Torgeir Bruun Wyller

• Moorey, Hannah; Botfield, Hannah F; Krogseth, Maria; Selbæk, Geir; Wilson, Daisy & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2026). CCL2 and CXCL2 are markers of delirium vulnerability in community dwelling older people. Age and Ageing. ISSN 0002-0729. 55(9). doi: 10.1093/ageing/afag290. Full text in Research Archive Show summary

  Abstract Background Delirium is common and age, frailty and dementia are risk-factors. The pathophysiology is complex and poorly understood, but age-related immune system changes may be key. This study aimed to measure markers of immune cell migration, accelerated immune ageing and blood–brain barrier permeability in community-dwelling, older people comparing those who developed ≥1 episode of delirium over 2 years with those that did not. Methods Baseline samples were collected from CASCADE participants who were followed up for 2 years. Delirium screening was performed weekly; positive screens or hospital admission triggered a delirium assessment. Serum was isolated, stored and analysed using a multiplex panel comparing levels between participants with and without delirium episodes. Results About 98 participants were included. Median age was 88 (IQR: 81.8–92.0), with 90.8% classified as frail. Forty-three participants (43.9%) experienced ≥1 delirium episodes. CCL2 (MCP-1) and CXCL2 (MIP-2α), measured in a stable state at baseline, were significantly higher in the delirium group compared to the no delirium group (13.38 (11.21–17.93) vs. 10.83 (9.03–14.64) P = .004) and (17.23 (11.80–24.22) vs. 13.49 (10.19–17.98) P = .031), respectively. When stratified by dementia status, the associations of CCL2 with delirium were maintained in both groups, but CXCL2 was only significantly higher in delirium in the subgroup without dementia. Discussion CCL2 and CXCL2 are chemokines involved in immune cell recruitment and markers of accelerated immune ageing. Future work should elucidate the role of immune cell recruitment and brain infiltration in delirium, to identify treatment targets. Furthermore, work should explore whether targeting immune ageing can reduce delirium risk.

• Vahedi, Ali; Eriksdotter, Maria; Ihle-Hansen, Hege Beate; Wyller, Torgeir Bruun; Øksengård, Anne Rita & Fure, Brynjar (2026). Impact of Acute Functional Decline on Frailty and Mortality in Acutely Hospitalized Older Persons. Aging Medicine. ISSN 2475-0360. p. 1–10. doi: 10.1002/agm2.70104. Full text in Research Archive
• Eilertsen, Helle; Larsen, Kristin Tveitan; Forfang, Elisabeth; Pennlert, Johanna; Glader, Eva Lotta & Kruuse, Christina [Show all 19 contributors for this article] (2026). Study of Antithrombotic Treatment After Intracerebral Haemorrhage-Antiplatelets: A Randomized Trial. Stroke. ISSN 0039-2499. 57(8), p. 2287–2294. doi: 10.1161/STROKEAHA.125.054990. Full text in Research Archive Show summary

  BACKGROUND: Patients surviving spontaneous intracerebral hemorrhage (ICH) who have indications for antithrombotic treatment face increased risks of both hemorrhagic and ischemic events. The aim of STATICH (Study of Antithrombotic Treatment After Intracerebral Haemorrhage) was to assess the safety and efficacy of long-term antithrombotic treatment after ICH. METHODS: STATICH Antiplatelets (EudraCT 2014-002636-13; Unique identifier: NCT03186729) was a randomized, multicenter, open, blinded end point parallel-group trial, including adults with an indication for antiplatelet treatment to either start or avoid antiplatelet treatment. The target sample size was 500 participants. Patients were allocated 1:1 by a Web-based randomization system and followed for a minimum of 2 years. Outcome assessments were done by personnel blinded to treatment. Participants were not blinded. The primary safety outcome was recurrent symptomatic ICH. RESULTS: The trial was stopped early due to slow recruitment. Sixty-nine patients were included between August 2018 and December 2022: 34 were randomized to start antiplatelet treatment, and 35 were randomized to avoid antiplatelet treatment. No patients were excluded from analyses. The median age was 75 (Q1–Q3, 66–80) years, and 43 (75%) had previous ischemic stroke or transient ischemic attack. Five patients in the start antiplatelet treatment group (15% [95% CI, 6%–31%]), and 1 in the avoid group (3% [95% CI, 0%–18%]) experienced recurrent ICH, while 3 (9% [95% CI, 3%–24%]) and 7 (20% [95% CI, 10%–37%]), respectively, experienced a major ischemic event. A total of 88 serious adverse events and no suspected unexpected serious adverse reactions were registered. CONCLUSIONS: There were numerically more recurrent ICHs and fewer ischemic events in patients starting antiplatelet treatment after ICH compared with those avoiding antiplatelet treatment. The slow recruitment might be due to clinicians being certain of the best treatment strategy or patients being too frail to participate. STATICH will contribute to a planned collaborative individual patient-data meta-analysis to resolve this dilemma.

• Berntsen, Thea; Blennow, Kaj; Zetterberg, Henrik; Brekke, Ingrid Fæhn; Hella, Mathias Nikolai Petersen & Lian, Tom [Show all 16 contributors for this article] (2026). Increased cerebrospinal fluid YKL-40 concentration in hip fracture patients with delirium. Brain Communications. 8(1). doi: 10.1093/braincomms/fcag005. Full text in Research Archive Show summary

  The underlying mechanisms of the neuropsychiatric syndrome delirium are still unknown, but neuroinflammation is a central hypothesis. Chitinase-3-like-protein-1 (YKL-40/CHI3L1) is considered a marker of neuroinflammation when measured in cerebrospinal fluid (CSF). The aim of this study was to examine concentrations of CSF YKL-40 in patients with and without delirium, to enhance the understanding of delirium pathophysiology. A total of 545 hip fracture patients were included from two similar cohorts. CSF samples were collected in conjunction with spinal anaesthesia for hip fracture surgery. The patients were screened for delirium both pre- and postoperatively. Those with delirium were further divided into subgroups based on whether they developed it before surgery (prevalent delirium) or after surgery (incident delirium). Among patients without delirium, those who met some, but not all diagnostic criteria, were classified as having subsyndromal delirium. Prefracture cognitive function was assessed, and American Society of Anaesthesiologists physical status score was included as a marker of comorbidity. In total, 257 (47%) of the patients developed delirium. These patients were older and had a higher prevalence of dementia and severe systemic diseases. Among the patients without dementia, those with delirium had higher median concentration of CSF YKL-40 compared with those without delirium (first cohort: 175 versus 132 ng/mL, P = 0.01, second cohort: 243 versus 174 ng/mL, P < 0.001). No association was found among the patients with dementia. The results remained consistent when adjusting for age and comorbidity. No difference in median CSF YKL-40 concentration was found between patients who had delirium at the time of surgery (prevalent delirium) and those who developed it afterwards (incident delirium). Our findings support the hypothesis of neuroinflammation as a mechanism for delirium in patients without dementia.

• Ringstad, Ingrid Beate; Skovlund, Eva; Santervas, Leonor Roa; Kersten, Hege; Fjeld, Katrine Gahre & Hove, Lene Hystad [Show all 9 contributors for this article] (2026). Association Between Anticholinergic Burden and Dry Mouth Severity in Acutely Ill Older Adults. Drugs & Aging. ISSN 1170-229X. 43(4), p. 361–371. doi: 10.1007/s40266-026-01286-w. Full text in Research Archive Show summary

  Background: Dry mouth is a common and burdensome condition in older adults and its severity may increase with use of anticholinergic medications. The aims were to describe anticholinergic medication use among acutely ill older adults, examine the association between anticholinergic burden and dry mouth severity using the composite Dry Mouth Severity Points (DMSP) measure and investigate whether the association differs by sex. Methods: Patients ≥70 years admitted to Oslo municipal inpatient acute care unit were eligible. Anticholinergic burden (ACB) was assessed using the ACB calculator and classified as 0, lower (ACB = 1-2) or high (ACB = ≥ 3). Dry mouth severity was quantified with DMSP, range 0-4, assigning one point for each indicator above cut-off: General Xerostomia Question ≥ 3, Summated Xerostomia Inventory ≥ 11, Clinical Oral Dryness Score ≥ 6 and unstimulated whole saliva secretion rate ≤ 0.1 mL/min. Associations were examined with ordinal logistic regression. Results: Of 382 examined patients, 256 (mean age 84 ± 7 years, 70% women) had complete data. Mean [standard deviation (SD)] ACB score was 2.0 (1.7); 18% had ACB = 0, 50% had ACB = 1-2 and 32% had ACB = ≥ 3. DMSP scores of 0, 1, 2 and ≥ 3 were present in 29%, 36%, 23% and 12%, respectively. Compared with patients with ACB = 0, those with ACB = 1-2 [odds ratio (OR) = 2.06, 95% confidence interval (CI) 1.07-3.97) and ACB = ≥ 3 (OR = 2.25, 95% CI 1.09-4.63) had higher odds of more severe dry mouth. Women had significantly higher ACB and DMSP scores than men. Conclusions: Even lower anticholinergic burden was associated with greater dry mouth severity, highlighting the need for early recognition and proactive management in acutely ill older adults.

• 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
• López-Toribio, María; Dalleur, Olivia; Adda, Tokandji Rostand; Saint-Hubert, Marie De; Dikeos, Dimitris & Tsoutsi, Vagioula [Show all 19 contributors for this article] (2025). Mapping care trajectories for hospital-initiated benzodiazepine deprescribing in older adults: a multicentre qualitative study. BMC Health Services Research. 25(1). doi: 10.1186/s12913-025-13725-2. Full text in Research Archive Show summary

  Background Long-term prescription of benzodiazepine receptor agonists (BZRAs) for insomnia in adults over 65 years of age is considered a low-value care practice. Although deprescribing has emerged as a possible solution, the implementation of BZRA deprescribing has been considered insufficient in routine clinical care. Mapping care trajectories relative to BZRA deprescribing can help identify inefficiencies in current care and propose strategies to enhance the implementation of deprescribing interventions in the long term. This study aims to map care trajectories and characterise contextual factors relevant to hospital-initiated BZRA deprescribing in older adults. Methods A qualitative study was conducted with local researchers, healthcare professionals (HCPs), patients, and informal carers in six European countries (Belgium, Greece, Norway, Poland, Spain, and Switzerland). Three theoretical frameworks were used to guide data collection and analyses: 1) the ‘6W’ multidimensional model of care trajectories; 2) the patient-centred deprescribing process; and 3) the Context and Capabilities for Integrating Care framework. Data was collected online through self-administered questionnaires, individual interviews, and group validation interviews. Data were transcribed verbatim and analysed using a combination of deductive and inductive thematic analyses. Results We collected 18 responses to surveys, and conducted 53 interviews (6 local researchers, 36 HCPs, 11 patients or informal carers) and 7 group interviews (comprising 28 HCPs, 4 patients). We developed nine validated care trajectory maps by hospital department and type of unit, and two general comparative maps for inpatient and outpatient care. Hospital-initiated BZRA deprescribing emerged as a complex healthcare process that is likely to involve several HCPs from hospital and primary care. Participants considered patient involvement in shared decision-making (SDM) to be crucial in deprescribing, but implementation was scarce in routine care. The type of HCPs involved and the communication channels between them were specific to each country. Fragmented care and poor communication in the care trajectory hindered follow-up and continuity of care. Conclusions Deprescribing interventions should include context-sensitive strategies to promote patient participation in SDM, foster the use of guidelines, and enhance interprofessional collaboration along the care trajectory. Care trajectory maps can be used as an implementation tool to translate BZRA deprescribing interventions into routine practice.

• Shapoval, Vladyslav; Hubert, Marie de Saint; Pétein, Catherine; Viaud, Claire; Adda, Tokandji & Aubert, Carole Elodie [Show all 21 contributors for this article] (2025). Barriers to discontinuing benzodiazepine receptor agonists in older adults: a survey of older adults across Europe. Age and Ageing. ISSN 0002-0729. 54(12). doi: 10.1093/ageing/afaf342. Full text in Research Archive Show summary

  Abstract Background Various factors hinder older adults from discontinuing benzodiazepine receptor agonists (BZRAs). Identifying and prioritising these barriers is essential for designing effective interventions to discontinue BZRAs. Objective To identify barriers to BZRA discontinuation among older adults and factors associated with their willingness to reduce or stop use. Methods A cross-sectional survey was conducted among adults 65+ using BZRA for sleep problems, recruited from hospitals across six European countries. Barriers were identified via a 27-item questionnaire grounded in the Theoretical Domains Framework (TDF), which systematically identifies individual and contextual determinants of behaviour. Responses were analysed using descriptive statistics. Multivariable logistic regressions identified factors associated with patients’ willingness to reduce or stop BZRA. Results Among 183 participants, 59.1% were willing to reduce and 42.7% to stop BZRA if recommended by their doctor. Half understood why discontinuation is necessary. Barriers were present for most participants across multiple TDF domains. They included: high satisfaction with BZRA, perceived low risk of side effects, limited coping skills or ability to stop, fear of discontinuation and lack of support from physicians or social networks. Higher scores in the TDF domains of Goals, Emotion and Social Influences were associated with greater willingness to reduce BZRA. These domains and Reinforcement, Environmental context and resources were also linked to a greater willingness to stop. Conclusions These findings highlight the opportunities and challenges of discontinuing BZRA in older adults. While half know the need to discontinue and are willing to try, future interventions must address pervasive barriers across many behavioural domains.

• Bøhn, Benedicte Huseby; Krogseth, Maria; Jøranson, Nina; Wyller, Torgeir Bruun; Selbæk, Geir & Tangen, Gro Gujord (2025). Malnutrition as an independent risk factor for incident delirium in cohort of older adults receiving domiciliary care services. GeroScience. ISSN 2509-2715. 48(5), p. 7115–7124. doi: 10.1007/s11357-025-02040-7. Full text in Research Archive Show summary

  Abstract Background Malnutrition and frailty frequently affect older adults receiving domiciliary care services, increasing their vulnerability to adverse events such as delirium. Despite this, the role of malnutrition as a risk factor for delirium in this population remains under-researched. The aim of this study was to examine the relationship between nutritional status and the development of delirium over a 2-year period among older adults who received domiciliary care services. Method In this 2-year prospective cohort study, we included 210 participants aged 65 years or older who received domiciliary care services at least once per week. Nutritional status was assessed using the Mini Nutritional Assessment at the time of inclusion, while delirium was assessed weekly, upon admission to hospital, and upon clinical indication according to DSM-5 criteria. Logistic regression analysis was used to examine the relationship between malnutrition and delirium. Results Of the sample, 116 (55.2%) were malnourished/at risk of malnutrition at the time of inclusion. Over a 2-year period, 42.4% developed delirium. The odds ratio for developing delirium was 2.00 (95% CI 1.08–3.72, P  = 0.028), for the group with malnutrition/risk of malnutrition, adjusted for covariates. Conclusion Malnutrition is an independent risk factor for delirium in older adults receiving domiciliary care services. These findings highlight the importance of regular nutritional assessments and interventions to potentially reduce the risk of delirium in this vulnerable population.

• 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.

• Dejgaard, Magnhild Skråmestø; Eide, Per Kristian; Tangen, Gro Gujord; Skovlund, Eva; Selbæk, Geir & Wyller, Torgeir Bruun (2025). Cognitive profile and frailty in patients with idiopathic normal pressure. Frontiers in Neurology. 16. doi: 10.3389/fneur.2025.1644507. Full text in Research Archive Show summary

  Background Cognition and frailty are sparsely studied in patients with idiopathic normal pressure hydrocephalus (iNPH). We aimed to describe the preoperative cognitive function compared with normative data and frailty profile in iNPH patients accepted for shunt surgery. Methods All patients were diagnosed according to international guidelines and underwent a standardized cognitive and physical examination and a geriatric assessment prior to surgery. Z -scores for the cognitive tests were calculated based on age and education adjusted population norms. Results The study cohort included 276 iNPH patients accepted for shunt surgery. Mean ± SD age was 73.1 ± 5.7 years, education 12.5 ± 3.8 years, and 61% were male. The median (IQR) score on the Mini-Mental State Evaluation was 27 (24–29), and the median (IQR) Clock Drawing test score was 4 (3–5). Mean (SD) z -score for immediate verbal recall was −1.74 (0.98), for delayed recall −1.66 (1.01), for figure copying −0.85 (1.35) for Trail Making Test A -1.50 (1.09), for Trail Making Test B −1.88 (1.03), for phonemic fluency −1.46 (1.10), and for semantic fluency −1.59 (1.20). Cluster analysis identified three groups, mainly differing regarding visuospatial function. The mean (SD) Frailty Index score was 0.23 (0.13), indicating mild frailty. The frailty domain most affected was physical function. Conclusion iNPH patients showed reduced cognitive function across all domains. The patient group is rather heterogeneous regarding cognitive symptoms, and no specific cognitive profile was identified. Cognitive assessment offers limited utility for diagnosing a typical pattern specific for iNPH but is important due to the complex needs for this patient group. Whether cognitive and frailty profile can be used to identify shunt responders, must be assessed in longitudinal studies.

