Forskningsartikler

Background: Older, frail patients with multimorbidity are at an especially high risk for disease severity and death from COVID-19. The social restrictions proved challenging for the residents, their relatives, and the care staff. While these restrictions clearly impacted daily life in Norwegian nursing homes, knowledge about how the pandemic influenced nursing practice is sparse.

Aim: The aim of the study was to illuminate ethical difficult situations experienced by Norwegian nurses working in nursing homes during the COVID-19 pandemic.

Research design and participants: The research design involved semistructured individual interviews conducted with 15 nurses working in 8 nursing homes in 3 health regions in Norway, within both urban and rural areas. Ethical considerations: Oral and written information about the study was provided before the participants gave their written consent. The transcribed interviews were de-identified. The study was approved by the Norwegian Centre for Research Data.

Findings: Four ethical difficult situations were identified: (a) turning the nursing home into a prison; (b) using medication to maintain peace and order; (c) being left alone with the responsibility; and (d) s. impact on decision-making.

Conclusions: The nurses’ ethical challenges were intertwined with external factors, such as national and local guidelines, and the nurses’ own internalized factors, which were connected to their subjective professionality. This duality inflicted emotional distress and gave nurses few opportunities to perform nursing in a professionally sound and safe manner.

Hillestad, A.H., Rokstad, A.M.M., Tretteteig, S., Julnes S.G., Lichtwarck, B. & Eriksen, S.

Introduction
Quality of life (QoL) and function are important outcomes for older adults with cancer. We aimed to assess differences in trends in patient-reported outcomes (PROs) during radiotherapy (RT) between (1) groups with curative or palliative treatment intent and (2) groups defined according to the number of geriatric impairments.
Materials and Methods
A prospective observational study including patients aged ≥65 years receiving curative or palliative RT was conducted. Geriatric assessment (GA) was performed before RT, and cut-offs for impairments within each domain were defined. Patients were grouped according to the number of geriatric impairments: 0, 1, 2, 3, and ≥ 4. Our primary outcomes, global QoL and physical function (PF), were assessed by The European Organisation for Research and Treatment of Cancer Quality-of-Life Core Questionnaire (EORTC) (QLQ-C30) at baseline, RT completion, and two, eight, and sixteen weeks later. Differences in trends in outcomes between the groups were assessed by linear mixed models.
Results
301 patients were enrolled, mean age was 73.6 years, 53.8% received curative RT. Patients receiving palliative RT reported significantly worse global QoL and PF compared to the curative group. The prevalence of 0, 1, 2, 3 and ≥ 4 geriatric impairments was 16.6%, 22.7%, 16.9%, 16.3% and 27.5%, respectively. Global QoL and PF gradually decreased with an increasing number of impairments. These group differences remained stable from baseline throughout follow-up without any clinically significant changes for any of the outcomes.
Discussion
Increasing number of geriatric impairments had a profound negative impact on global QoL and PF, but no further decline was observed for any group or outcome, indicating that RT was mainly well tolerated. Thus, geriatric impairments per se should not be reasons for withholding RT. GA is key to identifying vulnerable patients in need of supportive measures, which may have the potential to improve treatment tolerance.

Guro Falk Eriksen, Jūratė Šaltytė Benth, Bjørn Henning Grønberg, Siri Rostoft, Lene Kirkhus, Øyvind Kirkevold, Line Merethe Oldervoll, Asta Bye, Anne Hjelstuen, Marit Slaaen

Abstract
Epidemiological literature on the relationship between physical activity and chronic pain is scarce and inconsistent. Hence, our aim was to assess the relationship applying comprehensive methodology, including self-reported and accelerometer measures of physical activity and different severity levels of chronic pain. We used data from the Tromsø Study (2015-2016). All residents in the municipality, aged 40 years and older were invited to participate (n=32,591, 51% women). A total of 21,083 (53% women) reported on questionnaires. Additionally, 6,778 participants (54% women) were invited to wear accelerometers (6,125 with complete measurements). Our exposure measures were self-reported leisure time physical activity, exercise frequency, duration and intensity and two accelerometer-measures (steps per day and minutes of moderate to vigorous physical activity per day). Outcome measurements were chronic pain and moderate-to-severe chronic pain. We used Poisson regression to estimate chronic pain prevalence and prevalence ratios for each physical activity measure, with adjustments for sex, age, education level, smoking history, and occupational physical activity. Our main analyses showed an inverse dose-response relationships between all physical activity measures and both severity measures of chronic pain, except that the dose-response relationship with exercise duration was only found for moderate-to-severe pain. All findings were stronger for the moderate-to-severe pain outcomes than for chronic pain. Robustness analyses gave similar results as the main analyses. We conclude that an inverse dose-response association between physical activity and chronic pain is consistent across measures. To summarize, higher levels of physical activity is associated with less chronic pain and moderate-to-severe chronic pain.

