Espen Saxhaug Kristoffersen

• Santervas, Leonor Roa; Skovlund, Eva; Ringstad, Ingrid Beate; Kristoffersen, Espen Saxhaug; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 9 contributors for this article] (2026). Frailty in relation to general and oral health-related quality of life among older adults in municipal acute care. Journal of Frailty & Aging (JFA). ISSN 2260-1341. 15(5). doi: 10.1016/j.tjfa.2026.100207. Full text in Research Archive Show summary

  Frailty is associated with poorer health-related quality of life (HRQoL) in older adults, but studies rarely assess general and oral HRQoL concurrently in acute care populations. Objectives: To examine the associations between frailty and general as well as oral HRQoL among older adults admitted to a municipal in-patient acute care (MipAC) unit. Design: Cross-sectional study. Setting: Oslo MipAC unit, Norway. Participants: A total of 382 patients aged 70 years or older admitted to the MipAC unit between January and September 2023. Measurements: Frailty was assessed using the Clinical Frailty Scale (CFS). General HRQoL was measured with the 15D instrument and a single-item global life satisfaction question. Oral HRQoL was assessed using the Oral Health Impact Profile-14 (OHIP 14). Associations between frailty and HRQoL were analyzed using linear, ordinal logistic, and binary logistic regression. Exploratory analyses of 15D and OHIP-14 dimensions were performed using non-parametric trend tests. Results: Increasing frailty was significantly associated with lower 15D scores (adjusted B -0.053, 95% CI -0.061 to -0.045), higher odds of lower life satisfaction (adjusted OR 1.19, 95% CI 1.02 to 1.39), and higher odds of reporting oral health impacts on the OHIP-14 (adjusted OR 1.25, 95% CI 1.05 to 1.48). Most 15D dimensions declined with increasing frailty, except distress. For OHIP-14, significant associations were observed for functional limitation, physical pain, and psychological disability. Conclusions: Frailty assessed with the CFS was consistently associated with reduced general and oral HRQoL in older adults admitted to a MipAC unit. These findings support the clinical relevance of simple frailty assessment during acute admission and suggest that it may help identify patients at risk of poorer quality of life.

• Jahr, Silje Holt; Koubaa, Nojoud; Hillestad, Vigdis; Larsen, Kristin Tveitan; Selseth, Maiken Nordahl & Lied-Herland, Trine [Show all 10 contributors for this article] (2026). Incidence, clinical characteristics and outcome of spontaneous cerebellar intracerebral haemorrhage in a Norwegian population. European Stroke Journal. ISSN 2396-9873. 11(7). doi: 10.1093/esj/aakag073. Full text in Research Archive
• Romoli, Michele; Molina, Carlos A.; Zapata-Arriaza, Elena; Jaikumar, Vinay; Jesser, Jessica & Heldner, Mirjam Rachel [Show all 96 contributors for this article] (2026). Emergent Carotid Stenting for Acute Anterior Circulation Ischemic Stroke With Tandem Lesions: The Multicenter CERES-TANDEM Study. Neurology. ISSN 0028-3878. 106(2), p. e214528–e214528. doi: 10.1212/WNL.0000000000214528. Full text in Research Archive
• Gollion, Cédric; Chiang, Chia Chun; Lee, Mi Ji; Dominguez-Moreno, Rogelio; Schankin, Christoph J. & Harriott, Andrea [Show all 11 contributors for this article] (2026). Migraine and white matter hyperintensities: Protocol for a systematic review and meta-analysis. Cephalalgia Reports. 9. doi: 10.1177/25158163261472105.
• Poole, Amalie Christine; Stubberud, Anker; Simpson, Melanie Rae; Øie, Lise Rystad; Tronvik, Erling Andreas & Kristoffersen, Espen Saxhaug [Show all 19 contributors for this article] (2026). App-based self-administered biofeedback for the prevention of episodic migraine: A randomized controlled trial. Cephalalgia. ISSN 0333-1024. 46(9). doi: 10.1177/03331024261480724. Full text in Research Archive
• Jahr, Silje Holt; Selseth, Maiken Nordahl; Larsen, Kristin Tveitan; REICHENBACH, ANTJE; Altmann, Marianne & Sundseth, Antje [Show all 14 contributors for this article] (2026). Diagnostic performance of prehospital large-vessel occlusion detection scales in patients with suspected acute stroke: a retrospective validation study. The Akershus Study of Ischemic Stroke and Thrombolysis. European Stroke Journal. ISSN 2396-9873. 11(6). doi: 10.1093/esj/aakag067. Full text in Research Archive
• Pohl, Heiko; Do, Thien Phu; Gantenbein, Andreas R.; Genç, Hamit; Kristoffersen, Espen Saxhaug & Hansen, Jakob Møller [Show all 15 contributors for this article] (2026). The value of nonfactual information in distinguishing primary from secondary headache disorders results of a Delphi study. Cephalalgia Reports. 9. doi: 10.1177/25158163261420753. Full text in Research Archive
• Dahl, Iselin Teresa; Dhami, Sanpreet Kaur Grewal; Sousa, Diana Aguiar de; Nakken, Ola; Zarnovicky, Svetozar & Faiz, Kashif Waqar [Show all 9 contributors for this article] (2026). Enhancing risk prediction for cerebral venous thrombosis: evaluation of an integrated approach with clinical CVT probability score and D-dimer levels. BMC Neurology. 26(1). doi: 10.1186/s12883-026-04687-x. Full text in Research Archive
• Faisal, Fahim; Poole, Amalie Christine; Danelakis, Antonios; Wergeland, Tore; Bjørk, Marte-Helene & Khanevski, Andrej [Show all 19 contributors for this article] (2026). Forecasting migraine with time-series machine learning from mobile health data. The Journal of Headache and Pain. ISSN 1129-2369. 27. doi: 10.1186/s10194-026-02346-7. Full text in Research Archive Show summary

  Background: Machine learning provides a powerful framework to model the complex patterns underlying migraine attack onset from real-world high dimensional datasets. In this study, we used machine learning to forecast headache days using mobile health (mHealth) data from a migraine biofeedback treatment app. Method: This was a machine learning analysis of data from the BioCer clinical trial (NCT05616741) evaluating app-based biofeedback for preventive treatment of episodic migraine. Participants completed three months of daily biofeedback sessions with wearables measuring trapezius muscle tension, heart rate variability, and peripheral skin temperature. Input data for the models included summary metrics from the biofeedback sessions and daily headache diary entries. The outcome of interest was the presence of a moderate-to-severe headache (defined as an intensity of 4 or higher on an 11-point scale of 0–10) on the next calendar day and the next three calendar days. The dataset was randomly split into training, validation, and test sets. Multiple standard machine learning architectures, foundation models, and time-series models were trained and optimized using the area under the receiver operating characteristics curve (AUC) as the primary scoring metric. Among these three classes of machine learning models, the best optimized model in each class identified during training was applied on the unseen test set. Permutation feature importance (PFI) was created for model explainability. Results: 146 individuals, with a total of 21,550 headache days, were included in the forecasting models. For the next calendar day predictions, the top performing standard machine learning approach (decision tree) and foundation model achieved a test set AUC of 0.59 (95% CI 0.56 to 0.61) and 0.55 (95% CI 0.55 to 0.56), respectively. The best time-series model achieved a test set AUC of 0.84 (95% CI 0.82 to 0.85). For the three-calendar day forecasting window, the test set performances were 0.55 (95% CI 0.53 to 0.56), 0.55 (95% CI 0.54 to 0.57), and 0.76 (95% CI 0.74 to 0.77), respectively. The most important features were headache intensity, duration of the headache, and heart rate scores. Conclusion: Time-series machine learning models using a relatively large dataset could forecast moderate-to-severe headaches with good accuracy in patients with episodic migraine.

• Santervas, Leonor Roa; Skovlund, Eva; Kristoffersen, Espen Saxhaug; Ringstad, Ingrid Beate; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 9 contributors for this article] (2026). Collaborative medication reviews during acute primary care admissions for older adults with polypharmacy: a randomised controlled trial. Age and Ageing. ISSN 0002-0729. 55(2). doi: 10.1093/ageing/afag029. Full text in Research Archive
• Murugesu, Elakkyen; Liu, Qinghui; SCHELLHORN, TILL; Kristoffersen, Espen Saxhaug; Groote, Inge Rasmus & Bjørnerud, Atle [Show all 8 contributors for this article] (2026). Monitoring the lateral ventricles in the presence of intracranial hemorrhage using automated dual segmentation. Medical Physics. ISSN 0094-2405. 53(2). doi: 10.1002/mp.70308. Full text in Research Archive Show summary

  Abstract Background Segmentation of intracranial hemorrhage (ICH) alongside the brain's ventricles can provide crucial information in the management stroke or traumatic brain injury (TBI). Automated computed tomography (CT) based segmentation is time‐efficient and desirable when manual annotation is not feasible. Purpose To develop a fully automated and simultaneous segmentation method capable of quantifying ICH and the lateral ventricle volumes. Segmentation results are evaluated in patients with a range of TBI conditions and patients with hemorrhage in the ventricles, known as intraventricular hemorrhage (IVH). Methods Five deep learning models were trained using 154 non‐contrast CT images with manual annotations of the ICH and lateral ventricles. Model performance was evaluated using Dice and Hausdorff Distance metrics. A top performing model was applied to three clinical samples: 1) N  = 591 patients with mild TBI without ICH; 2) N  = 91 moderate‐to‐severe TBI with baseline and follow‐up CT; and 3) N  = 5 patients with IVH and repeat CT. Statistical tests assessed model performance, and one model was selected to: test for relationship between lateral ventricle volume and age and sex, and investigate volume estimates from baseline to follow‐up. Results Significant segmentation differences were observed between models for the Dice score ( F  = 3.3, p  = 0.012), but not Hausdorff Distance ( F  = 0.58, p  = 0.68). The 3D nnU‐Net model had the highest performance with a mean Dice score of 0.92 ± 0.05 for the lateral ventricles and 0.88 ± 0.05 for ICH. In mild TBI, a quadratic association between lateral ventricle volume and age was found for the whole sample and after stratifying by sex. There were six ICH false positives out of 591 with mild TBI. In moderate‐to‐severe TBI patients, volume changes in both lateral ventricle and ICH were observed from baseline and follow‐up ( p  < 0.04, Wilcoxon signed rank test). Follow‐up lateral ventricle volume was significantly associated with the baseline estimates, but this was not the case for serial ICH estimates. The IVH case series demonstrated the feasibility of measuring lateral ventricle volume changes despite the presence of IVH. Conclusions Automated dual segmentation of lateral ventricles and ICH using deep learning provides a reliable method to monitor TBI severity over time. The approach yielded clinically relevant information, including ICH and lateral ventricle volume changes across sessions. This approach offers an efficient analysis of CT images in ICH and particularly patients that develop IVH.

• Ghoreishi, Abdoreza; Gaikwad, Abhijit; Stępień, Adam; Slowik, Agnieszka & Arango, Akemi [Show all 265 contributors for this article] (2025). Recanalization Outcomes and Procedural Complications in Patients With Acute Ischemic Stroke and COVID-19 Receiving Endovascular Treatment. Journal of Stroke (JOS). ISSN 2287-6391. 27(1), p. 128–132. doi: 10.5853/jos.2024.04077. Full text in Research Archive
• Meinel, Thomas R.; Bücke, Philipp; D’Anna, Lucio; Merlino, Giovanni; Sousa, Diana Aguiar de & Poli, Sven [Show all 62 contributors for this article] (2025). Intravenous Thrombolysis in Patients With Recent Intake of Direct Oral Anticoagulants: A Target Trial Analysis and Comparison With Reversal Agent Use. Stroke. ISSN 0039-2499. 56(10), p. 2836–2845. doi: 10.1161/strokeaha.125.051384. Full text in Research Archive Show summary

  BACKGROUND: Intravenous thrombolysis (IVT) in patients with recent ingestion of direct oral anticoagulants (DOACs) is a frequent challenge and remains controversial. The benefit of DOAC reversal before IVT is uncertain. METHODS: Using target trial methodology, we analyzed data from 28 comprehensive stroke centers. Patients on DOACs were included if they met IVT criteria, had a National Institutes of Health Stroke Scale score of ≥2, and last DOAC intake within 48 hours or was undeterminable. Safety and efficacy outcomes (symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, major bleeding, 90-day mortality, and good functional outcome [modified Rankin Scale score of 0–2 or return to baseline]) were compared between those receiving IVT versus no IVT and IVT with versus without reversal. In addition, a comparison was made with patients from the New Zealand stroke registry, all of whom underwent reversal with idarucizumab. We adjusted for covariates known to be associated with safety and efficacy outcomes, including age, stroke severity, intended thrombectomy, blood glucose, blood pressure, DOAC reversal, and time from last intake. RESULTS: Overall, 1342 patients fulfilled the target trial criteria. The median age was 80 (interquartile range, 73–86) years, median National Institutes of Health Stroke Scale score was 11, 50% were female, and 52% of patients received endovascular therapy. IVT was given in 342 of 1342 (25%) patients. Of these, 141 (41.2%) had verified DOAC intake <12 hours before admission, and 92 (26.9%) within 12 to 24 hours. Symptomatic intracerebral hemorrhage occurred in 10 of 328 (3.0%) of patients receiving IVT and 54 of 921 (5.9%) patients not receiving IVT (adjusted difference, −2.1% [95% CI, −5.3% to +1.2]). Patients receiving IVT were more likely to have good functional outcomes (adjusted difference, +14.4% [95% CI, +7.1% to +21.8%]). Comparing 289 patients with reversal (from the additional New Zealand registry) and 283 patients without reversal before IVT (from the target trial population), there was no significant difference in symptomatic intracerebral hemorrhage, major bleeding, or efficacy outcomes. CONCLUSIONS: This target trial confirms previous observational data regarding the safety of off-label IVT in patients with recent DOAC intake. More data and dedicated trials are needed for patients with confirmed high DOAC plasma levels and regarding the efficacy and safety of DOAC reversal before IVT.