• Shapoval, Vladyslav; Evrard, Perrine; Sibille, François‐Xavier; López‐Toribio, María; Dalleur, Olivia & Aubert, Carole E. [Show all 19 contributors for this article] (2025). Barriers to and Enablers of Supporting Deprescribing Benzodiazepines in Older Adults: A Survey of European Nonphysician Healthcare Professionals. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 137(4). doi: 10.1111/bcpt.70100. Full text in Research Archive Show summary

  Although physicians are primarily responsible for Benzodiazepine Receptor Agonist (BZRA) deprescribing, nonphysician healthcare professionals (HCPs) can support deprescribing. This study explored barriers to and enablers of BZRA deprescribing among nonphysician HCPs. We surveyed 258 HCPs (63.2% nurses) working in hospital settings across six European countries using a questionnaire based on the Theoretical Domain Framework (TDF). Logistic regression assessed associations between TDF domains and both intentions to support and routine engagement in BZRA deprescribing. Major barriers (TDF items with mean < 3) were found in the goals (competing priorities), environmental context and resources (time and staff lack) and social influences (patient reluctance) domains. Five TDF domains were associated with a stronger intention to support deprescribing: social/professional role and identity (OR, 3.08; 95% CI, 1.77–5.46); beliefs about consequences (OR, 1.91; 95% CI, 1.07–3.34); memory, attention and decision processing (OR, 1.80; 95% CI, 1.16–2.82); intention to promote alternatives (OR, 1.63; 95% CI, 1.07–2.49); and reinforcement (OR, 1.57; 95% CI, 1.08–2.29). Knowledge was the only domain associated with routine BZRA deprescribing support (OR, 1.16; 95% CI, 1.06–1.27). Different categories of HCPs face similar major barriers, but barriers vary across HCP categories and countries. Context‐specific, targeted interventions may enhance support for BZRA deprescribing.

• Shapoval, Vladyslav; Hubert, Marie de Saint; Evrard, Perrine; Sibille, François-Xavier; Aubert, Carole E. & Bolt, Lucy [Show all 18 contributors for this article] (2025). Barriers to Deprescribing Benzodiazepines in Older Adults in a Survey of European Physicians. JAMA Network Open. 8(3). doi: 10.1001/jamanetworkopen.2024.59883. Full text in Research Archive Show summary

  Importance The use of benzodiazepine receptor agonists (BZRA) poses serious health risks to older adults. Although several guidelines recommend deprescribing, implementation in clinical practice remains limited. Objective To identify physicians’ barriers to and enablers of deprescribing BZRA in adults aged 65 years and older taking a BZRA for sleep problems; to determine factors associated with hospital physicians’ intention to deprescribe BZRA and their self-reported routine BZRA deprescribing. Design, Setting, and Participants This survey study included hospital physicians and general practitioners (GPs) working across 6 European Countries (Belgium, Greece, Norway, Poland, Spain, and Switzerland) between December 2022 and March 2023. Main Outcomes and Measures Barriers identification via a 35-item questionnaire based upon the Theoretical Domains Framework (TDF). Responses were categorized as major barriers, moderate barriers, and enablers based on their mean scores. Multivariable logistic regressions were used to identify background characteristics and TDF-based domains associated with hospital physicians’ intention to deprescribe and self-reported routine deprescribing. Results Questionnaires from 240 hospital physicians and 96 GPs were analyzed. Most participants were women: 144 (61.0%) hospital physicians and 52 (54.2%) GPs. In terms of experience, the most common reported time in practice was less than 5 years for hospital physicians (76 [31.7%]) and between 10 and 14 years for GPs (35 [36.5%]). Most reported deprescribing BZRA routinely (135 hospital physicians [57.2%] and 66 GPs [72.5%]). Major barriers (and TDF domains) were similar for hospital physicians and GPs across the 6 countries. These barriers included: lack of training (skills), low self-efficacy (beliefs about capabilities), prioritization of other health issues (goals), frustration with the challenges of deprescribing (emotions), insufficient staff and time, absence of local policies (environmental context and resources), and reluctance from patients (social influence). Intention to deprescribe was significantly associated with country, occupation type, and 5 TDF domains: memory, attention, and decision process (odds ratio [OR], 1.70; 95% Ci, 1.22-2.40); social and/or professional role and identity (OR, 5.92; 95% CI, 3.28-11.07); beliefs about capabilities (OR, 2.35; 95% CI, 1.55-3.63); beliefs about consequences (OR, 3.00; 95% CI, 1.61-5.71); and reinforcement (OR, 1.49; 95% CI, 1.05-2.15). Routine deprescribing was significantly associated with 3 TDF domains: memory, attention, and decision processes; intentions; and emotions. Conclusion In this theory-based survey study of physicians, physicians and general practitioners described numerous barriers to deprescribing BZRA in older adults. Our findings indicate that effective deprescribing efforts require approaches that address both reflective processes (eg, enhancing capability) and impulsive processes (eg, managing emotions).

• Ringstad, Ingrid Beate; Romskaug, Rita; Santervas, Leonor Roa; Fjeld, Katrine Gahre; Hove, Lene Hystad & Skovlund, Eva [Show all 8 contributors for this article] (2025). Oral Health, Xerogenic Medications, and Frailty in Acutely Ill Older Adults. Journal of The American Geriatrics Society. ISSN 0002-8614. 73(8), p. 2466–2474. doi: 10.1111/jgs.19564. Full text in Research Archive Show summary

  Background Oral health is an essential part of overall health and well-being in older adults and may be influenced by medications and frailty. This study aimed to describe the prevalence of xerostomia and hyposalivation and examine their associations with xerogenic medications and frailty in acutely ill older adults. Methods This cross-sectional study included patients aged ≥ 70 years admitted to the Municipal In-Patient Acute Care unit in Oslo, Norway. General xerostomia was defined as a score ≥ 3 on the General Xerostomia Question (GXQ). Specific xerostomia was measured with the Summated Xerostomia Inventory (SXI). Objective dry mouth measures included unstimulated whole saliva (UWS) secretion rate and the Clinical Oral Dryness Score (CODS), with hyposalivation defined as UWS ≤ 0.1 mL/min. Examination of dentition included numbers of missing teeth and posterior occluding pairs of teeth. Medication data included total drug burden and number of xerogenic medications. Frailty was assessed using the Clinical Frailty Scale (CFS). Associations were analyzed using logistic regression models. Results Among 382 patients (mean age 84 years, 72% women), general xerostomia was present in 30% and hyposalivation in 56%. Mean number (SD) of xerogenic medications was 3.7 (±2.2). The number of xerogenic medications used was significantly associated with general xerostomia in both unadjusted (OR: 1.17, 95% CI: 1.05–1.29) and adjusted models (OR: 1.13, 95% CI: 1.01–1.26). Median UWS declined numerically with increasing number of xerogenic medications. Higher CFS scores were associated with increased subjective xerostomia scores (GXQ and SXI), elevated CODS, more missing teeth, and reduced occlusion, but not with general xerostomia or hyposalivation when predefined cut-off values were applied. Conclusion Xerostomia and hyposalivation were common among acutely ill older adults. General xerostomia was associated with xerogenic medication use and frailty. Our findings highlight the need to incorporate oral health assessments into routine geriatric care and emphasize the importance of interdisciplinary collaborations.

• Sibille, François-Xavier; Salbert, Joanna; Bolt, Lucy; Tsoutsi, Vagioula; Callegari, Enrico & Dalleur, Olivia [Show all 20 contributors for this article] (2025). Equipping physicians for benzodiazepine receptor agonists deprescription in older adults: theory-based development of the BE-SAFE intervention. Research in Social and Administrative Pharmacy. ISSN 1551-7411. 21(9), p. 714–721. doi: 10.1016/j.sapharm.2025.05.002. Full text in Research Archive Show summary

  Background Benzodiazepine receptor agonists (BZRA) are still widely used for sleep problems in older adults despite an unfavourable risk-benefit ratio. The hospital setting presents an opportunity for optimising medication use in older adults. The BE-SAFE project follows a rigorous sequential approach for developing a theory-informed intervention towards BZRA deprescription initiated in the hospital setting in 6 European countries (Belgium, Greece, Norway, Poland, Spain, and Switzerland). Objectives The objectives of this paper are to describe the development of the physicians' intervention, the results of on the acceptability and perceived feasibility with physicians, and the finalised BE-SAFE intervention. Methods The intervention was built upon preliminary work and developed in four main steps: selection of behaviour change techniques; identification of existing resources and assessment of needs and preferences of hospital physicians; development of intervention components and modes of delivery; and end-users’ evaluation and refinement of intervention. Results A total of 11 behaviour change techniques were selected, addressing 6 main barriers into a 6-component intervention: senior physician endorsement, training, self-monitoring, deprescription algorithm, communication to patients and other healthcare professionals. These core elements will be delivered allowing local adaptability. Twenty-four physicians evaluated the intervention. They confirmed that the intervention effectively targets the barriers highlighted in preliminary work and provided feedback for improvement regarding clarity and time issues. Conclusions A 6-component physician's intervention to enhance BZRA deprescription initiated in hospital settings was developed by systematically addressing implementation issues in a theory informed manner. This intervention will be evaluated in a multi-country cluster randomised controlled trial.

• Dakhil, Shams; Djuv, Ane; Saltvedt, Ingvild Tina; Wyller, Torgeir Bruun; Frihagen, Frede & Johnsen, Lars Gunnar [Show all 10 contributors for this article] (2025). Postoperative outcomes in patients operated for extra- and intracapsular hip fractures – a secondary analysis of two randomized controlled trials. BMC Musculoskeletal Disorders. 26. doi: 10.1186/s12891-025-08404-6. Full text in Research Archive Show summary

  Background: Hip fractures are among the most common and serious injuries in older adults. There has been a perception that extracapsular hip fractures have worse outcome than intracapsular hip fractures. We aimed to examine postoperative outcomes in patients operated for extra- and intracapsular hip fractures. Methods: This is a secondary analysis of data from two randomized controlled trials evaluating the effect of orthogeriatric care. Bivariate analyses were conducted, comparing patients with extracapsular fracture to patients with intracapsular fracture. Mortality, length of hospital stay (LOS), new nursing home admissions, operative data and measures of functional and cognitive performance were assessed as endpoints. Results: The primary analysis included 711 patients; 283 patients had an extracapsular fracture and 428 an intracapsular fracture. At four months follow-up, the intracapsular fracture group had significantly better Short Physical Performance Battery (SPPB) (5.0 vs. 4.0, p = 0.007), personal Activities of Daily Living (p-ADL) (17.0 vs. 16.0, p = 0.007) and instrumental ADL (i-ADL) (32.5 vs. 28.0, p = 0.049). There were no statistically significant differences between the groups at 12 months. Conclusions: Patients with an extracapsular fracture had worse mobility and ADL levels four months postoperatively, but there were no clinically relevant differences at 12 months postoperatively.

• Hella, Mathias Nikolai Petersen; Evensen, Sigurd Storhaug; Rudi, Eli; Norum, Hilde Margrethe; Wøien, Hilde & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Delirium hos eldre i og utenfor sykehus. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(1). doi: 10.4045/tidsskr.24.0299. Full text in Research Archive Show summary

  Delirium er en akutt endring i oppmerksomhet og bevissthet som fluktuerer og ledsages av kognitiv svikt. Pasienter med delirium kan ha persepsjonsforstyrrelser som hallusinasjoner og vrangforestillinger. Tilstanden utløses av akutt sykdom eller skade, og risikoen er størst hos syke eldre og intensivpasienter. Da delirium er forbundet med dårlig prognose, er det viktig å forebygge delirium, raskt identifisere pasienter som likevel utvikler tilstanden, samt å behandle utløsende årsaker. I denne kliniske oversiktsartikkelen presenterer vi oppdatert kunnskap om delirium hos eldre i og utenfor sykehus.

• 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.

• Aksnes, Mari; Schibstad, Mari Haavig; Chaudhry, Farrukh Abbas; Neerland, Bjørn Erik; Caplan, Gideon A. & Saltvedt, Ingvild Tina [Show all 17 contributors for this article] (2024). Differences in metalloproteinases and their tissue inhibitors in the cerebrospinal fluid are associated with delirium. Communications Medicine. 4(1). doi: 10.1038/s43856-024-00558-z. Full text in Research Archive Show summary

  Background The aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration. Methods Using a 13-plex Discovery Assay®, we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer’s disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium. Results Here we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status. Conclusions Several CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored.

• Forfang, Elisabeth; Larsen, Kristin Tveitan; Salman, Rustam Al-Shahi; Bell, Simon M.; Wester, Per & Berge, Eivind [Show all 8 contributors for this article] (2023). Antithrombotic treatment after intracerebral hemorrhage: Surveys among stroke physicians in Scandinavia and the United Kingdom. Health Science Reports. 6(1), p. 1–8. doi: 10.1002/hsr2.1059. Full text in Research Archive Show summary

  Background and Aims It is unclear whether patients with previous intracerebral hemorrhage (ICH) should receive antithrombotic treatment to prevent ischemic events. We assessed stroke physicians' opinions about this, and their views on randomizing patients in trials assessing this question. Methods We conducted three web-based surveys among stroke physicians in Scandinavia and the United Kingdom. Results Eighty-nine of 205 stroke physicians (43%) responded to the Scandinavian survey, 161 of 180 (89%) to the UK antiplatelet survey, and 153 of 289 (53%) to the UK anticoagulant survey. In Scandinavia, 19 (21%) stroke physicians were uncertain about antiplatelet treatment after ICH for ischemic stroke or transient ischemic attack (TIA) and 21 (24%) for prior myocardial infarction. In the United Kingdom, 116 (77%) were uncertain for ischemic stroke or TIA and 115 (717%) for ischemic heart disease. In Scandinavia, 32 (36%) were uncertain about anticoagulant treatment after ICH for atrial fibrillation, and 26 (29%) for recurrent deep vein thrombosis or pulmonary embolism. In the United Kingdom, 145 (95%) were uncertain about anticoagulants after ICH in at least some cases. In both regions combined, 191 of 250 (76%) would consider randomizing ICH survivors in a trial of starting versus avoiding antiplatelets, and 176 of 242 (73%) in a trial of starting versus avoiding anticoagulants. Conclusion Considerable proportions of stroke physicians in Scandinavia and the United Kingdom were uncertain about antithrombotic treatment after ICH. A clear majority would consider randomizing patients in trials assessing this question. These findings support the need for such trials.

• Dakhil, Shams; Saltvedt, Ingvild Tina; Benth, Jurate Saltyte; Thingstad, Anne Pernille Mæhle; Watne, Leiv & Wyller, Torgeir Bruun [Show all 10 contributors for this article] (2023). Longitudinal trajectories of functional recovery after hip fracture. PLOS ONE. 18(3). doi: 10.1371/journal.pone.0283551. Full text in Research Archive Show summary

  Background There is limited evidence regarding predictors of functional trajectories after hip fracture. We aimed to identify groups with different trajectories of functional recovery the first year after hip fracture, and to determine predictors for belonging to such groups. Methods This longitudinal study combined data from two large randomized controlled trials including patients with hip fracture. Participants were assessed at baseline, four and 12 months. We used the Nottingham Extended Activities of Daily Living (NEADL) as a measure of instrumental ADL (iADL) and Barthel Index for personal ADL (pADL). A growth mixture model was estimated to identify groups of patients following distinct trajectories of functioning. Baseline characteristics potentially predicting group-belonging were assessed by multiple nominal regression. Results Among 726 participants (mean age 83.0; 74.7% women), we identified four groups of patients following distinct ADL trajectories. None of the groups regained their pre-fracture ADL. For one of the groups identified in both ADL outcomes, a steep decline in function was shown the first four months after surgery, and none of the groups showed functional recovery between four and 12 months after surgery. Conclusions No groups regained their pre-fracture ADL. Some of the patients with relatively high pre-fracture function, had a steep ADL decline. For this group there is a potential for recovery, but more knowledge and research is needed in this group. These findings could be useful in uncovering groups of patients with different functioning after a hip fracture, and aid in discharge planning.

