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Shear wave velocity information is valuable in many aspects of seismic exploration and characterization of reservoirs. However, shear wave logs are not always available in the interval of interest due to cost and time-saving purposes. In this study, we present a tailored supervised learning approach to estimate shear wave velocity from well-log measurements in the Lower Cretaceous succession of the Valdemar and Boje fields in the Danish North Sea. Our objective is to investigate the performance of four supervised learning regression models (linear, random forest, support vector and multi-layer perceptron). A limited well-log data set from six wells is used for training and testing the supervised learning models. A set of well data containing normalized gamma ray, compressional wave velocity, neutron porosity and medium resistivity logs gave reasonable shear wave velocity estimates in the test wells with root-mean-square error scores within the range of other published studies. Based on limited input data and complex geology, the multi-layer perceptron was the most successful model in predicting the reservoir sections of the test wells. However, all models lacked stability in the overburden zones. Lastly, re-training the multi-layer perceptron on the six wells to predict missing shear wave velocity in a nearby well showed promising results for further reservoir characterization. The obtained results can yield useful input into, for example, seismic pre-stack inversion, amplitude versus offset analysis and rock physics analysis.

The main tool in drug safety monitoring, spontaneous reporting of adverse effects, is unlikely to detect delayed adverse drug effects including cancer. Hypothesis-free screening studies based on administrative data could improve ongoing drug safety monitoring. Using Danish health registries, we conducted a series of case–control studies by identifying individuals with incident cancer in Denmark from 2001 to 2018, matching each case with 10 population controls on age, sex, and calendar time. ORs were estimated using conditional logistic regression accounting for matching factors, educational level, and selected comorbidities. A total of 13,577 drug–cancer associations were examined for individual drugs and 8,996 for drug classes. We reviewed 274 drug–cancer pairs where an association with high use and a cumulative dose–response pattern was present. We classified 65 associations as not readily attributable to bias of which 20 were established as carcinogens by the International Agency for Research on Cancer and the remaining 45 associations may warrant further study. The screening program identified drugs with known carcinogenic effects and highlighted a number of drugs that were not established as carcinogens and warrant further study. The effect estimates in this study should be interpreted cautiously and will need confirmation targeted epidemiologic and translational studies.Significance:This study provides a screening tool for drug carcinogenicity aimed at hypothesis generation and explorative purposes. As such, the study may help to identify drugs with unknown carcinogenic effects and, ultimately, improve drug safety as part of the ongoing safety monitoring of drugs.

Online Supplementary Material for publication containing additional information on covariate definitions (table S1 - S2) and statistical methods (methods S3) as well as the number of cases and examined drugs for each cancer under examination (table S4).

Objectives The Tampa Scale of Kinesiophobia (TSK) is a valid and reliable tool to assess somatic focus and activity avoidance in patients. Currently, the test-retest reliability and measurement error for the Danish version is unknown. The aim of the study was to determine standard error of measurement (SEM) and smallest detectable change (SDC) for three Danish lengths of the TSK in patients with chronic pain. Methods Waiting-list patients (n = 77) completed the TSK-17 twice from home with a test interval between 7 and 14 days. Based on COSMIN recommendations, the test-retest reliability was estimated using intraclass correlation coefficient (ICC2,1), and measurement error in terms of standard error of measurement (SEMagreement) and SDC95% were calculated. Results All three versions showed good test-retest reliability with ICC2,1-values (CI95%) of 0.86(0.79–0.91), 0.88(0.82–0.92) and 0.87(0.81–0.92) for the TSK-17, TSK-13, and TSK-11. The SEM-values were 3.08, 2.42 and 2.10 respectively and SDC95%-values were 8.53, 6.71 and 5.82. Conclusions The Danish versions of TSK-11, TSK-13 and TSK-17 showed good to excellent test-retest reliability. SEM and SDC95% values in patients with chronic pain are reported. The TSK-11 did not show systematic bias between test and retest and may be preferred to minimize responder burden.