• Goeldlin, Martina B.; Küttner, Rosa; Drop, Boudewijn; Siepen, Bernhard Matthias; Rauch, Janis Patricia & Auer, Elias [Show all 32 contributors for this article] (2025). Incidence of Diffusion-Weighted Imaging Lesions in Patients With Intracerebral Hemorrhage in the Acute and Subacute Time Periods. Neurology. ISSN 0028-3878. 105(2). doi: 10.1212/wnl.0000000000213837. Full text in Research Archive
• Polymeris, Alexandros A.; Koga, Masatoshi; Strbian, Daniel; Vedamurthy, Adhiyaman; Krishnan, Manju & Branca, Mattia [Show all 25 contributors for this article] (2025). Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis. Journal of Stroke (JOS). ISSN 2287-6391. 27(2), p. 217–227. doi: 10.5853/jos.2024.04322. Full text in Research Archive Show summary

  Background and Purpose Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.Methods A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.Results Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66–1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65–1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30–1.08], HRweighted 0.57 [0.30–1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56–6.63], HRweighted 1.88 [0.56–6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.Conclusion Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.

• Polymeris, Alexandros A.; Rossel, Jean Benoît; Koga, Masatoshi; Strbian, Daniel; Vedamurthy, Adhiyaman & Krishnan, Manju [Show all 28 contributors for this article] (2025). Once- versus twice-daily direct oral anticoagulants after ischemic stroke in atrial fibrillation – A post-hoc analysis of the ELAN trial. European Stroke Journal. ISSN 2396-9873. 11(1). doi: 10.1177/23969873251360974. Full text in Research Archive Show summary

  Introduction: Whether the risk-benefit profile of once-daily versus twice-daily direct oral anticoagulants (DOAC) differs after atrial fibrillation(AF)-associated ischemic stroke is unclear. We explored this in a post-hoc analysis of ELAN trial data (NCT03148457). Patients and methods: We compared the risk of the primary outcome (recurrent ischemic stroke, systemic embolism, intracranial hemorrhage (ICH), major extracranial bleeding, vascular death) from treatment initiation to the trial’s 90-day follow-up in participants treated with once-daily or twice-daily DOAC after AF-associated stroke using Firth’s logistic and Cox proportional hazards regression in unadjusted, inverse-probability-of-treatment-weighted and augmented-inverse-probability-weighted models to address confounding. Secondary outcomes were the primary outcome components and non-major bleeding. We calculated the net clinical benefit (NCB) of twice-daily over once-daily DOAC by subtracting the weighted rate of excess bleeding attributable to twice-daily DOAC from the rate of excess ischemic events possibly prevented by twice-daily DOAC. Results: We analyzed 1890/2013 (94%) participants (median age 77 years, 45% female), of whom 384 (20%) received once-daily and 1506 (80%) twice-daily DOAC. The primary outcome occurred in 64 (3.4%) participants, and did not differ between DOAC types in logistic (ORunadjusted 0.89 (95% CI 0.50–1.66); ORweighted 1.34 (0.71–2.79); ORaugmented 1.45 (0.81–3.21); twice-daily vs once-daily DOAC) nor in Cox models. We identified no clear differences in any secondary outcome. NCB analysis revealed a near-neutral net effect of twice-daily versus once-daily DOAC (+0.28 to +0.67 weighted events possibly prevented/100 person-months for ICH weights 1.5–3.3). Discussion and conclusion: The risk-benefit profile of once-daily versus twice-daily DOAC after AF-associated ischemic stroke does not seem to differ.

• Jahr, Silje Holt; Sandset, Else Charlotte; Selseth, Maiken Nordahl; Larsen, Kristin Tveitan; Hillestad, Vigdis & Faiz, Kashif Waqar [Show all 8 contributors for this article] (2025). Prehospital blood pressure in acute stroke. Emergency Medicine Journal. ISSN 1472-0205. 42(9), p. 593–598. doi: 10.1136/emermed-2024-214462. Full text in Research Archive Show summary

  Background Blood pressure (BP) is a potential target for early stroke treatment and triage, yet our knowledge about prehospital BP is limited. We aimed to investigate whether prehospital BP differs by stroke type and severity in patients with suspected acute stroke and explore associations between prehospital BP and outcomes. Methods This single-centre retrospective study analysed consecutive patients with suspected stroke admitted to a primary hospital within 4.5 hours of symptom onset, comparing prehospital BP by discharge diagnosis, ischaemic stroke subtypes and stroke severity. Associations between prehospital BP and 90-day modified Rankin Scale and National Institutes of Health Stroke Scale (NIHSS) score changes within 24 hours of admission were analysed using logistic and ordinal regression. Results Of the 1165 patients included, 64% (742) had acute stroke and 36% (423) were stroke mimics. Patients who had an acute stroke had higher mean prehospital systolic BP (SBP) than mimics (162±31 mm Hg vs 152±29 mm Hg, p<0.001). Patients with intracerebral haemorrhage (ICH) had the highest SBP (173±34 mm Hg). Among ischaemic strokes, lacunar stroke had higher SBP than non-lacunar stroke (169±33 vs 158±29 mm Hg, p=0.002), and large vessel occlusion (LVO) had lower SBP than non-LVO (150±28 vs 164±30 mm Hg, p<0.001). Patients with NIHSS score >15 had lower SBP than patients with NIHSS score ≤5 (155±34 vs 165±29 mm Hg, p=0.009). In ischaemic stroke, higher SBP was associated with less chance of early neurological improvement (adjusted OR 0.95, (95% CI, 0.91 to 0.98)). Conclusion Prehospital BP varies by stroke subtype and severity and is associated with outcome. Blood pressure was higher in ICH than in ischaemic stroke, with lacunar infarcts showing the highest BP among ischaemic subtypes. The association between prehospital BP and poor outcomes in observational studies highlights the need for further research on early BP management across different stroke subtypes.

• Rønning, Ole Morten; Nordby, Linn Marie; Logallo, Nicola; Kvistad, Christopher Elnan; Kristoffersen, Espen Saxhaug & Ihle-Hansen, Håkon [Show all 12 contributors for this article] (2025). Association between blood pressure and outcome in patients with acute ischemic stroke treated with alteplase. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 35(1). doi: 10.1016/j.jstrokecerebrovasdis.2025.108518. Full text in Research Archive Show summary

  Background The role of blood pressure (BP) in acute stroke remains unclear. We investigated the impact of BP trajectories during the first 24 hours (h) after hospital admission on outcomes in acute ischemic stroke patients treated with intravenous alteplase. Methods In 424 ischemic stroke patients from the NOR-TEST I trial treated with alteplase, we assessed systolic BP (sBP) at baseline, change in sBP between 0 h and 24 h, and increase in sBP over the same period. Outcomes included modified Rankin Scale (mRS) at 3 months, NIHSS at 24 h, and symptomatic intracerebral haemorrhage (sICH) within 48 h. Logistic and linear regression analyses were used to explore the association of blood pressure trajectories and outcome adjusted for age, sex, time from onset of symptoms to intravenous thrombolysis (IVT) and NIHSS at admittance (NIHSSadm). Results Mean sBP at baseline (admittance), 2 h and 24 h were 155, 147 and 142 mmHg, respectively. An increase in sBP from baseline to 24 h was seen in 115 patients (27 %), while 409 showed an overall change. In unadjusted analyses, sBP increase (but not baseline sBP or change in sBP) was associated with worse mRS at 3 months. This remained significant after adjustment (OR 0.933, 95 %CI 0.876 – 0.993). Higher baseline sBP and sBP increase predicted worse NIHSS at 24 h. sBP increase and baseline sBP were also associated with sICH within 48 h, but only baseline sBP remained significant after adjustment (OR 1.022, 95 % CI 1.003–1.042). Conclusions An increase in sBP within the first 24 h was associated with worse neurological and functional outcomes at 3 months, while higher baseline sBP was linked to worse neurological outcomes and sICH in acute ischemic stroke patients treated with alteplase.

• Argren, Maria Bengtson Argren; Engstrand, Helene; Husøy, Andreas Kattem; Kristoffersen, Espen Saxhaug; Toft, Mathias & Pripp, Are Hugo [Show all 8 contributors for this article] (2025). Prevalence of headache disorders in Norway: results from the population based PopHEAD study. The Journal of Headache and Pain. ISSN 1129-2369. 26(1). doi: 10.1186/s10194-025-02216-8. Full text in Research Archive Show summary

  Background Reliable and up-to-date prevalence estimates of headache disorders are essential for public health planning. Despite previous large-scale studies, there is a lack of validated and up-to-date population-representative prevalence estimates from Europe. Here, we aimed to estimate the one-year prevalence of the major headache disorders in Norway using a validated diagnostic tool. Methods PopHEAD is a population-based Norwegian cross-sectional study. A random sample of 28,753 individuals aged 18–70 years was invited to complete a digital version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, adapted and translated into Norwegian. Headache diagnoses were made using a standardized algorithm based on the International Classification of Headache Disorders (ICHD-3) criteria and validated by telephone interview in a sub-sample. Prevalence estimates were calculated as crude proportions with 95% confidence intervals and sequentially adjusted for age and sex, measurement error and selection bias. Associations with demographic variables were investigated. Results A total of 8,265 participants (3,344 men and 4,921 women; mean age 47.3 years) responded. The crude one-year prevalence was 29.6% for migraine (36.5% in women, 19.4% in men), 52.7% for tension-type headache (TTH) (51.4% in women, 54.6% in men), and 5.1% for probable medication-overuse headache (pMOH) (6.5% in women, 3.1% in men). After adjusting for age, sex, measurement error, and selection bias, the estimated prevalence was 20.3% for migraine, 47.9% for TTH, and 5.9% for pMOH. Migraine prevalence was highest among participants with low income and low education, while TTH prevalence was highest in participants with high socioeconomic status. pMOH prevalence was highest in participants aged 26–45 years and in participants with low education. Conclusion The PopHEAD study provides updated, validated and bias-adjusted prevalence estimates for migraine, TTH and pMOH in the Norwegian adult population. These data may inform health resource allocation for headache management in similar populations.

• Santervas, Leonor Roa; Wyller, Torgeir Bruun; Skovlund, Eva; Kristoffersen, Espen Saxhaug & Romskaug, Rita (2025). Associations Between Frailty, Illness Severity, and Long-Term Mortality Among Older Adults Admitted to Municipal Acute Care. Journal of the American Medical Directors Association. ISSN 1525-8610. 26(8). doi: 10.1016/j.jamda.2025.105718. Full text in Research Archive Show summary

  Objectives: Important risk factors for mortality include frailty and illness severity. The National Early Warning Score 2 (NEWS2) is widely used to assess acute illness severity and mortality risk, but age and frailty's impact on the association between NEWS2 and mortality is less understood, particularly in nonhospital settings. This study aimed to examine the associations between frailty, NEWS2, and 1-year postdischarge mortality in older adults admitted to the Oslo Municipal In-Patient Acute Care (MipAC) unit. Design: Prospective observational study. Setting and participants: Patients admitted to the MipAC unit with 1-year follow-up for all-cause mortality. Methods: Frailty was assessed using the Clinical Frailty Scale (CFS). The maximum registered NEWS2 during admission was obtained from patient records. Associations with 1-year mortality were analyzed using a Cox model and Kaplan-Meier survival analysis. Results: Among 382 patients (mean age, 84.3 years; 72% female), 58 died during the 1-year follow-up period. Both CFS and NEWS2 were independently associated with 1-year mortality in an age-adjusted Cox proportional hazards model. The adjusted hazard ratios were 1.33 (95% CI, 1.07-1.66) per unit increase in CFS and 1.26 (95% CI, 1.14-1.39) per unit increase in NEWS2. A supplementary analysis of the vital signs contributing to NEWS2 revealed that elevated respiratory rate and hypotension were independently associated with increased 1-year mortality, with adjusted hazards ratios being 2.71 (95% CI, 1.35-5.46) and 3.05 (95% CI, 1.54-6.01), respectively. When combining CFS and NEWS2, moderately to severely frail patients (CFS ≥6) with low NEWS2 (0-4) showed a tendency toward increased mortality, whereas among those with high NEWS2 (≥5), frailty did not appear to further influence mortality risk. Conclusions and implications: CFS, NEWS2, and the vital signs elevated respiratory rate and hypotension are associated with 1-year mortality in patients admitted to a MipAC unit.

