Knut Stavem

• Stavem, Knut; Einvik, Gunnar; Lerum, Tøri Vigeland; Meltzer, Carin; Rivero, Jezabel Rodriguez & Ashraf, Haseem [Show all 10 contributors for this article] (2026). Long-term chest CT abnormalities up to 4.5 years after COVID-19 hospitalization and their association with dyspnea and fatigue: a prospective cohort study. Respiratory Research. ISSN 1465-9921. 27(1). doi: 10.1186/s12931-026-03771-7. Full text in Research Archive
• Dhayyat, Adam; Stavem, Knut; Jervan, Øyvind; Hilde, Janne Mykland; Rashid, Diyar Nori Mohamad & Gleditsch, Jostein [Show all 8 contributors for this article] (2026). Stress Echocardiography to Detect Exercise Pulmonary Hypertension in Patients With Chronic Thromboembolic Pulmonary Disease. Pulmonary Medicine. ISSN 2090-1836. 2026(1). doi: 10.1155/pm/4127338. Full text in Research Archive
• Stavem, Knut & Garratt, Andrew Malcolm (2026). Validity of EQ-5D-5L breathing and cognition bolt-ons in non-hospitalized patients after COVID-19. Quality of Life Research. ISSN 0962-9343. 35(2). doi: 10.1007/s11136-025-04133-4. Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David G.T.; Stavem, Knut & Barra, Mathias (2025). Is There a General Preference for the Worse Off? A Discrete Choice Experiment Using Individually Calibrated Health State Valuations. Value in Health. ISSN 1098-3015. 28(9), p. 1390–1398. doi: 10.1016/j.jval.2025.05.017. Full text in Research Archive Show summary

  Objectives We aimed to develop and demonstrate a method for examining public preferences for priority setting in healthcare, using EQ-5D-5L health states valued at an individual level. We examine the Norwegian population’s preferences for prioritizing the “worse off” in terms of health at a cost to health maximization. This intuition is a part of healthcare priority setting frameworks in several countries. Preference studies help explore the legitimacy of such policies, but most studies do not use individual-level health state values, which may distort their conclusions. Methods Task-based face-to-face interviews were conducted in the Norwegian general population. First, respondents valued a set of EQ-5D-5L health states using time trade-off. Second, discrete choice tasks were administered, describing health state improvements that contrasted utility maximization and benefit to the worse off, according to each respondent’s valuation. Analysis used mixed-effects models with choice and respondent properties. Results We conducted 606 interviews, of which 468 respondents were included in the priority setting exercise. Respondents’ choices were influenced by the size of the health improvement, but not by an option being worse in terms of a lower pretreatment health state value. Choice behavior was influenced by respondents’ gender, religion, and age. On average, the choices indicate a preference for prioritizing the better off. Conclusions Our two-stage design using individual health state values is feasible, although there are trade-offs and room for development with such a design. We found no support for a preference for prioritizing the worse off when using individual-level health state valuations.

• Raijmakers, Ruud P.H.; Lund-Berven, Lise; Keijmel, Stephan P.; Rodrigo, Chaturaka; Wyller, Vegard Bruun Bratholm & Katz, Ben Z. [Show all 20 contributors for this article] (2025). Immunological associations in post-infective fatigue syndromes including Long COVID—a systematic review and meta-analysis. EBioMedicine. 121. doi: 10.1016/j.ebiom.2025.105970. Full text in Research Archive Show summary

  Background The pathophysiology of post-infective fatigue syndromes (PIFS), including Long COVID, is unknown. This systematic review and meta-analysis aimed to investigate if PIFS is associated with persistent immune activation. Methods PubMed, EMBASE, and Web of Science were searched for terms related to infection, fatigue, persistent symptoms, and immunological markers. Population: adults and adolescents; Exposure: documented acute infection; Comparator: those who developed PIFS vs. recovered controls from the same exposure; and Outcomes: immunological biomarkers. Studies which documented acute infection, applied diagnostic criteria for PIFS, and assayed circulating immunologic markers were eligible. Findings From 14,985 studies screened, 30 articles were included (n = 5102 participants; 833 PIFS/PIFS-like cases, n = 4269 recovered control participants) with many studies excluded by inadequate quality in eligibility criteria. The meta-analysis (11 studies; n = 413 PIFS cases, analysed with random-effects models) showed PIFS cases had increased: white cell counts at 3–6 months (Cohen's d: 0.41, 95% CI 0.09–0.74); and circulating levels of RANTES and TNFα at 6–12 months (Cohen's d: 0.45 [95% CI 0.16–0.73] and 0.30 [95% CI 0.04–0.57], respectively) compared to controls recovered from the same exposure. Interpretation These findings provide cautious support for persistent immune activation in PIFS, but warrant further replication. Future studies should include better documentation of acute infection and PIFS case characterisation. Funding ARL is supported by a National Health and Medical Research Council Practitioner Fellowship (Grant 1041897). CXS is supported by a Cancer Institute New South Wales Early Career Fellowship (2021/ECF1310). BZK is supported by the National Institute of Allergy and Infectious Diseases (AI 105781). RAE is supported by the National Institute for Health and Care.

• Maksimovic, Nina; Neumann, Kirill; Aamodt, Henrik; Eggum, Rune; Reier-Nilsen, Frode & Wesche, Jarlis [Show all 7 contributors for this article] (2025). Robot-assisted thoracic surgery (RATS): learning curve and outcomes for 200 consecutive pulmonary lobectomies in a Norwegian hospital. Journal of Thoracic Disease (JTD). ISSN 2072-1439. 17(8), p. 5936–5950. doi: 10.21037/jtd-2024-2240. Full text in Research Archive Show summary