Mats Kirkeby Fjeld, Anders Pedersen Årnes, Bo Engdahl, Bente Morseth, Laila Arnesdatter Hopstock, Alexander Horsch, Audun Stubhaug, Bjørn Heine Strand, Christopher Sivert Nielsen, Ólöf Anna Steingrímsdóttir

Background
The complexity of past trauma and ongoing post-migration stressors challenges the existing mental health treatment for trauma-affected refugees. Therefore, interventions are needed to accommodate these complex challenges in mental health treatment. This study examines the effect of an add-on integrated care intervention compared to treatment as usual (TAU) for trauma-affected refugees in a randomised controlled trial (RCT).
Methods
The study is carried out at a Danish outpatient clinic and will include 197 treatment-seeking refugees with post-traumatic stress disorder (PTSD) who are unemployed and affiliated with municipal employment services. Mental health TAU comprises 10 sessions with a medical doctor (pharmacological treatment and psychoeducation) and 16–20 sessions with a psychologist (manual-based cognitive behavioural therapy) for a period of eight to 12 months. The add-on intervention strengthens coordination between mental health treatment and employment interventions with three cross-sectoral collaborative meetings during the mental health treatment. The integrated care intervention draws attention to the bidirectional impact of mental health problems and post-migration stressors and focuses on cross-sectoral shared plans. The primary outcome is functioning, measured by WHODAS 2.0, the interviewer-administered 12-item version, with secondary outcomes measuring quality of life, mental health symptoms, and post-migration stressors.
Discussion
The RCT is novel in intervention design for trauma-affected refugees and will bring forward new perspectives and knowledge of integrated care interventions for trauma-affected refugees. The integrated care intervention is expected to reduce post-migration stressors that negatively affect the treatment of trauma-related mental health problems, thereby improving preconditions for enhanced treatment outcomes. The intervention builds on existing practices in the Danish healthcare and employment sectors, which ensures high scalability and sustainability for future practices.

Maja Bruhn, Henriette Laugesen, Matilde Kromann-Larsen, Cathrine Selnes Trevino, Lene Eplov, Carsten Hjorthøj, Jessica Carlsson

Objectives
To investigate the course of depressive symptoms in newly admitted nursing home (NH) residents and how resident characteristics were associated with the symptoms. To identify groups of residents following the same symptom trajectory.
Design
An observational, multicenter, longitudinal study over 36 months with 7 biannual assessments.
Setting and Participants
Representing 47 Norwegian NHs, 696 residents were included at admission to a NH.
Methods
Depressive symptoms were assessed with the Cornell Scale for Depression in Dementia (CSDD). We selected severity of dementia, functional impairment, physical health, pain, use of antidepressants, age, and sex as covariates. Time trend in CSDD score was assessed by a linear mixed model adjusting for covariates. Next, a growth mixture model was estimated to investigate whether there were groups of residents following distinct trajectories in CSDD scores. We estimated a nominal regression model to assess whether the covariates at admission were associated to group membership.
Results
There was a nonlinear trend in CSDD score. More severe dementia, a lower level of functioning, poorer physical health, more pain, use of antidepressants, and younger age at admission were associated with higher CSDD scores. Growth mixture model identified 4 groups: (1) persistent mild symptoms (32.6%), (2) persistent moderate symptoms (50.8%), (3) increasing symptoms (5.1%), and (4) severe but decreasing symptoms (11.6%). A lower level of functioning, poorer physical health, more pain, use of antidepressants, and younger age at admission were associated with higher odds for belonging to the severe but decreasing symptoms group compared with the persistent mild symptoms group.
Conclusions and Implications
Most NH residents were in trajectory groups with persistent mild or moderate depressive symptoms. Residents with more severe dementia, lower levels of functioning, poor physical health, severe pain, younger age at admittance, and who are using antidepressants should be monitored closely and systematically with respect to depression. Taking actions toward a more personalized treatment for depression in NHs is a priority and should be investigated in future studies.

