Older people's experiences of vulnerability in a trust-based welfare society affected by the COVID-19 pandemic.

The early coronavirus disease 2019 (COVID-19) outbreak inflicted vulnerability on individuals and societies on a completely different scale than we have seen previously. The pandemic developed rapidly from 1 day to the next, and both society and individuals were put to the test. Older people's experiences of the early outbreak were no exception. Using an abductive analytical approach, the study explores the individual experiences of vulnerability as described by older people hospitalised with COVID-19 in the early outbreak. In these older people, we found that the societal context and the individual experiences of vulnerability were inextricable linked. The study demonstrates that despite significant individual stress, informants displayed an interesting ability to also view their situation to reorient their perspective. The experience of vulnerability is both conditional and individual, which imposes a degree of unpredictability that neither they nor others were able to negotiate. The article discusses the phenomenon of unpredictability in light of a modern society with regard to how individuals and society may encounter unexpected events in the future where the potential to reorient will be vital.

Stroke and bleeding risk in atrial fibrillation with CHA2DS2-VASC risk score of one: the Norwegian AFNOR study.

BACKGROUND AND AIMS: The benefit of oral anticoagulant (OAC) therapy in atrial fibrillation (AF) and intermediate stroke risk is debated. In a nationwide Norwegian cohort with a non-sex CHA2DS2-VASc risk score of one, this study aimed to investigate (i) stroke and bleeding risk in AF patients with and without OAC treatment, and (ii) the risk of stroke in non-anticoagulated individuals with and without AF. METHODS: A total of 1 118 762 individuals including 34 460 AF patients were followed during 2011-18 until ischaemic stroke, intracranial haemorrhage, increased CHA2DS2-VASc score, or study end. One-year incidence rates (IRs) were calculated as events per 100 person-years (%/py). Cox regression models provided adjusted hazard ratios (aHRs [95% confidence intervals]). RESULTS: Among AF patients, the ischaemic stroke IR was 0.51%/py in OAC users and 1.05%/py in non-users (aHR 0.47 [0.37-0.59]). Intracranial haemorrhage IR was 0.28%/py in OAC users and 0.19%/py in non-users (aHR 1.23 [0.88-1.72]). Oral anticoagulant use was associated with an increased risk of major bleeding (aHR 1.37 [1.16-1.63]) but lower risk of the combined outcome of ischaemic stroke, major bleeding, and mortality (aHR 0.57 [0.51-0.63]). Non-anticoagulated individuals with AF had higher risk of ischaemic stroke compared to non-AF individuals with the same risk profile (aHR 2.47 [2.17-2.81]). CONCLUSIONS: In AF patients at intermediate risk of stroke, OAC use was associated with overall favourable clinical outcomes. Non-anticoagulated AF patients had higher risk of ischaemic stroke compared to the general population without AF with the same risk profile.

Impaired glucose utilization in the brain of patients with delirium following hip fracture.

Alterations in brain energy metabolism have long been proposed as one of several neurobiological processes contributing to delirium. This is supported by previous findings of altered CSF lactate and neuron-specific enolase concentrations and decreased glucose uptake on brain-PET in patients with delirium. Despite this, there are limited data on metabolic alterations found in CSF samples, and targeted metabolic profiling of CSF metabolites involved in energy metabolism has not been performed. The aim of the study was to investigate whether metabolites related to energy metabolism in the serum and CSF of patients with hip fracture are associated with delirium. The study cohort included 406 patients with a mean age of 81 years (standard deviation 10 years), acutely admitted to hospital for surgical repair of a hip fracture. Delirium was assessed daily until the fifth postoperative day. CSF was collected from all 406 participants at the onset of spinal anaesthesia, and serum samples were drawn concurrently from 213 participants. Glucose and lactate in CSF were measured using amperometry, whereas plasma glucose was measured in the clinical laboratory using enzymatic photometry. Serum and CSF concentrations of the branched-chain amino acids, 3-hydroxyisobutyric acid, acetoacetate and ß-hydroxybutyrate were measured using gas chromatography-tandem mass spectrometry (GC-MS/MS). In total, 224 (55%) patients developed delirium pre- or postoperatively. Ketone body concentrations (acetoacetate, ß-hydroxybutyrate) and branched-chain amino acids were significantly elevated in the CSF but not in serum among patients with delirium, despite no group differences in glucose concentrations. The level of 3-hydroxyisobutyric acid was significantly elevated in both CSF and serum. An elevation of CSF lactate during delirium was explained by age and comorbidity. Our data suggest that altered glucose utilization and a shift to ketone body metabolism occurs in the brain during delirium.

Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-ß42 and phosphorylated tau181. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging.

'A Story of Being Invisible': A Single Case Study on the Significance of Being Recognised When Needing Acute Healthcare in the Early COVID-19 Pandemic.