  Background: When starting with new surgical procedures, a gradual improvement in skills and results is expected. Pulmonary resection for early-stage non-small cell lung cancer (NSCLC) has advanced with technology, making robot-assisted thoracic surgery (RATS) an increasingly preferred method. At Akershus University Hospital (Ahus), exploring the learning curve associated with RATS offered valuable insights for optimizing surgical efficiency and improving patient outcomes. This study analyzes key operational variables and outcomes to highlight the skill acquisition process at a leading Norwegian healthcare center, aiming to describe the learning curve involved in transitioning from video-assisted thoracic surgery (VATS) to RATS for lung cancer lobectomies. Methods: This study was a retrospective analysis of the first 200 consecutive pulmonary lobectomies and bi-lobectomies with RATS in Norwegian University Hospital. We used cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) analyses to evaluate operative times and perioperative complications. Results: The 200 patients had a median age of 70 (25th-75th percentile, 62-75) years; 109 (55%) were female, 159 (80%) had preoperative stage 0-IB, and 34 (17%) stage IIA-IIB. Of the procedures, 196 were lobectomies and 4 bi-lobectomies. Median operating time was 160 (25th-75th percentile, 120-195) minutes. Complications (Clavien-Dindo grade ≥2) were observed in 25.5% of cases. The conversion rate to thoracotomy was 1.5% and re-operation rate 3.0%. CUSUM analysis indicated a bi-phasic learning curve for operative times, with ongoing improvements observed after the 117th procedure. The RA-CUSUM analysis showed a steady decline in perioperative complications after the 94th procedure. Conclusions: The findings suggest that the transition from VATS to RATS as a standard surgical approach for pulmonary lobectomies was associated with an acceptable development of proficiency, procedure duration, and complication rates over time. Hence, implementation of the new RATS program was feasible and effective.

• Øvrebotten, Tarjei; Tholin, Birgitte; Berge, Kristian; Myhre, Peder Langeland & Stavem, Knut (2025). Cardiac events and procedures following COVID-19 compared with other pneumonias: a national register study. Open heart. 12(1). doi: 10.1136/openhrt-2024-002914. Full text in Research Archive Show summary

  Background Studies have shown an increased risk of cardiac disease following COVID-19, but how it compares to pneumonia of other etiologies is unclear. Aims To determine the incidence and HRs of cardiac disease in patients hospitalised with COVID-19 compared with other viral or bacterial pneumonias. Methods Using nationwide registry data, we estimated the incidence of cardiac events after hospitalisation with COVID-19 (n=2082) in February to November 2020 vs hospitalisation with viral (n=9018) or bacterial (n=29 339) pneumonia in 2018–2019. We defined outcomes using ICD-10 codes for incident myocarditis, acute myocardial infarction, atrial fibrillation/flutter, heart failure, ischaemic heart disease, other cardiac disease and total cardiac disease (any heart condition). We used Cox regression and logistic regression for analysis. Results Patients with COVID-19 had a mean (SD) age of 60 (18) years, compared with 69 (19) years for viral and 72 (17) years for bacterial pneumonia. Those with COVID-19 were more often male and had fewer comorbidities and fewer prior hospitalisations. Patients with COVID-19 had a lower hazard of new-onset cardiac disease compared with viral (HR 0.79 [95%CI 0.66 to 0.93]) and bacterial pneumonia (HR 0.66 [95%CI 0.57 to 0.78]), adjusted for age, sex, comorbidity, hospital admission prior year and respiratory support. Results were similar when including recurrent events. Conclusion Patients hospitalised with COVID-19 had a lower hazard of new-onset cardiac disease during the first 9 months after hospitalisation compared with patients with other viral or bacterial pneumonias after adjusting for multiple possible confounders. However, there may still be residual confounding from other or unknown factors.

• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Holst, Rene & Gleditsch, Jostein [Show all 13 contributors for this article] (2025). Exercise capacity, dyspnea, and quality of life 6 months after exercise-based rehabilitation in patients with persistent dyspnea following pulmonary embolism. Research and Practice in Thrombosis and Haemostasis (RPTH). 9(2). doi: 10.1016/j.rpth.2025.102736. Full text in Research Archive Show summary

  Background Exercise is safe and effective in the short-term following pulmonary embolism. To date, little is known about the long-term effects. Objectives The aim of the study was to investigate whether the effects of exercise-based rehabilitation are maintained 6 months after completion in patients with persistent dyspnea following pulmonary embolism when compared with usual care. Methods A 2-center, randomized controlled trial compared 8 weeks of exercise-based rehabilitation with usual care. Patients were reassessed postintervention and 6 months later. Exercise capacity was measured with the incremental shuttle walk test (ISWT). Dyspnea was assessed with the Shortness of Breath Questionnaire, and health-related quality of life was assessed with disease-specific (Pulmonary Embolism Quality of Life Questionnaire) and generic questionnaires. Results In total, 159 of 211 randomized patients attended follow-up 6 months postintervention. The significant improvement on the ISWT in the rehabilitation group was maintained at the 6-month follow-up (96 m; SE: 15 m; 95% CI: 66, 127). There were no changes on the ISWT in the control group at either time point. From postintervention to 6×-month follow-up, the rehabilitation group had further improvements in dyspnea compared with the control group (−3 points; SE: 1.4; 95% CI: −6, −1; P = .02). Health-related quality of life improved in both groups although superior improvements were seen in the rehabilitation group. Conclusion The improvement in exercise capacity after 8 weeks of exercise-based rehabilitation in patients with pulmonary embolism and persistent dyspnea was maintained at the 6-month follow-up, while no improvement was observed in the control group, highlighting the relevance of offering rehabilitation to these patients.

• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Hubin, Aliaksandr & Tavoly, Mazdak [Show all 10 contributors for this article] (2025). The effect of exercise-based rehabilitation on objective physical activity levels in patients with persistent dyspnoea following pulmonary embolism. Thrombosis Research. ISSN 0049-3848. 252. doi: 10.1016/j.thromres.2025.109362. Full text in Research Archive Show summary

  Background Rehabilitation improves exercise capacity following pulmonary embolism (PE), but it is unclear whether this improvement is transferred into increased physical activity. Objectives. To explore the effect of exercise-based rehabilitation on objective measures of physical activity in patients with persistent dyspnoea following PE compared to standard care. Methods This pre-planned substudy compared an eight-week exercise-based rehabilitation program to usual care. Number of steps per day and time spent in sedentary, low, moderate and vigorous physical activity (in number of metabolic equivalent of tasks) were measured for seven consecutive days at baseline prior to intervention start and at post-intervention using accelerometery. Data were analysed with a mixed-effect generalised linear model. Results Complete data was provided by 48 patients at both timepoints (mean age 58 years, 54 % men) with 54 % randomised to rehabilitation. There were no significant differences between groups at baseline. The majority of time (717 min per day) was spent in sedentary activity and mean number of steps per day was 6701. At post-intervention, there were no significant differences between groups in any of the objectively measured physical activity parameters (p > 0.05). Conclusion In this cohort, exercise-based rehabilitation following PE did not change daily physical activity levels compared to usual care control group.

