Morten Valberg

• Yaqub, Sheraz; Valberg, Morten; Bjørnbeth, Bjørn Atle; Angelsen, Jon-Helge; Brudvik, Kristoffer Watten & Eilertsen, Ina [Show all 43 contributors for this article] (2026). Aspirin after curative-intent treatment of colorectal cancer liver metastases (ASAC): a multicentre, phase 3, randomised, double-blind, placebo-controlled trial. The Lancet Gastroenterology and Hepatology. ISSN 2468-1253. doi: 10.1016/s2468-1253(26)00260-8. Full text in Research Archive Show summary

  Background Colorectal cancer frequently metastasises to the liver. Recurrence after curative-intent treatment of colorectal cancer liver metastases is common. Aspirin has shown preventive and antitumour effects in colorectal cancer, but its role after treatment of metastatic disease is uncertain. We aimed to establish whether adjuvant aspirin improves disease-free survival after curative-intent treatment of colorectal cancer liver metastases. Methods In this phase 3, randomised, double-blind, placebo-controlled trial conducted at 14 centres in Norway, Sweden, and Denmark, patients who had undergone curative-intent treatment for colorectal cancer liver metastases were randomly assigned (1:1), stratified by study site using a centrally generated computerised sequence with variable block sizes, to aspirin 160 mg per day or matching placebo for up to 3 years or until recurrence, death, or treatment discontinuation. The primary outcome was disease-free survival in the full analysis set, comprising all patients who initiated study treatment. The trial is completed and this is the final analysis. This trial is registered with ClinicalTrials.gov, NCT03326791, and EudraCT, 2014-003601-15. Findings Between Dec 15, 2017, and Jan 27, 2022, 466 patients were randomly assigned, of whom 428 initiated study treatment and were included in the full analysis set (217 assigned aspirin and 211 assigned placebo); 272 (64%) were male, 156 (36%) were female, and the mean age was 62·2 years. 269 disease-free survival events occurred (138 in the aspirin group and 131 in the placebo group). Aspirin did not improve disease-free survival (hazard ratio [HR] for recurrence or death 1·08 [95·44% CI 0·85–1·38]; p=0·58). Median disease-free survival was 1·13 years (95·44% CI 0·92–1·44) with aspirin and 1·40 years (1·11–1·69) with placebo. Overall survival at 36 months was 76% (95% CI 69·4–82·7) with aspirin and 85% (79·5–90·8) with placebo (HR for death 1·64 [95% CI 1·01–2·65]; p=0·045). Time to recurrence did not differ between groups (adjusted cause-specific HR 1·06 [95% CI 0·83–1·35]; p=0·64). 24 serious adverse events occurred in 17 (8%) of 217 patients in the aspirin group and five serious adverse events occurred in four (2%) of 211 patients in the placebo group. Clinically relevant adverse events and serious adverse events that occurred more commonly in the aspirin group than in the placebo group were myocardial infarction (two vs 0), epistaxis (four vs 0), duodenal ulcer (two vs 0), and cerebral haemorrhage (two vs 0). There were no treatment-related deaths. Interpretation Adjuvant aspirin did not improve disease-free survival and was associated with lower overall survival and more serious adverse events. These findings do not support routine use of aspirin after curative-intent treatment of colorectal cancer liver metastases.

• Giorcelli, Anastasia; Valberg, Morten; Green, Adele C.; Veierød, Marit Bragelien; Costa, Denise Reis & Gran, Jon Michael [Show all 11 contributors for this article] (2026). Risk of recurrence of stage I to III melanoma in Norway, 2008–2022. European Journal of Cancer. ISSN 0959-8049. 245. doi: 10.1016/j.ejca.2026.116940. Full text in Research Archive
• Perrier, Flavie; Ahimbisibwe, Ashley; Valberg, Morten; Green, Adele C.; Ghiasvand, Reza & Rueegg, Corina Silvia [Show all 10 contributors for this article] (2026). Exploring the paradoxical association of sun exposure and melanoma-specific mortality: The Norwegian Women and Health (NOWAC) Study. European Journal of Cancer. ISSN 0959-8049. 241. doi: 10.1016/j.ejca.2026.116787. Full text in Research Archive Show summary

  Background Paradoxically, some studies have found that high sun exposure, a well-known cause of melanoma, is associated with lower mortality among melanoma patients. In the Norwegian Women and Health cohort, we aimed to investigate associations between pre-diagnosis sun exposure and melanoma-specific and overall death, and the potential impact of unmeasured confounding and selection bias (conditioning on melanoma diagnosis) on any observed association between markers of high sun exposure and death. Methods We estimated hazard ratios (HRs) by Cox regression, observed covariate E-values, bias-adjusted HRs, and performed frailty analysis. Results Among 2234 patients with a first melanoma (311 deaths, 168 from melanoma; mean follow-up 8.0 years), we found significantly reduced risk of melanoma-specific (HR=0.41, 95% confidence interval (CI)=0.24–0.68) and overall (HR=0.49, 95%CI=0.33–0.72) death for ever- versus never-sunburn and a negative trend for cumulative number of sunburns (ptrend≤0.001), but not for sunbathing vacations (HR=0.69, 95%CI=0.37–1.27, melanoma-specific death). Neither the E-value approach nor bias-adjusted HRs suggested a large degree of unmeasured confounding for the sunburn-death association. However, frailty analysis suggested that selection may partly explain the association. Conclusion While sunburns appear protective, this association might reflect unobserved heterogeneity in melanoma risk and selection bias, and the associations may not represent a true causal effect.