• Krogseth, Maria; Davis, Daniel; Jackson, Thomas A; Zetterberg, Henrik; Watne, Leiv & Lindberg, Morten [Show all 10 contributors for this article] (2023). Delirium, neurofilament light chain, and progressive cognitive impairment: analysis of a prospective Norwegian population-based cohort. The Lancet Healthy Longevity. 4(8), p. e399–e408. doi: 10.1016/S2666-7568(23)00098-3. Full text in Research Archive Show summary

  Background: Previous population-based, longitudinal studies have shown that delirium is associated with an increased risk of dementia and cognitive decline. However, the underlying biological mechanisms are largely unknown. We aimed to assess the effects of delirium on both cognitive trajectories and any neuronal injury, measured via neurofilament light chain (NfL). Methods: In this analysis of a prospective, 2-year follow-up, cohort study of participants aged 65 years or older living in Sandefjord municipality, Norway, we included cohort participants who were receiving domiciliary care services at least once per week between May 12, 2015, and July 8, 2016. Individuals with a life expectancy of less than 1 week, with Lewy body dementia, with psychiatric illness (except dementia), or for whom substance misuse was the principal indication for domiciliary services were excluded. Participants had a comprehensive assessment at 6-month intervals for 2 years, which included the Montreal Cognitive Assessment (MoCA) and a blood sample for NfL to measure neuronal injury. All information on clinical diagnoses and medications were cross-referenced with medical records. During any acute change in mental status or hospitalisation (ie, admission to hospital), participants were assessed once per day for delirium with Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. We also measured NfL from blood samples taken from participants who were acutely hospitalised. Findings: Between May 12, 2015, and July 8, 2016, 210 participants were eligible for inclusion and assessed at baseline (138 [66%] of whom were female and 72 [34%] of whom were male), 203 completed cognitive assessment, and 141 were followed up for 2 years. 160 (76%) of 210 had moderate or severe frailty and 112 (53%) were living with dementia. During the 2-year follow-up, 89 (42%) of 210 participants were diagnosed with one or more episodes of delirium. Incident delirium was independently associated with a decrease in MoCA score at the next 6-month follow-up, even after adjustment for age, sex, education, previous MoCA score, and frailty (adjusted mean difference –1·5, 95% CI –2·9 to –0·1). We found an interaction between previous MoCA score and delirium (β –0·254, 95% CI –0·441 to –0·066, p=0·010), with the largest decline being observed in people with better baseline cognition. Participants with delirium and good previous cognitive function and participants with a high peak concentration of NfL during any hospitalisation had increased NfL at the next 6-month follow-up. Mediation analyses showed independent pathways from previous MoCA score to follow-up MoCA score with contributions from incident delirium (–1·7, 95% CI –2·8 to –0·6) and from previous NfL to follow-up MoCA score with contributions from acute NfL concentrations (–1·8, –2·5 to –1·1). Delirium was directly linked with a predicted value of 1·2 pg/mL (95% CI 1·02 to 1·40, p=0·029) increase in NfL. Interpretation: In people aged 65 years or older, an episode of delirium was associated with a decline in MoCA score. Greater neuronal injury during acute illness and delirium, measured by NfL, was associated with greater cognitive decline. For clinicians, our finding of delirium associated with both signs of acute neuronal injury, measured via NfL, and cognitive decline is important regarding the risk of long-term cognitive deterioration and to acknowledge that delirium is harmful for the brain.

• Næss, Gro; Wyller, Torgeir Bruun & Gjevjon, Edith Roth (2023). Clinical Leadership – An Important Precondition for the Success of Proactive and Interdisciplinary Follow-up of Frail Older Recipients of Home Healthcare. Home Health Care Management & Practice. ISSN 1084-8223. 0(0). doi: 10.1177/10848223231170599. Full text in Research Archive Show summary

  Early identification and follow-up of sub-acute and acute functional decline in older persons living with multimorbidity at home require integrated and proactive care by interdisciplinary health personnel. Yet, in the context of the task-oriented and fragmented home healthcare services, early identification is challenging. Therefore, the aim of this study was to identify preconditions for the success of a proactive and interdisciplinary follow-up of older recipients of home healthcare. We conducted a qualitative secondary analysis of data from 6 focus group interviews with registered nurses and nurse leaders. In addition, we performed and analyzed data from 2 new focus group interviews with general practitioners and RNs who had a role as super users in a developmental project which introduced a clinical instrument for early identification of sub-acute and acute functional decline (sub-acute functional decline in the elderly—SAFE). Their experiences with using SAFE constituted the backdrop for the study. In total, 41 representatives of the interprofessional primary care staff of 3 city districts participated. Having a common goal, sharing tasks and having reciprocal understanding of each health profession’s contribution, systems and tools and clinical leadership were all seen as important factors for succeeding in the proactive and interdisciplinary follow-up of older recipients of home healthcare. Clinical leadership was deemed the strongest precondition, and clear leadership which promotes integrative and proactive care by facilitating interdisciplinary collaboration appears to be the main key for success.

• Vlachos, Georgios; Ihle-Hansen, Hege Beathe; Wyller, Torgeir Bruun; Brækhus, Anne; Mangset, Margrete & Hamre, Charlotta [Show all 7 contributors for this article] (2023). Factors Determining Not Returning to Full-Time Work 12 Months After Mild Ischemic Stroke. Archives of Rehabilitation Research and Clinical Translation. 5(1). doi: 10.1016/j.arrct.2022.100245. Full text in Research Archive Show summary

  Objective To evaluate prevalence and factors determining not returning to full-time work 1 year after first-ever mild ischemic stroke. Design Prospective, observational cohort study with 12-month follow-up. Setting Stroke units and outpatient clinics at 2 Norwegian hospitals. Participants We included 84 (N=84) full-time working, cognitively healthy patients aged 70 years or younger who suffered an acute first-ever mild ischemic stroke, defined as National Institutes of Health Stroke Scale (NIHSS) score ≤3 points. Interventions Not applicable. Main Outcome Measures Vascular risk factors, sociodemographic factors, stroke localization, and etiology were recorded at inclusion. Cognitive impairment, anxiety, depression, fatigue, and apathy 12 months after stroke were assessed with validated instruments. Logistic regression analyses were performed to find correlates of not returning to full-time employment. Results Of 78 patients assessed 1 year after stroke, 63 (81%) had returned to work, 47 (60%) to full-time employment status. Modified Rankin scale score >1 (adjusted odds ratio, 12.44 [95% confidence interval, 2.37-65.43], P=.003) at follow-up was significantly associated, and diabetes (adjusted odds ratio, 10.56 [95% confidence interval, 0.98-113.47], P=.052) was borderline significantly associated with not returning to full-time work. Female sex, NIHSS at discharge, anxiety per point on the anxiety scale, depression per point on the depression scale, and fatigue per point on the fatigue scale were significantly associated with not returning to full-time work after 1 year, but these associations were only seen in the unadjusted models. Conclusions Low functional level that persists 12 months after stroke is related to not returning to full-time work. Patients with diabetes mellitus, female patients, and patients with a higher score on fatigue, anxiety, and depression scales may also be at risk of not returning to full-time work post stroke. Working patients should be followed up with a particular focus on factors determining participation in work and social life.

• Munthe-Kaas, Ragnhild; Aam, Stina; Saltvedt, Ingvild; Wyller, Torgeir Bruun; Pendlebury, Sarah T. & Lydersen, Stian [Show all 10 contributors for this article] (2022). Is Frailty Index a better predictor than pre-stroke modified Rankin Scale for neurocognitive outcomes 3-months post-stroke? BMC Geriatrics. 22(1). doi: 10.1186/s12877-022-02840-y. Full text in Research Archive Show summary

  Background The prognostic value of frailty measures for post-stroke neurocognitive disorder (NCD) remains to be evaluated. Aims The aim of this study was to compare the predictive value of pre-stroke FI with pre-stroke modified Rankin Scale (mRS) for post-stroke cognitive impairment. Further, we explored the added value of including FI in prediction models for cognitive prognosis post-stroke. Methods We generated a 36-item Frailty Index (FI), based on the Rockwood FI, to measure frailty based on pre-stroke medical conditions recorded in the Nor-COAST multicentre prospective study baseline assessments. Consecutive participants with a FI score and completed cognitive test battery at three months were included. We generated Odds Ratio (OR) with NCD as the dependent variable. The predictors of primary interest were pre-stroke frailty and mRS. We also measured the predictive values of mRS and FI by the area (AUC) under the receiver operating characteristic curve. Results 598 participants (43.0% women, mean/SD age = 71.6/11.9, mean/SD education = 12.5/3.8, mean/SD pre-stroke mRS = 0.8/1.0, mean/SD GDS pre-stroke = 1.4/0.8, mean/SD NIHSS day 1 3/4), had a FI mean/SD score = 0.14/0.10. The logistic regression analyses showed that FI (OR 3.09), as well as the mRS (OR 2.21), were strong predictors of major NCD. When FI and mRS were entered as predictors simultaneously, the OR for mRS decreased relatively more than that for FI. AUC for NCD post-stroke was higher for FI than for mRS, both for major NCD (0.762 vs 0.677) and for any NCD (0.681 vs 0.638). Conclusions FI is a stronger predictor of post-stroke NCD than pre-stroke mRS and could be a part of the prediction models for cognitive prognosis post-stroke.

• Gravningen, Kirsten; Nymark, Petter Sunde; Wyller, Torgeir Bruun & Kacelnik, Oliver (2022). A new automated national register-based surveillance system for outbreaks in long-term care facilities in Norway detected three times more severe acute respiratory coronavirus virus 2 (SARS-CoV-2) clusters than traditional methods. Infection control and hospital epidemiology. ISSN 0899-823X. 44(9), p. 1451–1457. doi: 10.1017/ice.2022.297. Full text in Research Archive Show summary

  Objective: To develop and test a new automated surveillance system that can detect, define and characterize infection clusters, including coronavirus disease 2019 (COVID-19), in long-term care facilities (LTCFs) in Norway by combining existing national register data. Background: The numerous outbreaks in LTCFs during the COVID-19 pandemic highlighted the need for accurate and timely outbreak surveillance. As traditional methods were inadequate, we used severe acute respiratory coronavirus virus 2 (SARS-CoV-2) as a model to test automated surveillance. Methods: We conducted a nationwide study using data from the Norwegian preparedness register (Beredt C19) and defined the study population as an open cohort from January 2020 to December 2021. We analyzed clusters (≥3 individuals with positive SARS-CoV-2 test ≤14 days) by 4-month periods including cluster size, duration and composition, and residents’ mortality associated with clusters. Results: The study population included 173,907 individuals; 78% employees and 22% residents. Clusters were detected in 427 (43%) of 993 LTCFs. The median cluster size was 4–8 individuals (maximum, 50) by 4-month periods, with a median duration of 9–17 days. Employees represented 60%–82% of cases in clusters and were index cases in 60%–90%. In the last 4-month period of 2020, we detected 107 clusters (915 cases) versus 428 clusters (2,998 cases) in the last period of 2021. The 14-day all-cause mortality rate was higher in resident cases from the clusters. Varying the cluster definitions changed the number of clusters. Conclusion: Automated national surveillance for SARS-CoV-2 clusters in LTCFs is possible based on existing data sources and provides near real-time detailed information on size, duration, and composition of clusters. Thus, this system can assist in early outbreak detection and improve surveillance.

• Veddeng, Sigbjørn; Madland, Håkon; Molden, Espen; Wyller, Torgeir Bruun & Romskaug, Rita (2022). Association between statin use and physical performance in home-dwelling older patients receiving polypharmacy: cross-sectional study. BMC Geriatrics. 22(1), p. 242–242. doi: 10.1186/s12877-022-02942-7. Full text in Research Archive Show summary

  Background In older patients with polypharmacy and multiple comorbidities, even low grades of statin-associated muscle symptoms may have clinical implications. The aim of this study was therefore to investigate the potential associations between statin use and measures of physical performance and muscle function. Methods Participants were aged 70+, treated with at least seven regular systemic medications, and not expected to die or become institutionalized within 6 months. Physical performance measured as gait speed and Short Physical Performance Battery (SPPB) score, and muscle function measured as grip strength, were compared between users and non-users of statins. In the subgroup of statin users, the dose-response relationship was assessed using harmonized simvastatin equivalents adjusted for statin potency, pharmacokinetic interactions and SLCO1B1 c.521 T > C genotype. Multiple linear regression analyses were applied to investigate potential associations between stain use and exposure as independent variables, and physical performance and muscle function as outcomes, adjusted for age, gender, body mass, comorbidity, disability and dementia. Results 174 patients (87 users and 87 non-users of statins) with a mean (SD) age of 83.3 (7.3) years were included. In analyses adjusted only for gender, grip strength was significantly higher in users than in non-users of statins [regression coefficient (B) 2.7, 95% confidence interval (CI) 1.0 to 4.4]. When adjusted for confounders, the association was no longer statistically significant (B 1.1, 95% CI − 0.5 to 2.7). SPPB and gait speed was also better in statin users than in non-users, but the differences were not statistically significant. In dose-response analyses adjusted for confounders, we found a statistically significant increase in SPPB score (B 0.01, 95% CI 0.00 to 0.02) and gait speed (B 0.001, 95% CI 0.000 to 0.002) per mg increase in simvastatin equivalents. Conclusions In contrast to our hypothesis, statin use and exposure was associated with better measures of physical performance and muscle function in older patients with complex drug treatment. The unexpected findings of this cross-sectional, observational study should be further investigated by comparing physical performance before and after statin initiation or statin withdrawal in prospective studies. Trial registration ClinicalTrials.gov identifier: NCT02379455, registered March 5, 2015.

• Wang-Hansen, Marte Sofie; Kersten, Hege; Benth, Jurate Saltyte & Wyller, Torgeir Bruun (2022). The association between geriatric treatment and 30-day readmission risk among medical inpatients aged ≥75 years with multimorbidity. PLOS ONE. 17(1). doi: 10.1371/journal.pone.0262340. Full text in Research Archive Show summary

  Background: Readmission to hospital is frequent among older patients and reported as a post-discharge adverse outcome. The effect of treatment in a geriatric ward for acutely admitted older patients on mortality and function is well established, but less is known about the possible influence of such treatment on the risk of readmission, particularly in the oldest and most vulnerable patients. Our aim was to assess the risk for early readmission for multimorbid patients > 75 years treated in a geriatric ward compared to medical wards and to identify risk factors for 30-day readmissions. Methods: Prospective cohort study of patients acutely admitted to a medical department at a Norwegian regional hospital. Eligible patients were community-dwelling, multimorbid, receiving home care services, and aged 75+. Patients were consecutively included in the period from 1 April to 31 October 2012. Clinical data were retrieved from the referral letter and medical records. Results: We included 227 patients with a mean (SD) age of 86.0 (5.7) years, 134 (59%) were female and 59 (26%) were readmitted within 30 days after discharge. We found no statistically significant difference in readmission rate between patients treated in a geriatric ward versus other medical wards. In adjusted Cox proportional hazards regression analyses, lower age (hazard ratio (95% confidence interval) 0.95 (0.91-0.99) per year), female gender (2.17 (1.15-4.00)) and higher MMSE score (1.03 (1.00-1.06) per point) were significant risk factors for readmission. Conclusions: Lower age, female gender and higher cognitive function were the main risk factors for 30-day readmission to hospital among old patients with multimorbidity. We found no impact of geriatric care on the readmission rate.