• Cestelli, Lucia; Johannessen, Ane; Gulsvik, Amund; Stavem, Knut & Nielsen, Rune (2025). Risk Factors, Morbidity, and Mortality in Association With Preserved Ratio Impaired Spirometry and Restrictive Spirometric Pattern: Clinical Relevance of Preserved Ratio Impaired Spirometry and Restrictive Spirometric Pattern. Chest. ISSN 0012-3692. 167(2), p. 548–560. doi: 10.1016/j.chest.2024.08.026. Full text in Research Archive Show summary

  Background: Preserved ratio impaired spirometry (PRISm) and restrictive spirometric pattern (RSP) are often considered interchangeable in identifying restrictive impairment in spirometry. Research Question: Do PRISm and RSP have different individual associations with risk factors, morbidity, and mortality? Study Design and Methods: In a cross-sectional and longitudinal study, including 26,091 Norwegian general population men (30 to 46 years of age), we explored the association of PRISm and RSP with smoking habits, BMI, education, respiratory symptoms, self-reported cardiopulmonary disease, and mortality after 26 years of follow-up. PRISm was defined as FEV1/FVC ≥ lower limit of normal (LLN) and FEV1 < LLN, and RSP was defined as FEV1/FVC ≥ LLN and FVC < LLN. We compared the associations of PRISm and RSP to airflow obstruction and normal spirometry, both as mutually (PRISm alone, RSP alone) and nonmutually exclusive (PRISm, RSP) categories, adjusting for age, BMI, smoking, and education. We also conducted sensitivity analyses using Global Initiative for Chronic Obstructive Lung Disease criteria to define spirometric abnormalities. Results: The prevalence of the mutually exclusive spirometric patterns was as follows: normal 82.4%, obstruction 11.0%, PRISm alone 1.4%, RSP alone 1.7%, and PRISm + RSP 3.5%. PRISm alone patients frequently had obesity (11.2%) and had active or previous tobacco use, commonly reporting cough, phlegm, wheeze, asthma, and bronchitis. RSP alone patients had both obesity (14.6%) and underweight (2.9%), with increased breathlessness, but similar smoking habits to patients with normal spirometry. The prevalence of heart disease was 4.6% in PRISm alone, 2.7% in RSP alone, and 1.6% in obstruction. With normal spirometry as a reference, RSP alone had increased all-cause (hazard ratio [HR], 1.57; 95% CI, 1.21-2.04), cardiovascular (HR, 1.48; 95% CI, 0.88-2.48), diabetes (HR, 6.43; 95% CI, 1.88-21.97), and cancer (excluding lung) mortality (HR, 1.51; 95% CI, 0.95-2.42). PRISm alone had increased respiratory disease mortality (HR, 4.00; 95% CI, 1.22-13.16). Patients with PRISm + RSP had intermediate characteristics and the worst prognosis. Findings were overall confirmed with nonmutually exclusive categories and Global Initiative for Chronic Obstructive Lung Disease criteria. Interpretation: Our findings indicate that PRISm and RSP are spirometric patterns with distinct risk factors, morbidity, and mortality, which should be differentiated in future studies.

• Garratt, Andrew & Stavem, Knut (2024). COVID-19 and self-reported health of the Norwegian adult general population: A longitudinal study 3 months before and 9 months into the pandemic. PLOS ONE. 19(10). doi: 10.1371/journal.pone.0312201. Full text in Research Archive Show summary

  The COVID-19 pandemic had a global impact on daily lives, and this study aimed to assess the effects on broader aspects of health in the general population of Norway. This population-based cohort study assessed changes in health of the Norwegian general population from 3 months before to 9 months during the COVID-19 pandemic. Sampling was based on the results of Norwegian surveys designed for collecting general population norms for health measurement instruments. In December 2019, 12,790 randomly selected adults aged ≥18 years received a postal questionnaire. The 3,200 respondents received a similar follow-up postal questionnaire including the EQ-5D-5L, PROMIS-29 instruments, and questions about respondents having or having had COVID-19. Score changes were compared to estimates for the minimal important change (MIC) and age-related change. Association of instrument change scores with baseline characteristics, health problems, and having had COVID-19 was determined using multivariable linear regression. Of 3101 respondents with unchanged addresses, 2423 (78.1%) responded to the second survey. For all respondents, EQ VAS and PROMIS-29 scores for 6 of 8 domains were slightly poorer (p<0.01) than before COVID-19, and the mean change was below the MIC. In multivariable analyses, the greatest number of poorer outcomes were associated with being female, 18–29 years, or ≥80 years of age (p<0.01); > MIC for ≥ 80 years of age and EQ-5D index, PROMIS-29 physical function and social participation. Respondents who had COVID-19 had poorer outcomes for PROMIS-29 social participation (> MIC). Those reporting COVID-19 in their partner/family and not themselves, had poorer outcomes for PROMIS-29 anxiety and social participation. About 9 months into the COVID-19 pandemic, EQ-5D-5L and PROMIS-29 domain scores showed slightly poorer health in the Norwegian adult general population compared to 1 year earlier in the same respondents. The overall changes were less than expected for age-related change. Relatively poor outcomes defined as important, included general health and social participation for the elderly, and the latter for those having had COVID-19. In conclusion, this study found no evidence for a decline in important aspects of adult general population health in Norway that might be attributed to the pandemic at approximately 9 months.

• Cestelli, Lucia; Stavem, Knut; Johannessen, Ane; Gulsvik, Amund & Nielsen, Rune (2024). Outcome-based Definition of the Lower Limit of Normal in Spirometry: A Study of 26,000 Young Adult Men. Annals of the American Thoracic Society. ISSN 2329-6933. 21(9), p. 1261–1271. doi: 10.1513/AnnalsATS.202312-1027OC. Full text in Research Archive Show summary