Refereed/Peer-reviewed Aims: Drug-induced diabetes is underreported in conventional drug safety monitoring and may contribute to the increasing incidence of type 2 diabetes. Therefore, we used routinely collected prescription data to screen all commonly used drugs for diabetogenic effects. Methods: Leveraging the Danish nationwide health registries, we used a case-only symmetry analysis design to evaluate all possible associations between drug initiation and subsequent diabetes. The study was conducted among individuals aged ≥40 years with a first-ever prescription for any antidiabetic drug 1996-2018 (n = 348 996). Sequence ratios (SRs) and 95% confidence intervals (CIs) were obtained for all possible drug class-diabetes combinations. A lower bound of the 95% CI >1.00 was considered a signal. Signals generated in Denmark were replicated using the Services Australia, Pharmaceutical Benefits Scheme 10% data extract. Results: Overall, 386 drug classes were investigated, of which 70 generated a signal. In total, 43 were classified as previously known based on the SIDER database or a literature review, for example, glucocorticoids (SR 1.67, 95% CI 1.62-1.72) and β-blockers (SR 1.20, 95% CI 1.16-1.23). Of 27 new signals, three drug classes yielded a signal in both the Danish and Australian data source: digitalis glycosides (SR 2.15, 95% CI 2.04-2.27, and SR 1.76, 95% CI 1.50-2.08), macrolides (SR 1.20, 95% CI 1.16-1.24, and SR 1.11, 95% CI 1.06-1.16) and inhaled β2-agonists combined with glucocorticoids (SR 1.35, 95% CI 1.28-1.42, and SR 1.14, 95% CI 1.06-1.22). Conclusion: We identified 70 drug-diabetes associations, of which 27 were classified as hitherto unknown. Further studies evaluating the hypotheses generated by this work are needed, particularly for the signal for digitalis glycosides.

Background: Observational studies on corona virus disease 2019 (COVID-19) vaccines compare event rates in vaccinated and unvaccinated person time using Poisson or Cox regression. In Cox regression, the chosen time scale needs to account for the time-varying incidence of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection and COVID-19 vaccination.We aimed to quantify bias in person-time based methods, with and without adjustment for calendar time, using simulations and empirical data analysis. Methods: We simulated 500,000 individuals who were followed for 365 days, and a point exposure resembling COVID-19 vaccination (cumulative incidence 80%). We generated an effectiveness outcome, emulating the incidence of severe acute respiratory syndrome corona virus 2 infection in Denmark during 2021 (risk 10%), and a safety outcome with seasonal variation (myocarditis, risk 1/5,000). Incidence rate ratios (IRRs) were set to 0.1 for effectiveness and 5.0 for safety outcomes. IRRs and hazard ratios (HRs) were estimated using Poisson and Cox regression with a time under observation scale, and a calendar time scale. Bias was defined as estimated IRR or HR−true IRR. Further, we obtained estimates for both outcomes using data from the Danish health registries. Results: Unadjusted IRRs (biaseffectivenes +0.16; biassafety −2.09) and HRs estimated using a time-under-observation scale (+0.28;-2.15) were biased. Adjustment for calendar time reduced bias in Cox (+0.03; +0.33) and Poisson regression (0.00; −0.28). Cox regression using a calendar time scale was least biased (0.00, +0.12). When analyzing empirical data, adjusted Poisson and Cox regression using a calendar time scale yielded estimates in accordance with existing evidence. Conclusion: Lack of adjustment for the time-varying incidence of COVID-19 related outcomes may severely bias estimates.