Severe illness is often an existential threat that triggers emotions like fear, stress, and anxiousness. Such emotions can affect ill patients' encounters with healthcare personnel. We present a single case study of an older woman who contracted COVID-19 and her challenge to be recognised by healthcare personnel in the early pandemic. Storytelling is vital to understand how patients can create meaning in illness as it gives them the opportunity to reshape and restore their past and to project a future. We used Arthur Frank's dialogical narrative analysis to explore how one patient experienced her encounters with healthcare personnel. Although she felt very ill from COVID-19, she experienced being almost invisible and not being believed by healthcare personnel in a system marked by high stress levels and uncertainty. Despite rejections and illness, she managed to mobilise her resources, even though she depended on significant others. Her story brings forward altered self-understanding and growth. The importance of facilitating dialogical settings for healthcare professionals through patient storytelling also contributes to a broader societal understanding of illness beyond a biological perspective.

Left atrial dyssynchrony in veteran endurance athletes with and without paroxysmal atrial fibrillation.

BACKGROUND: Prolonged endurance exercise increase the risk of atrial fibrillation (AF) in men. Functional parameters may help separate physiological from pathological atrial remodeling in athletes. LA mechanical dispersion (LA MD) is associated with AF in the general population, but the associations between prolonged exercise, LA MD and AF are not known. PURPOSE: To describe LA MD in veteran athletes with and without paroxysmal AF (pAF) and to investigate LA MD's ability to identify veteran athletes with pAF. METHODS: Two hundred and ninety-three men, skiers with (n = 57) and without (n = 87) pAF, and controls with (n = 61) and without pAF (n = 88) underwent an echocardiographic exam in sinus rhythm. LA reservoir strain (LASr) was measured, and LA MD defined as the standard deviation of time-to-peak strain (SD-TPS). RESULTS: Skiers (mean age 70.7 ± 6.7 years) reported an average of 40-50 years of endurance exercise. LA volumes were associated with pAF and athletic status (p < .001). SD-TPS was associated with pAF (p < .001) but not athletic status (p = .173). We found no significant trend between years of exercise and SD-TPS in individuals without AF (p = .893). SD-TPS did not add incremental value in identifying athletes with pAF in addition to clinical markers, QRS width, LA volume, and LASr (p = .056). CONCLUSION: LA MD was associated with pAF regardless of athletic status but not related to years of endurance exercise, suggesting LA MD could be a promising marker of pathological atrial remodeling in athletes. However, we found no incremental value of LA MD identifying athletes with pAF when LASr was included in the model.

Rationale and design of the Birkebeiner Ageing Study - a prospective cohort study of older endurance athletes.

BACKGROUND: While regular physical activity is associated with reduced mortality and morbidity in general populations, health outcomes and functional capacity related to upholding strenuous endurance exercise beyond the age of 65 years are only sparsely studied. The aim of this study is to assess associations of prolonged strenuous endurance sport practice with ageing, functional decline, morbidity and longevity among older recreational endurance athletes, during long-term follow-up. METHODS: Prospective cohort study of older recreational endurance athletes in Norway. All skiers aged 65 years and older who participated in a long-distance endurance competition, the annual 54-km Birkebeiner cross-country ski race in 2009 or 2010, were invited. The participants answered an extensive baseline questionnaire about lifestyle habits, including leisure-time physical activity and endurance sport participation, diseases, medication use and physical and mental health, with follow-up questionnaires planned every fifth year until 2029. New participants may be invited with the aim to increase the study size. Endpoints such as all-cause and disease-specific mortality, incidence and cumulative prevalence of diseases, use of medication, physical and mental health and functional decline will be assessed subsequently. Out of 658 invited skiers (51 women), 551(84%) completed the baseline questionnaire and were included in the study. The mean age was 68.8 years (median 68, range 65- 90). At baseline, the participants had completed the Birkebeiner race for an average of 16.6 years and reported an average of 33.4 years of regular endurance exercise, with one out of five reporting at least 50 years of exercise. In all, 479 (90%) reported that they were still practicing leisure-time physical activity of moderate or vigorous intensity at least twice weekly. The prevalence of cardiovascular risk factors and diseases was low. DISCUSSION: This prospective study of a cohort of recreational athletes exposed to prolonged and strenuous endurance exercise, could complement population-based studies by providing data on associations between life-long endurance sport participation, aging, functional decline and health outcomes during long-term follow-up.

Sykdomsforløp blant pasienter innlagt på Bærum sykehus med delta- og omikronvariantene av SARS-CoV-2-viruset.