• Perrier, Flavie; Ahimbisibwe, Ashley; Ghiasvand, Reza; Rueegg, Corina Silvia; Green, Adele C. & Borch, Kristin Benjaminsen [Show all 11 contributors for this article] (2025). Physical activity and mortality in melanoma patients within the Norwegian Women and Cancer study (NOWAC). International Journal of Cancer. ISSN 0020-7136. 157(5), p. 846–857. doi: 10.1002/ijc.35430. Full text in Research Archive Show summary

  Pre- and post-diagnosis physical activity (PA) have been associated with decreased mortality and recurrence in cancer patients, but its effect is under-studied in patients with cutaneous melanoma. We investigated the association between pre-diagnosis PA (most recent level and long-term trajectories) and melanoma-specific, other-cause, and overall mortality. Additionally, PA levels before and after a melanoma diagnosis were compared. We used information at recruitment and follow-ups in the prospective population-based Norwegian Women and Cancer cohort linked to the Cancer Registry of Norway. In total 1829 women were diagnosed with a first primary melanoma in 1991─2020, aged 34–93 years. We used Cox regression adjusted for age at diagnosis, education, smoking status, region of residence, melanoma thickness, and summary stage. Most recent pre-diagnosis PA was non-significantly associated with lower risk of melanoma-specific mortality (hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.44─1.07, high vs. low) and significantly associated with other-cause (HR = 0.50, 95% CI = 0.28─0.89) and overall mortality (HR = 0.59, 95% CI = 0.42─0.82). Four pre-diagnosis PA trajectory classes were identified using a latent class mixed model (low, decreasing, moderate, and high). The PA trajectory classes were not significantly associated with melanoma-specific mortality. However, significantly decreased risks of other-cause (HR = 0.51, 95% CI = 0.30─0.87) and overall mortality (HR = 0.59, 95% CI = 0.42─0.84) were found in the moderate versus low class. Only 275 patients reported both pre- and post-diagnosis PA, and among those, 69% had a similar PA level before and after melanoma diagnosis. Our results suggest that pre-diagnosis PA reduces mortality in middle-aged Norwegian women with melanoma.

• Gjefsen, Elisabeth; Bråten, Lars Christian Haugli; Ponzi, Erica; Dagestad, Magnhild Hammersland; Marchand, Gunn Hege & Kadar, Thomas Istvan Edelsvärd [Show all 22 contributors for this article] (2025). Efficacy of a Tumor Necrosis Factor Inhibitor in Chronic Low-Back Pain With Modic Type 1 Changes: A Randomized Controlled Trial. Arthritis & Rheumatology. ISSN 2326-5191. 77(5), p. 615–623. doi: 10.1002/art.43073. Full text in Research Archive Show summary

  Objective: The efficacy of tumor necrosis factor inhibitors for treating chronic low-back pain with Modic changes is uncertain. This study investigated the superiority of infliximab over placebo in patients with Modic type 1 changes. Methods: In this multicenter, randomized, triple-blind, placebo-controlled trial, patients aged 18 to 65 years with moderate to severe chronic low-back pain and Modic type 1 changes were enrolled from five Norwegian public hospitals between January 2019 and October 2022. Participants were randomly assigned to four intravenous infusions of 5 mg/kg infliximab or placebo. The primary outcome was difference in change in the Oswestry Disability Index (ODI) score from baseline to five months. Secondary outcomes included changes in low-back pain intensity, disability, and health-related quality of life. A linear mixed model was used for efficacy analyses. Results: A total of 128 patients (mean age 43 years, 65.6% women) participated (64 in each group). All patients who received at least one dose of the allocated infusion were included in the primary analyses. The average ODI score (±SD) change was −7.0 (±9.7) in the group who received infliximab and −6.4 (±10.4) in the group who received placebo. The difference in the ODI score change between the two groups was 1.3 ODI points (95% confidence interval −2.1 to 4.6, P = 0.45). Analyses showed no effect of infliximab compared to placebo on secondary outcomes. Adverse event rates were similar between groups. Conclusion: Infliximab did not demonstrate superiority over placebo in reducing pain-related disability in patients with moderate to severe chronic low-back pain with Modic type 1 changes at five months.