• Vlachos, Georgios; Ihle-Hansen, Hege; Wyller, Torgeir Bruun; Brækhus, Anne; Mangset, Margrete & Hamre, Sophia Charlotta [Show all 7 contributors for this article] (2022). Predictors of cognitive and emotional symptoms 12 months after first-ever mild stroke. Neuropsychological Rehabilitation. ISSN 0960-2011. doi: 10.1080/09602011.2022.2038211. Full text in Research Archive Show summary

  Even mild strokes may affect the patients’ everyday life by impairing cognitive and emotional functions. Our aim was to study predictors of such impairments one year after first-ever mild stroke. We included cognitively healthy patients ≤ 70 years with acute mild stroke. Vascular risk factors, sociodemographic factors and stroke classifications were recorded. At one-year post-stroke, different domains related to cognitive and emotional function were assessed with validated instruments. Logistic regression analyses were performed to identify predictors of cognitive and emotional outcome. Of 117 patient assessed at follow-up, only 21 patients (18%) scored within the reference range on all cognitive and emotional assessments. Younger age, multiple infarcts, and being outside working life at stroke onset were independent predictors of cognitive impairments (psychomotor speed, attention, executive and visuospatial function, memory). Female gender and a higher National Institutes of Health Stroke Scale (NIHSS) score at discharge were significantly associated with emotional impairments (anxiety, depressive symptoms, fatigue, apathy, emotional lability) after one year, but these associations were only seen in the unadjusted models. In conclusion, patients in working age may profit from a follow-up during the post-stroke period, with extra focus on cognitive and emotional functions.

• Vahedi, Ali; Eriksdotter, Maria; Ihle-Hansen, Hege; Wyller, Torgeir Bruun; Øksengård, Anne Rita & Fure, Brynjar (2022). Cognitive impairment in people with physical frailty using the phenotype model: A systematic review and meta analysis. International Journal of Geriatric Psychiatry. ISSN 0885-6230. 37(11), p. 1–12. doi: 10.1002/gps.5822. Full text in Research Archive Show summary

  Objective We performed a systematic review and meta-analysis to study the relationship between cognitive functioning and phenotypic frailty status. Methods We searched Pubmed, Cochrane Library and Epistemonikos from 2000 until March 2022, and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Samples included both sexes, age ≥55 years, assessed with standardized measures of the different cognitive domains and the frailty phenotype model and analyzing the relationship between the frailty subtypes pre-frail, frail and robust and specific cognitive function. Results Eleven studies published from 2008 until March 2022 fulfilled the inclusion criteria, and 10 were included in our meta-analyses. Sample sizes varied from 104 to 4649 individuals. Mean Mini-Mental State Examination (MMSE) scores ranged from 17.0 to 27.6, with mean difference (MD) of −2.55 (95% confidence interval [CI] −3.32, −1.78) in frail compared to robust, MD −1.64 (95% CI −2.21, −1.06) in frail compared to prefrail and MD −0.68 (95% CI −0.94, −0.43) in prefrail compared to robust. In subgroup analyses, frail persons had lower scores in the memory domain with standardized mean difference (SMD) −1.01 (95% CI −1.42, −0.59). Conclusion MMSE scores were significantly lower in frail compared to robust and prefrail persons and in prefrail compared to robust persons. Subgroup analysis of memory revealed significantly poorer scores in frail compared to robust. The results indicate a strong relationship between physical frailty and cognitive impairment suggesting incorporation of cognitive function in frailty assessments.

• Hamre, Sophia Charlotta; Fure, Brynjar; Helbostad, Jorunn L.; Wyller, Torgeir Bruun; Ihle-Hansen, Hege & Vlachos, Georgios [Show all 8 contributors for this article] (2021). Factors Associated with Level of Physical Activity After Minor Stroke. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 30(4). doi: 10.1016/j.jstrokecerebrovasdis.2021.105628. Full text in Research Archive Show summary

  Objectives: To explore factors from the acute phase, and after three and 12 months, associated with level of self-reported physical activity 12 months after a minor ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 in persons 70 years or younger. Materials and method: In this longitudinal cohort study patients were recruited consecutively from two stroke units. Activity level were measured with three sets of questions addressing the average number of frequency (times exercising each week), the average intensity, and duration (the average time), and a sum score was constructed. The association between physical activity 12 months after stroke and sociodemographic factors, NIHSS, body mass index, balance, and neuropsychiatric symptoms were explored using multiple linear regression. Results: This study included 101 patients, with mean age (SD) 55.5 (11.4) years, NIHSS median (Q1, Q3) 0.0 (0.0, 1.0), and 20 % were female. Multiple linear regression analyses showed sick leave status at stroke onset, balance at three and 12 months, and anxiety, depression, apathy, and fatigue at 12 months to be factors associated with physical activity at 12 months after stroke. Conclusion: We found that pre-stroke sick leave, post-stroke balance, and neuropsychiatric symptoms were associated with the level of physical activity one year after minor stroke. This might be of importance when giving information about physical activity and deciding about post-stroke follow-up.

• Hamre, Charlotta; Fure, Brynjar; Helbostad, Jorunn L.; Wyller, Torgeir B.; Ihle-Hansen, Hege & Vlachos, Georgios [Show all 8 contributors for this article] (2021). Balance and gait after first minor ischemic stroke in people 70 years of age or younger: A prospective observational cohort study. Physical Therapy. ISSN 0031-9023. 100(5), p. 798–806. doi: 10.1093/PTJ/PZAA010. Full text in Research Archive Show summary

  BACKGROUND: Two-thirds of patients with stroke experience only mild impairments in the acute phase, and the proportion of patients <70 years is increasing. Knowledge about balance and gait and predictive factors are scarce for this group. OBJECTIVE: The objective of this study was to explore balance and gait in the acute phase and after 3 and 12 months in patients <=70 years with minor ischemic stroke (National Institutes of Health Stroke Scale score <=3). This study also explored factors predicting impaired balance after 12 months. DESIGN: This study was designed as an explorative longitudinal cohort study. METHODS: Patients were recruited consecutively from 2 stroke units. Balance and gait were assessed with the Mini-Balance Evaluation Systems Test (Mini-BESTest), Timed Up and Go, and preferred gait speed. Predictors for impaired balance were explored using logistic regression. RESULTS: This study included 101 patients. Mean (SD) age was 55.5 (11.4) years, 20% were female, and mean (SD) National Institutes of Health Stroke Scale score was 0.6 (0.9) points. The Mini-BESTest, gait speed, and Timed Up and Go improved significantly from the acute phase to 3 months, and gait speed also improved from 3 to 12 months. At 12 months, 26% had balance impairments and 33% walked slower than 1.0 m/s. Poor balance in the acute phase (odds ratio = 0.92, 95% confidence interval = 0.85-0.95) was the only predictor of balance impairments (Mini-BESTest score <=22) at 12 months poststroke. LIMITATIONS: Limitations include lack of information about pre-stroke balance and gait impairment and poststroke exercise. Few women limited the generalizability. CONCLUSION: This study observed improvements in both balance and gait during the follow-up; still, about one-third had balance or gait impairments at 12 months poststroke. Balance in the acute phase predicted impaired balance at 12 months.

• Krogseth, Maria; Rostoft, Siri; Benth, Jurate Saltyte; Selbæk, Geir & Wyller, Torgeir Bruun (2021). Skrøpelighet blant eldre pasienter med hjemmesykepleie. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(4), p. 1–10. doi: 10.4045/tidsskr.20.0688. Full text in Research Archive Show summary

  BAKGRUNN: Det er et politisk ønske at eldre personer med hjelpebehov skal kunne bo hjemme så lenge som mulig og motta helsetjenester utenfor institusjon. Denne gruppens grad av skrøpelighet samt risiko for akuttinnleggelser og død, er lite studert. Hensikten med prosjektet var å studere dette gjennom to år i en middelsstor norsk kommune. MATERIALE OG METODE: Et utvalg pasienter i Sandefjord kommune, 65 år eller eldre, med ukentlig offentlig hjemmesykepleie ble inkludert. Pasientene gjennomgikk en geriatrisk vurdering i eget hjem hvert halvår i to år. Grad av skrøpelighet ble beregnet ved hjelp av Skrøpelighetsindeks (Frailty Index). Forekomst av dødsfall og akutte sykehusinnleggelser ble registrert i to år. RESULTATER: Av 271 forespurte pasienter ble 210 inkludert. 160 pasienter (76 %) ble klassifisert som moderat eller alvorlig skrøpelige. I løpet av observasjonsperioden ble det registrert 307 akuttinnleggelser med til sammen 1 235 liggedøgn i sykehus. Sammenliknet med pasienter med alvorlig skrøpelighet var pasienter med mild skrøpelighet sjeldnere innlagt på sykehus (hasardratio (HR) 0,33; 95 % konfidensintervall (KI) 0,19–0,60). 63 (30 %) av deltakerne døde i løpet av to års observasjonstid. Dødeligheten var høyest blant pasienter med alvorlig skrøpelighet. Ved justert Cox-regresjon var økende alder assosiert med økt risiko for død, men ikke med akuttinnleggelser. FORTOLKNING: Eldre pasienter som mottar hjemmesykepleie, har høy grad av skrøpelighet, og grad av skrøpelighet er assosiert med risiko for sykehusinnleggelser og død.

• Wyller, Torgeir Bruun (2021). Foretaksmodellen innebærer at sykehusene driftes etter kvasikapitalistiske prinsipper. Det fører til at de prioriterer bedriftsøkonomisk «lønnsomhet» foran helsefaglig og samfunnsøkonomisk ansvarlighet. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(12), p. 1–3. doi: 10.4045/tidsskr.21.0573. Full text in Research Archive
• Cheng, Socheat; Siddiqui, Tahreem Ghazal; Gossop, Michael; Wyller, Torgeir Bruun; Kristoffersen, Espen Saxhaug & Lundqvist, Anders Christofer (2021). The patterns and burden of multimorbidity in geriatric patients with prolonged use of addictive medications. Aging Clinical and Experimental Research. ISSN 1594-0667. 33, p. 2857–2864. doi: 10.1007/s40520-021-01791-5. Full text in Research Archive Show summary

  <i>Background</i> - Multimorbidity and prolonged use of addictive medications are prevalent among older patients, and known to increase the risk of adverse drug events. Yet, the relationship between these two entities has remained understudied.<br><br> <i>Aims</i> - This study explored the association between multimorbidity burden and prolonged use of addictive medications in geriatric patients, adjusted for clinically important covariates. Furthermore, we identified comorbidity patterns in prolonged users.<br><br> <i>Methods</i> - We conducted a cross-sectional study on a consecutive sample of 246 patients, aged 65–90 years, admitted to a large public university hospital in Norway. We defined prolonged use of addictive medications as using benzodiazepines, opioids and/or z-hypnotics beyond the duration recommended by clinical guidelines (≥ 4 weeks). Multimorbidity was assessed with the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), based on diagnoses made by independent physicians.<br><br> <i>Results</i> - Compared to non-prolonged use, prolonged use was significantly more common among patients who had psychiatric (19/27, 70%), liver (19/22, 86%), upper gastrointestinal tract (21/32, 66%), musculoskeletal (52/96, 54%), or nervous system disorders (46/92, 50%). Patients with prolonged use had a higher multimorbidity burden than those without such use (CIRS-G score, mean = 7.7, SD = 2.7 versus mean = 4.6, SD = 2.2, <i>p</i> < 0.001). Multivariable logistic regression indicated a significant association between multimorbidity burden and prolonged addictive medication use (OR = 1.72, 95% CI 1.42–2.08). Predictive margins postestimation showed a systematic increase in the predicted CIRS-G scores when the number of addictive drug used increases.<br><br> <i>Conclusions</i> - Multimorbidity is strongly associated with prolonged use of addictive medications. Multiple substance use may aggravate disease burden of older patients.

• Schellhorn, Till; Zucknick, Manuela; Askim, Torunn; Munthe-Kaas, Ragnhild; Ihle-Hansen, Hege & Seljeseth, Yngve Müller [Show all 13 contributors for this article] (2021). Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study. BMC Geriatrics. 21:362(362), p. 1–10. doi: 10.1186/s12877-021-02327-2. Full text in Research Archive Show summary

  Background: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. Methods: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. Results: Patients’ (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3).

• Dakhil, Shams; Thingstad, Pernille; Frihagen, Frede; Johnsen, Lars Gunnar; Lydersen, Stian & Skovlund, Eva [Show all 10 contributors for this article] (2021). Orthogeriatrics prevents functional decline in hip fracture patients: report from two randomized controlled trials. BMC Geriatrics. 21(208). doi: 10.1186/s12877-021-02152-7. Full text in Research Archive Show summary

  Background The incidence of hip fractures are expected to increase in the following years. Hip fracture patients have in addition to their fracture often complex medical problems, which constitute a substantial burden on society and health care systems. It is thus important to optimize the treatment of these patients to reduce negative outcomes. The aim of this study was to assess the effect of comprehensive orthogeriatric care (CGC) on basic and instrumental activities of daily living (B-ADL and I-ADL). Methods This study is based on two randomized controlled trials; the Oslo Orthogeriatric Trial and the Trondheim Hip Fracture Trial. The two studies were planned in concert, and data were pooled and analyzed using linear mixed models. I-ADL function was assessed by the Nottingham Extended ADL Scale (NEADL) and B-ADL by the Barthel ADL (BADL) at four and twelve months after surgery. Results Seven hundred twenty-six patients were included in the combined database, of which 365 patients received OC and 361 patients received CGC. For the primary endpoint, I-ADL at four months was better in the CGC group, with a between-group difference of 3.56 points (95 % CI 0.93 to 6.20, p = 0.008). The between-group difference at 12 months was 4.28 points (95 % CI 1.57 to 7.00, p = 0.002). For B-ADL, between-group difference scores were only statistically significant at 12 months. When excluding the patients living at a nursing home at admission, both I-ADL and B-ADL function was significantly better in the CGC group compared to the OC group at all time points. Conclusions Merged data of two randomized controlled trials showed that admitting hip fracture patients to an orthogeriatric care unit directly from the emergency department had a positive effect on ADL up to twelve months after surgery.

• Wyller, Torgeir Bruun; Kittang, Bård Reiakvam; Ranhoff, Anette Hylen; Harg, Pernille & Myrstad, Marius (2021). Dødsfall i sykehjem etter covid-19-vaksine. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(10), p. 1–8. doi: 10.4045/tidsskr.21.0383. Full text in Research Archive Show summary

  Bakgrunn: I perioden 27.12.2020–15.2.2021 ble om lag 29 400 av Norges ca. 35 000 sykehjemspasienter vaksinert med mRNA-vaksinen BNT162b2. I samme tidsrom mottok Statens legemiddelverk 100 meldinger om mistenkte fatale bivirkninger av vaksinen. En ekspertgruppe har gransket meldingene og vurdert grad av årsakssammenheng mellom vaksinering og dødsfallene. Materiale og metode: Ekspertgruppen arbeidet i to par som gransket 50 anonymiserte meldinger hver. Hvert medlem gransket først meldingene alene og klassifiserte sammenhengen som usannsynlig, mulig, sannsynlig, sikker eller ikke-klassifiserbar. Deretter drøftet hvert ekspertpar seg frem til konsensus. Alle de fire ekspertene vurderte et tilfeldig utvalg på 20 meldinger. Graden av enighet ble vurdert med vektet kappa og McNemars symmetritest. Resultater: Pasientenes gjennomsnittsalder var 87,7 år (spredning 61–103 år). Blant 100 meldte dødsfall ble en sammenheng med vaksinen vurdert som sannsynlig i 10 tilfeller, som mulig i 26 og som usannsynlig i 59 tilfeller. Fem var ikke-klassifiserbare. Vektet kappa var henholdsvis 0,40 og 0,38 i de to ekspertparene. Fortolkning: De fleste sykehjemspasienter har kort forventet gjenstående levetid, men vaksineringen kan i noen få tilfeller ha bidratt til å akselerere en pågående dødsprosess. Sykehjemspasienter bør fortsatt prioriteres for vaksine, men hos de mest skrøpelige bør nytte versus risiko avveies grundig. Hovedfunn: For flertallet av sykehjemspasienter var det ingen åpenbar sammenheng mellom vaksinasjon og død. Noen få pasienter med høy grad av skrøpelighet fikk vaksinebivirkninger som sannsynligvis akselererte en allerede pågående dødsprosess.