BACKGROUND: Waves of infection have formed the pattern of the COVID-19 pandemic. A wave dominated by the delta variant of the SARS-CoV-2 virus in autumn 2021 was superseded by the omicron variant over the course of a few weeks around Christmas. We describe how this transition affected the population of patients admitted to a Norwegian local hospital with COVID-19. MATERIAL AND METHOD: All patients admitted to Bærum Hospital with confirmed SARS-CoV-2 virus were included in a quality study which aimed to describe patient characteristics and clinical course. We present patients admitted in the periods 28 June 2021-31 December 2021 and 1 January 2022-12 June 2022, described here as the delta wave and the omicron wave. RESULTS: The SARS-CoV-2-virus was confirmed in a total of 144 patients who were admitted during the delta wave, and in 261 patients during the omicron wave, where 14/144 (10 %) and 89/261 (34 %) were admitted for reasons other than COVID-19. Patients with COVID-19 during the delta wave were younger on average (59 vs. 69 years) and had a lower Charlson comorbidity index score (2.6 vs. 4.9) and a lower Clinical Frailty Scale score (2.8 vs. 3.7) than patients in the omicron wave. Among 302/405 patients admitted with COVID-19 as the principal diagnosis, 88/130 (68 %) patients had respiratory failure during the delta wave and 59/172 (34 %) during the omicron wave, with a median number of 8 bed days (interquartile range 5-15) and 5 (interquartile range 3-8). INTERPRETATION: The transition from the wave of infection that was dominated by the delta variant of the SARS-CoV-2 virus to the wave dominated by the omicron variant had a considerable effect on the characteristics and clinical course of patients admitted to hospital with SARS-CoV-2 infection.

Ten-year mortality among older male recreational endurance athletes in the Birkebeiner Aging Study in comparison with older men from the Tromsø Study.

BACKGROUND: Physical activity (PA) is associated with reduced mortality. However, whether there is an added benefit of long-term endurance training is unclear. Thus, we aimed to examine 10-year mortality in older male endurance athletes compared with an older male general population. METHOD: Male athletes (n = 503) participating in an annual long-distance ski race (median years of participation: 14, range: 1-53) from the Norwegian Birkebeiner Aging study (BiAS), and non-athletic men (n = 1867) attending the sixth Tromsø Study (Tromsø6) aged ≥65 years were included. Associations with endurance sport practice and joint exposures of endurance sport practice and self-reported leisure-time PA with all-cause mortality were examined. We analyzed the data with Cox proportional hazard models and regression standardization. RESULTS: After 10 years (median: 10.4, range: 0.5-11.1) the mortality rate was lower in athletes (hazard ratio (HR) 0.34, 95% confidence interval (CI): 0.24-0.49) compared with non-athletes, corresponding to a 15% (95% CI: 12-19%) absolute risk reduction associated with endurance sport practice. In joint analyses categorized according to PA and endurance sport practice, we observed an inverse dose-response relationship with mortality (p < 0.001). Compared to inactive non-athletes, PA was associated with lower mortality in both active non-athletes and athletes. However, the observed benefit among participants reporting moderate-to-vigorous PA was larger in athletes (HR: 0.21, 95% CI: 0.14-0.32) than non-athletes (HR: 0.43, 95% CI: 0.31-0.59) (p < 0.01). CONCLUSION: Endurance sport practice was associated with reduced 10-year mortality, beyond the effect of PA in older men. This study suggests that long-term endurance sport practice maintained into older adulthood promotes longevity.

Sex-specific associations of matrix metalloproteinases in Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-ß (Aß) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD. METHODS: In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aß and tau pathology as well as disease progression. Further, we studied sex-specific interactions. RESULTS: MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aß biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women. CONCLUSION: Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.

Delirium screening in a stroke unit by nurses using 4AT: Results from a quality improvement project.

AIM: To assess the feasibility of delirium screening with the screening tool 4AT conducted by stroke unit nurses. DESIGN: Observational. METHODS: Patients with confirmed acute stroke admitted to the stroke unit at Baerum Hospital, Norway, from March to October 2020, were consecutively recruited. Nurses performed delirium screening using the rapid screening tool 4AT within 24 h of admission, at discharge and when delirium was suspected, and filled out a questionnaire assessing their experiences with the delirium screening. A geriatrician validated the delirium diagnosis. RESULTS: In all, 62 patients were included, mean age 73.3 years. 4AT was performed according to protocol in 49 (79.0%) and 39 (62.9%) patients at admission and discharge respectively. Lack of time (40%) was reported as the most common reason for not performing delirium screening. The nurses reported that the felt competent to carry out the 4AT screening, and did not experience it as significant extra workload. Five patients (8%) were diagnosed with delirium. Delirium screening performed by stroke unit nurses seemed feasible and the nurses experienced that 4AT was a useful tool for this purpose.

Effects of training adaption in endurance athletes with atrial fibrillation: protocol for a multicentre randomised controlled trial.