  Rationale: The definition of the lower limit of normal (LLN) of spirometric variables is not well established. Objectives: To investigate the relationship between spirometric abnormalities defined with different thresholds of the LLN and clinical outcomes and to explore the possibility of using different LLN thresholds according to the pretest probability of disease. Methods: We studied the associations between prebronchodilator spirometric abnormalities (forced expiratory volume in the first second [FEV1] < LLN, forced vital capacity [FVC] < LLN, airflow obstruction, spirometric restriction) defined with different thresholds of the LLN (10th, 5th, 2.5th, 1st percentile) and multiple outcomes (prevalence of spirometric abnormalities, respiratory symptoms, all-cause and respiratory mortality) in 26,091 30- to 46-year-old men who participated in a general population survey in Norway in 1988-1990 and were followed for 26 years. Analyses were performed with both local and Global Lung Function Initiative (GLI)-2012 reference equations, stratified by pretest risk (presence or absence of respiratory symptoms), and adjusted for age, body mass index, smoking, and education. Results: In the total population, the prevalence of airflow obstruction was 11.6% with GLI-LLN10, 11.0% with Local-LLN5, 6.1% with GLI-LLN5, 7.6% with Local-LLN2.5, and 3.5% with GLI-LLN2.5. The prevalence of spirometric restriction was 5.9% with GLI-LLN10, 5.2% with Local-LLN5, and 2.8% with GLI-LLN5. Increasingly lower thresholds of the LLN were associated with increasingly higher odds of respiratory symptoms and hazard of mortality for all spirometric abnormalities with both reference equations. Spirometric abnormalities defined with Local-LLN2.5 in asymptomatic subjects were associated with lower hazard of all-cause mortality (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.15-1.95 for FEV1 < LLN) than those defined with Local-LLN5 in the general population (HR, 1.67; 95% CI, 1.50-1.87 for FEV1 < LLN) and symptomatic subjects (HR, 1.67; 95% CI, 1.46-1.91 for FEV1 < LLN). Overall, the prevalence of spirometric abnormalities and associations with outcomes obtained with Local-LLN5 were comparable to those obtained with GLI-LLN10 and those obtained with Local-LLN2.5 to GLI-LLN5. Conclusions: There is a relationship between statistically based thresholds of the LLN of spirometric variables and clinical outcomes. Different thresholds of the LLN may be used in different risk subgroups of subjects, but the choice of the threshold needs to be evaluated together with the choice of reference equations.

• Dhayyat, Adam; Hilde, Janne Mykland; Jervan, Øyvind; Rashid, Diyar Nori Mohamad; Gleditsch, Jostein & Stavem, Knut [Show all 8 contributors for this article] (2024). Exercise pulmonary hypertension in chronic thromboembolic pulmonary disease: A right heart catheterization study. Pulmonary Circulation (PC). ISSN 2045-8932. 14(4). doi: 10.1002/pul2.70018. Full text in Research Archive Show summary

  Many patients with chronic thromboembolic pulmonary disease (CTEPD) suffer from exertional dyspnea. It is unclear if CTEPD is associated with exercise pulmonary hypertension (ePH). This cross-sectional study aimed to determine the occurrence of ePH in patients with CTEPD and to identify the haemodynamic changes during exercise. We recruited 36 patients with persistent dyspnoea and residual perfusion defects by ventilation/perfusion scintigraphy from a large cohort of patients with previous pulmonary embolism. All patients underwent exercise right heart catheterization before being classified into the following groups: (1) CTEPD without ePH; comprising patients with normal mean pulmonary artery pressure (mPAP) of ≤20 mmHg, but with mPAP/cardiac output (CO) slope of ≤3 mmHg/L/min, (2) CTEPD with ePH (CTEPD-ePH); those with CTEPD with an mPAP/CO slope of >3 mmHg/L/min, (3) chronic thromboembolic pulmonary hypertension (CTEPH); those with mPAP >20 mmHg, pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg and pulmonary vascular resistance >2 WU. The postcapillary contribution during exercise was considered present if the PAWP/CO slope of >2 mmHg/L/min. CTEPD without resting pulmonary hypertension (PH) was present in 29 (81%) of the 36 patients, of whom six (21%) had ePH, while five (14%) had CTEPH. Two patients had unclassified PH. Two (33%) of the six patients with CTEPD-ePH had a PAWP/CO slope of >2 mmHg/L/min, compared with two (40%) of the five of those with CTEPH. In conclusion, about 20% of patients with CTEPD and exertional dyspnoea had ePH. Exercise right heart catheterization revealed a notable proportion of patients with postcapillary contribution.

• Røsjø, Helge Rørvik; Solberg, Ole Geir; Aaberge, Lars; Bosse, Gerhard; Omland, Torbjørn & Stavem, Knut [Show all 7 contributors for this article] (2024). Trans-Cardiac Gradient of Secretoneurin in Patients with Takotsubo Syndrome. Cardiology. ISSN 0008-6312. 149(5), p. 466–471. doi: 10.1159/000539094. Full text in Research Archive
• Øvrebotten, Tarjei; Mecinaj, Albulena; Stavem, Knut; Ghanima, Waleed; Brønstad, Eivind & Durheim, Michael Thomas [Show all 14 contributors for this article] (2024). Trajectory of cardiac troponin T following moderate-to-severe COVID-19 and the association with cardiac abnormalities. BMC Cardiovascular Disorders. 24(1). doi: 10.1186/s12872-024-03854-7. Full text in Research Archive Show summary

  Background COVID-19 has been associated with cardiac troponin T (cTnT) elevations and changes in cardiac structure and function, but the link between cardiac dysfunction and high-sensitive cardiac troponin T (hs-cTnT) in the acute and convalescent phase is unclear. Objective To assess whether hs-cTnT concentrations are associated with cardiac dysfunction and structural abnormalities after hospitalization for COVID-19, and to evaluate the performance of hs-cTnT to rule out cardiac pathology. Methods Patients hospitalized with COVID-19 had hs-cTnT measured during the index hospitalization and after 3-and 12 months, when they also underwent an echocardiographic study. A subset also underwent cardiovascular magnetic resonance imaging (CMR) after 6 months. Cardiac abnormalities were defined as left ventricular hypertrophy or dysfunction, right ventricular dysfunction, or CMR late gadolinium. Results We included 189 patients with hs-cTnT concentrations measured during hospitalization for COVID-19, and after 3-and 12 months: Geometric mean (95%CI) 13 (11–15) ng/L, 7 (6–8) ng/L and 7 (6–8) ng/L, respectively. Cardiac abnormalities after 3 months were present in 45 (30%) and 3 (8%) of patients with hs-cTnT ≥ and < 5 ng/L at 3 months, respectively (negative predictive value 92.3% [95%CI 88.5–96.1%]). The performance was similar in patients with and without dyspnea. Hs-cTnT decreased from hospitalization to 3 months (more pronounced in intensive care unit-treated patients) and remained unchanged from 3 to 12 months, regardless of the presence of cardiac abnormalities. Conclusion Higher hs-cTnT concentrations in the convalescent phase of COVID-19 are associated with the presence of cardiac pathology and low concentrations (< 5 ng/L) may support in ruling out cardiac pathology following the infection.