• Nguyen, Huong Thu; Moger, Tron Anders; Valberg, Morten; Degerud, Eirik; Page, Christian Magnus & Leblanc, Marissa [Show all 7 contributors for this article] (2024). Individual heterogeneity, educational attainment and cardiovascular mortality: a pooled analysis of Norwegian health surveys. BMJ Public Health. 2. doi: 10.1136/bmjph-2023-000104. Full text in Research Archive Show summary

  Background: Smoking, physical inactivity, cholesterol level and systolic blood pressure are well-established risk factors for cardiovascular diseases (CVD). However, even among individuals with similar levels of these factors, a substantial degree of variation in risk may still remain. We investigated the variation in this unexplained risk across educational levels. Methods: The study population (N=451 800) was from Norwegian health surveys and linked to the National Education Database and the Norwegian Cause of Death Registry. We used survival analysis with frailty models to measure unobserved heterogeneity (frailty variation). Models were stratified by three educational levels. We highlight the degree of heterogeneity by presenting Gini coefficients and indicate how much the unobserved heterogeneity differed across levels of education from the estimated parameters of the frailty distributions. Lorenz curves were plotted for a graphical representation of inequalities in individual risk. Main results: The estimated frailty variances were 24.96, 34.12 and 42.37 in the low, middle and high education groups, respectively, before adjusting for risk factors and 3.76, 7.12 and 7.82 after adjusting for risk factors. The corresponding Gini coefficients were 0.75, 0.84 and 0.86 for low, middle and high education groups, respectively. Conclusion: A large share of the variation in CVD mortality was explained by the observed risk factors. However, a substantial individual unobserved variation in CVD mortality remained after adjusting for these risk factors. Our findings indicate that the unobserved variation in CVD mortality could vary somewhat between educational groups, but that education does not explain the major share of the remaining substantial heterogeneity.

• Eick, Frode; Vallersnes, Odd Martin; Fjeld, Heidi E; Sørbye, Ingvil Krarup; Valberg, Morten & Dahl, Cecilie (2024). Perinatal mortality among pregnant undocumented migrants in Norway 1999–2020: A register-based population study. Social Science and Medicine. ISSN 0277-9536. 353. doi: 10.1016/j.socscimed.2024.117055. Full text in Research Archive Show summary

  Background Irregular legal status is a recognized health risk factor in the context of migration. However, undocumented migrants are rarely included in health surveys and register studies. Adverse perinatal outcomes are especially important because they have long-term consequences and societal risk factors are modifiable. In this study, we compare perinatal outcomes in undocumented migrants to foreign-born and Norwegian-born residents, using a population-based register. Methods We included women 18–49 years old giving birth to singletons as registered in the Medical Birth Registry of Norway from 1999 to 2020. Women were categorized as ‘undocumented migrants’ (without an identity number), ‘documented migrants’ (with an identity number and born abroad), and ‘non-migrants’ (with an identity number and born in Norway). The main outcome was perinatal mortality, i.e., death of a foetus ≥ gestational week 22, or neonate up to seven days after birth. We used log-binominal regression to estimate the association between legal status and perinatal mortality, adjusting for several maternal pre-gestational and gestational factors. Direct standardization was used to adjust for maternal region of origin. Ethical approval Regional Ethical Committee (REK South East, case number 68329). Results We retrieved information on 5856 undocumented migrant women who gave birth during the study period representing 0.5% of the 1 247 537 births in Norway. Undocumented migrants had a relative risk of 6.17 (95% confidence interval 5.29 ̶7.20) of perinatal mortality compared to non-migrants and a relative risk of 4.17 (95% confidence interval 3.51 ̶4.93) compared to documented migrants. Adjusting for maternal region of origin attenuated the results slightly. Conclusion Being undocumented is strongly associated with perinatal mortality in the offspring. Disparities were not explained by maternal origin or maternal health factors, indicating that social determinants of health through delays in receiving adequate care and factors negatively influencing gestational length may be of importance.

• Choi, Hye Jung; Leblanc, Marissa Erin; Moger, Tron Anders; Valberg, Morten; Page, Christian Magnus & Aamodt, Geir [Show all 7 contributors for this article] (2023). Geographical variation in cardiovascular disease mortality in Norway: The role of life course socioeconomic position and parental health. Health and Place. ISSN 1353-8292. 83. doi: 10.1016/j.healthplace.2023.103095. Full text in Research Archive Show summary

  Despite substantial geographical variation in cardiovascular (CVD) mortality within countries, little is known about whether this variation can be explained by individuals' life course socioeconomic position (SEP) or differences in family history of premature CVD deaths. Cox proportional hazards models were used to investigate the association between the county of residence at ages 50–59 and CVD death in Norwegians born between 1940 and 1959 and survived to at least age 60, using national data. Individual life course SEP and family history of premature CVD death reduced the geographical variation in CVD mortality across Norwegian counties, but some significant differences remained. Furthermore, CVD risk varied by residents' migration histories between two counties with distinct CVD and socioeconomic profiles.