• Ihle-Hansen, Håkon; Ihle-Hansen, Hege; Fure, Brynjar; Thommessen, Bente; Helland, Gisle Berg & Øksengård, Anne Rita [Show all 10 contributors for this article] (2021). Carotid Atherosclerosis and Longitudinal Changes of MRI Visual Rating Measures in Stroke Survivors: A Seven-Year Follow-Up Study. Journal of Stroke & Cerebrovascular Diseases. ISSN 1052-3057. 30(10), p. 1–6. doi: 10.1016/j.jstrokecerebrovasdis.2021.106010. Full text in Research Archive Show summary

  Objectives We aimed to assess longitudinal changes in MRI measures of brain atrophy and white matter lesions in stroke and transient ischemic attack (TIA) survivors, and explore whether carotid stenosis predicts progression of these changes, assessed by visual rating scales. Materials and Methods All patients with a first-ever stroke or TIA admitted to Bærum Hospital, Norway, in 2007/2008, were invited in the acute phase and followed for seven years. Carotid ultrasound was performed during the hospital stay. Carotid stenosis was defined as ≥50% narrowing of lumen. MRI was performed one and seven years after the index event and analyzed according to the visual rating scales Fazekas scale (0-3), Medial Temporal Lobe Atrophy (MTLA) (0-4) score, and Global Cortical Atrophy (GCA) scale (0-3). Patients with MRI scans at both time points were included in this sub-study. Results Of 227 patients recruited, 76 had both MRI examinations. Mean age 73.9±10.6, 41% women, and 9% had ≥50% carotid stenosis. Mean Fazekas scale was 1.7±0.9 and 1.8±1.0, mean MTLA score 1.0 ±1.0 and 1.7±1.0, and mean GCA scale score 1.4±0.7 and 1.4±0.6 after one and seven years, respectively. 71% retained the same Fazekas scale score, while 21% showed progression. Deterioration in GCA scale was seen in 20% and increasing MTLA score in 57%. Carotid stenosis was not associated with progression on Fazekas score, MTLA score or GCA scale. Conclusions Three out of five showed progression on the MTLA score. Carotid stenosis was not associated with longitudinal change of visual rating scales.

• Schellhorn, Till; Aamodt, Eva Birgitte; Lydersen, Stian; Aam, Stina; Wyller, Torgeir Bruun & Saltvedt, Ingvild [Show all 7 contributors for this article] (2021). Clinically accessible neuroimaging predictors of post-stroke neurocognitive disorder: a prospective observational study. BMC Neurology. 21(1), p. 1–11. doi: 10.1186/s12883-021-02117-8. Full text in Research Archive Show summary

  Background Neurocognitive disorder (NCD) is common in stroke survivors. We aimed to identify clinically accessible imaging markers of stroke and chronic pathology that are associated with early post-stroke NCD. Methods We included 231 stroke survivors from the “Norwegian Cognitive Impairment after Stroke (Nor-COAST)” study who underwent a standardized cognitive assessment 3 months after the stroke. Any NCD (mild cognitive impairment and dementia) and major NCD (dementia) were diagnosed according to “Diagnostic and Statistical Manual of Mental Disorders (DSM-5)” criteria. Clinically accessible imaging findings were analyzed on study-specific brain MRIs in the early phase after stroke. Stroke lesion volumes were semi automatically quantified and strategic stroke locations were determined by an atlas based coregistration. White matter hyperintensities (WMH) and medial temporal lobe atrophy (MTA) were visually scored. Logistic regression was used to identify neuroimaging findings associated with major NCD and any NCD. Results Mean age was 71.8 years (SD 11.1), 101 (43.7%) were females, mean time from stroke to imaging was 8 (SD 16) days. At 3 months 63 (27.3%) had mild NCD and 65 (28.1%) had major NCD. Any NCD was significantly associated with WMH pathology (odds ratio (OR) = 2.73 [1.56 to 4.77], p = 0.001), MTA pathology (OR = 1.95 [1.12 to 3.41], p = 0.019), and left hemispheric stroke (OR = 1.8 [1.05 to 3.09], p = 0.032). Major NCD was significantly associated with WMH pathology (OR = 2.54 [1.33 to 4.84], p = 0.005) and stroke lesion volume (OR (per ml) =1.04 [1.01 to 1.06], p = 0.001). Conclusion WMH pathology, MTA pathology and left hemispheric stroke were associated with the development of any NCD. Stroke lesion volume and WMH pathology were associated with the development of major NCD 3 months after stroke. These imaging findings may be used in the routine clinical setting to identify patients at risk for early post-stroke NCD.

• Vlachos, Georgios; Ihle-Hansen, Hege; Wyller, Torgeir Bruun; Brækhus, Anne; Mangset, Margrete & Hamre, Sophia Charlotta [Show all 7 contributors for this article] (2021). Cognitive and emotional symptoms in patients with first-ever mild stroke: The syndrome of hidden impairments. Journal of Rehabilitation Medicine. ISSN 1650-1977. 53:jrm00135, p. 1–7. doi: 10.2340/16501977-2764. Full text in Research Archive Show summary

  Objective: To evaluate the prevalence of cognitive and emotional impairments one year after first-ever mild stroke in younger patients Design: Prospective, observational, cohort study. Subjects: A consecutive sample of 117 previously cognitively healthy patients aged 18–70 years with mild stroke (National Institutes of Health Stroke Scale score ≤ 3) were included in 2 hospitals in Norway during a 2-year period. Methods: At 12-month follow-up, patients were assessed using validated instruments for essential cognitive domains, fatigue, depression, anxiety, apathy and pathological laughter and crying. Results: In total, 78 patients (67%) had difficulty with one or a combination of the cognitive domains psychomotor speed, attention, executive and visuospatial function, and memory. Furthermore, 50 patients (43%) had impairment in either one or a combination of the emotional measures for anxiety, depressive symptoms, fatigue, apathy or emotional lability. A total of 32 patients (28%) had both cognitive and emotional impairments. Only 21 patients (18%) scored within the reference range in all the cognitive and emotional tools. Conclusion: Hidden impairments are common after first-ever mild stroke in younger patients. Stroke physicians should screen for hidden impairments using appropriate tools.

• Henjum, Kristi; Godang, Kristin; Quist-Paulsen, Else; Idland, Ane-Victoria; Neerland, Bjørn Erik & Sandvig, Heidi Vihovde [Show all 13 contributors for this article] (2021). Cerebrospinal fluid catecholamines in delirium and dementia. Brain Communications. 3(3), p. 1–11. doi: 10.1093/braincomms/fcab121. Full text in Research Archive Show summary

  Dopamine and noradrenaline are functionally connected to delirium and have been targets for pharmacological interventions but the biochemical evidence to support this notion is limited. To study the CSF levels of dopamine, noradrenaline and the third catecholamine adrenaline in delirium and dementia, these were quantified in three patient cohorts: (i) cognitively normal elderly patients (n¼122); (ii) hip fracture patients with or without delirium and dementia (n¼118); and (iii) patients with delirium precipitated by another medical condition (medical delirium, n¼26). Delirium was assessed by the Confusion Assessment Method. The hip fracture cohort had higher CSF levels of noradrenaline and adrenaline than the two other cohorts (both P<0.001). Within the hip fracture cohort those with delirium (n¼65) had lower CSF adrenaline and dopamine levels than those without delirium (n¼52, P¼0.03, P¼0.002). Similarly, the medical delirium patients had lower CSF dopamine levels than the cognitively normal elderly (P<0.001). Age did not correlate with the CSF catecholamine levels. These findings with lower CSF dopamine levels in hip fracture- and medical delirium patients challenge the theory of dopamine excess in delirium and question use of antipsychotics in delirium. The use of alpha-2 agonists with the potential to reduce noradrenaline release needs further examination.

• Engvig, Andreas; Wyller, Torgeir Bruun; Skovlund, Eva; Ahmed, Marc; Hall, Trygve Sørdahl & Rockwood, Kenneth [Show all 8 contributors for this article] (2021). Association between clinical frailty, illness severity and post-discharge survival: a prospective cohort study of older medical inpatients in Norway. European Geriatric Medicine. ISSN 1878-7649. p. 1–9. doi: 10.1007/s41999-021-00555-8. Full text in Research Archive Show summary

  Purpose Study associations between frailty, illness severity and post-discharge survival in older adults admitted to medical wards with acute clinical conditions. Methods Prospective cohort study of 195 individuals (mean age 86; 63% females) admitted to two medical wards with acute illness, followed up for all-cause mortality for 20 months after discharge. Ward physicians screened for frailty and quantified its degree from one to eight using Clinical Frailty Scale (CFS), while clinical illness severity was estimated by New Early Warning Score 2 (NEWS2) and laboratory illness severity was calculated by a frailty index (FI-lab) using routine blood tests. Results CFS, NEWS2 and FI-lab scores were independently associated with post-discharge survival in an adjusted Cox proportional hazards model with age, ward category (acute geriatric and general medical) and comorbidity as covariates. Adjusted hazard ratios and 95% confidence intervals were 1.54 (1.24–1.91) for CFS, 1.12 (1.03–1.23) for NEWS2, and 1.02 (1.00–1.05) for FI-lab. A frailty × illness severity category interaction effect (p = 0.003), suggested that the impact of frailty on survival was greater in those experiencing higher levels of illness severity. Among patients with at least moderate frailty (CFS six to eight) and high illness severity according to both NEWS2 and FI-lab, two (13%) were alive at follow-up. Conclusion Frailty screening aided prognostication of survival following discharge in older acutely ill persons admitted to medical wards. The prognostic value of frailty increased when combined with readily available illness severity markers acquired during admission.

• Ernst, Gernot Walter; Watne, Leiv Otto; Frihagen, Frede; Wyller, Torgeir Bruun; Dominik, Andreas & Rostrup, Morten (2021). Low Heart Rate Variability Predicts Stroke and Other Complications in the First Six Postoperative Months After a Hip Fracture Operation. Frontiers in Cardiovascular Medicine. 8, p. 1–8. doi: 10.3389/fcvm.2021.640970. Full text in Research Archive
• Sajjad, Muhammad Umar; Blennow, Kaj; Knapskog, Anne Brita; Idland, Ane-Victoria; Chaudhry, Farrukh Abbas & Wyller, Torgeir Bruun [Show all 8 contributors for this article] (2020). Cerebrospinal Fluid Levels of Interleukin-8 in Delirium, Dementia, and Cognitively Healthy Patients. Journal of Alzheimer's Disease. ISSN 1387-2877. 73(4), p. 1363–1372. doi: 10.3233/JAD-190941. Full text in Research Archive Show summary

  Background: Delirium is a common and serious complication in geriatric patients. The pathophysiology of delirium is not known. Objective: The objective of the current study was to test the hypothesis that cerebrospinal fluid (CSF) levels of inflammatory markers at the time of spinal anesthesia for hip surgery are associated with delirium. Methods: In total 133 hip fracture patients and 125 cognitively healthy controls undergoing elective surgery, together with 73 Alzheimer’s disease (AD) dementia patients, were recruited at Oslo University Hospital and Diakonhjemmet Hospital, Oslo, Norway. Delirium was evaluated daily in hip fracture patients by the Confusion Assessment Method (CAM). Depression was evaluated by Cornell Scale for Depression in Dementia (CSDD). Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-8 (IL-8) levels were measured in CSF using a Mesoscale Discovery (MSD) immunoassay. Results: Hip fracture patients had significantly higher IL-8 levels (p < 0.001) compared to cognitively healthy controls or patients with stable AD dementia. Furthermore, preoperative IL-8 levels were significantly higher (p = 0.013) in hip fracture patients who developed delirium (incident delirium) after surgery as compared to patients with no delirium. However, subgroup analyses showed that IL-8 levels were only significantly higher in delirium patients without dementia (p = 0.006). In contrast, depression subgroup analysis showed that IL-8 concentration was significantly higher (p = 0.002) in delirium patients with depression. Both TNF-α and IL-1β were undetected in most patients. Conclusions: Our study suggests that IL-8 levels are associated with delirium onset and that underlying depression or dementia influences IL-8 levels.

• Mehlum, Maria Hollund; Liestøl, Knut; Kjeldsen, Sverre; Wyller, Torgeir Bruun; Julius, Stevo & Rothwell, Peter M. [Show all 10 contributors for this article] (2020). Blood pressure-lowering profiles and clinical effects of angiotensin receptor blockers versus calcium channel blockers. Hypertension. ISSN 0194-911X. 75(6), p. 1584–1592. doi: 10.1161/HYPERTENSIONAHA.119.14443. Full text in Research Archive
• Hamre, Sophia Charlotta; Fure, Brynjar; Helbostad, Jorunn L.; Wyller, Torgeir Bruun; Ihle-Hansen, Hege & Vlachos, Georgios [Show all 8 contributors for this article] (2020). Impairments in spatial navigation during walking in patients 70 years or younger with mild stroke. Topics in Stroke Rehabilitation. ISSN 1074-9357. 27, p. 601–609. doi: 10.1080/10749357.2020.1755814. Full text in Research Archive Show summary

  Background: Spatial navigation, the ability to determine and maintain a route from one place to another, is needed for independence in everyday life. Knowledge about impairments in spatial navigation in people with mild stroke is scarce. Objectives: To explore impairments in spatial navigation in patients ≤70 years after first-ever mild ischemic stroke (NIHSS≤3) and to explore which variables are associated with these impairments 12 months later. Methods: Patients were examined in the acute phase, and after 3 and 12 months. To assess impairments in spatial navigation, we used the Floor Maze Test (FMT), with time and FMT-errors as outcomes. Patients’ perceived navigational skills were collected using self-report. Logistic regression was used to explore which variables (sociodemographic data, stroke characteristics, cognition, and mobility) were associated with impaired navigation ability. Results: Ninety-seven patients (20 females) were included. The mean (SD) age was 55.5 (11.4) years. Timed FMT improved significantly from the acute phase to 12 months (p = <.001). At 12 months, 24 (24.7%) of the participants walked through the maze with errors, and 22 (22.7%) reported spatial navigational problems. The Trail Making Test (TMT)-B was the only variable from the acute phase associated with FMT-errors at 12 months, and being female was the only variable associated with self-reported navigational problems at 12 months. Conclusion: Nearly one in four patients experienced spatial navigation problems 12 months after a mild stroke. Executive function (TMT-B), measured in the acute phase, was associated with navigational impairments (FMT-errors) at 12 months, and being female was associated with self-reported navigational problems

• Hagberg, Guri; Ihle-Hansen, Hege; Fure, Brynjar; Thommessen, Bente; Ihle-Hansen, Håkon & Øksengård, Anne Rita [Show all 11 contributors for this article] (2020). No evidence for amyloid pathology as a key mediator of neurodegeneration post-stroke - A seven-year follow-up study. BMC Neurology. 20, p. 1–11. doi: 10.1186/s12883-020-01753-w. Full text in Research Archive Show summary

  Background Cognitive impairment (CI) with mixed vascular and neurodegenerative pathologies after stroke is common. The role of amyloid pathology in post-stroke CI is unclear. We hypothesize that amyloid deposition, measured with Flutemetamol (18F-Flut) positron emission tomography (PET), is common in seven-year stroke survivors diagnosed with CI and, further, that quantitatively assessed 18F-Flut-PET uptake after 7 years correlates with amyloid-β peptide (Aβ42) levels in cerebrospinal fluid (CSF) at 1 year, and with measures of neurodegeneration and cognition at 7 years post-stroke. Methods 208 patients with first-ever stroke or transient Ischemic Attack (TIA) without pre-existing CI were included during 2007 and 2008. At one- and seven-years post-stroke, cognitive status was assessed, and categorized into dementia, mild cognitive impairment or normal. Etiologic sub-classification was based on magnetic resonance imaging (MRI) findings, CSF biomarkers and clinical cognitive profile. At 7 years, patients were offered 18F-Flut-PET, and amyloid-positivity was assessed visually and semi-quantitatively. The associations between 18F-Flut-PET standardized uptake value ratios (SUVr) and measures of neurodegeneration (medial temporal lobe atrophy (MTLA), global cortical atrophy (GCA)) and cognition (Mini-Mental State Exam (MMSE), Trail-making test A (TMT-A)) and CSF Aβ42 levels were assessed using linear regression. Results In total, 111 patients completed 7-year follow-up, and 26 patients agreed to PET imaging, of whom 13 had CSF biomarkers from 1 year. Thirteen out of 26 patients were diagnosed with CI 7 years post-stroke, but only one had visually assessed amyloid positivity. CSF Aβ42 levels at 1 year, MTA grade, GCA scale, MMSE score or TMT-A at 7 years did not correlate with 18F-Flut-PET SUVr in this cohort. Conclusions Amyloid binding was not common in 7-year stroke survivors diagnosed with CI. Quantitatively assessed, cortical amyloid deposition did not correlate with other measures related to neurodegeneration or cognition. Therefore, amyloid pathology may not be a key mediator of neurodegeneration 7 years post-stroke. Trial registration Clinicaltrials.gov (NCT00506818). July 23, 2007. Inclusion from February 2007, randomization and intervention from May 2007 and trial registration in July 2007.