• Garratt, Andrew; Stavem, Knut; Shaw, James W. & Rand, Kim (2024). EQ-5D-5L value set for Norway: a hybrid model using cTTO and DCE data. Quality of Life Research. ISSN 0962-9343. doi: 10.1007/s11136-024-03837-3. Full text in Research Archive Show summary

  Purpose To develop the Norwegian value set for the EQ-5D-5L based on interviews with a representative sample of the Norwegian adult population. Methods Random and quota sampling were used to recruit the sample of adults (age> 18 years) representative of the Norwegian general population. Data collection followed EQ-VT 2.1 undertaken before and after the COVID-19 pandemic from November 2019 to December 2022, using PC-assisted and video conferencing interviews, respectively. Each respondent valued 10 health states using composite time trade-off (cTTO) and 7 health states using a discrete choice experiment (DCE). Different statistical models were assessed for logical consistency and predictive accuracy using cTTO and DCE data alone or in combination as hybrid models. Results Of the 1,321 respondents, 1,237 met inclusion criteria. All statistical models demonstrated logical consistency. The weighted hybrid model combining both cTTOand DCE data was preferred and had the highest predictive accuracy. Predicted values ranged from -0.453 to 1, and the dimension of anxiety/depression was the most highly valued by respondents, followed by pain/discomfort, self-care, mobility, and usual activities. These findings are not dissimilar to those for most Western European countries, and regression coefficients are closest to those for other Scandinavian countries. Conclusion This study provides the Norwegian value set for the EQ-5D-5L based on health state values obtained from members of the adult general population in Norway. This is an important contribution to economic evaluation and the broader application ofthe EQ-5D-5L in Norway including clinical and health services research, and quality measurement.

• Aaløkken, Trond Mogens; Ashraf, Haseem; Einvik, Gunnar; Lerum, Tøri Vigeland; Meltzer, Carin & Rivero, Jezabel Rodriguez [Show all 8 contributors for this article] (2024). CT abnormalities 3 and 12 months after hospitalization for COVID-19 and association with disease severity: A prospective cohort study. PLOS ONE. 19(5). doi: 10.1371/journal.pone.0302896. Full text in Research Archive Show summary

  Objectives To investigate changes in chest CT between 3 and 12 months and associations with disease severity in patients hospitalized for COVID-19 during the first wave in 2020. Materials and methods Longitudinal cohort study of patients hospitalized for COVID-19 in 2020. Chest CT was performed 3 and 12 months after admission. CT images were evaluated using a CT severity score (CSS) (0–12 scale) and recoded to an abbreviated version (0–3 scale). We analyzed determinants of the abbreviated CSS with multivariable mixed effects ordinal regression. Results 242 patients completed CT at 3 months, and 124 (mean age 62.3±13.3, 78 men) also at 12 months. Between 3 and 12 months (n = 124) CSS (0–12 scale) for ground-glass opacities (GGO) decreased from median 3 (25th–75th percentile: 0–12) at 3 months to 0.5 (0–12) at 12 months (p<0.001), but increased for parenchymal bands (p<0.001). In multivariable analysis of GGO, the odds ratio for more severe abbreviated CSS (0–3 scale) at 12 months was 0.11 (95%CI 0.11 0.05 to 0.21, p<0.001) compared to 3 months, for WHO severity category 5–7 (high-flow oxygen/non-invasive ventilation/ventilator) versus 3 (non-oxygen use) 37.16 (1.18 to 43.47, p = 0.032), and for age ≥60 compared to <60 years 4.8 (1.33 to 17.6, p = 0.016). Mosaicism was reduced at 12 compared to 3 months, OR 0.33 (95%CI 0.16 to 0.66, p = 0.002). Conclusions GGO and mosaicism decreased, while parenchymal bands increased from 3 to 12 months. Persistent GGO were associated with initial COVID-19 severity and age ≥60 years.

• Veenstra, Marijke; Selle, Maria Lie; Johannessen, Ane; Gulsvik, Amund & Stavem, Knut (2024). Occupational class inequalities in all-cause and cardiovascular mortality in Norwegian men and women: a population-based approach with 45 years follow-up. Public Health. ISSN 0033-3506. 236, p. 230–238. doi: 10.1016/j.puhe.2024.07.033. Full text in Research Archive Show summary

  Objectives This study assessed associations of three theoretically different occupational class schemes with all-cause and cardiovascular mortality in Norwegian men and women. Study design Pooled survey and register data from four Norwegian cohort studies. Methods We pooled survey data from four general population cohorts (N = 97,469) linked to national mortality registries with follow-up over 45 years. Survival was modelled using accelerated failure time models stratified by sex for three class schemes: The European Socio-Economic Classification (ESeC), The Oslo Register Data Class scheme (ORDC) and The International Socio-Economic Index (ISEI). Main analyses were adjusted for age, birth cohort, and study. Secondary analyses included smoking behaviour as a mediator. Results During median 27.6 years of observation, 37,488 participants had died (13,243 from cardiovascular disease). Hazard ratios for male all-cause mortality were lowest in the highest occupational class categories ORDC 2: 0.68 (0.65–0.72), ESeC 1: 0.76 (0.73–0.79) and ISEI 5th quintile: 0.80 (0.77–0.82) compared to working class reference categories. Female mortality risks were lowest for Cultural Lower Middle class ORDC 7: 0.84 (0.72–0.98), Small Employers and Self-employed ESeC4: 0.70 (0.50–0.97) and ISEI 5th quintile: 0.79 (0.70–0.90). Patterns for cardiovascular mortality were similar to all-cause mortality. Including smoking behaviour as a mediator attenuated associations, but overall mortality patterns according to occupational class remained unchanged. Conclusion The results underline that mortality inequalities do not simply consist of higher risks in the most disadvantaged groups. The association of occupational class with mortality is found across different categories of occupational class schemes, illustrating their continued relevance for studying social determinants of health.