• Goeldlin, Martina B.; Fandler-Höfler, Simon; Pezzini, Alessandro; Manikantan, Anusha; Rauch, Janis & Hald, Stine Munk [Show all 39 contributors for this article] (2025). Location and Timing of Recurrent, Nontraumatic Intracerebral Hemorrhage. JAMA Neurology. ISSN 2168-6149. 82(4), p. 355–363. doi: 10.1001/jamaneurol.2025.0026. Full text in Research Archive
• Kneihsl, Markus; Hakim, Arsany; Goeldlin, Martina B.; Meinel, Thomas R.; Branca, Mattia & Rohner, Roman [Show all 24 contributors for this article] (2025). Early vs Late Anticoagulation After Ischemic Stroke in Patients With Atrial Fibrillation and Covert Brain Infarcts. Neurology. ISSN 0028-3878. 104(1). doi: 10.1212/WNL.0000000000210157. Full text in Research Archive Show summary

  Background and Objectives Covert brain infarcts (CBIs) in patients with first-ever ischemic stroke (IS) and atrial fibrillation (AF) are associated with an increased risk of stroke recurrence. We aimed to assess whether CBIs modify the treatment effect of early vs late initiation of direct oral anticoagulants (DOACs) in patients with IS and AF. Methods We conducted a post hoc analysis of the international, multicenter, randomized-controlled ELAN trial, which compared early (<48 hours after ischemic stroke for minor and moderate stroke, 6–7 days for major stroke) vs late (>48 hours for minor, 3–4 days for moderate, 12–14 days for major stroke) initiation of DOACs in patients with IS and AF. The primary outcome was a composite of recurrent IS, symptomatic intracranial hemorrhage (sICH), major extracranial bleeding, systemic embolism, or vascular death within 30 days after stroke; secondary outcomes were the individual components. We estimated outcomes based on the presence of CBIs (any CBI vs no CBI) on prerandomization imaging (core-lab rating) using adjusted risk differences (aRDs) between treatment arms. Point estimates and 95% CIs are presented without reporting p values. Results Of the 1,694 participants with first-ever IS included (median age: 77 years, 45.9% female), 678 (40.0%) had CBI. The imaging core-lab interrater reliability for the presence of CBI was 0.87 (0.81–0.94). The primary outcome occurred in 8 (2.3%; recurrent IS: 3/342) of 342 participants with CBI assigned to the early treatment arm vs 20 (6.0%; recurrent IS: 12/336) of 336 assigned to the late treatment arm (aRD: −3.6%, 95% CI −6.6 to −0.6) (p for interaction: 0.063). With early DOAC treatment, IS recurrence risk was lower in participants with CBI (aRD: −2.7%, 95% CI −5.0 to −0.4), but not in participants without CBI (aRD: −0.4, 95% CI −2.1 to 1.2). No sICH was observed in the early treatment group. Discussion The presence of CBI may indicate a subgroup of patients with first-ever IS and AF who particularly benefits from early DOAC initiation to prevent ischemic event recurrence, without increasing harm. Our findings should be considered in clinical decision making regarding timely DOAC treatment in patients with stroke and AF. Classification of Evidence This study provides Class II evidence that in patients with covert brain infarcts, atrial fibrillation, and first-ever ischemic stroke, early (vs late) initiation of DOACs is associated with lower risk of recurrent stroke with no increase in harm. Trial Registration Information URL: clinicaltrials.gov/study/NCT03148457; Unique identifier: NCT03148457; submitted: April 7, 2017; first patient enrolled: November 6, 2017.

• Lunder, Oda Vardenær; Wisløff, Torbjørn; Wølneberg, Linn-marie; Smedsrud, Aina Paulsen; Aasbakken, Linda Hagen & Hole, Inger Louise [Show all 10 contributors for this article] (2025). Multidisciplinary headache treatment with work-focus in Norway: An observational study. Cephalalgia. ISSN 0333-1024. 45(4). doi: 10.1177/03331024251332572. Full text in Research Archive
• Munckhof, Anita van de; Kammen, Mayte Sánchez van; Tatlisumak, Turgut; Krzywicka, Katarzyna; Aaron, Sanjith & Antochi, Florina [Show all 52 contributors for this article] (2025). Direct oral anticoagulants versus vitamin K antagonists for cerebral venous thrombosis (DOAC-CVT): an international, prospective, observational cohort study. Lancet Neurology. ISSN 1474-4422. 24(3), p. 199–207. doi: 10.1016/S1474-4422(24)00519-2. Full text in Research Archive
• Kristoffersen, Espen Saxhaug; Seiffge, David Julian & Meinel, Thomas Raphael (2025). Intravenous thrombolysis and mechanical thrombectomy in acute stroke patients on direct oral anticoagulants. Journal of Neurology. ISSN 0340-5354. 272(1). doi: 10.1007/s00415-024-12832-0. Full text in Research Archive Show summary

  Intravenous thrombolysis and mechanical thrombectomy reduce morbidity and improve functional outcome in ischemic stroke. However, acute recanalization therapies may increase the risk of symptomatic intracranial hemorrhage due to its effects on the brain tissue. An increasing proportion of patients with ischemic stroke are using direct oral anticoagulants (DOACs). While current international guidelines recommend against intravenous thrombolysis in patients with intake of DOACs within the last 48 h, they also highlight lack of evidence in the area. Based on these guidelines, a significant proportion of patients are consequently disqualified from intravenous thrombolysis. Measuring anticoagulant activity before intravenous thrombolysis has been suggested as a way to select patients with low risk of symptomatic intracranial hemorrhage, but uncertainty exists about feasibility, validity, availability and costs. Reversal agents have demonstrated potential in facilitating safer intravenous thrombolysis administration, though their efficacy is not established in randomized controlled trials, and logistical and cost-related barriers limit their widespread use. During the last couple of years several large cohort studies reported no significant increase in symptomatic intracranial hemorrhage among selected patients on DOACs receiving intravenous thrombolysis compared to those not on anticoagulants, even without the use of DOAC plasma levels or reversal agents. Mechanical thrombectomy appears to be generally safe in patients with recent DOAC intake. The aim of this review is to discuss the uncertainty around the safety and efficacy of intravenous thrombolysis and thrombectomy in patients with a recent intake of DOAC, summarize existing knowledge, and outline potential approaches.

• Larsen, Kristin Tveitan; Jahr, Silje Holt; Selseth, Maiken Nordahl; Lied-Herland, Trine; Hillestad, Vigdis & Ihle-Hansen, Hege Beate [Show all 9 contributors for this article] (2025). Impact of white matter lesions on associations between prehospital blood pressure and outcomes in spontaneous intracerebral hemorrhage. European Stroke Journal. ISSN 2396-9873. 10(4), p. 1402–1412. doi: 10.1177/23969873251343495. Full text in Research Archive Show summary

  Introduction: There are concerns about the safety of intensive blood pressure (BP) lowering in intracerebral hemorrhage (ICH) patients with white matter lesions (WML). We explored the impact of WML on associations between i) prehospital BP, and ii) BP change, and outcomes in acute, spontaneous ICH. Patients and methods: This retrospective study included consecutive patients with acute spontaneous ICH, admitted 2011–2020. WML on non-contrast computed tomography were categorized as none-to-mild (0–1) or moderate-to-severe (2–3) on the Fazekas scale. The first systolic BP (SBP) and mean arterial pressure (MAP) from the ambulance and admission, and absolute BP change between these time points, were collected. The outcomes were in-hospital mortality, mortality at 180 days, modified Rankin Scale (mRS) scores at 3 months, and hematoma expansion. Results: Of 548 patients, 260 (47%) had moderate-to-severe WML. Compared to patients with none-to-mild WML, these patients had a stronger association between higher prehospital MAP and in-hospital mortality (p interaction 0.017). WML did not modify associations between prehospital BP and other outcomes. WML modified associations between MAP change and in-hospital mortality (p interaction 0.049), MAP change and mRS score 3–6 at 3 months (p interaction 0.032), and SBP change and mRS score 3–6 at 3 months (p interaction 0.022). These outcomes were poorer with greater BP decrease in patients with moderate-to-severe compared to none-to-mild WML. Discussion and conclusion: In acute ICH, WML modified the influence of prehospital BP and BP change on clinical outcomes, with a trend toward worse outcomes associated with higher prehospital BP and greater spontaneous BP decrease.

• Seiffge, David; Polymeris, Alexandros; Pfeilschifter, Waltraud; Apostolaki-Hansson, Trine; Ip, Bonaventure & Kristoffersen, Espen Saxhaug [Show all 8 contributors for this article] (2025). Reversal of anticoagulation in patients with intracerebral haemorrhage related to oral anticoagulants: State of the evidence. European Stroke Journal. ISSN 2396-9873. 10(1S), p. 14–23. doi: 10.1177/23969873241281477. Full text in Research Archive Show summary

  Purpose: About 20%–25% of all intracerebral haemorrhages are associated with oral anticoagulation therapy. Reflecting changings prescription patterns in the general population, the spectrum of oral anticoagulation-associated intracerebral haemorrhage has substantially changed in the last decade. In many European countries, direct oral anticoagulant-associated intracerebral haemorrhage is now more frequent than vitamin K antagonist-associated intracerebral haemorrhage. Outcome in patients with anticoagulation-associated intracerebral haemorrhage is poor, likely mediated by a high incidence of haematoma expansion. Reversal of anticoagulation is an essential part of current care pathways for hyperacute treatment of intracerebral haemorrhage aiming to limit haematoma expansion and thereby improving outcome. Methods: In this review, we summarise the latest evidence regarding reversal therapy for vitamin K antagonist-, direct thrombin inhibitor- and factor Xa inhibitor-associated intracerebral haemorrhage. Findings: Two randomised controlled trials have shown that the use of prothrombin complex concentrate (compared to fresh frozen plasma) for reversing vitamin K antagonist-associated intracerebral haemorrhage and andexanet alfa (compared to usual care, mainly prothrombin complex concentrate) for factor Xa inhibitor-associated intracerebral haemorrhage had superior haemostatic efficacy. However, the incidence of thromboembolic complications was high in both trials. For reversal of Vitamin K antagonist-associated intracerebral haemorrhage, the overall rate was 18% but due to crossovers, it is impossible to determine the rate for any specific treatment. For factor-Xa inhibitor associated intracerebral haemorrhage, andexanet alfa led to an increase in the incidence of thromboembolic events. Moreover, these two randomised controlled trials were not powered to detect differences in mortality or functional outcomes and lacked long-term follow-up. Idarucizumab has shown promising results in a single-arm case series of patients with intracerebral haemorrhage associated with the direct thrombin inhibitor dabigatran, yet no randomised controlled trial is available to support these findings. Conclusion: Given that haematoma expansion is strongly associated with poor outcome, current evidence underlines the importance of rapid, targeted and effective reversal of anticoagulation in patients with anticoagulation-associated intracerebral haemorrhage. While haematoma expansion is a key prognostic factor, no randomised controlled trial has demonstrated a clear improvement in functional outcome. Future research should weigh the advantages of preventing haematoma expansion against the risks of increased thromboembolic events, and aim to identify the patients who would derive the most benefit from reversal treatments.

• Nasreldein, Ahmed; Asyraf, Wan; Nguyen, Thanh N; Martins, Sheila; Lioutas, Vasileios-Arsenios & Elbassiouny, Ahmed [Show all 31 contributors for this article] (2025). Global challenges in the access of endovascular treatment for acute ischemic stroke (global MT access). International Journal of Stroke. ISSN 1747-4930. 20(6), p. 660–668. doi: 10.1177/17474930251314395. Full text in Research Archive
• Peacock, Meabh; Drumm, Brian; Klein, Piers; Raymond, Jean; Huo, Xiaochuan & Chen, Yimin [Show all 66 contributors for this article] (2024). Basilar artery occlusion management: An international survey of gender influence on management. Interventional Neuroradiology. ISSN 1591-0199. doi: 10.1177/15910199241265590. Full text in Research Archive
• Siepen, Bernhard M.; Forfang, Elisabeth; Branca, Mattia; Drop, Boudewijn; Mueller, Madlaine & Goeldlin, Martina B. [Show all 36 contributors for this article] (2024). Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries. Stroke and Vascular Neurology. ISSN 2059-8688. doi: 10.1136/svn-2023-002813. Full text in Research Archive Show summary

  Background We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation. Methods This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013–2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0–2) and mortality at 3 months. Results Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6–25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)). Conclusions The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.