• Wyller, Torgeir Bruun (2020). «Hvileskjær» i pandemien må brukes til bedre planlegging for de eldste. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 140(8), p. 1–4. doi: 10.4045/tidsskr.20.0325. Full text in Research Archive
• Munthe-Kaas, Ragnhild; Aam, Stina; Saltvedt, Ingvild; Wyller, Torgeir Bruun; Pendlebury, Sarah T. & Lydersen, Stian [Show all 7 contributors for this article] (2020). Test Accuracy of the Montreal Cognitive Assessment in Screening for Early Poststroke Neurocognitive Disorder. Stroke. ISSN 0039-2499. 52(1), p. 317–320. doi: 10.1161/STROKEAHA.120.031030. Full text in Research Archive Show summary

  Background. Human immunodeficiency virus (HIV)–infected immunological nonresponders (INRs) fail to reconstitute their CD4+ T-cell pool after initiation of antiretroviral therapy, and their prognosis is inferior to that of immunological responders (IRs). A prevailing hypothesis is that the INR phenotype is caused by a persistently disrupted mucosal barrier, but assessments of gut mucosal immunology in different anatomical compartments are scarce. Methods. We investigated circulating markers of mucosal dysfunction, immune activation, mucosal Th17 and Th22 cells, and mucosa-adherent microbiota signatures in gut mucosal specimens from sigmoid colon and terminal ileum of 19 INRs and 20 IRs in addition to 20 HIV-negative individuals. Results. INRs had higher blood levels of the enterocyte damage marker intestinal fatty acid–binding protein than IRs. In gut mucosal biopsies, INRs had lower fractions of CD4+ T cells, higher fractions of interleukin 22, and a tendency to higher fractions of interleukin 17–producing CD4+ T cells. These findings were all restricted to the colon and correlated to circulating markers of enterocyte damage. There were no observed differences in gut microbial composition between INRs and IRs. Conclusions. Restricted to the colon, enterocyte damage and mucosal immune dysfunction play a role for insufficient immune reconstitution in HIV infection independent of the gut microbiota.

• Munthe-Kaas, Ragnhild; Aam, Stina; Ihle-Hansen, Hege; Lydersen, Stian; Knapskog, Anne Brita & Wyller, Torgeir Bruun [Show all 15 contributors for this article] (2020). Impact of different methods defining post-stroke neurocognitive disorder: The Nor-COAST study. Alzheimer's and Dementia: Translational Research and Clinical Interventions. 6:e12000(1), p. 1–9. doi: 10.1002/trc2.12000. Full text in Research Archive Show summary

  Introduction Post‐stroke neurocognitive disorder (NCD) is common; prevalence varies between studies, partially related to lack of consensus on how to identify cases. The aim was to compare the prevalence of post‐stroke NCD using only cognitive assessment (model A), DSM‐5 criteria (model B), and the Global Deterioration Scale (model C) and to determine agreement among the three models. Methods In the Norwegian Cognitive Impairment After Stroke study, 599 patients were assessed 3 months after suffering a stroke. Results The prevalence of mild NCD varied from 174 (29%) in model B to 83 (14%) in model C; prevalence of major NCD varied from 249 (42%) in model A to 68 (11%) in model C. Cohen's kappa and Cohen's quadratic weighted kappa showed fair to very good agreement among models; the poorest agreement was found for identification of mild NCD. Discussion The findings indicate a need for international harmonization to classify post‐stroke NCD.

• Idland, Ane-Victoria; Llonch, Roser Sala; Watne, Leiv; Brækhus, Anne; Hansson, Oskar & Blennow, Kaj [Show all 11 contributors for this article] (2020). Biomarker Profiling Beyond Amyloid and Tau: Cerebrospinal Fluid Markers, Hippocampal Atrophy, and Memory Change in Cognitively Unimpaired Older Adults. Neurobiology of Aging. ISSN 0197-4580. 93, p. 1–15. doi: 10.1016/j.neurobiolaging.2020.04.002. Full text in Research Archive Show summary

  Brain changes occurring in aging can be indexed by biomarkers. We used cluster analysis to identify subgroups of cognitively unimpaired individuals (n = 99, 64-93 years) with different profiles of the cerebrospinal fluid biomarkers beta amyloid 1-42 (Aβ42), phosphorylated tau (P-tau), total tau, chitinase-3-like protein 1 (YKL-40), fatty acid binding protein 3 (FABP3), and neurofilament light (NFL). Hippocampal volume and memory were assessed across multiple follow-up examinations covering up to 6.8 years. Clustering revealed one group (39%) with more pathological concentrations of all biomarkers, which could further be divided into one group (20%) characterized by tauopathy and high FABP3 and one (19%) by brain β-amyloidosis, high NFL, and slightly higher YKL-40. The clustering approach clearly outperformed classification based on Aβ42 and P-tau alone in prediction of memory decline, with the individuals with most tauopathy and FABP3 showing more memory decline, but not more hippocampal volume change. The results demonstrate that older adults can be classified based on biomarkers beyond amyloid and tau, with improved prediction of memory decline

• Kjeldsen, Sverre; Halvorsen, Sigrun; Wyller, Torgeir Bruun; Bath, Philip M. & Sandercock, Peter (2020). Eivind Berge, MD, PhD, 1964-2020: Cardiologist Who Was Fighting Stroke. Stroke. ISSN 0039-2499. 51(5), p. 1353–1355. doi: 10.1161/STROKEAHA.120.029351. Full text in Research Archive
• Myrstad, Marius; Kittang, Bård Reiakvam; Ranhoff, Anette Hylen; Neerland, Bjørn Erik & Wyller, Torgeir Bruun (2020). Kortikosteroider til sykehjemspasienter med covid-19? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. Full text in Research Archive
• Romskaug, Rita; Wyller, Torgeir Bruun; Straand, Jørund; Kersten, Hege & Molden, Espen (2020). Prescribed Doses of CYP2D6-Metabolized Drugs and Hemodynamic Responses in Relation to CYP2D6 Genotype Among Older Patients Exposed to Polypharmacy. Drugs & Aging. ISSN 1170-229X. 37(6), p. 425–433. doi: 10.1007/s40266-020-00763-0. Full text in Research Archive Show summary

  Background: Many drugs with dose-dependent effects on hemodynamic variables are metabolized by cytochrome P450 2D6 (CYP2D6). The aim of this study was to compare prescribed dosages and hemodynamic responses of such drugs in relation to pharmacogenetic variability in CYP2D6 metabolism among patients aged ≥ 70 years exposed to polypharmacy. Materials and methods: We included 173 patients with detailed information about drug use. The patients were retrospectively subjected to CYP2D6 genotyping, which comprised the most common variant alleles encoding reduced, absent, or increased CYP2D6 metabolism. In order to compare dosages across different CYP2D6-metabolized drugs, all prescribed daily doses were harmonized to the 'percent of a daily defined dose' (DDD). The mean harmonized DDD was compared between genotype-predicted normal metabolizers (NMs) and patients with reduced or absent CYP2D6 enzyme activity, defined as intermediate or poor metabolizers (IMs/PMs). Blood pressure, pulse, and patient proportions with orthostatism and bradycardia were also compared between genotype subgroups. Results: The genotype-predicted phenotype subgroups comprised 79 NMs (45.7%), 75 IMs (43.4%), and 16 PMs (9.2%). There were no differences in dosing of CYP2D6 substrates between NMs and IMs/PMs (p = 0.76). A higher proportion of CYP2D6 IMs/PMs experienced orthostatism (p = 0.03), while there were no significant subgroup differences for the other hemodynamic variables. Conclusion: In this real-life clinical setting of patients aged ≥ 70 years, dosing of CYP2D6 substrates were not adjusted according to genotype-predicted CYP2D6 metabolism. The increased occurrence of orthostatism in patients with reduced/absent CYP2D6 metabolism may indicate that individualized dosing based on genotype has the potential to prevent adverse effects in these vulnerable patients.

• Hvidsten, Lara H. Thomasgaard; Engedal, Knut; Selbæk, Geir; Wyller, Torgeir Bruun; Benth, Jurate Saltyte & Kersten, Hege (2019). Quality of Life of Family Carers of Persons with Young-Onset Dementia: A Nordic Two-Year Observational Multicenter. PLOS ONE. 14(7). doi: 10.1371/journal.pone.0219859. Full text in Research Archive Show summary

  Objectives To identify factors associated with QOL in carers of persons with young-onset Alzheimer’s (AD) and frontotemporal dementia (FTD) and explore development in QOL over a two-year period. Methods Eighty-eight family carers of community-dwelling people with young-onset AD (n = 50) and FTD (n = 38) recruited from Nordic memory clinics. Carer QOL was assessed using the Quality of Life–Alzheimer’s Disease questionnaire. Carer burden was assessed by the Relatives’ Stress scale and depressive symptoms by the Montgomery-Åsberg Depression Rating Scale. Factors associated with QOL in YOD and development in QOL over time were explored with growth mixture model trajectories and mixed model analyses. Results We identified two carer groups of persons with YOD following trajectories with better (n = 53) versus poorer (n = 30) QOL. Carers who reported more burden at baseline had greater odds of belonging to the poorer QOL group (OR 1.1 (1.0–1.2), p = 0.004). Analyses of the development in QOL showed a significant decline in QOL–AD scores among the AD-carers from baseline to two-year follow-up (p = 0.044), while the score remained stable among the FTD-carers. The FTD-carer group had significantly higher mean QOL–AD scores at one- and two-year follow-up (p = 0.022 and 0.045, respectively). However, the difference between the two groups regarding time trend was non-significant. Poorer QOL was associated with increased carer burden (p = 0.01), more depressive symptoms (p = 0.024), and being male carer (p = 0.038). Conclusion Higher care burden, more depressive symptoms, and being a male carer was associated with poorer QOL in family carers for persons with YOD. Carers of persons with AD may experience greater challenges in preserving QOL compared to carers of persons with FTD.

• Kirkhus, Lene; Benth, Jurate Saltyte; Grønberg, Bjørn Henning; Hjermstad, Marianne Jensen; Rostoft, Siri & Harneshaug, Magnus [Show all 9 contributors for this article] (2019). Frailty identified by geriatric assessment is associated with poor functioning, high symptom burden and increased risk of physical decline in older cancer patients: Prospective observational study. Palliative Medicine. ISSN 0269-2163. 33(3), p. 312–322. doi: 10.1177/0269216319825972. Full text in Research Archive Show summary

  Background: Maintaining quality of life including physical functioning is highly prioritized among older cancer patients. Geriatric assessment is a recommended approach to identify patients with increased vulnerability to stressors (frailty). How frailty affects quality of life and physical functioning in older cancer patients has scarcely been investigated. Aim: Focusing on physical functioning and global quality of life, we investigated whether frailty identified by a geriatric assessment was associated with higher risk of quality-of-life deterioration during cancer treatment and follow-up. Design: Prospective, observational study. Patients were classified as frail or non-frail by a modified geriatric assessment. Quality of life was measured using the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire at inclusion, 2, 4, 6 and 12 months. Setting: Eight Norwegian outpatient cancer clinics. Participants: Patients ⩾70 years with solid tumours referred for palliative or curative systemic medical cancer treatment. Results: Among 288 patients included, 140 (49%) were frail and 148 (51%) non-frail. Frail patients consistently reported poorer scores on all functioning and symptom scales. Independent of age, gender and major cancer-related factors, frail patients had significantly poorer physical functioning and global quality of life during follow-up, and opposed to non-frail patients they had both a clinically and statistically significant decline in physical functioning from baseline until 12 months. Conclusions: Geriatric assessment identifies frail patients with increased risk of physical decline, poor functioning and high symptom burden during and following cancer treatment. Frail patients should therefore receive early supportive or palliative care.

• Halaas, Nathalie Bodd; Henjum, Kristi; Blennow, Kaj; Dakhil, Shams; Idland, Ane-Victoria & Nilsson, Lars [Show all 13 contributors for this article] (2019). CSF sTREM2 and Tau Work Together in Predicting Increased Temporal Lobe Atrophy in Older Adults. Cerebral Cortex. ISSN 1047-3211. 00, p. 1–12. doi: 10.1093/cercor/bhz240. Full text in Research Archive Show summary

  Neuroinflammation may be a key factor in brain atrophy in aging and age-related neurodegenerative disease. The objective of this study was to test the association between microglial expression of soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2), as a measure of neuroinflammation, and brain atrophy in cognitively unimpaired older adults. Brain magnetic resonance imagings (MRIs) and cerebrospinal fluid (CSF) sTREM2, total tau (t-tau), phosphorylated181 tau (p-tau), and Aβ42 were analyzed in 115 cognitively unimpaired older adults, classified according to the A/T/(N)-framework. MRIs were repeated after 2 (n = 95) and 4 (n = 62) years. High baseline sTREM2 was associated with accelerated cortical thinning in the temporal cortex of the left hemisphere, as well as bilateral hippocampal atrophy, independently of age, Aβ42, and tau. sTREM2-related atrophy only marginally increased with biomarker positivity across the AD continuum (A−T− #x2292; A+T− #x2292; A+T+) but was significantly stronger in participants with a high level of p-tau (T+). sTREM2-related cortical thinning correlated significantly with areas of high microglial-specific gene expression in the Allen Human Brain Atlas. In conclusion, increased CSF sTREM2 was associated with accelerated cortical and hippocampal atrophy in cognitively unimpaired older participants, particularly in individuals with tau pathology. This suggests a link between neuroinflammation, neurodegeneration, and amyloid-independent tauopathy.

• Hvidsten, Lara H. Thomasgaard; Engedal, Knut; Selbæk, Geir; Wyller, Torgeir Bruun; Benth, Jurate Saltyte & Kersten, Hege (2019). Quality of Life in People with Young-Onset Dementia: A Nordic Two-Year Observational Multicenter Study. Journal of Alzheimer's Disease. ISSN 1387-2877. 67(1), p. 197–210. doi: 10.3233/JAD-180479. Full text in Research Archive Show summary

  Background:Cross-sectional studies of quality of life (QOL) of people with young-onset dementia show diverging results. Objective:To identify factors associated with QOL in people with young-onset Alzheimer’s (AD) and frontotemporal dementia (FTD) and explore development in QOL over a two-year period, including differences between the two subtypes. Methods:A two-year cohort study of 88 community-dwelling people with young-onset AD and FTD recruited from Nordic memory clinics. QOL was assessed using the proxy version of the Quality of Life – Alzheimer’s Disease questionnaire, dementia severity was rated with the Clinical Dementia Rating scale, depressive symptoms by the Cornell Scale for Depression in Dementia, awareness with the Reed anosognosia scale, and needs using the Camberwell Assessment of Needs in the Elderly questionnaire. Factors associated with QOL and development in QOL over time were explored with growth mixture model trajectories and mixed model analyses. Results:We identified two groups of people following trajectories with better (n = 35) versus poorer (n = 53) QOL. People with more depressive symptoms at baseline had higher odds of belonging to poorer QOL group, OR 1.2 (CI 1.1; 1.5, p = 0.011). Having Alzheimer’s disease was associated with significantly better QOL (p = 0.047 at baseline, p = 0.009 at T1 and p = 0.033 at T2). Increasing number of unmet needs was significantly associated with poorer QOL at baseline (p = 0.007), but not later in follow-up. Conclusion:Early assessment and treatment based on dementia subtype, depression, and individual needs may enhance quality of life in young-onset dementia. Keywords: Alzheimer’s disease, depression, frontotemporal dementia, quality of life, young-onset

• Hagberg, Guri; Fure, Brynjar; Sandset, Else Charlotte; Thommessen, Bente; Ihle-Hansen, Håkon & Øksengård, Anne Rita [Show all 9 contributors for this article] (2019). Long-term effects on survival after a 1-year multifactorial vascular risk factor intervention after stroke or TIA: Secondary analysis of a randomized controlled trial, a 7-year follow-up study. Vascular Health and Risk Management. ISSN 1176-6344. 15, p. 11–18. doi: 10.2147/VHRM.S191873. Full text in Research Archive Show summary

  <p><i>Background - </i>Stroke and coronary heart disease share the same risk factors, and a multifactorial intervention after stroke may potentially result in the same reduction in cardiovascular mortality as seen after coronary events. We aimed to evaluate the effect on survival 7 years after a 1-year multifactorial risk factor intervention, and identify clinical predictors for long-term survival in a hospital-based cohort of patients with first-ever stroke or transient ischemic attack (TIA). <p><i>Materials and methods - </i>We performed a secondary analysis of a randomized controlled trial including patients between February 2007 and July 2008 comparing an intensive risk factor intervention vs usual care the first year poststroke to prevent cognitive impairment. From February 2014 to July 2016, all patients were invited to a follow-up. For patients dying throughout the follow-up period, date of death was obtained from the medical record. Examination at baseline and 1-year follow-up included extensive assessment of vascular risk factors and cognitive assessments. <p><i>Results - </i>A total of 195 patients were randomized. Mean (SD) age was 71.6 (12.5) years, 53.3% were male, mean (SD) body mass index (BMI) was 25.6 (4.1) kg/m². During follow-up, 35 patients in the intervention group and 41 in the control group died. Kaplan–Meier survival estimates show no significant difference in intention-to-treat (ITT) population or complete case (CC) population (log-rank <i>P</i>=0.29 vs log-rank <i>P</i>=0.07). In multivariable Cox proportional hazards regression analyses, lower age and higher BMI was independently associated with long-term survival, adjusted HR (95% CI) 1.08 (1.05–1.11) per year and 0.91 (0.85–0.97) per kg/m². <p><i>Conclusion - </i>In this post hoc analysis, we found no significant effect on survival after 7 years of a multifactorial risk factor program given during the first year after first-ever stroke or TIA. Higher BMI was an independent predictor for long-term survival in this cohort.

