Forskningsartikler

ABSTRACT
Introduction: Half of patients with limited stage small cell lung cancer (LS SCLC) are >70 years, but account for <20% of participants in most trials. Comorbidities, reduced organ- and physical function might lead to more treatment toxicity and population-based studies indicate that fewer older than younger LS SCLC patients receive standard chemoradiotherapy, although there is limited evidence for such a policy.
Methods: We compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health related quality of life (HRQoL) and treatment outcomes between patients >70 and <70 years in an open label randomized phase II trial comparing twice-daily thoracic radiotherapy (TRT) of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC. All patients received concurrent platinum/etoposide chemotherapy.
Results: 170 patients who were >18 years and had performance status (PS) 0-2 were randomized. Of these, 53 patients (60 Gy:25, 45 Gy:28) were >70 years and 117 (60 Gy:64, 45 Gy:53) were younger. There were no significant differences in baseline characteristics, treatment completion rates, toxicity, or response rates across age groups. HRQoL mean scores was similar during year one, but older patients reported more decline on functional scales than younger patients during year two. OS was significantly shorter for older patients while there was no significant difference in PFS or TTP.
Conclusion: Patients >70 years tolerated concurrent twice daily chemoradiotherapy and achieved similar disease control as younger patients, indicating that older patients should receive the same treatment as younger patients.

Kristin Toftaker Killingberg, Bjørn Henning Grønberg, Marit Slaaen, Øyvind Kirkevold, Tarje Onsøien Halvorsen

Summary

Despite evidence suggesting that insomnia is associated with the risk of dementia and cognitive dysfunction, studies have shown mixed results. Dementia has a long prodromal phase, and studies with long follow-up are required to avoid reverse causality. In our 11-year follow-up study, we assessed whether probable insomnia disorder (PID) based on diagnostic criteria, and insomnia symptoms were associated with risk of all-cause dementia, Alzheimer’s disease (AD) and cognition, measured with the Montreal Cognitive Assessment scale. We also examined if Apolipoprotein E genotype modified any associations with dementia through interaction. We analysed data from 7492 participants in the Norwegian Trøndelag Health Study. PID was not associated with all-cause dementia (odds ratio = 1.03, 95% confidence interval = 0.74–1.43), AD (odds ratio = 1.07, 95% confidence interval = 0.71–1.60) or Montreal Cognitive Assessment score (regression coefficient = 0.37, 95% confidence interval = −0.06 to 0.80). The insomnia symptom “difficulties maintaining sleep” was associated with a lower risk of all-cause dementia (odds ratio = 0.81, 95% confidence interval = 0.67–0.98), AD (odds ratio = 0.73, 95% confidence interval = 0.57–0.93), and better Montreal Cognitive Assessment score, mean 0.40 units (95% confidence interval = 0.15–0.64). No interaction with Apolipoprotein E genotype was found. PID and insomnia symptoms did not increase the risk of dementia in our study. More research with longer follow-up is needed, and future studies should explore if the associations to dementia risk vary across insomnia subtypes.

Selma Selbæk-Tungevåg, Geir Selbæk, Bjørn Heine Strand, Christian Myrstad, Gill Livingston, Stian Lydersen, Sverre Bergh, Linda Ernstsen

BACKGROUND: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanisms underlying delirium, particularly in relation to the KP, remain elusive.
METHODS: We undertook a multicenter observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and 1-year mortality.
RESULTS: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA) (OR 2.26 [1.78, 2.87], P < 0.001) to be increased and also found increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL) (β 0.43, P < 0.001) and was a strong predictor of 1-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, P < 0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons.
CONCLUSION: Our data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP.

Leiv Otto Watne, Christian Thomas Pollmann, Bjørn Erik Neerland, Else Quist-Paulsen, Nathalie Bodd Halaas, Ane-Victoria Idland, Bjørnar Hassel, Kristi Henjum, Anne-Brita Knapskog, Frede Frihagen, Johan Raeder, Aasmund Godø, Per Magne Ueland, Adrian McCann, Wender Figved, Geir Selbæk, Henrik Zetterberg, Evandro F Fang, Marius Myrstad, Lasse M Giil

Beboere med covid-19-sykdom på norske sykehjem hadde høy risiko for alvorlig forløp og død. Hensikten med denne studien var å utforske sykehjemslegers erfaringer med å ivareta behandlingsansvaret for beboere med covid-19 og hvordan de samarbeidet med pårørende og sykepleiere. Denne intervjustudien inkluderte ti sykehjemsleger med erfaring fra covid-19 i sykehjem fra tre av de fire helseregionene i Norge. Vi gjorde en kvalitativ innholdsanalyse av de transkriberte intervjuene. Analysen identifiserte følgende tre hovedfunn: 1) Krevende ansvar for medisinskfaglige vurderinger og avgjørelser, 2) Kommunikasjon og samarbeid med pårørende – viktig og tidkrevende, og 3) Sykepleierne – en viktig samarbeidspartner. Sykehjemslegene opplevde et krevende ansvar og utfordringer med å ivareta multimorbide og skrøpelige beboere under pandemien. Dette illustrerer behovet for gode rutiner samt lokale og nasjonale retningslinjer. Samarbeidet med erfarne og rutinerte sykepleiere ga trygghet. Sykehjemslegenes beskrivelse av følelsesmessige utfordringer under covid-19-pandemien understreker behovet for faste, kollegiale og faglige nettverk.

Signe Gunn Julnes, Bjørn Lichtwarck, Siren Eriksen, Adelheid Hummelvoll Hillestad, Anita Nilsen, Signe Tretteteig og Anne Marie Mork Rokstad

Objective: To study the association between hearing loss severity, hearing aid use, and subjective memory complaints in a large cross-sectional study in Norway.

Methods: Data were drawn from the fourth wave of the Trøndelag Health Study (HUNT4 Hearing, 2017–2019). Hearing threshold was defined as the pure tone average of 0.5, 1, 2 and 4 kHz in the better ear. The participants were divided into five groups: normal hearing or slight/mild/moderate/severe hearing loss. Subjective self-reported short-term and long-term memory complaints was measured by the nine-item Meta-Memory Questionnaire (MMQ). The sample included 20,092 individuals (11,675 women, mean age 58,3 years) who completed both hearing and MMQ tasks. Multivariate analysis of variance (adjusted for covariates of age, sex, education, and health cofounders) was used to evaluate the association between hearing status and hearing aid use (in the hearing-impaired groups) and long-term and short-term subjective memory complaints.

Results: Multivariate analysis of variance, followed by univariate ANOVA and pairwise comparisons showed that hearing loss was associated only with more long-term subjective memory complaints and not with short-term subjective memory complaints. In the hearing-impaired groups, the univariate main effect of hearing aid use was only observed for subjective long-term memory complaints and not for subjective short-term memory complaints. Similarly, the univariate interaction of hearing aid use and hearing status was significant for subjective long-term memory complaints and not for subjective short-term memory complaints. Pairwise comparisons, however, revealed no significant differences between hearing loss groups with respect to subjective long-term complaints.

Conclusion: This cross-sectional study indicates an association between hearing loss and subjective long-term memory complaints, but not with subjective short-term memory complaints. In addition, an interaction between hearing status and hearing aid use for subjective long-term memory complaints was observed in hearing-impaired groups, which calls for future research to examine the effects of hearing aid use on different memory systems.

Shahram Moradi, Bo Lars Engdahl, Aud Johannessen, Geir Selbæk, Lisa Aarhus og Gro Gade Haanes