Alejandro Arana,1 Anton Pottegård,2 Josephina G Kuiper,3 Helen Booth,4 Johan Reutfors,5 Brian Calingaert,6 Lars Christian Lund,2 Elizabeth Crellin,4 Marcus Schmitt-Egenolf,5,7 James A Kaye,8 Karin Gembert,5 Kenneth J Rothman,8 Helle Kieler,5 Daniel Dedman,4 Eline Houben,3 Lia Gutiérrez,1 Jesper Hallas,2 Susana Perez-Gutthann1 1Department of Epidemiology, RTI Health Solutions, Barcelona, 08028, Spain; 2Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense C, 5000, Denmark; 3The PHARMO Institute, Utrecht, 3528 AE, the Netherlands; 4Clinical Practice Research Datalink (CPRD), The Medicines and Healthcare Products Regulatory Agency, London, E14 4PU, UK; 5Centre for Pharmacoepidemiology, Karolinska Institutet, Solna, 171 76, Stockholm, Sweden; 6Department of Epidemiology, RTI Health Solutions, Research Triangle Park, NC, 27709-2194, USA; 7Department of Public Health and Clinical Medicine, Umeå University, Umeå, 901 87, Sweden; 8Department of Epidemiology, RTI Health Solutions, Waltham, MA, 02451-1623, USACorrespondence: Alejandro AranaDepartment of Epidemiology, RTI Health Solutions, Av. Diagonal 605, 9-1, Barcelona, 08028, SpainTel +34 93 362 2805Fax +34 93 414 2610Email aarana@rti.orgPurpose: Evidence is insufficient to infer whether topical calcineurin inhibitors (TCIs; tacrolimus and pimecrolimus) cause malignancy. The study objective was to estimate the long-term risk of skin cancer and lymphoma associated with topical TCI use in adults and children, separately.Patients and Methods: A cohort study in Denmark, Sweden, UK, and the Netherlands was conducted. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for nonmelanoma skin cancer (NMSC), melanoma, cutaneous T-cell lymphoma (CTCL), non-Hodgkin lymphoma (NHL) excluding CTCL, and Hodgkin lymphoma (HL) in new users of TCIs versus users of moderate/high-potency topical corticosteroids.Results: The study included 126,908/61,841 adults and 32,605/27,961 children initiating treatment with tacrolimus/pimecrolimus, respectively. Follow-up was ≥ 10 years for 19% of adults and 32% of children. Incidence rate ratios and (95% confidence intervals) for tacrolimus versus corticosteroid users in adults were < 1 for melanoma, non-Hodgkin lymphoma, and Hodgkin lymphoma; and 1.80 (1.25– 2.58) for cutaneous T-cell lymphoma. For pimecrolimus, IRRs in adults were < 1 for non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and Hodgkin’s lymphoma; and 1.21 (1.03– 1.41) for melanoma; and 1.28 (1.20– 1.35) for nonmelanoma skin cancer. In children, results were inconclusive due to few events. In adults, incidence rate ratios ≥ 5 years after first topical calcineurin inhibitor exposure were not higher than in overall analyses.Conclusion: Overall, we found little evidence associating use of topical calcineurin inhibitors with skin cancer and lymphoma; confounding by indication, surveillance bias, and reverse causation may have influenced these results. Even if causal, the public health impact of these excess risks would be low and confined to the first years of exposure.Keywords: tacrolimus, pimecrolimus, cutaneous T-cell lymphoma, malignant melanoma, non-melanoma skin cancer, database study

Objectives Musculoskeletal pain is common among children and adolescents. Despite the lack of evidence regarding harms and benefits, musculoskeletal pain is often managed with pain medication. The aim of this systematic review is to assess the prevalence of pain medication use for musculoskeletal pain among children and adolescents and the factors and side effects associated with use. Content Three databases (EMBASE, CINAHL and PsychINFO) were systematically searched to identify studies designed to examine the prevalence, frequency or factors associated with the use of pain medication for musculoskeletal pain in children and adolescents (aged 6–19 years). The included studies were assessed for study quality and data were extracted. Summary The search initially provided 20,135 studies. After screening titles, abstracts and full-texts, 20 studies were included. In school settings, 8–42% of children used pain medication for musculoskeletal pain, and 67–75% of children in sports clubs and from pain clinics used pain medication. The most consistent factors associated with the use of pain medications were pain characteristics and psychological factors (e.g. being bullied, low-self-esteem), while mixed evidence was found for increasing age and female gender. Only two studies reported on the duration of use and only one study on adverse effects related to the use of pain medication. Outlook We found that 8–42% of adolescents from school-based samples use pain medication for MSK pain, while the prevalence among adolescents from sports clubs and pain clinics is higher (67–75%). Pain characteristics (pain duration, severity, intensity, disability levels and the presence of ≥2 pain conditions or multisite pain) and psychological factors were associated with a higher use of pain medication, while for higher age and female gender the evidence of association was mixed. Future studies should systematically collect information on the type, duration of use of pain medication and side effects to confirm the findings of this review.

The main tool in drug safety monitoring, spontaneous reporting of adverse effects, is unlikely to detect delayed adverse drug effects including cancer. Hypothesis-free screening studies based on administrative data could improve ongoing drug safety monitoring. Using Danish health registries, we conducted a series of case–control studies by identifying individuals with incident cancer in Denmark from 2001 to 2018, matching each case with 10 population controls on age, sex, and calendar time. ORs were estimated using conditional logistic regression accounting for matching factors, educational level, and selected comorbidities. A total of 13,577 drug–cancer associations were examined for individual drugs and 8,996 for drug classes. We reviewed 274 drug–cancer pairs where an association with high use and a cumulative dose–response pattern was present. We classified 65 associations as not readily attributable to bias of which 20 were established as carcinogens by the International Agency for Research on Cancer and the remaining 45 associations may warrant further study. The screening program identified drugs with known carcinogenic effects and highlighted a number of drugs that were not established as carcinogens and warrant further study. The effect estimates in this study should be interpreted cautiously and will need confirmation targeted epidemiologic and translational studies. Significance: This study provides a screening tool for drug carcinogenicity aimed at hypothesis generation and explorative purposes. As such, the study may help to identify drugs with unknown carcinogenic effects and, ultimately, improve drug safety as part of the ongoing safety monitoring of drugs.