Tom Borza, Geir Selbæk, Bjørn Lichtwarck, Jūratė Šaltytė Benth, Sverre Bergh

High blood pressure is a well-established risk factor of dementia. However, the timing of the risk remains controversial. The aim of the present study was to compare trajectories of systolic blood pressure (SBP) over a 35-year follow-up period in the Health Survey in Trøndelag (HUNT) from study wave 1 to 4 in people with and without a dementia diagnosis at wave 4 (HUNT4). This is a retrospective cohort study of participants aged ≥ 70 years in HUNT4, where 9,720 participants were assessed for dementia. In the HUNT study all residents aged ≥ 20 years have been invited to four surveys: HUNT1 1984–86, HUNT2 1995–97, HUNT3 2006–08 and HUNT4 2017–19. The study sample was aged 70–102 years (mean 77.6, SD 6.0) at HUNT4, 54% were women and 15.5% had dementia, 8.8% had Alzheimer’s disease (AD), 1.6% had vascular dementia (VaD) and 5.1% had other types of dementia. Compared to those without dementia at HUNT4, those with dementia at HUNT4 had higher SBP at HUNT1 and HUNT2, but lower SBP at HUNT4. These differences at HUNT1 and 2 were especially pronounced among women. Results did not differ across birth cohorts. For dementia subtypes at HUNT4, the VaD group had a higher SBP than the AD group at HUNT2 and 3. Age trajectories in SBP showed that the dementia group experienced a steady increase in SBP until 65 years of age and a decrease from 70 to 90 years. SBP in the no- dementia group increased until 80 years before it leveled off from 80 to 90 years. The present study confirms findings of higher midlife SBP and lower late-life SBP in people with dementia. This pattern may have several explanations and it highlights the need for close monitoring of BP treatment in older adults, with frequent reappraisal of treatment needs.

Geir Selbæk, Josephine Stuebs, Knut Engedal, Vladimir Hachinski, Knut Hestad, Cathrine Selnes Trevino, Håvard Skjellegrind, Yehani Wedatilake and Bjørn Heine Strand

ABSTRACT
Introduction Given that exercise training reduces the risk of developing Alzheimer’s disease (AD), induces changes in the blood composition and has widespread systemic benefits, it is reasonable to hypothesise that exercised plasma (ExPlas) may have rejuvenative properties. The main objective is to test safety and tolerability of transfusing ExPlas from young, healthy, fit adults to patients with mild cognitive impairment (MCI) or early AD. The study is a pilot for a future efficacy study. The key secondary objectives are examining the effect of plasma transfusions on cognitive function, fitness level, vascular risk profile, assessment of cerebral blood flow and hippocampal volume, quality of life, functional connectivity assessed by resting state functional MRI and biomarkers in blood and cerebrospinal fluid.
Methods and analysis ExPlas is a double-blinded, randomised controlled clinical single-centre trial. Patients up to 75 years of age with diagnosis early symptomatic phase AD will be recruited from two Norwegian hospitals. ExPlas is plasma drawn by plasmapheresis once a month for 4 months, from a total of 30 fit male donors (aged 18–40, BMI≤27 kg/m2 and maximal oxygen uptake>55 mL/kg/min). All units will be virus inactivated by the Intercept method in accordance with procedures at St. Olavs University Hospital. Comparison with isotonic saline allows differentiation from a non-blood product. The main study consists of 6 rounds of examinations in addition to 12 plasma transfusions divided over three 4-week periods during study year-1. It is also planned to conduct follow-up examinations 2 and 5 years after baseline
Ethics and dissemination Written informed consent will be obtained from all participants and participation is voluntary. All participants have a next of kin who will follow them throughout the study to represent the patient’s interest. The study is approved by the Regional Committee for Medical and Health Research Ethics (REK 2018/702) and the Norwegian Medicines Agency (EudraCT No. 2018-000148-24). The study will be published in an open access journal and results will be presented at numerous national and international meetings as well as on social media platforms.

Atefe R Tari , Helene Haugen Berg, Vibeke Videm, Geir Bråthen, Linda R White, Ragnhild Nyhus Røsbjørgen, Katja Scheffler,  Havard Dalen, Espen Holte, Asta K Haberg, Geir Selbæk, Stian Lydersen, Emrah Duezel, Sverre Bergh, Kjell Rune Logan-Halvorsrud, Sigrid Botne Sando, Ulrik Wisløff

ABSTRACT
Purpose The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data.
Participants The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009–2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders.
Findings to date All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources.
Future plans The finish date of NorCog was originally in 2029. In 2021, the registry’s legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.

Ingrid Tøndel Medbøen, Karin Persson, Marit Nåvik, Torunn Holm Totland, Sverre Bergh, Cathrine Selnes Treviño, Ingun Ulstein, Knut Engedal, Anne-Brita Knapskog,  Anne Brækhus, Anne Rita Øksengård, Peter Otto Horndalsveen, Ingvild Saltvedt, Anne Liv Lyngroth, Anette Hylen Ranhoff, Dagny Bekkeheien Skrettingland, Mala Naik, Jelena Zugic Soares, Bente Johnsen, Geir Selbæk

Abstract
Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer’s disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.

Iris E. Jansen, Sven J. van der Lee, Duber Gomez-Fonseca, Itziar de Rojas, Maria Carolina Dalmasso, Benjamin Grenier-Boley, Anna Zettergren, Aniket Mishra, Muhammad Ali, Victor Andrade, Céline Bellenguez, Luca Kleineidam, Fahri Küçükali, Yun Ju Sung, Niccolo Tesí, Ellen M. Vromen, Douglas P. Wightman, Daniel Alcolea, Montserrat Alegret,…Sverre Bergh…Geir Selbæk… Wiesje van der Flier