• Jervan, Øyvind; Haukeland-Parker, Stacey Marie; Gleditsch, Jostein; Tavoly, Mazdak; Klok, Frederikus A. & Steine, Kjetil [Show all 14 contributors for this article] (2023). The Effects of Exercise Training in Patients With Persistent Dyspnea Following Pulmonary Embolism: A Randomized Controlled Trial. Chest. ISSN 0012-3692. 164(4), p. 981–991. doi: 10.1016/j.chest.2023.04.042. Full text in Research Archive Show summary

  Bakgrunn Vedvarende dyspné, funksjonelle begrensninger og redusert livskvalitet (QoL) er vanlig etter lungeemboli (PE). Rehabilitering er et potensielt behandlingsalternativ , men den vitenskapelige dokumentasjonen er begrenset. Forskningsspørsmål Forbedrer et treningsbasert rehabiliteringsprogram treningskapasiteten hos PE-overlevere med vedvarende dyspné? Studiedesign og metoder Denne randomiserte kontrollerte studien ble utført ved to sykehus. Pasienter med vedvarende dyspné etter PE diagnostisert 6 til 72 måneder tidligere, uten kardiopulmonale komorbiditeter, ble randomisert 1:1 til enten rehabiliterings- eller kontrollgruppen. Rehabiliteringsprogrammet besto av to ukentlige økter med fysisk trening i 8 uker og en pedagogisk økt. Kontrollgruppen fikk vanlig pleie. Det primære endepunktet var forskjellen i Incremental Shuttle Walk Test mellom grupper ved oppfølging. Sekundære endepunkter inkluderte forskjeller i Endurance Shuttle Walk Test (ESWT), QoL (EQ-5D og lungeemboli-QoL spørreskjemaer) og dyspné (Shortness of Breath spørreskjema). Resultater Totalt 211 forsøkspersoner ble inkludert: 108 (51 %) ble randomisert til rehabiliteringsgruppen og 103 (49 %) til kontrollgruppen. Ved oppfølging presterte deltakerne fordelt på rehabiliteringsgruppen bedre på ISWT sammenlignet med kontrollgruppen (gjennomsnittlig forskjell, 53,0 m; 95 % KI, 17,7-88,3; P = 0,0035). Rehabiliteringsgruppen rapporterte bedre skårer på spørreskjemaet lungeemboli-kvalitet (gjennomsnittlig forskjell, –4 %; 95 % KI, –0,09 til 0,00; P = 0,041) ved oppfølging, men det var ingen forskjeller i generisk livskvalitet, dyspné. score, eller ESWT. Ingen uønskede hendelser oppsto under intervensjonen. Tolkning Hos pasienter med vedvarende dyspné etter PE hadde de som gjennomgikk rehabilitering bedre treningskapasitet ved oppfølging enn de som fikk vanlig behandling. Rehabilitering bør vurderes hos pasienter med vedvarende dyspné etter PE. Ytterligere forskning er imidlertid nødvendig for å vurdere optimal pasientvalg, tidspunkt, modus og varighet av rehabilitering.

• Jervan, Øyvind; Dhayyat, Adam; Gleditsch, Jostein; Haukeland-Parker, Stacey Marie; Tavoly, Mazdak & Klok, Frederikus A. [Show all 10 contributors for this article] (2023). Demographic, clinical, and echocardiographic factors associated with residual perfusion defects beyond six months after pulmonary embolism. Thrombosis Research. ISSN 0049-3848. 229, p. 7–14. doi: 10.1016/j.thromres.2023.06.004. Full text in Research Archive Show summary

  Background Residual perfusion defects (RPD) after pulmonary embolism (PE) are common. Primary aim This study aimed to determine the prevalence of RPD in a cohort diagnosed with PE 6–72 months earlier, and to determine demographic, clinical, and echocardiographic variables associated with RPD. Methods Patients aged 18–75 years with prior PE, confirmed by computed tomography pulmonary angiography 6–72 months earlier, were included. Participants (N = 286) completed a diagnostic work-up consisting of transthoracic echocardiography and ventilation/perfusion scintigraphy. Demographic, clinical, and echocardiographic characteristics between participants with RPD and those without RPD were explored in univariate analyses using t-test or Mann-Whitney U test. Multiple logistic regression analysis was used to assess the association between selected variables and RPD. Results RPD were detected in 72/286 patients (25.2 %, 95 % CI:20.5 %–30.5 %). Greater tricuspid annular plane systolic excursion (TAPSE) (adjusted odds ratio (aOR) 1.10, 95 % CI:1.00–1.21, p = 0.048) at echocardiographic follow-up, greater thrombotic burden at diagnosis, as assessed by mean bilateral proximal extension of the clot (MBPEC) score 3–4 (aOR 2.08, 95 % CI:1.06–4.06, p = 0.032), and unprovoked PE (aOR 2.25, 95 % CI:1.13–4.48, p = 0.021) were independently associated with increased risk of RPD, whereas increased pulmonary artery acceleration time was associated with a lower risk of RPD (aOR 0.72, 95 % CI:0.62–0.83, p < 0.001, per 10 ms). Dyspnoea was not associated with RPD. Conclusion RPD were common after PE. Reduced pulmonary artery acceleration time and greater TAPSE on echocardiography at follow-up, greater thrombotic burden at diagnosis, and unprovoked PE were associated with RPD.

• Lerum, Tøri Vigeland; Meltzer, Carin; Rivero, Jezabel Rodriguez; Aaløkken, Trond Mogens; Brønstad, Eivind & Aarli, Bernt Bøgvald [Show all 12 contributors for this article] (2023). A prospective study of pulmonary outcomes and chest computed tomography in the first year after COVID-19. European Respiratory Journal Open Research (ERJ Open Research). 9(2). doi: 10.1183/23120541.00575-2022. Full text in Research Archive Show summary

  COVID-19 primarily affects the respiratory system. We aimed to evaluate how pulmonary outcomes develop after COVID-19 by assessing participants from the first pandemic wave prospectively 3 and 12 months following hospital discharge. Pulmonary outcomes included self-reported dyspnoea assessed with the modified Medical Research Council dyspnoea scale, 6-min walk distance (6MWD), spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), body plethysmography and chest computed tomography (CT). Chest CT was repeated at 12 months in participants with pathological findings at 3 months. The World Health Organization (WHO) ordinal scale for clinical improvement defined disease severity in the acute phase. Of 262 included COVID-19 patients, 245 (94%) and 222 (90%) participants attended the 3- and 12-month follow-up, respectively. Self-reported dyspnoea and 6MWD remained unchanged between the two time points, while DLCO and total lung capacity improved (0.28 mmol·min−1·kPa−1, 95% CI 0.12–0.44, and 0.13 L, 95% CI 0.02–0.24, respectively). The prevalence of fibrotic-like findings on chest CT at 3 and 12 months in those with follow-up chest CT was unaltered. Those with more severe disease had worse dyspnoea, DLCO and total lung capacity values than those with mild disease. There was an overall positive development of pulmonary outcomes from 3 to 12 months after hospital discharge. The discrepancy between the unaltered prevalence of self-reported dyspnoea and the improvement in pulmonary function underscores the complexity of dyspnoea as a prominent factor of long-COVID. The lack of increase in fibrotic-like findings from 3 to 12 months suggests that SARS-CoV-2 does not induce a progressive fibrotic process in the lungs.