• Brathovde, Mari; Moger, Tron Anders; Aalen, Odd O.; Grotmol, Tom; Veierød, Marit Bragelien & Valberg, Morten (2023). A lean additive frailty model: With an application to clustering of melanoma in Norwegian families. Statistics in Medicine. ISSN 0277-6715. p. 1–29. doi: 10.1002/sim.9856. Full text in Research Archive Show summary

  Additive frailty models are used to model correlated survival data. However, the complexity of the models increases with cluster size to the extent that practical usage becomes increasingly challenging. We present a modification of the additive genetic gamma frailty (AGGF) model, the lean AGGF (L‐AGGF) model, which alleviates some of these challenges by using a leaner additive decomposition of the frailty. The performances of the models were compared and evaluated in a simulation study. The L‐AGGF model was used to analyze population‐wide data on clustering of melanoma in 2 391 125 two‐generational Norwegian families, 1960‐2015. Using this model, we could analyze the complete data set, while the original model limited the analysis to a restricted data set (with cluster sizes ). We found a substantial clustering of melanoma in Norwegian families and large heterogeneity in melanoma risk across the population, where 52% of the frailty was attributed to the 10% of the population at highest unobserved risk. Due to the improved scalability, the L‐AGGF model enables a wider range of analyses of population‐wide data compared to the AGGF model. Moreover, the methods outlined here make it possible to perform these analyses in a computationally efficient manner.

• Ahimbisibwe, Ashley; Valberg, Morten; Green, Adele C.; Ghiasvand, Reza; Rüegg, Corina Silvia & Rimal, Raju [Show all 10 contributors for this article] (2023). Nevus Count, Pigmentary Characteristics, and Melanoma-specific Mortality among Norwegian Women with Melanoma >1.0 mm Thick. Acta Dermato-Venereologica. ISSN 0001-5555. 103. doi: 10.2340/actadv.v103.4403. Full text in Research Archive Show summary

  Little is known about if and how nevi and pigmentation are associated with melanoma-specific mortality. However, increased melanoma awareness in people with lighter pigmentation and many nevi may result in earlier diagnosis of thinner less-lethal tumors. The aim of this study was to investigate associations between nevus count (asymmetrical > 5 mm and small symmetrical), pigmentary characteristics (hair colour, eye colour, skin colour, freckling, pigmentary score), and melanoma-specific mortality in subjects with melanomas > 1 mm. Data from the Norwegian Women and Cancer cohort, established in 1991, with complete follow-up of melanoma patients until 2018 through the Cancer Registry of Norway, were used to estimate hazard ratios with 95% confidence intervals for the associations between nevus count, pigmentary characteristics, and melanoma-specific mortality, stratified by tumor thickness using Cox regression. Estimated hazard ratios consistently indicated a higher risk of melanoma death for those with darker vs lighter pigmentary characteristics in patients with tumors > 1.0–2.0 mm and > 2.0 mm thick (e.g. pigmentary score hazard ratio 1.25, 95% confidence interval (0.74–2.13)). Among women with melanomas >1.0 mm thick, lighter pigmentation and asymmetrical nevi may be associated with lower melanoma-specific mortality, suggesting that factors that increase the risk of melanoma may also be associated with decreased risk of death from melanoma.

• Methi, Fredrik; Gran, Jon Michael; Valberg, Morten; Kinge, Jonas Minet; Telle, Kjetil & Magnusson, Karin (2023). Third dose mRNA vaccination against SARS-CoV-2 reduces medical complaints seen in primary care: a matched cohort study. BMC Medicine. 21, p. 1–15. doi: 10.1186/s12916-023-02870-2. Full text in Research Archive Show summary

  Background SARS-CoV-2 mRNA vaccination has been associated with both side effects and a reduction in COVID-related complaints due to the decrease in COVID-19 incidence. We aimed to investigate if individuals who received three doses of SARS-CoV-2 mRNA vaccines had a lower incidence of (a) medical complaints and (b) COVID-19-related medical complaints, both as seen in primary care, when compared to individuals who received two doses. Methods We conducted a daily longitudinal exact one-to-one matching study based on a set of covariates. We obtained a matched sample of 315,650 individuals aged 18–70 years who received the 3rd dose at 20–30 weeks after the 2nd dose and an equally large control group who did not. Outcome variables were diagnostic codes as reported by general practitioners or emergency wards, both alone and in combination with diagnostic codes of confirmed COVID-19. For each outcome, we estimated cumulative incidence functions with hospitalization and death as competing events. Results We found that the number of medical complaints was lower in individuals aged 18–44 years who received three doses compared to those who received two doses. The differences in estimates per 100,000 vaccinated were as follows: fatigue 458 less (95% confidence interval: 355–539), musculoskeletal pain 171 less (48–292), cough 118 less (65–173), heart palpitations 57 less (22–98), shortness of breath 118 less (81–149), and brain fog 31 less (8–55). We also found a lower number of COVID-19-related medical complaints: per 100,000 individuals aged 18–44 years vaccinated with three doses, there were 102 (76–125) fewer individuals with fatigue, 32 (18–45) fewer with musculoskeletal pain, 30 (14–45) fewer with cough, and 36 (22–48) fewer with shortness of breath. There were no or fewer differences in heart palpitations (8 (1–16)) or brain fog (0 (− 1–8)). We observed similar results, though more uncertain, for individuals aged 45–70 years, both for medical complaints and for medical complaints that were COVID-19 related. Conclusions Our findings suggest that a 3rd dose of SARS-CoV-2 mRNA vaccine administered 20–30 weeks after the 2nd dose may reduce the incidence of medical complaints. It may also reduce the COVID-19-related burden on primary healthcare services.