• Bjelkarøy, Maria Torheim; Simonsen, Tone Breines; Siddiqui, Tahreem Ghazal; Halset, Sigrid; Cheng, Socheat & Grambaite, Ramune [Show all 10 contributors for this article] (2024). Brief Intervention as a Method to Reduce Z-Hypnotic Use by Older Adults: Feasibility Case Series. JMIR Formative Research. 8(1). doi: 10.2196/51862. Full text in Research Archive Show summary

  Background: Z-hypnotics or z-drugs are commonly prescribed for insomnia and sleep difficulties in older adults. These drugs are associated with adverse events and dependence and are not recommended for long-term use. Despite evidence of older adults being more sensitive to a wide array of adverse events and clinical guidelines advocating limiting use, inappropriate use in this population is still prevalent. Previous intervention studies have focused mainly on prescriber information. Simple, individually focused intervention designs are less studied. Brief intervention (BI) is a simple, easily transferable method mainly used to treat patients at risk of alcohol overuse. Objective: Our objective was to design and test the feasibility and acceptability of a BI intervention adapted to address individual, inappropriate use of z-hypnotics among older adults. This preparatory study aimed to optimize the intervention in advance of a quantitative randomized controlled trial investigating the treatment effect in a larger population. Methods: This feasibility case series was conducted at Akershus University Hospital, Norway, in autumn 2021. We included 5 adults aged ≥65 years with long-term (≥4 weeks) use of z-hypnotics and 2 intervening physicians. Additionally, 2 study investigators contributed with process evaluation notes. The BI consists of information on the risk of inappropriate use and individualized advice on how to reduce use. The focus of the intervention is behavioral and aims, in cooperation with the patient and based on shared decision-making, to change patient behavior regarding sleep medication rather than physician-based detoxification and termination of z-hypnotic prescriptions. Qualitative and descriptive quantitative data were collected from intervening physicians, study investigators, and participants at baseline, immediately after the intervention, and at the 6-week follow-up. Results: Data were obtained from 2 physicians, 2 study investigators, and 5 participants (4 women) with a median age of 84 years. The average time spent on the BI consultation was 15 minutes. All 5 participants completed the intervention without problems. The participants and 2 intervening physicians reported the intervention as acceptable and were satisfied with the delivery of the intervention. After the intervention, 2 participants stopped their use of z-hypnotics completely and participated in the follow-up interview. Study investigators identified logistical challenges regarding location and time requirements. Identified aspects that may improve the intervention and reduce dropouts included revising the intervention content, focusing on rebound insomnia, adding an information leaflet, and supporting the patient in the period between the intervention and follow-up. The notion that the intervention should best be located and conducted by the patient's own general practitioner was supported by the participants. Conclusions: We identified important aspects to improve the designed intervention and found that the BI is feasible and acceptable for incorporation into a larger randomized trial investigating the treatment effect of BI for reducing z-hypnotic use by older adults. Trial registration: ClinicalTrials.gov NCT03162081; http://tinyurl.com/rmzx6brn.

• Scutelnic, Adrian; Munckhof, Anita van de; Miraclin, Angel T.; Aaron, Sanjith; Hameed, Sajid & Wasay, Mohammad [Show all 46 contributors for this article] (2024). Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19. European Stroke Journal. ISSN 2396-9873. 9(3), p. 676–686. doi: 10.1177/23969873241241885. Full text in Research Archive
• Brakel, Benjamin A; Rebchuk, Alexander D; Ospel, Johanna; Chen, Yimin; Heran, Manraj KS & Goyal, Mayank [Show all 35 contributors for this article] (2024). International practice patterns and perspectives on endovascular therapy for the treatment of cerebral venous thrombosis. International Journal of Stroke. ISSN 1747-4930. doi: 10.1177/17474930241304206. Full text in Research Archive
• Kristoffersen, Espen Saxhaug; Waage, Siri; Pallesen, Ståle & Bjorvatn, Bjørn (2024). Changes in work schedule affect headache frequency among Norwegian nurses: A 3-year-follow-up study. Occupational and Environmental Medicine. ISSN 1351-0711. 81(4), p. 191–200. doi: 10.1136/oemed-2023-109164. Full text in Research Archive
• Kristoffersen, Espen Saxhaug; Pallesen, Ståle; Waage, Siri & Bjorvatn, Bjørn (2024). The long-term effect of work schedule, shift work disorder, insomnia and restless legs syndrome on headache among nurses: A prospective longitudinal cohort study. Cephalalgia. ISSN 0333-1024. 44(1). doi: 10.1177/03331024231226323. Full text in Research Archive Show summary

  Background The preset study aimed to explore whether work schedules and sleep disorders predict the onset of headache. Methods A longitudinal study was conducted with questionnaire data from 2014 (baseline) and 2017 (follow-up) on work schedule, number of night shifts, number of quick returns, insomnia, shift work disorder (SWD), restless legs syndrome (RLS) and validated headache diagnoses among 1560 Norwegian nurses. Associations were explored by multivariate regression analyses. Results Work related factors at baseline did not predict onset of headache three years later. In the adjusted logistic regressions, insomnia at baseline predicted increased risk of new onset of migraine (odds ratio (OR) = 1.58; 95% confidence interval (CI) = 1.08–2.33), chronic headache (OR = 2.02; 95% CI = 1.04–4.66) and medication-overuse headache (OR = 3.79; 95% CI = 1.26–11.42) at follow-up. SWD at baseline predicted new onset of migraine (OR = 1.64; 95% CI = 1.07–2.50) and RLS at baseline predicted new onset of headache ≥1 day per month (OR = 1.55; 95% CI = 1.01–2.36) and migraine (OR = 1.55; 95% CI = 1.03–2.32) at follow-up. No factors predicted tension-type headache. Conclusions Overall, work related factors did not predict the onset of headache three years later, whereas insomnia, SWD and RLS at baseline all increased the risk of future headaches.

• Aaseth, Kjersti; Dhami, Sanpreet Kaur Grewal; Kravdal, Gunnhild; Zarnovicky, Svetozar; Faiz, Kashif Waqar & Vetvik, Kjersti [Show all 7 contributors for this article] (2024). Diagnostic workup of acute headache and subarachnoid hemorrhage in a Norwegian population: An observational study. European Journal of Neurology. ISSN 1351-5101. 31(9). doi: 10.1111/ene.16385. Full text in Research Archive Show summary

  Background: Acute headache may be the primary symptom of subarachnoid hemorrhage (SAH). Recent guidelines suggest that non-contrast computed tomography (CT) is adequate to exclude aneurysmal SAH if performed within 6 h after symptom onset. However, most studies of acute headache including CT, lumbar puncture and SAH are multicenter studies from referral hospitals with highly selected patient populations. The main purpose of this study was to describe the diagnostic properties of head CT and cerebrospinal fluid (CSF) spectrophotometry for detecting SAH in an unselected primary hospital population with acute headache. Methods: A retrospective cross-sectional study conducted at a large primary hospital serving roughly 10% of the Norwegian population. Diagnostic workup from consecutive patients evaluated for acute headache in 2009–2020 were collected. All CSF-spectrophotometry reports were standardized and the same CT scanner was used during the study. Results: A total of 3227 patients were included. Median age was 45 years and 63% were women. In total, 170 (5.3% of all acute headache patients) had SAH. Of 3071 CT-negative patients, 2852 (93%) underwent lumbar puncture. Of the CSF reports, 2796 (98%) were negative for xanthochromia. Overall, the rate for detection of aneurysmal SAH by positive xanthochromia was 9 in 2852 cases (3‰). The miss rate for the detection of an aneurysmal SAH with a CT scan within 6 h was 0 and within 12 h 1 in 2852 cases (0.3‰). Conclusion: In acute headache, a CT scan taken within 6 h is practically 100% sensitive for detecting any SAH.

• Mitsikostas, Dimos-Dimtirios D.; Caronna, Edoardo; De Tommaso, Marina; Deligianni, Christina I.; Ekizoglu, Esme & Bolay, Hayrunnisa [Show all 14 contributors for this article] (2024). Headaches and facial pain attributed to SARS-CoV-2 infection and vaccination: a systematic review. European Journal of Neurology. ISSN 1351-5101. 31(6). doi: 10.1111/ene.16251. Full text in Research Archive Show summary

  Background and purpose The aim was to provide insights to the characteristics of headache in the context of COVID-19 on behalf of the Headache Scientific Panel and the Neuro-COVID-19 Task Force of the European Academy of Neurology (EAN) and the European Headache Federation (EHF). Methods Following the Delphi method the Task Force identified six relevant questions and then conducted a systematic literature review to provide evidence-based answers and suggest specific diagnostic criteria. Results No data for facial pain were identified in the literature search. (1) Headache incidence during acute COVID-19 varies considerably, with higher prevalence rates in prospective compared to retrospective studies (28.9%–74.6% vs. 6.5%–34.0%). (2) Acute COVID-19 headache is usually bilateral or holocranial and often moderate to severe with throbbing pain quality lasting 2–14 days after first signs of COVID-19; photo-phonophobia, nausea, anosmia and ageusia are common associated features; persistent headache shares similar clinical characteristics. (3) Acute COVID-19 headache is presumably caused by immune-mediated mechanisms that activate the trigeminovascular system. (4) Headache occurs in 13.3%–76.9% following SARS-CoV-2 vaccination and occurs more often amongst women with a pre-existing primary headache; the risk of developing headache is higher with the adenoviral-vector-type vaccines than with other preparations. (5) Headache related to SARS-CoV-2 vaccination is mostly bilateral, and throbbing, pressing, jolting or stabbing. (6) No studies have been conducted investigating the underlying mechanism of headache attributed to SARS-CoV-2 vaccines. Conclusion The results of this joint EAN/EHF initiative provide a framework for a better understanding of headache in the context of SARS-CoV-2 infection and vaccination.

• Qu, Kang; Li, Ming-Xi; Yu, Peng; Palotie, Aarno; Pressman, Alice & Belin, Andrea C. [Show all 72 contributors for this article] (2024). HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study. Scientific Reports. 14(1). doi: 10.1038/s41598-024-61628-9. Full text in Research Archive Show summary

  Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30–1.84, P = 6.87 × 10−7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

• Larsen, Kristin Tveitan; Sandset, Else Charlotte; Selseth, Maiken Nordahl; Jahr, Silje Holt; Koubaa, Nojoud & Hillestad, Vigdis [Show all 8 contributors for this article] (2023). Antithrombotic Treatment, Prehospital Blood Pressure, and Outcomes in Spontaneous Intracerebral Hemorrhage. Journal of the American Heart Association (JAHA). 12(5), p. 1–12. doi: 10.1161/JAHA.122.028336. Full text in Research Archive Show summary

  Background In acute intracerebral hemorrhage, both elevated blood pressure (BP) and antithrombotic treatment are associated with poor outcome. Our aim was to explore interactions between antithrombotic treatment and prehospital BP. Methods and Results This observational, retrospective study included adult patients with spontaneous intracerebral hemorrhage diagnosed by computed tomography within 24 hours, admitted to a primary stroke center during 2012 to 2019. The first recorded prehospital/ambulance systolic and diastolic BP were analyzed per 5 mm Hg increment. Clinical outcomes were in‐hospital mortality, shift on the modified Rankin Scale at discharge, and mortality at 90 days. Radiological outcomes were initial hematoma volume and hematoma expansion. Antithrombotic (antiplatelet and/or anticoagulant) treatment was analyzed both together and separately. Modification of associations between prehospital BP and outcomes by antithrombotic treatment was explored by multivariable regression with interaction terms. The study included 200 women and 220 men, median age 76 (interquartile range, 68–85) years. Antithrombotic drugs were used by 252 of 420 (60%) patients. Compared with patients without, patients with antithrombotic treatment had significantly stronger associations between high prehospital systolic BP and in‐hospital mortality (odds ratio [OR], 1.14 versus 0.99, P for interaction 0.021), shift on the modified Rankin Scale (common OR, 1.08 versus 0.96, P for interaction 0.001), and hematoma volume (coef. 0.03 versus −0.03, P for interaction 0.011). Conclusions In patients with acute, spontaneous intracerebral hemorrhage, antithrombotic treatment modifies effects of prehospital BP. Compared with patients without, patients with antithrombotic treatment have poorer outcomes with higher prehospital BP. These findings may have implications for future studies on early BP lowering in intracerebral hemorrhage.

• Scutelnic, Adrian; Munckhof, Anita van de; Krzywicka, Katarzyna; Kammen, Mayte Sánchez van; Lindgren, Erik & Cordonnier, Charlotte [Show all 186 contributors for this article] (2023). Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19. European Stroke Journal. ISSN 2396-9873. 8(4), p. 1001–1010. doi: 10.1177/23969873231185213. Full text in Research Archive
• Klein, Piers; Huo, Xiaochuan; Chen, Yimin; Abdalkader, Mohamad; Qiu, Zhongming & Nagel, Simon [Show all 76 contributors for this article] (2023). Specialist Perspectives on the Imaging Selection of Large Vessel Occlusion in the Late Window. Clinical Neuroradiology. ISSN 1869-1439. 33(3), p. 801–811. doi: 10.1007/s00062-023-01284-0. Full text in Research Archive
• Bjelkarøy, Maria Torheim; Benth, Jurate Saltyte; Simonsen, Tone Breines; Siddiqui, Tahreem Ghazal; Cheng, Socheat & Kristoffersen, Espen Saxhaug [Show all 7 contributors for this article] (2023). Measuring pain intensity in older adults. Can the visual analogue scale and the numeric rating scale be used interchangeably? Progress in Neuro-psychopharmacology and Biological Psychiatry. ISSN 0278-5846. 130. doi: 10.1016/j.pnpbp.2023.110925. Full text in Research Archive Show summary

  Objectives Visual analogue scale (VAS) and numeric rating scale (NRS) are two commonly used instruments for measuring pain intensity. Both instruments are validated for use in both clinical and research settings, and share a range of similar aspects. Some studies have shown that the two instruments may be used interchangeably, but the results are conflicting. In this study we assessed whether the VAS and the NRS instruments may be used interchangeably when measuring pain intensity in older adults. Methods Data were collected in a cross-sectional study, as part of the follow-up in a larger longitudinal study conducted at the Akershus University Hospital, Norway 2021 to 2022 and included 39 older adults aged ≥65. Participants were regarded as a normal older adult population as they were not recruited on basis of a specific condition or reports of pain. The participants were asked to rate their pain intensity on an average day using VAS and NRS. Bland-Altman analysis was performed to assess agreement between the two instruments. Results Thirty-seven participants with mean (SD) age of 77 (5.9) were included in the analysis. Mean (SD) pain assessed by VAS and NRS was 2.8 (1.8) and NRS 4.7 (2.2), respectively. A mean difference (SD) of 2.0 (1.9) between the scores of the two instruments was statistically significantly different from zero (p < 0.001) confirming bias. The 95% limits of agreement were estimated to be −1.7 to 5.7. A post-hoc analysis, removing an outlier, resulted in similar conclusions. Conclusion There was poor agreement between the VAS and NRS scale for measuring pain intensity in older adults. This suggests that the two instruments should not be used interchangeably when assessing pain intensity in this population.