Endurance athletes have a high prevalence of atrial fibrillation (AF), probably caused by exercise-induced cardiac remodelling. Athletes diagnosed with AF are often advised to reduce the intensity and amount of training but the efficacy of this intervention has not been investigated in endurance athletes with AF. Effects of detraining in endurance athletes with atrial fibrillation is a two-arm international multicentre randomised (1:1) controlled trial on the effects of a period of training adaption on AF burden in endurance athletes with paroxysmal AF. One-hundred-and-twenty endurance athletes diagnosed with paroxysmal AF are randomised to a 16-week period of intervention (training adaption) or a control group. We define training adaption as training with a heart rate (HR) not exceeding 75% of the individual maximum HR (HRmax), and total duration of weekly training not exceeding 80% of the self-reported average before the study. The control group is instructed to uphold training intensity including sessions with HR ≥85% of HRmax. AF burden is monitored with insertable cardiac monitors, and training intensity with HR chest-straps and connected sports watches. The primary endpoint, AF burden, will be calculated as the cumulative duration of all AF episodes lasting ≥30sec divided by total duration of monitoring. Secondary endpoints include number of AF episodes, adherence to training adaption, exercise capacity, AF symptoms and health-related quality of life, echocardiographic signs of cardiac remodelling and risk of cardiac arrhythmias related to upholding training intensity. Trial registration number: NCT04991337. Study protocol version: 4.7 (Date 9 March 2023).

Impact of frailty on the performance of the National Early Warning Score 2 to predict poor outcome in patients hospitalised due to COVID-19.

BACKGROUND: The National Early Warning Score 2 (NEWS2) is a scoring tool predictive of poor outcome in hospitalised patients. Older patients with COVID-19 have increased risk of poor outcome, but it is not known if frailty may impact the predictive performance of NEWS2. We aimed to investigate the impact of frailty on the performance of NEWS2 to predict in-hospital mortality in patients hospitalised due to COVID-19. METHODS: We included all patients admitted to a non-university Norwegian hospital due to COVID-19 from 9 March 2020 until 31 December 2021. NEWS2 was scored based on the first vital signs recorded upon hospital admission. Frailty was defined as a Clinical Frailty Scale score ≥ 4. The performance of a NEWS2 score ≥ 5 to predict in-hospital mortality was assessed with sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) according to frailty status. RESULTS: Out of 412 patients, 70 were aged ≥ 65 years and with frailty. They presented less frequently with respiratory symptoms, and more often with acute functional decline or new-onset confusion. In-hospital mortality was 6% in patients without frailty, and 26% in patients with frailty. NEWS2 predicted in-hospital mortality with a sensitivity of 86%, 95% confidence interval (CI) 64%-97% and AUROC 0.73, 95% CI 0.65-0.81 in patients without frailty. In older patients with frailty, sensitivity was 61%, 95% CI 36%-83% and AUROC 0.61, 95% CI 0.48-0.75. CONCLUSION: A single NEWS2 score at hospital admission performed poorly to predict in-hospital mortality in patients with frailty and COVID-19 and should be used with caution in this patient group. Graphical abstract summing up study design, results and conclusion.

Resting heart rate, self-reported physical activity in middle age, and long-term risk of hip fracture. A NOREPOS cohort study of 367,386 men and women.

Enhanced knowledge regarding modifiable risk factors for hip fractures are warranted. We aimed to study the associations between two indicators of physical fitness (resting heart rate and level of physical activity) in middle-aged individuals, and the risk of hip fractures during the subsequent three decades. Data on objectively measured resting heart rate and self-reported leisure time physical activity from a national health survey (1985-1999) was linked to a database including all hip fractures treated in Norwegian hospitals from 1994 through 2018. We calculated hazard ratios (HR) with 95 % confidence intervals (95 % CI) for hip fractures according to categories of resting heart rate (mean of two repeated measures), and leisure time physical activity level in adjusted Cox proportional hazard models. In total, 367,386 persons (52 % women) aged 40 to 45 years were included, of whom 5482 persons sustained a hip fracture during a mean follow-up of 24.8 years. Higher resting heart rate was associated with higher hip fracture risk. Men with a resting heart rate above 80 bpm, who also reported low levels of physical activity, had a HR of 1.82 (95 % CI 1.49-2.22) for hip fracture compared to men with a resting heart rate below 70 bpm who reported high levels of physical activity. The same measure of association for women was 1.62 (95 % CI 1.28-2.06). Physical fitness measured by low resting heart rate in middle age, and a high physical activity level were associated with a lower long-term risk of hip fractures in both men and women.

Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients.

BACKGROUNDThe 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.METHODSWe 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.RESULTSIn 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) (ß 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.CONCLUSIONOur 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.FUNDINGNorwegian Health Association and South-Eastern Norway Regional Health Authorities.