• Choi, Hye Jung; Leblanc, Marissa Erin; Moger, Tron Anders; Valberg, Morten; Aamodt, Geir & Page, Christian Magnus [Show all 8 contributors for this article] (2022). Stroke survival and the impact of geographic proximity to family members: A population-based cohort study. Social Science and Medicine. ISSN 0277-9536. 309. doi: 10.1016/j.socscimed.2022.115252. Full text in Research Archive Show summary

  Introduction Familial support may be important for post-stroke survival. Objective To determine if geographical proximity between stroke survivors and their family members, i.e having a spouse/partner or distance to a nearest first-degree relative (parents, siblings, and offspring), as a proxy for familial support, is related to survivor mortality. Methods This study included all stroke survivors (n=128,227) hospitalised in Norway from 1994 to 2009, who were 30 years or older at the time of the stroke (born before 1965). National registries and censuses were used to calculate the distance to the nearest first-degree relative in the hospitalisation year. Cox proportional hazards models estimated hazard ratios (HRs) of all-cause mortality from 1994 to 2014 (mean 6.4 years follow-up), adjusting for sociodemographic and clinical covariates. Results Living up to 30 km from the nearest first-degree relative was associated with a higher mortality (HR 1.04, 95% CI: 1.03 to 1.06) than those living in the same household or neighbourhood as their nearest first-degree relatives. The association was more pronounced (1.13, 1.08 to 1.19 for ≤30 km; 1.25, 1.16 to 1.35 for >30 km) in survivors hospitalised at age ≤65 years, compared to older survivors. Among familial care predictors, having a spouse/partner was the most prominent predictor of reduced mortality (0.80, 0.78 to 0.82) in stroke survivors. Conclusion Living close to first-degree relatives was weakly associated with better survival in stroke patients while having a spouse/partner exhibited a stronger association. Both associations were larger for survivors hospitalised at age ≤65 years. Our findings thus suggest that the impact of familial support on survival after stroke may differ by familial support condition and patient's age at a stroke hospitalisation.

• Skulberg, Arne Kristian; Tylleskär, Ida; Valberg, Morten; Braarud, Anne-Cathrine; Dale, Jostein & Heyerdahl, Fridtjof [Show all 10 contributors for this article] (2022). Comparison of intranasal and intramuscular naloxone in opioid overdoses managed by ambulance staff: a double-dummy, randomised, controlled trial. Addiction. ISSN 0965-2140. 117(6), p. 1658–1667. doi: 10.1111/add.15806. Full text in Research Archive
• Myhrvold, Ståle; BROUWER, ESPEN FREMMO; Andresen, Tor Kristian Molstad; Rydevik, Karin; Amundsen, Madeleine & Grün, Wolfram [Show all 10 contributors for this article] (2022). Nonoperative or Surgical Treatment of Acute Achilles' Tendon Rupture. New England Journal of Medicine. ISSN 0028-4793. 386(15), p. 1409–1420. doi: 10.1056/NEJMoa2108447. Full text in Research Archive Show summary

  Background Whether surgical repair of an acute Achilles’ tendon rupture by an open-repair or minimally invasive approach is associated with better outcomes than nonsurgical treatment is not clear. Methods We performed a multicenter, randomized, controlled trial that compared nonoperative treatment, open repair, and minimally invasive surgery in adults with acute Achilles’ tendon rupture who presented to four trial centers. The primary outcome was the change from baseline in the Achilles’ tendon Total Rupture Score (scores range from 0 to 100, with higher scores indicating better health status) at 12 months. Secondary outcomes included the incidence of tendon rerupture. Results A total of 554 patients underwent randomization, and 526 patients were included in the final analysis. The mean changes in the Achilles’ tendon Total Rupture Score were −17.0 points in the nonoperative group, −16.0 points in the open-repair group, and −14.7 points in the minimally invasive surgery group (P=0.57). Pairwise comparisons provided no evidence of differences between the groups. The changes from baseline in physical performance and patient-reported physical function were similar in the three groups. The number of tendon reruptures was higher in the nonoperative group (6.2%) than in the open-repair or minimally invasive surgery group (0.6% in each). There were 9 nerve injuries in the minimally invasive surgery group (in 5.2% of the patients) as compared with 5 in the open-repair group (in 2.8%) and 1 in the nonoperative group (in 0.6%). Conclusions In patients with Achilles’ tendon rupture, surgery (open repair or minimally invasive surgery) was not associated with better outcomes than nonoperative treatment at 12 months. (Funded by the South-Eastern Norway Regional Health Authority and Akershus University Hospital; ClinicalTrials.gov number, NCT01785264. opens in new tab.)

• 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. 21:698, p. 1–14. doi: 10.1186/s12891-020-03720-5. Full text in Research Archive Show summary

  Low back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes.Methods/design: The BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18–65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients’ clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes..Discussion: Finding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes.