• Edwards, Christopher; Drumm, Brian; Siegler, James E.; Schonewille, Wouter J.; Klein, Piers & Huo, Xiaochuan [Show all 58 contributors for this article] (2023). Basilar artery occlusion management: Specialist perspectives from an international survey. Journal of Neuroimaging (JON). ISSN 1051-2284. 33(3), p. 422–433. doi: 10.1111/jon.13084. Full text in Research Archive
• Munckhof, Anita Van De; Borhani-Haghighi, Afshin; Aaron, Sanjith; Krzywicka, Katarzyna; Kammen, Mayte Sánchez van & Cordonnier, Charlotte [Show all 48 contributors for this article] (2023). Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries. International Journal of Stroke. ISSN 1747-4930. 18(9), p. 1112–1120. doi: 10.1177/17474930231182901. Full text in Research Archive
• Ken-Dror, Gie; Sharma, Pankaj; Kristoffersen, Espen Saxhaug & Group, CVT VITT Study (2023). ABO blood group associated with cerebral venous thrombosis after Oxford-AstraZeneca COVID-19 vaccination: a case-control study. Journal of the Royal Society of Medicine. ISSN 0141-0768. doi: 10.1177/01410768231214341. Full text in Research Archive Show summary

  Objectives To determine whether blood group influences development of cerebral venous thrombosis (CVT) after administration of the coronavirus disease 2019 (COVID-19) AstraZeneca ChAdOx1-S vaccine. Design A case–control study. Univariate and multivariate logistic regression was used to determine the association between blood type and COVID-19 vaccination status. Setting Vaccinated and unvaccinated patients recruited from the international Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis study and the Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group. Participants All patients were of European descent and age and sex matched. Cases ( n = 82) were patients ≥18 years old who suffered a CVT within 28 days of a first dose of ChAdOx1-S vaccine. Controls ( n = 441) were unvaccinated CVT patients ≥18 years old. All patients were of European descent. Main outcome measures Frequency of blood type and ABO allele distribution by vaccination status. Results Blood group O was found to be more prevalent among CVT patients with vaccine-induced thrombotic thrombocytopenia (VITT-CVT) after ChAdOx1-S vaccination compared with unvaccinated CVT cases (43% vs. 17%, respectively, p &lt; 0.001). Blood group A was less prevalent, though still high, in the vaccinated group compared with the unvaccinated group (47% vs. 71%, respectively, p &lt; 0.001). No significant differences were observed in the VITT-CVT non-ChAdOx1-S vaccine group and unvaccinated pre-COVID-19 CVT group for blood group. Conclusions Blood group O is more prevalent among patients with VITT-CVT after ChAdOx1-S vaccination compared with unvaccinated cases, independent of well-established CVT risk factors. A larger dataset may be able to determine whether those of blood groups B and/or AB may be safely vaccinated with the low cost, readily available and easily transported ChAdOx1-S rather than adopting a complete ban.

• Strambo, Davide; Marto, João Pedro; Ntaios, George; Nguyen, Thanh N; Michel, Patrik & Herzig, Roman [Show all 51 contributors for this article] (2023). Effect of Asymptomatic and Symptomatic COVID-19 on Acute Ischemic Stroke Revascularization Outcomes. Stroke. ISSN 0039-2499. 55(1), p. 78–88. doi: 10.1161/STROKEAHA.123.043899. Full text in Research Archive Show summary

  BACKGROUND: The association of COVID-19 with higher bleeding risk and worse outcomes in acute ischemic stroke (AIS) undergoing revascularization may be related to the presence of infection symptoms. We aimed to assess the safety and outcomes of revascularization treatments in patients with AIS with asymptomatic COVID-19 (AS-COVID) or symptomatic COVID-19 (S-COVID). METHODS: We conducted an international multicenter retrospective cohort study of consecutive AIS tested for SARS-CoV-2, receiving intravenous thrombolysis and endovascular treatment between 2020 and 2021. We compared COVID-negative controls, AS-COVID, and S-COVID using multivariable regression. We assessed symptomatic intracranial hemorrhage (symptomatic intracerebral hemorrhage), mortality, and 3-month disability (modified Rankin Scale score). RESULTS: Among 15 124 patients from 105 centers (median age, 71 years; 49% men; 39% treated with intravenous thrombolysis only; and 61% with endovascular treatment±intravenous thrombolysis), 849 (5.6%) had COVID-19, of whom 395 (46%) were asymptomatic and 454 (54%) symptomatic. Compared with controls, both patients with AS-COVID and S-COVID had higher symptomatic intracerebral hemorrhage rates (COVID-controls, 5%; AS-COVID, 7.6%; S-COVID, 9.4%; adjusted odds ratio [aOR], 1.43 [95% CI, 1.03–1.99]; aOR, 1.63 [95% CI, 1.14–2.32], respectively). Only in patients with symptomatic infections, we observed a significant increase in mortality at 24 hours (COVID-controls, 1.3%; S-COVID, 4.8%; aOR, 2.97 [95% CI, 1.76–5.03]) and 3 months (COVID-controls, 19.5%; S-COVID, 40%; aOR, 2.64 [95% CI, 2.06–3.37]). Patients with COVID-19 had worse 3-month disability regardless of disease symptoms although disability was affected to a greater extent in symptomatic patients (aOR for worse modified Rankin Scale score shift: AS-COVID, 1.25 [95% CI, 1.03–1.51]; S-COVID, 2.10 [95% CI, 1.75–2.53]). S-COVID had lower successful recanalization (74.9% versus 85.6%; P<0.001), first pass recanalization (20.3% versus 28.3%; P=0.005), and a higher number of passes. CONCLUSIONS: In AIS undergoing revascularization treatments, both AS-COVID and S-COVID influence the risk of intracranial bleeding and worse clinical outcomes. The magnitude of this effect is more pronounced in symptomatic infections, which also present less favorable recanalization outcomes. These findings emphasize the impact of SARS-CoV-2 infection on the prognosis of revascularized AIS independent of symptom status.

• Munckhof, Anita van de; Kammen, Mayte Sánchez van; Krzywicka, Katarzyna; Aaron, Sanjith; Sousa, Diana Aguiar de & Antochi, Florina [Show all 31 contributors for this article] (2023). Direct oral anticoagulants for the treatment of cerebral venous thrombosis – a protocol of an international phase IV study. Frontiers in Neurology. 14. doi: 10.3389/fneur.2023.1251581. 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 Show summary

  Objective The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. Methods A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. Results The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. Interpretation This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713–726

• Meinel, Thomas R.; Wilson, Duncan; Gensicke, Henrik; Scheitz, Jan F.; Ringleb, Peter & Goganau, Ioana [Show all 50 contributors for this article] (2023). Intravenous thrombolysis in patients with ischemic stroke and recent ingestion of direct oral anticoagulants. JAMA Neurology. ISSN 2168-6149. 80(3), p. 233–243. doi: 10.1001/jamaneurol.2022.4782. Full text in Research Archive
• Fischer, Urs; Koga, Masatoshi; Strbian, Daniel; Branca, Mattia; Abend, Stefanie & Trelle, Sven [Show all 65 contributors for this article] (2023). Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. New England Journal of Medicine. ISSN 0028-4793. 388(26), p. 2411–2421. doi: 10.1056/NEJMoa2303048. Full text in Research Archive Show summary

  Background The effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear. Methods We performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days. Results Of 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, −1.18 percentage points; 95% confidence interval [CI], −2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days. Conclusions In this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457. opens in new tab.)

• MacIntosh, Bradley; Liu, Qinghui; SCHELLHORN, TILL; Beyer, Mona K.; Groote, Inge Rasmus & Morberg, Pål [Show all 20 contributors for this article] (2023). Radiological features of brain hemorrhage through automated segmentation from computed tomography in stroke and traumatic brain injury. Frontiers in Neurology. 14. doi: 10.3389/fneur.2023.1244672. Full text in Research Archive Show summary

  Introduction Radiological assessment is necessary to diagnose spontaneous intracerebral hemorrhage (ICH) and traumatic brain injury intracranial hemorrhage (TBI-bleed). Artificial intelligence (AI) deep learning tools provide a means for decision support. This study evaluates the hemorrhage segmentations produced from three-dimensional deep learning AI model that was developed using non-contrast computed tomography (CT) imaging data external to the current study. Methods Non-contrast CT imaging data from 1263 patients were accessed across seven data sources (referred to as sites) in Norway and Sweden. Patients were included based on ICH, TBI-bleed, or mild TBI diagnosis. Initial non-contrast CT images were available for all participants. Hemorrhage location frequency maps were generated. The number of estimated haematoma clusters was correlated with the total haematoma volume. Ground truth expert annotations were available for one ICH site; hence, a comparison was made with the estimated haematoma volumes. Segmentation volume estimates were used in a receiver operator characteristics (ROC) analysis for all samples (i.e., bleed detected) and then specifically for one site with few TBI-bleed cases. Results The hemorrhage frequency maps showed spatial patterns of estimated lesions consistent with ICH or TBI-bleed presentations. There was a positive correlation between the estimated number of clusters and total haematoma volume for each site (correlation range: 0.45–0.74; each p -value &amp;lt; 0.01) and evidence of ICH between-site differences. Relative to hand-drawn annotations for one ICH site, the VIOLA-AI segmentation mask achieved a median Dice Similarity Coefficient of 0.82 (interquartile range: 0.78 and 0.83), resulting in a small overestimate in the haematoma volume by a median of 0.47 mL (interquartile range: 0.04 and 1.75 mL). The bleed detection ROC analysis for the whole sample gave a high area-under-the-curve (AUC) of 0.92 (with sensitivity and specificity of 83.28% and 95.41%); however, when considering only the mild head injury site, the TBI-bleed detection gave an AUC of 0.70. Discussion An open-source segmentation tool was used to visualize hemorrhage locations across multiple data sources and revealed quantitative hemorrhage site differences. The automated total hemorrhage volume estimate correlated with a per-participant hemorrhage cluster count. ROC results were moderate-to-high. The VIOLA-AI tool had promising results and might be useful for various types of intracranial hemorrhage.

• Krzywicka, Katarzyna; Aguiar de Sousa, Diana; Cordonnier, Charlotte; Bode, Felix J.; Field, Thalia S. & Michalski, Dominik [Show all 52 contributors for this article] (2023). Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia. European Journal of Neurology. ISSN 1351-5101. 30(5), p. 1335–1345. doi: 10.1111/ene.15735. Full text in Research Archive Show summary

  Abstract Background and purpose Cerebral venous sinus thrombosis due to vaccine‐induced immune thrombotic thrombocytopenia (CVST‐VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination. CVST‐VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST‐VITT patients who underwent decompressive surgery are described and predictors of in‐hospital mortality in these patients are explored. Methods Data from an ongoing international registry of patients who developed CVST within 28 days of SARS‐CoV‐2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680–1689), were included. Results Decompressive surgery was performed in 34/128 (27%) patients with CVST‐VITT. In‐hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non‐surgical group ( p  &lt; 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non‐comatose; p  &lt; 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p  = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow‐up of 6 months, 8/10 of surgical CVST‐VITT who survived admission were functionally independent. Conclusions Almost two‐thirds of surgical CVST‐VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

• 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. 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.

