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Abstract 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.

BackgroundZ-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. ObjectiveOur 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. MethodsThis 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. ResultsData 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. ConclusionsWe 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 RegistrationClinicalTrials.gov NCT03162081; http://tinyurl.com/rmzx6brn

Introduction Two recent trials demonstrated a benefit for endovascular thrombectomy (EVT) in the treatment of basilar artery occlusion (BAO). Considering the expected increase in the utilization of EVT for BAO, we sought to understand the technique preferences of neurointerventionalists currently performing EVT for BAO. Methods We conducted an international online survey of physician opinions on the use of EVT in BAO between January to 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. Results More than 3,000 participants were invited yielding 1,245 respondents, of which 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 PCA, without regard for prior IVT. For BAO of embolic etiology, aspiration only thrombectomy was the preferred method with 50.3% of neurointerventionalists. For BAO of intracranial atherosclerotic disease (ICAD) etiology, combined stent retriever and aspiration thrombectomy was the preferred method with 40.5% of neurointerventionalists (Figure 1). The majority of neurointerventionalists (88.0%) would proceed to stenting after three or fewer failed passes for patients with BAO of ICAD etiology. In patients undergoing stenting, aspirin and clopidogrel was the most common antiplatelet regime (52.4%). Conclusions Amongst 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 ICAD, the majority of neurointerventionalists were willing to stent and do so most often after three 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 ICAD.

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.

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. 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. 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%). 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. Key Words

AbstractPurpose 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.Key pointsPractice-based research networks (PBRNs) are research infrastructures to overcome hurdles associated with conducting studies in primary careImproved 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 collaborationWe describe PraksisNett, a Norwegian PBRN consisting of 92 general practices including 492 GPs, serving almost 520,000 patientsAn advanced and secure IT infrastructure connects the general practices to PraksisNett and makes it possible to identify and recruit patients in a novel way, as well as reuse clinical dataPraksisNett will benefit both patients, GPs and society in terms of improved quality of careThis paper may inform and inspire initiatives to establish PBRNs elsewhere

Abstract Background A major barrier to adequate headache care is the relative lack of formal education and training of healthcare professionals. Concerted efforts should be made to pinpoint major gaps in knowledge in healthcare professionals to facilitate better educational policies in headache training. The aim of this study was to identify deficiencies and barriers in headache training among residents in neurology in Denmark. Methods We conducted a national cross-sectional survey of residents in neurology in Denmark from April 2019 to September 2019. The survey included questions on participant demographics, knowledge of and barriers in headache disorders, guidelines and diagnostic tools usage, contact with primary and tertiary care, medication overuse, and non-pharmacological interventions. Furthermore, respondents were asked to provide a ranked list from most to least interesting for six sub-specializations/disorders, i.e., cerebrovascular disease, dementia, epilepsy, headache, multiple sclerosis, Parkinson's disease. Results Sixty (40%) out of estimated a population of ~ 150 resident across Denmark accepted the invitation. Of these, 54/60 (90%) completed the survey. Although two-thirds, 35/54 (65%), of the respondents had prior formalized training in headache disorders, we identified gaps in all explored domains including diagnosis, management, and referral patterns. Particularly, there was an inconsistent use of guidelines and diagnostic criteria from the Danish Headache Society (2.74 (± 1.14)), the Danish Neurological Society (3.15 (± 0.86)), and the International Classification of Headache Disorders (2.33 (± 1.08)); 1: never/have not heard of, 4: always. Headache was ranked second to last out of six sub-specializations in interest. Conclusions Overall knowledge on headache disorders amongst neurology residents in Denmark do not meet the expectations set out by national and international recommendations. Stakeholders should make strategic initiatives for structured education in headache for improved clinical outcomes in parallel with costs reduction through resource optimization.

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. 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. 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

Abstract 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.

Abstract Background General practitioners (GPs) diagnose and manage a majority of headache patients seeking health care. With the aim to understand the potential for clinical improvement and educational needs, we performed a study to investigate Norwegian GPs knowledge about headache and its clinical management. Methods We invited GPs from a random sample of 130 Norwegian continuous medical education (CME) groups to respond to an anonymous questionnaire survey. Results 367 GPs responded to the survey (73% of invited CME groups, 7.6% of all GPs in Norway). Mean age was 46 (SD 11) years, with an average of 18 (SD 10) years of clinical experience. In general the national treatment recommendations were followed, while the International Classification of Headache Disorders and other international guidelines were rarely used. Overall, 80% (n = 292) of the GPs suggested adequate prophylactic medication for frequent episodic migraine, while 28% (n = 101) suggested adequate prophylactic medication for chronic tension-type headache (CTTH). Half (52%, n = 191)) of the respondents were aware that different types of acute headache medication can lead to medication-overuse headache (MOH), and 59% (n = 217) knew that prophylactic headache medication does not lead to MOH. GPs often used MRI in the diagnostic work-up. GPs reported that lack of good treatment options was a main barrier to more optimized treatment of headache patients. Conclusion The knowledge of management of CTTH and MOH was moderate compared to migraine among Norwegian GPs.

Abstract 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.

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.

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. Trial registration NCT03162081, 22 May 2017.

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) was an open-label, randomized, waitlist-controlled, multicenter trial. This study investigated 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 was 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 was prospectively collected through daily eDiary entries. Ethics and Dissemination Approval from the ethics committee and competent authorities was obtained prior to study initiation. Participation was voluntary and informed and written consent was 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