Background Venous thromboembolism (VTE) is a potentially fatal complication of SARS-CoV-2 infection and thromboprophylaxis should be balanced against risk of bleeding. This study aimed to examine risks of VTE and major bleeding in hospitalized and community-managed SARS-CoV-2 patients compared with control populations. Methods Using nationwide population-based registries, 30-day risks of VTE and major bleeding in SARS-CoV-2 positive patients were compared with those of SARS-CoV-2 test-negative patients and with an external cohort of influenza patients. Medical records of all COVID-19 patients at six departments of infectious diseases in Denmark were reviewed in detail. Results The overall 30-day risk of VTE was 0.4% (40/9,460) among SARS-CoV-2 patients (16% hospitalized), 0.3% (649/226,510) among SARS-CoV-2 negative subjects (12% hospitalized), and 1.0% (158/16,281) among influenza patients (59% hospitalized). VTE risks were higher and comparable in hospitalized SARS-CoV-2 positive (1.5%), SARS-CoV-2 negative (1.8%), and influenza patients (1.5%). Diagnosis of major bleeding was registered in 0.5% (47/9,460) of all SARS-CoV-2 positive individuals and in 2.3% of those hospitalized. Medical record review of 582 hospitalized SARS-CoV-2 patients observed VTE in 4% (19/450) and major bleeding in 0.4% (2/450) of ward patients, of whom 31% received thromboprophylaxis. Among intensive care patients (100% received thromboprophylaxis), risks were 7% (9/132) for VTE and 11% (15/132) for major bleeding. Conclusions Among people with SARS-CoV-2 infection in a population-based setting, VTE risks were low to moderate and were not substantially increased compared with SARS-CoV-2 test-negative and influenza patients. Risk of severe bleeding was low for ward patients, but mirrored VTE risk in the intensive care setting. BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and thromboprophylaxis should be balanced against risk of bleeding. This study examined risks of VTE and major bleeding in hospitalized and community-managed SARS-CoV-2 patients compared with control populations. METHODS: Using nationwide population-based registries, 30-day risks of VTE and major bleeding in SARS-CoV-2 positive patients were compared with those of SARS-CoV-2 test-negative patients and with an external cohort of influenza patients. Medical records of all COVID-19 patients at 6 departments of infectious diseases in Denmark were reviewed in detail. RESULTS: The overall 30-day risk of VTE was 0.4% (40/9460) among SARS-CoV-2 patients (16% hospitalized), 0.3% (649/226 510) among SARS-CoV-2 negative subjects (12% hospitalized), and 1.0% (158/16 281) among influenza patients (59% hospitalized). VTE risks were higher and comparable in hospitalized SARS-CoV-2 positive (1.5%), SARS-CoV-2 negative (1.8%), and influenza patients (1.5%). Diagnosis of major bleeding was registered in 0.5% (47/9460) of all SARS-CoV-2 positive individuals and in 2.3% of those hospitalized. Medical record review of 582 hospitalized SARS-CoV-2 patients observed VTE in 4% (19/450) and major bleeding in 0.4% (2/450) of ward patients, of whom 31% received thromboprophylaxis. Among intensive care patients (100% received thromboprophylaxis), risks were 7% (9/132) for VTE and 11% (15/132) for major bleeding. CONCLUSIONS: Among people with SARS-CoV-2 infection in a population-based setting, VTE risks were low to moderate and were not substantially increased compared with SARS-CoV-2 test-negative and influenza patients. Risk of severe bleeding was low for ward patients, but mirrored VTE risk in the intensive care setting.