• Cestelli, Lucia; Gulsvik, Amund; Johannessen, Ane; Stavem, Knut & Nielsen, Rune (2023). Reduced lung function and cause-specific mortality: A population-based study of Norwegian men followed for 26 years. Respiratory Medicine. ISSN 0954-6111. 219. doi: 10.1016/j.rmed.2023.107421. Full text in Research Archive Show summary

  Background and aim Reduced lung function is associated with increased mortality, but it is unclear how different spirometric patterns are related to specific deaths. Aim of this study was to investigate these associations in a large general population cohort. Methods The study population consisted of 26,091 men aged 30–46 years from the Pneumoconiosis Survey of Western Norway conducted in 1988–1990 with follow-up on date and cause of death for 26 years. Cox proportional hazard models were used to estimate the association between baseline FEV1, FVC, obstructive (OSP) and restrictive spirometric pattern (RSP) (z-scores calculated according to GLI-2012 equations) and mortality (European 2012 shortlist classification (E−2012)), after adjustment for age, body mass index, smoking habits, and education. Results In total, 2462 (9%) subjects died. A predominant reduction of FEV1 (and OSP) were associated with respiratory non-cancer (E−8) (HR for one unit FEV1 z-score decrease 2.29 (95% CI 1.90, 2.77) and lung cancer mortality (E−2.1.8) (1.27(1.12, 1.44)). A similar reduction of FEV1 and FVC (and RSP) were associated with diabetes (E−4.1) (FEV1 2.21(1.67, 2.92), FVC 2.41(1.75, 3.32)), cerebrovascular (E−7.3) (1.52(1.21, 1.91), 1.54(1.19, 1.98)), ischemic heart disease (E−7.1) (1.22(1.10, 1.35), 1.21(1.08, 1.36)), neurological (E−6.3) (1.56(1.21, 2.01), 1.61(1.22, 2.13)), suicide (E−17.2) (1.37(1.13, 1.65), 1.29(1.04, 1.59)) and hematological cancer mortality (E−2.1.19–21) (1.29(1.05, 1.58), (1.26(1.00, 1.58)). No association was found between reduced lung function and mortality due to accidents, alcohol abuse, digestive and genitourinary cancer. Conclusions Spirometric obstruction was mainly related to pulmonary mortality. Spirometric restriction was mainly related to extra-pulmonary mortality.

• Solberg, Ole Geir; Aaberge, Lars; Bosse, Gerhard; Ueland, Thor; Gullestad, Lars & Aukrust, Pål [Show all 7 contributors for this article] (2023). Microvascular function and inflammatory activation in Takotsubo cardiomyopathy. ESC Heart Failure. 10(5), p. 3216–3222. doi: 10.1002/ehf2.14461. Full text in Research Archive Show summary

  Aims - The aim of this study was to determine microvascular function in the acute phase of Takotsubo syndrome (TTS) and to identify inflammatory mediators that could reflect TTS-induced pathology.<p> <p>Methods and results - The study included 20 females [median age 65 years; interquarile range (IQR) = 58–70 years] with TTS according to the Mayo diagnostic criteria. During heart catheterization, we determined the index of microvascular resistance (IMR) and drew blood samples almost simultaneously from the aorta and coronary sinus. Cardiac magnetic resonance imaging (MRI) was done in the acute phase. We present descriptive coronary physiology and cardiac MRI data and compare inflammatory biomarkers between samples from the aorta, coronary sinus, and venous samples after 3 months using the Wilcoxon signed-rank test. For comparison, we also analysed the actual biomarkers in venous blood from 15 healthy female controls. A supplementary analysis explored Spearman's rank correlation between the inflammatory biomarkers, IMR, MRI data, and cardiac biomarkers. The median IMR was 16.5 mmHg·s (IQR = 10.5–28.2 mmHg·s), which was only slightly higher than that in the reference populations. Seven (35%) of the study subjects had IMR > 25 mmHg·s, suggesting a microvascular dysfunction. IMR was not affected by time from symptom onset. According to MRI, the apical region of the left ventricle was affected in 65% of the subjects. The median ejection fraction was 41% (IQR = 31–48%). Biomarker analyses revealed elevation of markers for extracellular matrix remodelling and fibrosis, inflammation, immune activation, and upstream inflammation as compared with healthy controls. Only the levels of interleukin (IL)-1 receptor antagonist and soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) were higher in the coronary sinus than in the aorta. No variable was significantly correlated with IMR. The IL-6 level in the aorta was inversely correlated with the left ventricular ejection fraction. Growth differentiation factor-15, osteoprotegerin, and von Willebrand factor levels in both aorta and coronary sinus were positively correlated with N-terminal-pro-brain-natriuretic peptide, while the correlations of IL-6 and sTIM-3 with N-terminal-pro-brain-natriuretic peptide were restricted to the aorta and coronary sinus, respectively. While most of the markers were within normal limits after 3 months, matrix metalloproteinase-9 increased during follow-up to reach levels higher than those in the healthy controls.<p> <p>Conclusion - The median IMR was only slightly elevated in this study, but about one-third of the patients had values indicating microvascular dysfunction. The present study supports the involvement of several inflammatory pathways in TTS, including monocyte/macrophage activation, with sTIM-3 as a potential novel marker.

