen, Marianne Bakke; Magnusson, Karin; Børte, Sigrid; Gabrielsen, Maiken Elvestad; Winsvold, Bendik K S & Skogholt, Anne Heidi [Show all 10 contributors for this article] (2021). Response to Letter to the Editor: ‘Comments on the paper presenting prediction models for incident hand OA in the HUNT study’. Osteoarthritis and Cartilage. ISSN 1063-4584. 29(2), p. 292–293. doi: 10.1016/j.joca.2020.10.012.
• Killingmo, Rikke Munk; Storheim, Kjersti; Zwart, John-Anker; Hartvigsen, Jan; Skonnord, Trygve T. & Vigdal, Ørjan Nesse [Show all 7 contributors for this article] (2020). Korsryggsmerter - tid for å endre praksis . Ryggstøtten. ISSN 1500-757X.
• Killingmo, Rikke Munk; Storheim, Kjersti; Zwart, John-Anker; Hartvigsen, Jan; Skonnord, Trygve T. & Vigdal, Ørjan Nesse [Show all 7 contributors for this article] (2020). Korsryggsmerter - tid for å endre praksis. Utposten. ISSN 0800-5680. 49(5), p. 6–7.
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