Background To facilitate research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a prospective cohort of all Danish residents tested for SARS-CoV-2 in Denmark is established. Data structure All Danish residents tested by reverse transcriptase polymerase chain reactions (RT-PCR) for SARS-CoV-2 in Denmark are included. The cohort is identified using the Danish Microbiology Database. Individual-level record linkage between administrative and health-care registries is facilitated by the Danish Civil Registration System. Information on outcomes related to SARS-CoV-2 infection includes hospital admission, intensive care unit admission, mechanical ventilation, and death and is retrieved from the five administrative Danish regions, the Danish National Patient Registry, and the Danish Register of Causes of Death. The Patient Registry further provides a complete hospital contact history of somatic and psychiatric conditions and procedures. Data on all prescriptions filled at community pharmacies are available from the Danish National Prescription Registry. Health-care authorization status is obtained from the Danish Register of Healthcare Professionals. Finally, selected laboratory values are obtained from the Register of Laboratory Results for Research. The cohort is governed by a steering committee with representatives from the Danish Medicines Agency, Statens Serum Institut, the Danish Health Authority, the Danish Health Data Authority, Danish Patients, the Faculties of Health Sciences at the Danish universities, and Danish regions. The steering committee welcomes suggestions for research studies and collaborations. Research proposals will be prioritized based on timeliness and potential clinical and public health implications. All research protocols assessing specific hypotheses for medicines will be made publicly available using the European Union electronic Register of Post-Authorisation Studies. Conclusion The Danish COVID-19 cohort includes all Danish residents with an RT-PCR test for SARS-CoV-2. Through individual-level linkage with existing Danish health and administrative registries, this is a valuable data source for epidemiological research on SARS-CoV-2.

A 15-year-old female experiencing lumbar pain without prior trauma. Despite being prescribed strong analgesics by her family physician, the symptoms intensified, and she was referred to diagnostic imaging. Magnetic resonance imaging revealed an intradural extramedullary tumor in the spinal canal, located behind the L3 corpora. The patient underwent neurosurgery with a complete resection of the tumor. The histopathologic examination revealed Ewing sarcoma by identifying EWSR1 gene in the extracted tissue. The patient was subsequently referred for extensive specialized oncological treatment including photon irradiation therapy and chemotherapy. Thirty-six months on from the initial diagnosis, the patient is doing well and suffers no sequelae apart from hypogonadism.

OBJECTIVES To evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. METHODS Using healthcare records from the capital region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. RESULTS We included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N=432) and the pooled risk ratio was 0.89 (CI 0.61-1.29) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (CI 0.85-1.48), while we observed no increased risk of bleeding (RR 0.60, 0.14-2.59). The relative risk of venous thromboembolism was 0.68 (CI: 0.33-1.38) in Sweden. Less than 5 VTE events were observed among individuals receiving LMWH in Denmark, preventing a meaningful analysis. CONCLUSION We found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH. Objectives: To evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. Methods: Using healthcare records from the Capital Region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. Results: We included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N = 432) and the pooled risk ratio was 0.91 (CI 0.60-1.38) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (0.76-1.66), while we observed no increased risk of bleeding 0.63 (0.13-2.94). The relative risk of venous thromboembolism was 0.80 (0.43-1.47). Conclusion: We found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH.

The mapping of faults provides essential information on many aspects of seismic exploration, characterisation of reservoirs for compartmentalisation and cap-rock integrity. However, manual interpretation of faults from seismic data is time-consuming and challenging due to limited resolution and seismic noise. In this study, we apply a convolutional neural network trained on synthetic seismic data with planar fault shapes to improve fault mapping in the Lower and Upper Cretaceous sections of the Valdemar Field in the Danish North Sea. Our objective is to evaluate the performance of the neural network model on post-stack seismic data from the Valdemar Field. Comparison with variance and ant-tracking attributes and a manual fault interpretation shows that the neural network predicts faults with more details that may improve the overall geological and tectonic understanding of the study area and add information on potential compartmentalisation that was previously overlooked. However, the neural network is sensitive to seismic noise, which can distort the fault predictions. Therefore, the proposed model should be treated as an additional fault interpretation tool. Nonetheless, the method represents a state-of-the-art fault mapping tool that can be useful for hydrocarbon exploration and CO2 storage site evaluations.

Oral presentation at Nordic Congress for General Practice, 2022, Stavanger. Oral presentation at Nordic Congress for General Practice, 2022, Stavanger.

Dansk forskning har skabt stor værdi i udviklingen af e-sporten samt bidraget til at ændre opfattelsen af sportens vækstpotentiale. Der er dog stadig meget, vi ikke ved endnu, som forskningen skal være med til at afdække, skriver en række forskere fra Aalborg, Aarhus og Københavns Universitet.