• Siddiqui, Tahreem Ghazal; Bjelkarøy, Maria Torheim; Cheng, Socheat; Kristoffersen, Espen Saxhaug; Grambaite, Ramune & Lundqvist, Christofer (2022). The effect of cognitive function and central nervous system depressant use on mortality—A prospective observational study of previously hospitalised older patients. PLOS ONE. 17(3). doi: 10.1371/journal.pone.0263024. Full text in Research Archive Show summary

  Background Older patients are often users of prolonged Central Nervous System Depressants (CNSD) (Z-hypnotics, benzodiazepines and opioids), which may be associated with reduced cognition. The long-term effects of CNSD use and reduced cognitive function in older patients are unclear. The aim of this study was to examine whether cognitive function and CNSD use at baseline hospitalisation were associated with all-cause mortality two years after discharge. Methods We conducted a prospective observational study, including baseline data (2017–2018) from previously hospitalised older patients (65–90 years), assessing all-cause mortality two years after discharge. We used logistic regression to assess the primary outcome, all-cause mortality two years after baseline hospitalisation. The primary predictors were cognitive function measured by The Mini Mental State Examination (MMSE) and prolonged CNSD use (continuous use ≥ 4 weeks). Adjustment variables: age, gender, education, the Hospital Anxiety and Depression Scale (HADS) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), using receiver operating characteristics (ROC) to compare the predictive power of the models. In a sub-analysis we used, the Neurobehavioural Cognitive State Examination (Cognistat) and the Clock Drawing Test. Results Two years after discharge, out of 246 baseline patients, 43 were deceased at follow-up, among these 27 (63%) were CNSD users, and 16 (36%) were non-users at baseline, (p = 0.002). In the multivariable models cognitive function (MMSE score) was a predictor of mortality (OR 0.81 (95% CI 0.69; 0.96), p = 0.014). CNSD use was associated with mortality (OR 2.71 (95% CI 1.06; 6.95), p = 0.038), with ROC AUC: 0.74–0.77 for these models. Results using Cognistat supported the findings. The Clock Drawing Test was not significant predictor of mortality. Conclusion Two years after discharge from the hospital, older patients with reduced cognitive function and CNSD use during hospital stay had higher mortality. This underlines that inappropriate (prolonged and concurrent) use of CNSDs should be avoided by older patients, particularly in patients with reduced cognitive function.

• Nguyen, Thanh; Klein, Piers; Berberich, Anne; Nagel, Simon; Abdalkader, Mohamad & Herning, Ana [Show all 66 contributors for this article] (2022). Late Window Imaging Selection for Endovascular Therapy of Large Vessel Occlusion Stroke: An International Survey. Stroke: Vascular and Interventional Neurology. 3(1), p. 1–15. doi: 10.1161/SVIN.122.000595. Full text in Research Archive Show summary

  Background - Current stroke guidelines recommend advanced imaging (computed tomography [CT] perfusion or magnetic resonance imaging) prior to endovascular therapy (EVT) in patients with late presentation of large vessel occlusion. Adherence to guidelines may be constrained by resources or timely access to imaging. We sought to understand the factors which influence late window imaging selection for EVT candidates with large vessel occlusion.<p> <p>Methods - We conducted an international survey from January to May 2022. The questions aimed to identify advanced imaging and treatment decisions based on access to imaging, time delays, and simulated patient scenarios.<p> <p>Results - There were 3000 invited participants and 1506 respondents, the majority (89.6%) from comprehensive stroke centers in high‐income countries. Neurointerventionalists comprised 31.8% and noninterventionalists 68.2% of respondents. Overall, 70.7% reported routine use of advanced imaging for late EVT selection, and 63.6% reported its usage in every case. There was greater availability of advanced imaging in comprehensive stroke centers versus primary stroke centers (67.0% versus 33.7%; P<0.0001), and high‐ versus low‐middle income countries (70.5% versus 44.5%; P<0.0001). When presented with a late window patient, 41.6% would complete CT perfusion or magnetic resonance imaging prior to EVT, 25.4% would perform CT perfusion or magnetic resonance imaging prior to IVT and EVT, and 25.8% would refer to EVT without advanced imaging. If advanced imaging was not readily available, 70.1% would refer a patient to EVT based on CT in the late window. Additional time delay within 20 minutes to obtain advanced imaging was considered acceptable in 77.7% of respondents.<p> <p>Conclusion - Current guidelines for imaging late window EVT candidates are inconsistent with imaging decisions by physicians. Most respondents consider an imaging delay of greater than 20 minutes unacceptable. Access to advanced imaging was greater in comprehensive stroke centers and high‐income countries. In the case of limited access most respondents would consider EVT based on CT only.

• Klein, Piers; Herning, Ana; Drumm, Brian; Raymond, Jean; Abdalkader, Mohamad & Siegler, James E. [Show all 56 contributors for this article] (2022). Basilar Artery Occlusion Thrombectomy Technique: An International Survey of Practice Patterns. Stroke: Vascular and Interventional Neurology. p. 1–10. doi: 10.1161/SVIN.122.000642. Full text in Research Archive Show summary

  Background: Two recent trials demonstrated a benefit for endovascular therapy (EVT) in the treatment of basilar artery occlusion (BAO). In light of the expected increase in the use of EVT for BAO, we sought to understand the technique preferences of neurointerventionalists performing EVT for BAO.<p> <p>Methods: We conducted an international online survey of physician opinions on the use of EVT in BAO between January and March 2022. The survey was distributed through stroke and neurointerventional organizations. Survey questions examined selection of patients for the procedure and the techniques currently used for EVT in BAO. Responses from neurointerventionalists were analyzed. <p>Results: More than 3000 participants were invited yielding 1245 respondents, of whom 543 were classified as neurointerventionalists across 52 countries and included in this analysis. Most neurointerventionalists would proceed to EVT for occlusions of the V4 segment, the basilar artery, or the posterior cerebral artery, without regard for prior intravenous thrombolysis. For BAO of embolic etiology, aspiration only thrombectomy was the preferred method of 50.3% of neurointerventionalists. For BAO of intracranial atherosclerotic disease etiology, combined stent retriever and aspiration thrombectomy was the preferred method of 40.5% of neurointerventionalists. The majority of neurointerventionalists (88.0%) would proceed to stenting after 3 or fewer failed passes for patients with BAO of intracranial atherosclerotic disease etiology. In patients undergoing stenting, aspirin and clopidogrel was the most common antiplatelet regime (52.4%). <p>Conclusions:Among the surveyed neurointerventionalists, the most common techniques for EVT of patients with BAO were contact aspiration or combined stent retriever with aspiration thrombectomy. For patients with BAO due to intracranial atherosclerotic disease, the majority of neurointerventionalists were willing to stent and do so most often after 3 or fewer failed passes and with the use of dual antiplatelet medications. Further study is needed to determine the optimal technique for EVT of BAO with or without intracranial atherosclerotic disease.

• Carlsen, Louise Ninett; Stefansen, Simon; Ahnfeldt-Mollerup, Peder; Jensen, Rigmor H; Kristoffersen, Espen Saxhaug & Hansen, Jakob Møller [Show all 7 contributors for this article] (2022). Diagnostics and management of headache in general practice. Family Practice. ISSN 0263-2136. 41(4), p. 470–476. doi: 10.1093/fampra/cmac121. Full text in Research Archive
• Drumm, Brian; Banerjee, Soma; Qureshi, Muhammad M.; Schonewille, Wouter J.; Klein, Piers & Huo, Xiaochuan [Show all 48 contributors for this article] (2022). Current Opinions on Optimal Management of Basilar Artery Occlusion: After the BEST of BASICS Survey. Stroke: Vascular and Interventional Neurology. 2(5), p. 1–14. doi: 10.1161/SVIN.122.000538. Full text in Research Archive Show summary

  Background The best management of basilar artery occlusion (BAO) remains uncertain. The BASICS (Basilar Artery International Cooperation Study) and the BEST (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment) trials reported neutral results. We sought to understand physicians’ approaches to BAOs and whether further BAO randomized controlled trials were warranted. Methods We conducted an online international survey from January to March 2022 to stroke neurologists and neurointerventionalists. Survey questions were designed to examine clinical and imaging parameters under which clinicians would offer (or rescind) a patient with BAO to endovascular therapy (EVT) or best medical management versus enrollment into a randomized clinical trial. Results Of >3002 invited participants, 1245 responded (41.4% response rate) from 73 countries, including 54.7% stroke neurologists and 43.6% neurointerventionalists. More than 95% of respondents would offer EVT to patients with BAO, albeit in various clinical circumstances. There were 70.0% of respondents who indicated that the BASICS and BEST trials did not change their practice. Only 22.1% of respondents would perform EVT according to anterior circulation occlusion criteria. The selection of patients for BAO EVT by clinical severity, timing, and imaging modality differed according to geography, specialty, and country income level. Over 80% of respondents agreed that further randomized clinical trials for BAO were warranted. Moreover, 45.6% of respondents indicated they would find it acceptable to enroll all trial‐eligible patients into the medical arm of a BAO trial, whereas 26.3% would not enroll. Conclusion Most stroke physicians continue to believe in the efficacy of EVT in selected patients with BAO in spite of BEST and BASICS. There is no consensus on which selection criteria to use, and few clinicians would use anterior circulation occlusion criteria for BAOs. Further randomized clinical trials for BAO are warranted.

• Kristoffersen, Espen Saxhaug; Bjorvatn, Bjørn; Halvorsen, Peder Andreas; Nilsen, Stein; Fossum, Guro Haugen & Fors, Egil Andreas [Show all 12 contributors for this article] (2022). The Norwegian PraksisNett: a nationwide practice-based research network with a novel IT infrastructure. Scandinavian Journal of Primary Health Care. ISSN 0281-3432. 40(2), p. 217–226. doi: 10.1080/02813432.2022.2073966. Full text in Research Archive Show summary

  Clinical research in primary care is relatively scarce. Practice-based research networks (PBRNs) are research infrastructures to overcome hurdles associated with conducting studies in primary care. In Norway, almost all 5.4 million inhabitants have access to a general practitioner (GP) through a patient-list system. This gives opportunity for a PBRN with reliable information about the general population. The aim of the current paper is to describe the establishment, organization and function of PraksisNett (the Norwegian Primary Care Research Network). Materials and Methods We describe the development, funding and logistics of PraksisNett as a nationwide PBRN. Results PraksisNett received funding from the Research Council of Norway for an establishment period of five years (2018–2022). It is comprised of two parts; a human infrastructure (employees, including academic GPs) organized as four regional nodes and a coordinating node and an IT infrastructure comprised by the Snow system in conjunction with the Medrave M4 system. The core of the infrastructure is the 92 general practices that are contractually linked to PraksisNett. These include 492 GPs, serving almost 520,000 patients. Practices were recruited during 2019–2020 and comprise a representative mix of rural and urban settings spread throughout all regions of Norway. Conclusion Norway has established a nationwide PBRN to reduce hurdles for conducting clinical studies in primary care. Improved infrastructure for clinical studies in primary care is expected to increase the attractiveness for studies on the management of disorders and diseases in primary care and facilitate international research collaboration. This will benefit both patients, GPs and society in terms of improved quality of care.

• Nguyen, Thanh N; Qureshi, Muhammad M; Klein, Piers; Yamagami, Hiroshi; Mikulik, Robert & Etminan, Nima [Show all 275 contributors for this article] (2022). Global impact of the COVID-19 pandemic on subarachnoid haemorrhage hospitalisations, aneurysm treatment and in-hospital mortality: 1-year follow-up. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. 93(10), p. 1028–1038. doi: 10.1136/jnnp-2022-329200. Full text in Research Archive
• 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.

• Scutelnic, Adrian; Krzywicka, Katarzyna; Mbroh, Joshua; Munckhof, Anita van de; Kammen, Mayte Sánchez van & Sousa, Diana Aguiar de [Show all 105 contributors for this article] (2022). Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination. Annals of Neurology. ISSN 0364-5134. 92(4), p. 562–573. doi: 10.1002/ana.26431. Full text in Research Archive
• Nguyen, Thanh N.; Qureshi, Muhammad M.; Klein, Piers; Yamagami, Hiroshi; Abdalkader, Mohamad & Mikulik, Robert [Show all 269 contributors for this article] (2022). Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality. Journal of Stroke (JOS). ISSN 2287-6391. 24(2), p. 256–265. doi: 10.5853/jos.2022.00752. Full text in Research Archive Show summary

  Background and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

• Clausen, Tobias Christian; Greve, Nikolaos Kalogeropoulos; Müller, Kai Ivar; Kristoffersen, Espen Saxhaug & Schytz, Henrik Winther (2022). Telemedicine in headache care: A systematic review. Cephalalgia. ISSN 0333-1024. 42(13), p. 1397–1408. doi: 10.1177/03331024221111554. Full text in Research Archive
• Drumm, Brian; Herning, Ana; Klein, Piers; Raymond, Jean; Abdalkader, Mohamad & Huo, Xiaochuan [Show all 65 contributors for this article] (2022). Basilar artery occlusion management: An international survey of middle versus high-income countries. Interventional Neuroradiology. ISSN 1591-0199. p. 1–10. doi: 10.1177/15910199221143190. Full text in Research Archive
• Yang, Min; Cheng, Hang; Wang, Xia; Ouyang, Menglu; Shajahan, Sultana & Carcel, Cheryl [Show all 12 contributors for this article] (2022). Antithrombotics prescription and adherence among stroke survivors: A systematic review and meta-analysis. Brain and Behavior. 12(10), p. 1–15. doi: 10.1002/brb3.2752. Full text in Research Archive Show summary

  Objectives We aimed to investigate the prescription of antithrombotic drugs (including anticoagulants and antiplatelets) and medication adherence after stroke. Methods We performed a systematic literature search across MEDLINE and Embase, from January 1, 2015, to February 17, 2022, to identify studies reporting antithrombotic medications (anticoagulants and antiplatelets) post stroke. Two people independently identified reports to include, extracted data, and assessed the quality of included studies according to the Newcastle–Ottawa scale. Where possible, data were pooled using random-effects meta-analysis. Results We included 453,625 stroke patients from 46 studies. The pooled proportion of prescribed antiplatelets and anticoagulants among patients with atrial fibrillation (AF) was 62% (95% CI: 57%–68%), and 68% (95% CI: 58%–79%), respectively. The pooled proportion of patients who were treated according to the recommendation of guidelines of antithrombotic medications from four studies was 67% (95% CI: 41%–93%). It was reported that 11% (95% CI: 2%–19%) of patients did not receive antithrombotic medications. Good adherence to antiplatelet, anticoagulant, and antithrombotic medications was 78% (95% CI: 67%–89%), 71% (95% CI: 57%–84%), and 73% (95% CI: 59%–86%), respectively. Conclusion In conclusion, we found that less than 70% of patients were prescribed and treated according to the recommended guidelines of antithrombotic medications, and good adherence to antithrombotic medications is only 73%. Prescription rate and good adherence to antithrombotic medications still need to be improved among stroke survivors.