• Skulberg, Arne Kristian; Tylleskär, Ida; Næss, Anne-Cathrine Braarud; Dale, Jostein; Heyerdahl, Fridtjof & Mellesmo, Sindre [Show all 8 contributors for this article] (2020). NTNU intranasal naloxone trial (NINA-1) study protocol for a double-blind, double-dummy, non-inferiority randomised controlled trial comparing intranasal 1.4 mg to intramuscular 0.8 mg naloxone for prehospital use. BMJ Open. 10:e041556(11), p. 1–8. doi: 10.1136/bmjopen-2020-041556. Full text in Research Archive Show summary

  Abstract Introduction Intranasal naloxone is widely used to treat opioid overdoses. The advantage of nasal administration compared to injection lies in its suitability for administration by lay people as it is needless. Approved formulations of nasal naloxone with bioavailability of approximately 50% have only undergone trials in healthy volunteers, while off-label nasal sprays with low bioavailability have been studied in patients. Randomised clinical trials are needed to investigate efficacy and safety of approved intranasal naloxone in patients suffering overdose. This study investigates whether the administration of 1.4 mg naloxone in 0.1 millilitres per dose is non- inferior to 0.8 mg intramuscular injection in patients treated for opioid overdose. Methods and analysis Sponsor is the Norwegian University of Science and Technology. The study has been developed in collaboration with user representatives. The primary endpoint is the restoration of spontaneous respiration ≥10 breaths/minute based on a sample of 200 opioid overdose cases. Double-dummy design ensures blinding, which will be maintained until the database is locked. Ethics and dissemination The study was approved by the Norwegian Medicines Agency and Regional Ethics Committees (REC: 2016/2000). It adheres to the Good Clinical Practice guidelines as set out by The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Informed consent will be sought through a differentiated model. This allows for deferred consent after inclusion for patients who have regained the ability to consent. Patients who are unable to consent prior to discharge by emergency services are given written information and can withdraw at a later date in line with user recommendations. Metadata will be published in the NTNU Open repository. De-identified individual participant data will be made available to recipients conditional of data processor agreement being entered. Trial registrations: EudraCT number: 2016-004072-22 and Clinicaltrials.gov NCT03518021

• Stensrud, Mats Julius; Aalen, John; Aalen, Odd O. & Valberg, Morten (2019). Limitations of hazard ratios in clinical trials. European Heart Journal. ISSN 0195-668X. 40(17), p. 1378–1383. doi: 10.1093/eurheartj/ehy770. Full text in Research Archive
• Stensrud, Mats Julius & Valberg, Morten (2019). Preventing cancer: mere rhetoric or a prosperous plan? Significance. ISSN 1740-9705. 16(2), p. 48–48. doi: 10.1111/j.1740-9713.2019.01259.x. Full text in Research Archive
• Bugge, Anders; Lund, May-Brith; Valberg, Morten; Brustugun, Odd Terje; Solberg, Steinar & Kongerud, Johny (2018). Cause-specific death after surgical resection for early-stage non-small-cell lung cancer. European Journal of Cardio-Thoracic Surgery. ISSN 1010-7940. 53(1), p. 221–227. doi: 10.1093/ejcts/ezx274. Full text in Research Archive
• Mohn, Cathrine Helene; Blix, Hege Salvesen; Halvorsen, Jon Anders; Nafstad, Per; Valberg, Morten & Lagerløv, Per (2018). Incidence Trends of Atopic Dermatitis in Infancy and Early Childhood in a Nationwide Prescription Registry Study in Norway. JAMA Network Open. 1(7). doi: 10.1001/jamanetworkopen.2018.4145. Full text in Research Archive Show summary

  Importance With increasing prevalence of atopic dermatitis (AD) and its manifestation in most countries, together with the supporting evidence of the progression to other atopic phenotypes, AD has developed into a worldwide public health concern. The presence of the disease of has increased since the 1950s, but some recent studies suggest a stationary or decreasing trend. Objective To analyze a nationwide health register based on prescription data to determine the incidence rate (IR) of AD in an entire pediatric population. Design, Setting, and Participants All children resident in Norway younger than 6 years from January 1, 2009, through December 31, 2015, were included in this cohort study. Medical diagnoses and disease-specific medications were used as a proxy for identifying children with AD in this population-based prescription registry study. The prescription study was terminated in 2016. The total number of 295 286 disease-specific prescriptions was analyzed from August 2016 through December 2017. The hypothesis was formulated before, during, and after the data collection. Main Outcomes and Measures All children with a medical diagnosis of AD or eczema based on at least 2 prescriptions of topical corticosteroids or at least 1 prescription of topical calcineurin inhibitors. Incidence rates per person-year (PY) and IR ratios were calculated. Results A total of 295 286 disease-specific prescriptions were dispensed to 122 470 children, of whom 63 460 had AD and 56 009 (88.3%) had reimbursed prescriptions and associated AD diagnoses. The annual Norwegian study population (aged <6 years) increased from 357 451 children in 2009 to 373 954 in 2015. The overall IR increased from 0.028 per PY (95% CI, 0.028-0.029 per PY) in 2009 to 0.034 per PY (95% CI, 0.033-0.035 per PY) in 2014. For children younger than 1 year, the IR increased from 0.052 per PY (95% CI, 0.050-0.053 PY) in 2009 to 0.073 per PY (95% CI, 0.071-0.075 per PY) in 2014. In this age group, the IR was 53% higher in boys compared with girls (IR ratio, 1.53; 95% CI, 1.49-1.57; P < .001). The incidence proportion before the age of 6 years was 17.4% (95% CI, 17.2%-17.7%). The primary seasons for the onset of AD were winter and spring. Conclusions and Relevance This nationwide study suggests an increase in the IR of pediatric AD, especially among children younger than 1 year. This study’s findings suggest that increase occurred with a higher IR during winter and spring seasons. Atopic dermatitis had an earlier onset in boys than in girls. During the study period, more than 1 in 6 children younger than 6 years had, at some point, been affected by AD.