• Evensen, Sigurd; Saltvedt, Ingvild; Lydersen, Stian; Wyller, Torgeir Bruun; Taraldsen, Kristin & Sletvold, Olav (2019). Delirium motor subtypes and prognosis in hospitalized geriatric patients ? A prospective observational study. Journal of Psychosomatic Research. ISSN 0022-3999. 122, p. 24–28. doi: 10.1016/j.jpsychores.2019.04.020. Full text in Research Archive Show summary

  Objective Delirium is common and associated with poor outcomes. Hypoactive motor subtype may predict worse outcome than no-subtype, hyperactive and mixed delirium, but uncertainty remains due to heterogeneity of results and subtyping tools. Other prognostic aspects across delirium motor subtypes are understudied. We investigated differences in one-year mortality, length of stay and institutionalization at discharge and after one year, across delirium motor subtypes in geriatric patients. Methods We conducted a prospective observational study, included 311 patients ≥75 years acutely admitted to a geriatric ward, diagnosed delirium using Diagnostic and Statistical Manual of Mental Disorder (5th ed.) criteria and used the Delirium Motor Subtype Scale for subtyping. Differences in mortality across subtypes were investigated using Cox proportional-hazard regression analyses, unadjusted and adjusted for age, comorbidity and delirium severity. We investigated differences in length of stay and institutionalization using the Kruskal-Wallis test and Pearson's chi-squared test with subsequent Hommel-adjusted pairwise comparisons. Results Ninety-three patients (30%) had delirium; 12 (13%) had no-subtype, 27 (29%) hyperactive, 30 (32%) hypoactive and 24 (26%) mixed delirium. There were no group differences regarding mortality (p = .61) or length of stay (p = .32). Analyses indicated group differences regarding discharge to an institution (p = .028), but pairwise comparisons showed no differences (smallest p = .071, no-subtype 45% vs hypoactive 85%). There were no group differences in institutionalization after one year (p = .26). Conclusion There were no significant differences in one-year mortality, length of stay or institutionalization across delirium motor subtypes in geriatric patients, although the study may indicate better prognosis in the no-subtype group.

• Neerland, Bjørn Erik; Wyller, Torgeir Bruun & Wyller, Vegard Bruun Bratholm (2019). Autonomic cardiovascular control in older patients with acute infection and delirium: a pilot study of orthostatic stress responses. BMC Geriatrics. 19(23), p. 1–8. doi: 10.1186/s12877-019-1035-0. Full text in Research Archive Show summary

  Background Alterations in autonomic nervous system (ANS) activity might be involved in the pathophysiology of delirium. The aim was to explore autonomic cardiovascular control in older patients with and without delirium. Methods Fourteen patients (five with delirium) acutely admitted to the geriatric ward with an infection were enrolled in the study. Patients with atrial fibrillation, a pacemaker, or on treatment with beta-blockers, calcium channel blockers or acetylcholinesterase inhibitors were not eligible. Continuous, non-invasive hemodynamic variables were measured during supine rest (5 min) and head-up tilt (HUT) to 15 degrees (10 min). Heart rate (HR), blood pressure (BP) and stroke volume (SV) were recorded beat-to-beat. Cardiac output (CO), total peripheral resistance (TPR), end-diastolic volume (EDV) and heart rate variability (HRV) values were calculated. Results Median age was 86 years. HR, BP, SV, CO, TPR and EDV were similar across the two groups at rest, but there was a trend towards a greater increase in systolic BP and HR during HUT in the delirium group. At rest, all HRV indices were higher in the delirium group, but the differences were not statistically significant. During HUT, the delirium group had higher power spectral density (PSD) (representing total variability) (p = 0.06) and a lower low frequency (LF)/high frequency (HF)-ratio (an index of sympathovagal balance) than the control group (p = 0.06). Also, delirious patients had a significantly greater reduction in standard deviation of RR-intervals (SDNN) (representing total variability) from baseline than controls (p = 0.01) during HUT. Conclusions This explorative pilot study on autonomic cardiovascular control in delirium suggests that there may be differences in HRV that should be further investigated in larger samples.

• Mehlum, Maria Hollund; Liestøl, Knut; Wyller, Torgeir Bruun; Hua, Tsushung A.; Rostrup, Morten & Berge, Eivind (2019). Blood pressure variability in hypertensive patients with atrial fibrillation in the VALUE trial. Blood Pressure. ISSN 0803-7051. 28(2), p. 77–83. doi: 10.1080/08037051.2018.1524707. Full text in Research Archive
• Romskaug, Rita; Skovlund, Eva; Straand, Jørund; Molden, Espen; Kersten, Hege & Pitkala, Kaisu H [Show all 8 contributors for this article] (2019). Effect of clinical geriatric assessments and collaborative medication reviews by geriatrician and family physician for improving health-related quality of life in home-dwelling older patients receiving polypharmacy: a cluster randomized clinical trial. JAMA Internal Medicine. ISSN 2168-6106. doi: 10.1001/jamainternmed.2019.5096. Full text in Research Archive Show summary

  Importance: Polypharmacy and inappropriate drug regimens are major health concerns among older adults. Various interventions focused on medication optimization strategies have been carried out, but the effect on patient-relevant outcomes remains uncertain. Objective: To investigate the effect of clinical geriatric assessments and collaborative medication reviews by geriatrician and family physician (FP) on health-related quality of life and other patient-relevant outcomes in home-dwelling older patients receiving polypharmacy. Design, Setting, and Participants: Cluster randomized, single-blind, clinical trial. Norwegian FPs were recruited from March 17, 2015, to March 16, 2017, to participate in the trial with their eligible patients. Participants were home-dwelling patients 70 years or older, using at least 7 medications regularly, and having their medications administered by the home nursing service. Patients in the control group received usual care. Randomization occurred at the FP level. A modified intent-to-treat analysis was used. Intervention: The intervention consisted of 3 main parts: (1) clinical geriatric assessment of the patients combined with a thorough review of their medications; (2) a meeting between the geriatrician and the FP; and (3) clinical follow-up. Main Outcomes and Measures: The primary outcome was health-related quality of life as assessed by the 15D instrument (score range, 0-1; higher scores indicate better quality of life, with a minimum clinically important change of ±0.015) at week 16. Secondary outcomes included changes in medication appropriateness, physical and cognitive functioning, use of health services, and mortality. Results: Among 174 patients (mean [SD] age, 83.3 [7.3] years; 67.8% women; 87 randomized to the intervention group and 87 randomized to the control [usual care] group) in 70 FP clusters (36 intervention and 34 control), 158 (90.8%) completed the trial. The mean (SD) 15D instrument score at baseline was 0.708 (0.121) in the intervention group and 0.714 (0.113) in the control group. At week 16, the mean (SD) 15D instrument score was 0.698 (0.164) in the intervention group and 0.655 (0.184) in the control group, with an estimated between-group difference of 0.045 (95% CI, 0.004-0.086; P = .03). Several secondary outcomes were also in favor of the intervention. There were more drug withdrawals, reduced dosages, and new drug regimens started in the intervention group. Conclusions and Relevance: This study’s findings indicate that, among older patients exposed to polypharmacy, clinical geriatric assessments and collaborative medication reviews carried out by a geriatrician in cooperation with the patient’s FP can result in positive effects on health-related quality of life.

• Kirkhus, Lene; Harneshaug, Magnus; Benth, Jurate Saltyte; Grønberg, Bjørn Henning; Rostoft, Siri & Bergh, Sverre [Show all 13 contributors for this article] (2019). Modifiable factors affecting older patients' quality of life and physical function during cancer treatment. Journal of Geriatric Oncology. ISSN 1879-4068. 10(6), p. 904–912. doi: 10.1016/j.jgo.2019.08.001. Full text in Research Archive Show summary

  BACKGROUND: Maintaining physical function and quality of life (QoL) are prioritized outcomes among older adults. We aimed to identify potentially modifiable factors affecting older patients' physical function and QoL during cancer treatment. METHODS: Prospective, multicenter study of 307 patients with cancer ≥70 years, referred for systemic treatment. Pre-treatment, a modified geriatric assessment (mGA) was performed, including registration of comorbidities, medications, nutritional status, cognitive function, depressive symptoms (Geriatric Depression Scale-15 [GDS]), and mobility (Timed Up and Go [TUG]). Patient-reported physical function (PF)-, global QoL-, and symptom scores were assessed at baseline, two, four, and six months by the EORTC Quality of Life Core Questionnaire-C30. The impact of mGA components and symptoms on patients' PF and global QoL scores during six months was investigated by linear mixed models. To identify groups following distinct PF trajectories, a growth mixture model was estimated. RESULTS: 288 patients were eligible, mean age was 76.9 years, 68% received palliative treatment. Higher GDS-scores and poorer TUG were independently associated with an overall level of poorer PF and global QoL throughout follow-up, as were more pain, dyspnea, and appetite loss, and sleep disturbance. Three groups with distinct PF trajectories were identified: a poor group exhibiting a non-linear statistically (p < .001) and clinically significant decline (≥10 points), an intermediate group with a statistically (p = .003), but not clinically significant linear decline, and a good group with a stable trajectory. Higher GDS-scores and poorer TUG, more pre-treatment pain and dyspnea were associated with higher odds of belonging to the poor compared to the good PF group. CONCLUSION: Depressive symptoms, reduced mobility, and more physical symptoms increased the risk of decrements in older patients' PF and global QoL scores during cancer treatment, and represent potential targets for interventions aiming at improving these outcomes.

• Næss, Gro; Wyller, Torgeir Bruun & Kirkevold, Marit (2019). Structured follow-up of frail home-dwelling older people in primary health care: Is there a special need, and could a checklist be of any benefit? A qualitative study of experiences from registered nurses and their leaders. Journal of Multidisciplinary Healthcare. 12, p. 675–690. doi: 10.2147/JMDH.S212283. Full text in Research Archive Show summary

  Aim: To identify experiences and opinions about the need for a structured follow-up and to identify potential benefits and barriers to the use of a checklist (Sub Acute Functional decline in the Older people [SAFE]) when caring for frail home-dwelling older people. Background: The complexity of older peoples’ health situation requires more coordinated health care across health care levels and a better structured follow-up than is currently being offered, especially in the transitional phase between hospital discharge and primary care, but also in more stable phases at home. Design: This was a qualitative study using focus group interviews. Methods: Data were collected during six focus group interviews in three districts in a municipality. Nineteen registered nurses (RNs) and seventeen leaders responsible for the follow-up of frail home-dwelling older people participated. Participants were representatives of the RNs in homecare and their leaders. Results: Our results highlight that although most RNs and their leaders saw a number of significant benefits to conducting a structured assessment and follow-up of frail older people home care recipients, a number of barriers made this difficult to realize on a daily basis. Conclusion: There is no common perception that a structured follow-up of frail homedwelling older people in primary health care is an important and contributing factor to better quality of health care. Despite this, most RNs and leaders found that the use of a structured checklist such as SAFE was a benefit to achieving a structured follow-up of the frail older people. We identified several factors of importance to whether a structured follow-up with a checklist is conducted in home care.

• Evensen, Sigurd Storhaug; Bourke, Alan; Lydersen, Stian; Sletvold, Olav; Saltvedt, Ingvild & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2019). Motor activity across delirium motor subtypes in geriatric patients assessed using body-worn sensors: a Norwegian cross-sectional study. BMJ Open. 9:e026401(2), p. 1–7. doi: 10.1136/bmjopen-2018-026401. Full text in Research Archive Show summary

  Objectives It remains unclear if geriatric patients with different delirium motor subtypes express different levels of motor activity. Thus, we used two accelerometer-based devices to simultaneously measure upright activity and wrist activity across delirium motor subtypes in geriatric patients. Design Cross-sectional study. Settings Geriatric ward in a university hospital in Norway. Participants Sixty acutely admitted patients, ≥75 years, with DSM-5-delirium. Outcome measures Upright activity measured as upright time (minutes) and sit-to-stand transitions (numbers), total wrist activity (counts) and wrist activity in a sedentary position (WAS, per cent of the sedentary time) during 24 hours ongoing Delirium Motor Subtype Scalesubtyped delirium. Results Mean age was 86.7 years. 15 had hyperactive, 20 hypoactive, 17 mixed and 8 had no-subtype delirium. We found more upright time in the no-subtype group than in the hypoactive group (119.3 vs 37.8 min, p=0.042), but no differences between the hyperactive, the hypoactive and the mixed groups (79.1 vs 37.8 vs 50.1 min, all p>0.28). The no-subtype group had a higher number of transitions than the hypoactive (54.3 vs 17.4, p=0.005) and the mixed groups (54.3 vs 17.5, p=0.013). The hyperactive group had more total wrist activity than the hypoactive group (1.238×104 vs 586×104 counts, p=0.009). The hyperactive and the mixed groups had more WAS than the hypoactive group (20% vs 11%, p=0.032 and 19% vs 11%, p=0.049). Conclusions Geriatric patients with delirium demonstrated a low level of upright activity, with no differences between the hyperactive, hypoactive and mixed groups, possibly due to poor gait function. The hyperactive and mixed groups had more WAS than the hypoactive group, indicating true differences in motor activity across delirium motor subtypes, also in geriatric patients. Wrist activity appears more suitable than an upright activity for both diagnostic purposes and activity monitoring in geriatric delirium.

• Hvidsten, Lara H. Thomasgaard; Engedal, Knut; Selbæk, Geir; Wyller, Torgeir Bruun; Benth, Jurate Saltyte & Bruvik, Frøydis Kristine [Show all 7 contributors for this article] (2019). Quality of life of family carers of persons with young-onset compared to late-onset dementia. Aging & Mental Health. ISSN 1360-7863. 24(9), p. 1394–1401. doi: 10.1080/13607863.2019.1617245. Full text in Research Archive Show summary

  Abstract OBJECTIVES: To compare quality of life (QOL) of family carers of persons with young- (YOD) to late-onset dementia (LOD). METHODS: This was a cross-sectional comparison of 88 carers of persons with YOD and 100 carers of persons with LOD. The Quality of Life - Alzheimer's Disease questionnaire (QOL-AD) was used to measure QOL of both carers and persons with dementia. Depressive symptoms were measured by the Geriatric Depression Scale (GDS) for carers and the Cornell Scale for Depression in Dementia for persons with dementia. Care burden was measured by the Relatives' Stress Scale. Activities of Daily Living (ADL) of the persons with dementia were assessed using the total score from the Lawton & Brody Instrumental-ADL scale and the Physical Self-Maintenance Scale. Multiple linear regression models with interactions between covariates and group (YOD versus LOD) were estimated. RESULTS: The QOL-AD scores of YOD-carers were significantly poorer compared to LOD-carers (mean difference 2.5 (95% CI 0.7; 4.3), p = 0.006). Poorer QOL of carers was associated with more depressive symptoms (mean QOL-AD change -0.5 (-0.6; -0.3), p < 0.001), but with no difference between the two groups. In contrast to LOD, QOL of carers of people with YOD was also significantly associated with symptom duration (p = 0.002), depressive symptoms of the persons with dementia (p = 0.030), ADL (p = 0.001), and carer burden (p = 0.002). CONCLUSION: YOD-carers reported significantly poorer QOL compared to LOD-carers. QOL was significantly associated with depressive symptoms in carers of both groups.