• Marto, João Pedro; Strambo, Davide; Ntaios, George; Nguyen, Thanh; Herzig, Roman & Czlonkowska, Anna [Show all 46 contributors for this article] (2022). Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry. Neurology. ISSN 0028-3878. 100(7), p. e739–e750. doi: 10.1212/WNL.0000000000201537. Full text in Research Archive Show summary

  Background and objectives: COVID-19 related inflammation, endothelial dysfunction and coagulopathy may increase the bleeding risk and lower efficacy of revascularization treatments in patients with acute ischemic stroke. We aimed to evaluate the safety and outcomes of revascularization treatments in patients with acute ischemic stroke and COVID-19. Methods: Retrospective multicenter cohort study of consecutive patients with acute ischemic stroke receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021, tested for SARS-CoV-2 infection. With a doubly-robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT). Results: Of a total of 15128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19. 5848 (38.7%) patients received IVT-only, and 9280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted odds ratio [OR] 1.53; 95% CI 1.16–2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20–2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23–1.99), 24-hour (OR 2.47; 95% CI 1.58–3.86) and 3-month mortality (OR 1.88; 95% CI 1.52–2.33). COVID-19 patients also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26–1.60). Discussion: Patients with acute ischemic stroke and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 treated patients. Current available data does not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in COVID-19 patients, or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring and establishing prognosis.

• 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 Show summary

  Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.

• Nguyen, Thanh; Qureshi, Muhammad M.; Klein, Piers; Yamagami, Hiroshi; Mikulik, Robert & Czlonkowska, Anna [Show all 50 contributors for this article] (2022). Global Effect of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events A 1-Year Follow-up. Neurology. ISSN 0028-3878. 100(4), p. e408–e421. doi: 10.1212/WNL.0000000000201426. Full text in Research Archive Show summary

  Background and Objectives Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). Methods We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1–6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1–4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4–5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6–0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31–1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82–2.97], 5,656/195,539) of all stroke hospitalizations. Discussion There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.

• Huo, Xiaochuan; Klein, Piers; Raynald, NN.; Drumm, Brian; Chen, Yimin & Qureshi, Muhammad M. [Show all 45 contributors for this article] (2022). Perceptions on basilar artery occlusion management in China versus other countries: Analysis of the after the BEST of BASICS (ABBA) survey. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 31(11). doi: 10.1016/j.jstrokecerebrovasdis.2022.106804. Full text in Research Archive
• Bergh, Elin; Jahr, Silje Holt; Rønning, Ole Morten; Askim, Torunn; Thommessen, Bente & Kristoffersen, Espen Saxhaug (2022). Reasons and predictors of non-thrombolysis in patients with acute ischemic stroke admitted within 4.5 h. Acta Neurologica Scandinavica. ISSN 0001-6314. 146(1), p. 61–69. doi: 10.1111/ane.13622. Full text in Research Archive Show summary

  Abstract Objectives Thrombolytic treatment in acute ischemic stroke (AIS) reduces stroke-related disability. Nearly 40% of all patients with AIS (<4.5 h) receive thrombolysis, but there is a large variation in the use between hospitals. Little is known about reasons and predictors for not giving thrombolytic treatment. Therefore, we aimed to investigate reasons for non-thrombolysis in patients admitted within 4.5 h. Methods All patients with AIS (<4.5 h) admitted to Akershus University Hospital, Norway, between January 2015 and December 2017 were examined. Patient characteristics and reasons for not giving thrombolysis were registered. Descriptive statistics and logistic regression analyses were performed. Results Of 535 patients admitted with AIS (<4.5 h), 250 (47%) did not receive thrombolysis and of these only 26% had an absolute contraindication to treatment. Among the 74% with relative contraindications, the most common reasons given were mild and improving symptoms. Previous stroke (OR 3.32, 95%CI 1.99–5.52), arriving between 3 h and 4.5 h after onset (OR 7.76, 95%CI 3.73–16.11) or having mild symptoms (OR 2.33, 95%CI 1.56–3.49) were all significant predictors of not receiving thrombolytic treatment in the multivariable logistic regression model. Conclusion A large proportion of patients with AIS do not receive thrombolysis. This study highlights up-to-date findings that arriving late in the time window, mild symptoms, and previous stroke are strong predictors of non-treatment. It is uncertain whether there is an underuse of thrombolysis in AIS. Increasing the utility of thrombolysis in the 4.5 h time window must be weighed against possible harms.

• Larsen, Kristin Tveitan; Selseth, Maiken Nordahl; Jahr, Silje Holt; Hillestad, Vigdis; Koubaa, Nojoud & Sandset, Else Charlotte [Show all 8 contributors for this article] (2022). Prehospital Blood Pressure and Clinical and Radiological Outcomes in Acute Spontaneous Intracerebral Hemorrhage. Stroke. ISSN 0039-2499. 53(12), p. 3633–3641. doi: 10.1161/STROKEAHA.121.038524. 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 Show summary

  Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.

• Do, Thien Phu; Dømgaard, Mikala; Stefansen, Simon; Kristoffersen, Espen Saxhaug; Ashina, Messoud & Hansen, Jakob Møller (2022). Barriers and gaps in headache education: a national cross-sectional survey of neurology residents in Denmark. BMC Medical Education. 22. doi: 10.1186/s12909-022-03299-6. Full text in Research Archive
• Romoli, Michele; Eusebi, Paolo; Forlivesi, Stefano; Gentile, Mauro; Giammello, Fabrizio & Piccolo, Laura [Show all 20 contributors for this article] (2021). Stroke network performance during the first COVID-19 pandemic stage: A meta-analysis based on stroke network models. International Journal of Stroke. ISSN 1747-4930. 16(7), p. 771–783. doi: 10.1177/17474930211041202. Full text in Research Archive
• Nogueira, Raul; Qureshi, Muhammad; Abdalkader, Mohamad; Martins, Sheila; Yamagami, Hiroshi & Qiu, Zhongming [Show all 50 contributors for this article] (2021). Global Impact of COVID-19 on Stroke Care and IV Thrombolysis. Neurology. ISSN 0028-3878. 96(23), p. e2824–e2838. doi: 10.1212/WNL.0000000000011885. Full text in Research Archive
• Kristoffersen, Espen Saxhaug; Jahr, Silje Holt; Faiz, Kashif Waqar; Storstein, Anette; Winsvold, Bendik K S & Sandset, Else Charlotte (2021). Acute stroke care during the first phase of COVID-19 pandemic in Norway. Acta Neurologica Scandinavica. ISSN 0001-6314. 143(4), p. 349–354. doi: 10.1111/ane.13392. Full text in Research Archive
• Stubberud, Anker; Buse, Dawn C.; Kristoffersen, Espen Saxhaug; Linde, Mattias & Tronvik, Erling Andreas (2021). Is there a causal relationship between stress and migraine? Current evidence and implications for management. The Journal of Headache and Pain. ISSN 1129-2369. 22, p. 1–11. doi: 10.1186/s10194-021-01369-6. Full text in Research Archive Show summary

  Background The purpose of this narrative review is to examine the literature investigating a causal relationship between stress and migraine and evaluate its implications for managing migraine. Methods PubMed, PsycINFO and CINAHL were searched from 1988 to August 2021, identifying 2223 records evaluating the relationship between stress and migraine. Records were systematically screened. All potentially relevant records were thematically categorized into six mechanistic groups. Within each group the most recent reports providing new insights were cited. Results First, studies have demonstrated an association of uncertain causality between high stress loads from stressful life events, daily hassles or other sources, and the incidence of new-onset migraine. Second, major stressful life events seem to precede the transformation from episodic to chronic migraine. Third, there is some evidence for changes in levels of stress as a risk factor for migraine attacks. Research also suggests there may be a reversed causality or that stress-trigger patterns are too individually heterogeneous for any generalized causality. Fourth, migraine symptom burden seems to increase in a setting of stress, partially driven by psychiatric comorbidity. Fifth, stress may induce sensitization and altered cortical excitability, partially explaining attack triggering, development of chronic migraine, and increased symptom burden including interictal symptom burden such as allodynia, photophobia or anxiety. Finally, behavioral interventions and forecasting models including stress variables seem to be useful in managing migraine. Conclusion The exact causal relationships in which stress causes incidence, chronification, migraine attacks, or increased burden of migraine remains unclear. Several individuals benefit from stress-oriented therapies, and such therapies should be offered as an adjuvant to conventional treatment and to those with a preference. Further understanding the relationship between stress, migraine and effective therapeutic options is likely to be improved by characterizing individual patterns of stress and migraine, and may in turn improve therapeutics.

• 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.

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• Devik, Kristina; Wergeland, Tore; Stubberud, Anker; Tronvik, Erling Andreas; Øie, Lise Rystad & Kristoffersen, Espen Saxhaug [Show all 8 contributors for this article] (2026). P014 BioTenCer study: Therapist-independed home-based biofeedback as preventive treatment for tension-type headache. The Journal of Headache and Pain. ISSN 1129-2369. 27(Suppl 1), p. 23–23. doi: 10.1186/s10194-026-02378-z. Full text in Research Archive Show summary

  Objective To assess the safety and efficacy of Cerebri-TTH, a therapist-independent biofeedback smartphone app, as preventive treatment in adults with frequent or chronic tension-type headache (TTH). Methods In this randomized, two-arm, wait-list controlled phase II trial, 300 adults with frequent or chronic TTH are included. After a 4-week run-in period using a daily headache diary, participants are randomized 1:1 to either a 12-week biofeedback app intervention or a wait-list control. The biofeedback is self-administered daily for 10 min using wearable sensors that monitor muscle tension, peripheral skin temperature, and heart rate variability. After the main phase, all participants are offered an optional 12-week extension. The primary efficacy endpoint is the change in mean Area-Under-the-headache-Curve (AUC) from baseline to the final 28 treatment days. Safety is evaluated via treatment-emergent adverse events (TEAEs). Results Data collection is expected to conclude in autumn 2025. We hypothesize that participants receiving Cerebri-TTH will experience a significant reduction in AUC compared to controls. Conclusion If shown to be safe and effective, Cerebri-TTH could represent a scalable, accessible, and non-pharmacological preventive treatment for TTH. Its therapist-independent, home-based format may be especially useful for populations such as pregnant or breastfeeding individuals, who are often restricted from using conventional medications.

• Faisal, Fahim; Poole, Amalie Christine; Danelakis, Antonios; Wergeland, Tore; Bjørk, Marte-Helene & Khanevski, Andrej [Show all 18 contributors for this article] (2025). Forecasting migraine with machine learning from mHealth data. Full text in Research Archive Show summary

  Question/Objective: To develop and evaluate machine learning (ML) models to forecast headache days using mobile health (mHealth) data from a migraine biofeedback treatment app. Method: This was a ML study of data from the BioCer clinical trial (NCT05616741) evaluating app-based biofeedback for preventive treatment of episodic migraine. Participants completed three months of daily biofeedback sessions with wearables measuring trapezius muscle tension, heart rate variability and peripheral skin temperature. Input data for the models included these parameters as summary metrics from the biofeedback sessions and daily headache entries. The outcomes of interest were the presence of a moderate to-intense headache (defined as an VAS intensity of 4 or higher on a scale of 0-10) within a 24-hour and 72 hour window the following day. The dataset was randomly split into train and test sets. A long range of ML architectures, foundation models (Tab-PFN), and time-series models (GRU-D) were trained and optimized using the area under the receiver operating characteristics curve (AUC). The best model identified during training was applied on the unseen test set. Result: 146 individuals, with a total of 26209 headache days were included in the forecasting models. For 24-hour window predictions, the top performing decision tree classifier achieved a test set AUC of 0.59. The Tab-PFN model and GRU-D model scored 0.58 and 0.51. For the 72-hour forecasting window, the test set performances were 0.55, 0.54, and 0.51, respectively (Fig. 1, Table 1). The most important features were self reported headache entries, duration of headache and previous neuromuscular conditions (Fig. 2). Conclusion: Despite the large scale of the available dataset, precisely and prospectively captured data, and extensive model testing, we were not able to forecast headache days with more than modest accuracy. Probably individual level autonomous nervous system parameters are too heterogeneous to be used to forecast migraine attacks on a group level.