• Mohn, Cathrine Helene; Halvorsen, Jon Anders; Salvesen, Hege Blix; Lagerløv, Per; Nafstad, Per & Valberg, Morten (2018). Incidence Trends of Atopic Dermatitis in Infancy and Early Childhood in a Nationwide Prescription Registry Study in Norway. JAMA Network Open. doi: 10.1001/jamanetworkopen.2018.4145. Full text in Research Archive
• Valberg, Morten; Stensrud, Mats Julius & Aalen, Odd O. (2018). The surprising implications of familial association in disease risk. BMC Public Health. 18, p. 135–135. doi: 10.1186/s12889-018-5033-5. Full text in Research Archive Show summary

  Background A wide range of diseases show some degree of clustering in families; family history is therefore an important aspect for clinicians when making risk predictions. Familial aggregation is often quantified in terms of a familial relative risk (FRR), and although at first glance this measure may seem simple and intuitive as an average risk prediction, its implications are not straightforward. Methods We use two statistical models for the distribution of disease risk in a population: a dichotomous risk model that gives an intuitive understanding of the implication of a given FRR, and a continuous risk model that facilitates a more detailed computation of the inequalities in disease risk. Published estimates of FRRs are used to produce Lorenz curves and Gini indices that quantifies the inequalities in risk for a range of diseases. Results We demonstrate that even a moderate familial association in disease risk implies a very large difference in risk between individuals in the population. We give examples of diseases for which this is likely to be true, and we further demonstrate the relationship between the point estimates of FRRs and the distribution of risk in the population. Conclusions The variation in risk for several severe diseases may be larger than the variation in income in many countries. The implications of familial risk estimates should be recognized by epidemiologists and clinicians.

• Stensrud, Mats Julius; Strohmaier, Susanne; Valberg, Morten & Aalen, Odd O. (2017). Can chance cause cancer? A causal consideration. European Journal of Cancer. ISSN 0959-8049. 75, p. 83–85. doi: 10.1016/j.ejca.2016.12.022. Full text in Research Archive
• Stensrud, Mats Julius; Aalen, Odd O.; Valberg, Morten & Røysland, Kjetil (2017). Exploring selection bias by causal frailty models: The magnitude matters. Epidemiology. ISSN 1044-3983. 28(3), p. 379–386. doi: 10.1097/EDE.0000000000000621. Full text in Research Archive
• Rancoita, Paola M. V.; Valberg, Morten; Demicheli, Romano; Biganzoli, Elia & Serio, Clelia di (2017). Tumor dormancy and frailty models: A novel approach. Biometrics. ISSN 0006-341X. 73(1), p. 260–270. doi: 10.1111/biom.12559. Full text in Research Archive
• Stensrud, Mats Julius & Valberg, Morten (2017). Inequality in genetic cancer risk suggests bad genes rather than bad luck. Nature Communications. 8(1165). doi: 10.1038/s41467-017-01284-y. Full text in Research Archive Show summary

  Heritability is often estimated by decomposing the variance of a trait into genetic and other factors. Interpreting such variance decompositions, however, is not straightforward. In particular, there is an ongoing debate on the importance of genetic factors in cancer development, even though heritability estimates exist. Here we show that heritability estimates contain information on the distribution of absolute risk due to genetic differences. The approach relies on the assumptions underlying the conventional heritability of liability model. We also suggest a model unrelated to heritability estimates. By applying these strategies, we describe the distribution of absolute genetic risk for 15 common cancers. We highlight the considerable inequality in genetic risk of cancer using different metrics, e.g., the Gini Index and quantile ratios which are frequently used in economics. For all these cancers, the estimated inequality in genetic risk is larger than the inequality in income in the USA.

• Valberg, Morten; Grotmol, Tom; Tretli, Steinar; Veierød, Marit Bragelien; Moger, Tron Anders & Devesa, Susan S. [Show all 7 contributors for this article] (2016). Prostate-specific antigen testing for prostate cancer: Depleting a limited pool of susceptible individuals? European Journal of Epidemiology (EJE). ISSN 0393-2990. 20(6), p. 511–520. doi: 10.1007/s10654-016-0185-z. Full text in Research Archive
• Aalen, Odd O.; Valberg, Morten; Grotmol, Tom & Tretli, Steinar (2015). Understanding variation in disease risk: the elusive concept of frailty. International Journal of Epidemiology. ISSN 0300-5771. 44(4), p. 1408–1421. doi: 10.1093/ije/dyu192. Full text in Research Archive
• Valberg, Morten; Grotmol, Tom; Tretli, Steinar; Veierød, Marit Bragelien; Moger, Tron Anders & Aalen, Odd O. (2014). A hierarchical frailty model for familial testicular germ-cell tumors. American Journal of Epidemiology. ISSN 0002-9262. 179(4), p. 499–506. doi: 10.1093/aje/kwt267. Full text in Research Archive
• Valberg, Morten; Grotmol, Tom; Tretli, Steinar; Veierød, Marit Bragelien; Devesa, Susan & Aalen, Odd O. (2012). Frailty modeling of age-incidence curves of osteosarcoma and Ewing sarcoma among individuals younger than 40 years. Statistics in Medicine. ISSN 0277-6715. 31(28), p. 3731–3747. doi: 10.1002/sim.5441. Full text in Research Archive