• Hagberg, Guri; Fure, Brynjar; Thommessen, Bente; Ihle-Hansen, Håkon; Øksengård, Anne Rita & Nygård, Ståle [Show all 10 contributors for this article] (2019). Predictors for Favorable Cognitive Outcome Post-Stroke: A-Seven-Year Follow-Up Study. Dementia and Geriatric Cognitive Disorders. ISSN 1420-8008. p. 1–11. doi: 10.1159/000501850. Full text in Research Archive
• Wang-Hansen, Marte Sofie; Wyller, Torgeir Bruun; Hvidsten, Lara H. Thomasgaard & Kersten, Hege (2019). Can screening tools for potentially inappropriate prescriptions in older adults prevent serious adverse drug events? European Journal of Clinical Pharmacology. ISSN 0031-6970. 75(5), p. 627–637. doi: 10.1007/s00228-019-02624-1. Full text in Research Archive Show summary

  Purpose The purpose of the study is to identify and explore risk factors of serious adverse drug events (SADE) and SADE-related admissions in acutely hospitalized multimorbid older adults and assess whether these could have been prevented by adherence to the prescription tools Screening Tool of Older Persons’ Prescriptions (STOPP) and The Norwegian General Practice (NORGEP) criteria. Methods Cross-sectional study of acutely admitted patients to a medical department in a Norwegian regional hospital. Eligible patients were community-dwelling, receiving home care services, and aged 75+, with ≥ 3 chronic diseases. Medications and information regarding the admission were retrieved from the referral letter and medical records, while an expert panel identified SADE using the Common Terminology Criteria for Adverse Events and SADE-related admissions. Results We included 232 patients. Mean (SD) age was 86 (5.7) years, 137 (59%) were female, 121 (52%) used 5–9 drugs whereas 65 (28%) used ≥ 10. We identified SADEs in 72 (31%) of the patients, and in 49 (68%) of these cases, the SADE was considered to cause the hospital admission. A low body mass index (BMI) and a high Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score were independent risk factors for SADEs. Among the SADEs identified, 32 (44%) and 11 (15%) were preventable by adherence to STOPP and NORGEP, respectively. Conclusions We found a high prevalence of SADE leading to hospitalization. Risk factors for SADE were high CIRS-G and low BMI. STOPP identified more SADEs than NORGEP, but adherence to the prescription tools could only to a limited degree prevent SADEs in this patient group.

• Hov, Karen Roksund; Neerland, Bjørn Erik; Undseth, Øystein; Wyller, Vegard Bruun Bratholm; MacLullich, Alasdair M.J. & Qvigstad, Eirik [Show all 8 contributors for this article] (2019). The Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial. International Journal of Geriatric Psychiatry. ISSN 0885-6230. 34(7), p. 974–981. doi: 10.1002/gps.5098. Full text in Research Archive Show summary

  Objectives The aim of this double‐blinded randomised placebo‐controlled trial was to investigate the efficacy of clonidine for delirium in medical inpatients greater than 65 years. Methods Acutely admitted medical patients greater than 65 years with delirium or subsyndromal delirium were eligible for inclusion. Included patients were given a loading dose of either placebo or clonidine; 75 μg every third hour up to a maximum of four doses to reach steady state and further 75 μg twice daily until delirium free for 2 days, discharge or a maximum of 7 days of treatment. The primary endpoint was the trajectory of the Memorial Delirium Assessment Scale (MDAS) for the 7 days of treatment. Presence of delirium according to the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) criteria and severity measured by MDAS were assessed daily until discharge or a maximum of 7 days after end of treatment. Results Because of slower enrolment than anticipated, the study was halted early. Ten patients in each group were studied. The low recruitment rate was mainly due to the presence of multiple patient exclusion criteria for patient safety. There was no significant difference between the treatment group in the primary endpoint comparing the trajectory of MDAS for the 7 days of treatment using mixed linear models with log transformation, (P = .60). The treatment group did not have increased adverse effects. Conclusions No effect of clonidine for delirium was found, although the study was under powered. Further studies in less frail populations are now required.

• Hall, Roanna J.; Watne, Leiv; Cunningham, Emma; Zetterberg, Henrik; Shenkin, Susan D & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2018). CSF biomarkers in delirium: a systematic review. International Journal of Geriatric Psychiatry. ISSN 0885-6230. 33(11), p. 1479–1500. doi: 10.1002/gps.4720. Full text in Research Archive

View all works in NVA

• Robberstad, Anne; Halvorsen, Marit & Wyller, Torgeir Bruun (2026). Ikke grunnlag for å konstatere vitenskapelig uredelighet. doi: https:/www.khrono.no/ikke-grunnlag-for-a-konstatere-vitenskapelig-uredelighet/1077093. Full text in Research Archive Show summary

  Sakens hovedspørsmål er om det i et konkret sak var snakk in "helseforskning" i helseforskningslovens forstand, eller kvalitetssikring med det formål å forbedre helsehjelpen (som ikke er helseforskning i lovens forstad).

• Kersten, Hege; Vaksvik, Tonje Marie Bø; Romskaug, Rita; Wyller, Torgeir Bruun; Jaioun, Keson & Botteri, Edoardo [Show all 7 contributors for this article] (2026). One year pre-diagnostic prevalence and associated factors of polypharmacy and potentially inappropriate medication use in community-dwelling adults with mild cognitive impairment or dementia in Norway (2014–2024): A registered report protocol. doi: 10.1371/journal.pone.0356275. Full text in Research Archive Show summary

  Background People with cognitive impairment frequently have multiple comorbidities, and polypharmacy is highly prevalent, affecting nearly half of individuals with mild cognitive impairment and dementia. The use of potentially inappropriate medications (PIMs), including those specifically problematic for cognitive impairment (PIMcog), increases with the total number of medications and may exacerbate cognitive symptoms or increase the risk of adverse drug events. However, the prevalence of polypharmacy and PIMcog use among patients diagnosed with MCI or dementia in Norwegian specialist outpatient clinics has not been described. Methods We will conduct a retrospective cohort study linking national health registries to estimate the prevalence of polypharmacy and PIMcog use in the year prior to diagnosis of mild cognitive impairment or dementia. Data from the Norwegian Registry of Persons Assessed for Cognitive Symptoms will be linked to dispensing data from the Norwegian Prescribed Drug Registry and comorbidity data from the Norwegian Patient Registry. The study population will include all patients diagnosed with mild cognitive impairment or dementia in Norwegian specialist outpatient clinics from 2014 to 2024. We will estimate the twelve-month prevalence of polypharmacy and PIMcog use preceding diagnosis, compare sociodemographic and clinical characteristics between PIMcog users and non-users, and identify factors associated with PIMcog use. Expected impact By describing the one-year prevalence and patterns of polypharmacy and PIMcog use and associated factors prior to mild cognitive impairment and dementia diagnosis, the findings may inform targeted deprescribing interventions and safer prescribing strategies for individuals with cognitive impairment.

• Brækhus, Anne; Persson, Karin Ester Torun; Selbæk, Geir; Bekkhus-Wetterberg, Peter & Wyller, Torgeir Bruun (2026). Demenssykdom er underdiagnostisert. 146, p. 1–8. doi: 10.4045/tidsskr.25.0705. Full text in Research Archive Show summary

  Forekomsten av demenssykdom i den eldre delen av befolkningen er høy, og antallet vil øke betydelig i årene fremover når antallet eldre i befolkningen øker. Det finnes i dag ca. 116 000 personer med demenssykdom, i år 2050 er antallet estimert til ca. 237 000 pasienter (1). I gruppen over 90 år har omtrent 50 % demenssykdom, og svært mange av disse er aleneboende (1). Demenssykdom medfører redusert evne til å gjennomføre aktiviteter i dagliglivet (ADL). I starten av sykdommen rammes kompliserte funksjoner som deltakelse i arbeids- og foreningsliv, bilkjøring og håndtering av egen økonomi. For å gi nødvendig bistand til det personen med demenssykdom ikke mestrer (særlig økonomiske forhold (vergebistand) og hjelp til administrering av medisiner), er det viktig at de kognitive symptomene utredes og demensdiagnosen stilles så tidlig som mulig. Flere studier, blant annet en norsk, viser derimot at bare et mindretall av dem med demens har fått diagnosen stadfestet (1, 2).

• Gisvold, Sven Erik; Wyller, Torgeir Bruun; Grøttumsbråten, Janne; Haug, Lene C.; Hove, Aud & Haukelien, Heidi [Show all 11 contributors for this article] (2025). Helseforetaksmodellen: En ulykke for norsk helsevesen. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Exploring Associations Between Medication Use, Frailty and Oral Health in Acutely Ill Older Adults. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Dry Mouth, Frailty and Polypharmacy in Acutely Ill Older Adults. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Preliminary data from the COOP II study - exploring oral and general health among older people in need of acute care. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2024). Preliminary data from the COOP II study – exploring oral and general health among older people in need of short-time acute care. Full text in Research Archive
• Wyller, Torgeir Bruun; Nordal, Eli Johanne & Kåvik, Berit Riise (2024). Fakkeltog erikke nok. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 144(6). doi: 10.4045/tidsskr.24.0127. 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
• 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.

• Gisvold, Sven Erik; Jensen, Bjarne; Haug, Lene; Wyller, Torgeir Bruun; Hove, Aud & Rangønes, Ingrid Ovidie [Show all 12 contributors for this article] (2023). Et todelt helsevesen. p. 42–43. Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2023). What happens to oral health when multimorbidity, polypharmacy and frailty comes along? Full text in Research Archive
• Ringstad, Ingrid Beate; Romskaug, Rita; Fjeld, Katrine Gahre; Hove, Lene Hystad; Santervas, Leonor Roa & Wyller, Torgeir Bruun [Show all 7 contributors for this article] (2023). Oral Health in Times of Frailty and Polypharmacy. Full text in Research Archive
• Wyller, Torgeir Bruun (2023). Betingelser for bærekraft. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(7). doi: 10.4045/tidsskr.23.0194. Full text in Research Archive
• Neerland, Bjørn Erik; Busund, Rolf; Haaverstad, Rune; Helbostad, Jorunn L.; Landsverk, Svein A. & Martinaityte, Ieva [Show all 19 contributors for this article] (2022). Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial. BMJ Open. 12(6). doi: 10.1136/bmjopen-2021-057460. Full text in Research Archive
• Wyller, Torgeir Bruun; Thorsen, Dag Einar & Jensen, Bjarne (2022). Som bestilt. Full text in Research Archive
• Wetterberg, Peter; Brækhus, Anne; Müller, Ebba Gløersen; Norvik, Monica Irene; Winsnes, Ingvild Elisabeth & Wyller, Torgeir Bruun (2022). Primær progressiv afasi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 142(17), p. 1477–1480. doi: 10.4045/tidsskr.22.0100. Full text in Research Archive Show summary

  I sjeldne tilfeller begynner degenerativ demenssykdom med isolerte vansker med språket, uten andre kognitive symptomer. Ofte kalles dette litt upresist for «ordleting». Det finnes flere varianter, forårsaket av ulike underliggende nevropatologiske forandringer. En sjelden gang er det problemer med talen snarere enn språkvansker som dominerer. Pasientene kan ha utelukkende språk- eller talesymptomer i mange år, men alle vil over tid utvikle en global demenssykdom. Denne kliniske oversikten beskriver primær progressiv afasi, som er en fellesbetegnelse for demenssykdommer som begynner med språkvansker.

• Ranhoff, Anette Hylen; Myrstad, Marius; Kittang, Bård Reiakvam & Wyller, Torgeir Bruun (2021). Bør alle sykehjemsbeboere vaksineres? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(3), p. 210–210. doi: 10.4045/tidsskr.21.0072. Full text in Research Archive
• Wyller, Torgeir Bruun; Gisvold, Sven Erik; Grøttumsbråten, Janne; Haug, Lene; Hove, Aud & Isumhaugen, Mariann [Show all 15 contributors for this article] (2021). Sykehusreformen har skapt mer byråkrati og svekket samarbeidet. p. 22–22. Full text in Research Archive
• Wyller, Torgeir Bruun; Gisvold, Sven Erik; Grøttumsbråten, Janne; Haug, Lene; Hove, Aud & Isumhaugen, Mariann [Show all 15 contributors for this article] (2021). Sykehusreformen har skapt byråkrati og svekket samarbeidet. p. 10–10. Full text in Research Archive
• Kirkhus, Lene; Saltyte-Benth, Jurate; Grønberg, Bjørn Henning; Hjermstad, Marianne Jensen; Rostoft, Siri & Harneshaug, Magnus [Show all 9 contributors for this article] (2020). Reply to the letter to the editor ‘Geriatric-oncology and palliative care: cautionary on using geriatric assessment as a sole basis to limit care’. Palliative Medicine. ISSN 0269-2163. 34(2), p. 255–256. doi: 10.1177/0269216319888987. Full text in Research Archive
• Wyller, Torgeir Bruun (2020). Reell samhandling forebygger reinnleggelse. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 140(1), p. 1–3. doi: 10.4045/tidsskr.19.0724. Full text in Research Archive
• Larsen, Kristin Tveitan; Forfang, Elisabeth; Pennlert, Johanna; Glader, Eva-Lotta; Kruuse, Christina & Wester, Per [Show all 12 contributors for this article] (2020). STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage: Protocol for a randomised controlled trial. European Stroke Journal. ISSN 2396-9873. 5(4), p. 414–422. doi: 10.1177/2396987320954671. Full text in Research Archive Show summary

  Background and aims - Many patients with prior intracerebral haemorrhage have indications for antithrombotic treatment with antiplatelet or anticoagulant drugs for prevention of ischaemic events, but it is uncertain whether such treatment is beneficial after intracerebral haemorrhage. STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage will assess (i) the effects of long-term antithrombotic treatment on the risk of recurrent intracerebral haemorrhage and occlusive vascular events after intracerebral haemorrhage and (ii) whether imaging findings, like cerebral microbleeds, modify these effects.<p> <p>Methods - STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is a multicentre, randomised controlled, open trial of starting versus avoiding antithrombotic treatment after non-traumatic intracerebral haemorrhage, in patients with an indication for antithrombotic treatment. Participants with vascular disease as an indication for antiplatelet treatment are randomly allocated to antiplatelet treatment or no antithrombotic treatment. Participants with atrial fibrillation as an indication for anticoagulant treatment are randomly allocated to anticoagulant treatment or no anticoagulant treatment. Cerebral CT or MRI is performed before randomisation. Duration of follow-up is at least two years. The primary outcome is recurrent intracerebral haemorrhage. Secondary outcomes include occlusive vascular events and death. Assessment of clinical outcomes is performed blinded to treatment allocation. Target recruitment is 500 participants.

• Romskaug, Rita & Wyller, Torgeir Bruun (2019). Farlig cocktail, eller ikke? | Klassekampen. doi: https:/klassekampen.no/artikkel/2019-11-08/farlig-cocktail-eller-ikke. Full text in Research Archive Show summary

  Lange medisinlister hos eldre er en utfordring for helsevesenet. Nå er vi på sporet av en bedre modell.

• Romskaug, Rita & Wyller, Torgeir Bruun (2019). Effekt av legemiddelgjennomganger utført av geriater og fastlege i samarbeid. Indremedisineren. ISSN 1891-1617. 04/2019. Full text in Research Archive
• Kirkhus, Lene; Benth, Jurate Saltyte; Grønberg, Bjørn Henning; Hjermstad, Marianne Jensen; Rostoft, Siri & Harneshaug, Magnus [Show all 9 contributors for this article] (2019). Reply to the letter to the editor 'Geriatric-oncology and palliative care: cautionary on using geriatric assessment as a sole basis to limit care'. Palliative Medicine. ISSN 0269-2163. doi: 10.1177/0269216319888987. 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.

View all works in NVA