• Poole, Amalie Christine; Stubberud, Anker; Simpson, Melanie Rae; Øie, Lise Rystad; Skalstad, Einar Tobias Vassbø & Bjørk, Marte-Helene [Show all 13 contributors for this article] (2025). Biofeedback therapy using Cerebri for the prevention of migraine attacks in adults with episodic migraine (BioCer): a randomized, wait-list controlled trial – the study protocol. doi: 10.12688/f1000research.149807.2. Full text in Research Archive Show summary

  Introduction Biofeedback is a non-pharmacological treatment option valued for its minimal risk of adverse events and offers a safe alternative for individuals seeking preventive care for migraine. Despite level A evidence for migraine prevention, biofeedback treatment is still unavailable to most patients. We developed a novel medical device (Cerebri) for multimodal biofeedback treatment that omits the need for healthcare personnel involvement. Cerebri consists of a smartphone application (app) and two wireless sensors. Unique in its approach, the Cerebri app seamlessly integrates three biofeedback modalities – heart rate variability, temperature, and electromyography – making it a comprehensive, therapist-independent solution for non-pharmacological migraine management. Methods Biofeedback therapy using Cerebri for the prevention of migraine attacks in adults with episodic migraine (The BioCer study) is an open-label, randomized, waitlist-controlled, multicenter trial. This study investigates the safety and efficacy of daily home-based biofeedback sessions using the Cerebri device. A total of 286 participants will be randomized to either a 12-week intervention arm or waitlist control arm. The primary outcome is the change in the mean number of migraine days from baseline to the last 28-day period during the treatment phase in the treatment group compared with the control group. The primary outcome variable is prospectively collected through daily eDiary entries. A limitation is the inability to conduct a sham-controlled trial of biofeedback. Ethics and Dissemination Approval from the ethics committee and competent authorities was obtained prior to study initiation. Participation is voluntary and informed and written consent is obtained prior to inclusion. The results of this trial will be published in peer-reviewed international medical journals and communicated to patients and healthcare personnel through the relevant channels. Trial registration numbers EUDAMED: CIV-NO-22-08-040446 REK (Regional Committees for Medical and Health Research Ethics): 502734 Date of approval 2022-10-14 Trial registration: NCT05616741, 2022-11-15, https://clinicaltrials.gov/study/NCT05616741

• Mitsikostas, Dimos-Dimtirios D.; Caronna, Edoardo; De Tommaso, Marina; Deligianni, Christina I.; Ekizoglu, Esme & Bolay, Hayrunnisa [Show all 14 contributors for this article] (2024). Reply to the letter: Headaches during/after SARS-CoV-2 infection/vaccination can be primary and secondary as well as acute and chronic, by Finsterer J and Mehri S. European Journal of Neurology. ISSN 1351-5101. doi: 10.1111/ene.16308. Full text in Research Archive
• Santervas, Leonor Roa; Wyller, Torgeir Bruun; Skovlund, Eva; Kristoffersen, Espen Saxhaug; Ringstad, Ingrid Beate & Jensen, Janicke Cecilie Liaaen [Show all 9 contributors for this article] (2024). Frailty and Health-Related Quality of Life in Older Adults Admitted to Oslo Municipal In-Patient Acute Care Unit. Full text in Research Archive
• Munckhof, Anita van de; Kammen, Mayte Sánchez van; Krzywicka, Katarzyna; Aaron, Sanjith; Sousa, Diana Aguiar de & Antochi, Florina [Show all 31 contributors for this article] (2024). Corrigendum: Direct oral anticoagulants for the treatment of cerebral venous thrombosis – a protocol of an international phase IV study. Frontiers in Neurology. 15. doi: 10.3389/fneur.2024.1481563. Full text in Research Archive
• Lunder, Oda Vardenær; Vetvik, Kjersti Grøtta; Kristoffersen, Espen Saxhaug; Wisløff, Torbjørn & Aaseth, Kjersti (2024). MultiHEAD – work-focused multidisciplinary headache treatment. Full text in Research Archive
• Santervas, Leonor Roa; Wyller, Torgeir Bruun; Skovlund, Eva; Jensen, Janicke Liaaen; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 11 contributors for this article] (2024). Cooperation across healthcare service levels for medication reviews in older people with polypharmacy admitted to a municipal in-patient acute care unit (The COOP II Study): study protocol for a randomized controlled trial. Trials. 25(1). doi: 10.1186/s13063-024-08442-w. Full text in Research Archive Show summary

  Background: Polypharmacy and inappropriate drug use are associated with adverse health outcomes in older people. Collaborative interventions between geriatricians and general practitioners have demonstrated effectiveness in improving clinical outcomes for complex medication regimens in home-dwelling patients. Since 2012, Norwegian municipalities have established municipal in-patient acute care (MipAC) units, designed to contribute towards reducing the number of hospital admissions. These units predominantly serve older people who typically benefit from multidisciplinary approaches. The primary objective of this study is to evaluate the effect of cooperative medication reviews conducted by MipAC physicians, supervised by geriatricians, and in collaboration with general practitioners, on health-related quality of life and clinical outcomes in MipAC patients ≥ 70 years with polypharmacy. Additionally, the study aims to assess the carbon footprint of the intervention. Methods: This is a randomized, single-blind, controlled superiority trial with 16 weeks follow-up. Participants will be randomly assigned to either the control group, receiving usual care at the MipAC unit, or to the intervention group which in addition receive clinical medication reviews that go beyond what is considered usual care. The medication reviews will evaluate medication appropriateness using a structured but individualized framework, and the physicians will receive supervision from geriatricians. Following the clinical medication reviews, the MipAC physicians will arrange telephone meetings with the participants’ general practitioners to combine their assessments in a joint medication review. The primary outcome is health-related quality of life as measured by the 15D instrument. Secondary outcomes include physical and cognitive functioning, oral health, falls, admissions to healthcare facilities, and mortality. Discussion: This study aims to identify potential clinical benefits of collaborative, clinical medication reviews within community-level MipAC units for older patients with polypharmacy. The results may offer valuable insights into optimizing patient care in comparable municipal healthcare settings. Trial registration: The study was registered prospectively on ClinicalTrials.gov 30.08.2023 with identifier NCT06020391.

• Bjelkarøy, Maria Torheim; Simonsen, Tone Breines; Siddiqui, Tahreem Ghazal; Halset, Sigrid; Cheng, Socheat & Grambaite, Ramune [Show all 10 contributors for this article] (2022). Brief intervention as a method for reducing use of z-hypnotics in older adult – a feasibility study. Full text in Research Archive
• Krzywicka, Katarzyna; Kammen, Mayte Sánchez Van; Sousa, Diana Aguiar de; Heldner, Mirjam R; Aron, S & Jiang, D. [Show all 32 contributors for this article] (2022). DIRECT ORAL ANTICOAGULANTS FOR THE TREATMENT OF CEREBRAL VENOUS THROMBOSIS (DOAC-CVT). Full text in Research Archive
• Dharmi, Sanpreet Grewal; Vetvik, Kjersti; Zarnovicky, Svetozar; Hansen, Jakob Møller; Faiz, Kashif Waqar & Kristoffersen, Espen Saxhaug (2022). CLINICAL PRESENTATION AND LONG-TERM OUTCOMES OF CEREBRAL VENOUS THROMBOSIS IN A NORWEGIAN POPULATION. Full text in Research Archive
• Bjelkarøy, Maria Torheim; Simonsen, Tone Breines; Siddiqui, Tahreem Ghazal; Halset, Sigrid; Cheng, Socheat & Grambaite, Ramune [Show all 10 contributors for this article] (2022). Brief intervention as a method for reducing use of z-hypnotics in older adult – a feasibility study. Full text in Research Archive
• Altmann, Marianne; Rønning, Ole Morten; Fure, Brynjar; Selnes, Per; Reichenbach, Antje & Kristoffersen, Espen Saxhaug [Show all 7 contributors for this article] (2022). SHORT- AND LONG-TERM MORTALITY AFTER LACUNAR INFARCT. Full text in Research Archive
• Larsen, Kristin Tveitan; Selseth, Maiken Nordahl; Jahr, Silje Holt; Hillestad, Vigdis; Koubaa, Nojoud & Sandset, Else Charlotte [Show all 8 contributors for this article] (2022). IMPACT OF ANTITHROMBOTIC TREATMENT ON ASSOCIATIONS BETWEEN PREHOSPITAL SYSTOLIC BLOOD PRESSURE AND OUTCOMES IN ACUTE, SPONTANEOUS INTRACEREBRAL HAEMORRHAGE. Full text in Research Archive
• Koubaa, Nojoud; Larsen, Kristin Tveitan; Hillestad, Vigdis; Selseth, Maiken Nordahl; Jahr, Silje Holt & Faiz, Kashif Waqar [Show all 13 contributors for this article] (2022). EPIDEMIOLOGY AND CLINICAL PRESENTATION OF SPONTANEOUS CEREBELLAR HEMORRHAGE IN A NORWEGIAN POPULATION. Full text in Research Archive
• Bjerkreim, Anna Therese; Jahr, Silje Holt; Faiz, Kashif Waqar; Larsen, Kristin Tveitan; Hillestad, Vigdis & Selseth, Maiken Nordahl [Show all 14 contributors for this article] (2022). TIME ON SCENE BEFORE ADMISSION OF ACUTE STROKE AND STROKE MIMICS: THE AKERSHUS STUDY OF ISCHEMIC STROKE AND THROMBOLYSIS-1. Full text in Research Archive
• Jahr, Silje Holt; Sandset, Else Charlotte; Faiz, Kashif Waqar; Larsen, Kristin Tveitan; Hillestad, Vigdis & Selseth, Maiken Nordahl [Show all 11 contributors for this article] (2022). PRE-HOSPITAL SYSTOLIC BLOOD PRESSURE AND DIAGNOSIS IN SUSPECTED STROKE: THE AKERSHUS STUDY OF ISCHEMIC STROKE AND THROMBOLYSIS-1. Full text in Research Archive
• 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. Full text in Research Archive 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

• Aaseth, Kjersti; Dharmi, Sanpreet Grewal; Kravdal, Gunnhild; Zarnovicky, Svetozar; Faiz, Kashif Waqar & Vetvik, Kjersti [Show all 7 contributors for this article] (2022). Diagnostic work-up of acute headache and subarachnoid haemorrhage in a Norwegian population. European Journal of Neurology. ISSN 1351-5101. doi: 10.1111/ene.15465. Full text in Research Archive
• Do, Thien Phu; Dømgaard, Mikala; Stefansen, Simon; Kristoffersen, Espen Saxhaug; Ashina, Messoud & Hansen, Jakob Møller (2022). Barriers and gaps in headache education: a national cross-sectional survey of neurology residents in Denmark. Full text in Research Archive
• Santervas, Leonor Roa; Romskaug, Rita; Wyller, Torgeir Bruun; Kristoffersen, Espen Saxhaug & Skovlund, Eva (2026). Older Adults Admitted to Municipal Acute Care in Norway: Frailty, Illness Severity, Health-Related Quality of Life, and the Effect of Collaborative Medication Reviews. Results from the COOP II study. Universitetet i Oslo. ISSN 9788234808623. Full text in Research Archive Show summary

  Municipal in-patient acute care (MipAC) units were introduced in Norway to help meet the challenges of an ageing population by reducing pressure on hospitals. These units admit mainly older adults who need institutional care but not specialist hospital treatment. Although MipAC units have been in place for more than a decade, little has been known about who these patients are, how frail or acutely ill they are, how they perceive their quality of life, and whether interventions such as structured medication reviews can improve their outcomes. The COOP II study (Cooperation for better treatment of polypharmacy in the community) aimed to gain clinically relevant knowledge about older adults admitted to the Oslo MipAC unit. This thesis presents results from an observational study and a randomized controlled trial (RCT). The observational study examined how frailty and acute illness severity relate to 1-year mortality, and how frailty is associated with both general and oral health-related quality of life (HRQoL). Frailty was measured with the Clinical Frailty Scale (CFS), illness severity with the National Early Warning Score (NEWS2), and HRQoL with the 15D instrument, a single life satisfaction question, and the Oral Health Impact Profile-14 (OHIP-14). The RCT included patients who were using six or more medications and compared a structured, collaborative medication review during MipAC admission with usual care, evaluating its effects on HRQoL and other clinically relevant outcomes 16 weeks after discharge. The findings show that both higher frailty and higher illness severity were independently associated with increased 1-year mortality among MipAC patients. Among individual NEWS2 components, elevated respiratory rate and hypotension were independently associated with mortality. Increasing frailty was consistently associated with poorer general and oral HRQoL across most dimensions. Collaborative medication reviews conducted during MipAC admission did not improve HRQoL, physical or cognitive function, oral health, health service use, or mortality at 16 weeks. Although more medication changes occurred in the intervention group during admission, pharmacotherapy generally converged between groups during follow-up. Overall, the thesis highlights frailty as a central characteristic of MipAC patients, supports routine frailty assessment to improve prognostic insight and individualized care, and suggests that medication reviews conducted during acute admissions may be insufficient as a stand-alone strategy to improve quality of life in this vulnerable group.

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