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• Ahimbisibwe, Ashley; Perrier, Flavie; Valberg, Morten; Green, Adele C.; Ghiasvand, Reza & Rueegg, Corina Silvia [Show all 10 contributors for this article] (2024). The counterintuitive association of sun exposure and melanoma-specific mortality in a cohort of Norwegian women. Full text in Research Archive
• Ahimbisibwe, Ashley; Perrier, Flavie; Valberg, Morten; Green, Adele C; Ghiasvand, Reza & Rueegg, Corina Silvia [Show all 10 contributors for this article] (2024). The counterintuitive association of sun exposure and melanoma-specific mortality in a cohort of Norwegian women. Full text in Research Archive
• Eick, Frode; Vallersnes, Odd Martin; Fjeld, Heidi; Sørbye, Ingvil Krarup; Valberg, Morten & Dahl, Cecilie (2023). Perinatal mortality among pregnant undocumented migrants in Norway 1999-2020: a register-based population study. Full text in Research Archive
• Valberg, Morten; Gran, Jon Michael; Rueegg, Corina Silvia & Leblanc, Marissa Erin (2022). Letter to the editor regarding “Covid-19 transmission in fitness centers in Norway - a randomized trial”. BMC Public Health. 22(1). doi: 10.1186/s12889-022-14800-7. Full text in Research Archive Show summary

  In a recently published paper in BMC Public Health (DOI: 10.1186/s12889-021-12073-0) we read about a randomized trial on Covid-19 transmission performed in five fitness centers in Oslo, Norway, during the spring of 2020. In our opinion, this study has major shortcomings in design and methodology, which have not been addressed by the authors.

• Hagemo, Jostein Skjalg; Skulberg, Arne Kristian; Rehn, Marius; Valberg, Morten; Pesonen, Maiju & Heimdal, Hans Julius [Show all 7 contributors for this article] (2022). Inhaled nitric oxide as temporary respiratory stabilization in patients with COVID-19 related respiratory failure (INOCOV): Study protocol for a randomized controlled trial. PLOS ONE. 17(5). doi: 10.1371/journal.pone.0268822. Full text in Research Archive Show summary

  Background In March 2020, WHO announced the COVID-19 a pandemic and a major global public health emergency. Mortality from COVID-19 is rapidly increasing globally, with acute respiratory failure as the predominant cause of death. Many patients experience severe hypoxia and life-threatening respiratory failure often requiring mechanical ventilation. To increase safety margins during emergency anaesthesia and rapid sequence intubation (RSI), patients are preoxygenated with a closed facemask with high-flow oxygen and positive end-expiratory pressure (PEEP). Due to the high shunt fraction of deoxygenated blood through the lungs frequently described in COVID-19 however, these measures may be insufficient to avoid harmful hypoxemia. Preoxygenation with inhaled nitric oxide (iNO) potentially reduces the shunt fraction and may thus allow for the necessary margins of safety during RSI. Methods and design The INOCOV protocol describes a phase II pharmacological trial of inhaled nitric oxide (iNO) as an adjunct to standard of care with medical oxygen in initial airway and ventilation management of patients with known or suspected COVID-19 in acute respiratory failure. The trial is parallel two-arm, randomized, controlled, blinded trial. The primary outcome measure is the change in oxygen saturation (SpO2), and the null hypothesis is that there is no difference in the change in SpO2 following initiation of iNO. Trial registration EudraCT number 2020-001656-18; WHO UTN: U1111-1250-1698. Protocol version: 2.0 (June 25th, 2021).

• Nguyen, Huong Thu; Næss, Øyvind Erik; Valberg, Morten; Page, Christian Magnus; Leblanc, Marissa Erin & Moger, Tron Anders (2021). Modelling unobserved heterogeneity by education level in cardiovascular disease mortality - A frailty analysis of Norwegian population-based health surveys. Full text in Research Archive
• Stensrud, Mats Julius; Valberg, Morten & Aalen, Odd O. (2017). Can collider bias explain paradoxical associations? Epidemiology. ISSN 1044-3983. 28(4), p. e39–e40. doi: 10.1097/EDE.0000000000000653. Full text in Research Archive
• Aalen, Odd O.; Valberg, Morten; Grotmol, Tom & Tretli, Steinar (2015). Authors' response: Understanding variation in disease risk. International Journal of Epidemiology. ISSN 0300-5771. 44(4), p. 1426–1428. doi: 10.1093/ije/dyv047. Full text in Research Archive

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