• Tholin, Birgitte; Ghanima, Waleed; Selle, Maria & Stavem, Knut (2023). Incidence and determinants of venous thromboembolism over 90 days in hospitalized and nonhospitalized patients with COVID-19. Journal of Internal Medicine. ISSN 0954-6820. 294(6), p. 721–729. doi: 10.1111/joim.13706. Full text in Research Archive Show summary

  Abstract Introduction COVID‐19 is associated with an increased risk of venous thromboembolism (VTE), but there is great variation among reported incidence rates. Most previous studies have focused on hospitalized patients with COVID‐19, and only a few reports are from population‐based registries. Methods We studied the 90‐day incidence of VTE, associated risk factors and all‐cause mortality in hospitalized and nonhospitalized patients with COVID‐19 in a nationwide cohort. Data on hospitalizations and outpatient visits were extracted from two national registries with mandatory reporting linked by a unique national identification number carried by all Norwegian residents. We performed Cox proportional hazards regression to determine risk factors for VTE after infection with SARS‐CoV‐2. Results Our study included 30,495 patients with positive SARS‐CoV‐2 polymerase chain reaction with a mean (SD) age of 41.9 (17.3) years, and 53% were males. Only 2081 (6.8%) were hospitalized. The 90‐day incidence of VTE was 0.3% (95% CI: 0.21–0.33) overall and 2.9% (95% CI: 2.3–3.7) in hospitalized patients. Age (hazard ratio [HR] 1.28 per decade, 95% CI: 1.11–1.48, p  &lt; 0.05), history of previous VTE (HR 4.69, 95% CI: 2.34–9.40, p  &lt; 0.05), and hospitalization for COVID‐19 (HR 23.83, 95% CI: 13.48–42.13, p &lt;  0.05) were associated with risk of VTE. Conclusions The 90‐day incidence of VTE in hospitalized and nonhospitalized patients with COVID‐19 was in the lower end compared with previous reports, with considerably higher rates in hospitalized than nonhospitalized patients. Risk factors for VTE were consistent with previously reported studies.

• Øvrebotten, Tarjei; Heck, Siri Lagethon; Skjørten, Ingunn; Einvik, Gunnar; Stavem, Knut & Ingul, Charlotte Ingeborg Björk [Show all 8 contributors for this article] (2023). Minor Myocardial Scars in Association with Cardiopulmonary Function after COVID-19. Cardiology. ISSN 0008-6312. 148(4), p. 300–306. doi: 10.1159/000530942. Full text in Research Archive Show summary

  Background: Myocardial scars detected by cardiovascular magnetic resonance (CMR) imaging after COVID-19 have caused concerns regarding potential long-term cardiovascular consequences. Objective: The objective of this study was to investigate cardiopulmonary functioning in patients with versus without COVID-19-related myocardial scars. Methods: In this prospective cohort study, CMR was performed approximately 6 months after moderate-to-severe COVID-19. Before (∼3 months post-COVID-19) and after (∼12 months post-COVID-19) the CMR, patients underwent extensive cardiopulmonary testing with cardiopulmonary exercise tests, 24-h ECG, and echocardiography. We excluded participants with overt heart failure. Results: Post-COVID-19 CMR was available in 49 patients with cardiopulmonary tests at 3 and 12 months after the index hospitalization. Nine (18%) patients had small late gadolinium enhancement-detected myocardial scars. Patients with myocardial scars were older (63.2 ± 13.2 vs. 56.2 ± 13.2 years) and more frequently men (89% vs. 55%) compared to those without scars. Cardiorespiratory fitness was similar in patients with and without scars, i.e., peak oxygen uptake: 82.1 ± 11.5% versus 76.3 ± 22.5% of predicted, respectively (p = 0.46). The prevalence of ventricular premature contractions and arrhythmias was low and not different by the presence of myocardial scar. Cardiac structure and function assessed by echocardiography were similar between the groups, except for a tendency of greater left ventricular mass in those with scars (75 ± 20 vs. 62 ± 14, p = 0.02 and p = 0.08 after adjusting for age and sex). There were no significant associations between myocardial scar and longitudinal changes in cardiopulmonary function from 3 to 12 months. Conclusion: Our findings imply that the presence of minor myocardial scars has limited clinical significance with respect to cardiopulmonary function after COVID-19.

• Øvrebotten, Tarjei; Myhre, Peder Langeland; Grimsmo, Jostein; Mecinaj, Albulena; Trebinjac, Divna & Nossen, Magnus Berger [Show all 12 contributors for this article] (2022). Changes in cardiac structure and function from 3 to 12 months after hospitalization for COVID-19. Clinical Cardiology. ISSN 0160-9289. 45(10), p. 1044–1052. doi: 10.1002/clc.23891. Full text in Research Archive Show summary

  Background Cardiac function may be impaired during and early after hospitalization for COVID-19, but little is known about the progression of cardiac dysfunction and the association with postacute COVID syndrome (PACS). Methods In a multicenter prospective cohort study, patients who had been hospitalized with COVID-19 were enrolled and comprehensive echocardiography was performed 3 and 12 months after discharge. Twenty-four-hour electrocardiogram (ECG) was performed at 3 and 12 months in patients with arrhythmias at 3 months. Results In total, 182 participants attended the 3 and 12 months visits (age 58 ± 14 years, 59% male, body mass index 28.2 ± 4.2 kg/m2). Of these, 35 (20%) had severe COVID-19 (treatment in the intensive care unit) and 74 (52%) had self-reported dyspnea at 3 months. From 3 to 12 months there were no significant overall changes in any measures of left or right ventricle (LV; RV) structure and function (p > .05 for all), including RV strain (from 26.2 ± 3.9% to 26.5 ± 3.1%, p = .29) and LV global longitudinal strain (from 19.2 ± 2.3% to 19.3 ± 2.3%, p = .64). Changes in echocardiographic parameters from 3 to 12 months did not differ by COVID-19 severity or by the presence of persistent dyspnea (p > .05 for all). Among patients with arrhythmia at 3 months, there was no significant change in arrhythmia burden to 12 months. Conclusion Following COVID-19, cardiac structure and function remained unchanged from 3 to 12 months after the index hospitalization, irrespective of COVID-19 severity and presence of persistent dyspnea. These results suggest that progression of cardiac dysfunction after COVID-19 is rare and unlikely to play an important role in PACS.

• Hansen, Tonya Moen; Stavem, Knut & Rand, Kim (2022). Sample Size and Model Prediction Accuracy in EQ-5D-5L Valuations Studies: Expected Out-of-Sample Accuracy Based on Resampling with Different Sample Sizes and Alternative Model Specifications. Medical Decision Making Policy & Practice. 7(1). doi: 10.1177/23814683221083839. Full text in Research Archive Show summary

  Background. National valuation studies are costly, with ∼1000 face-to-face interviews recommended, and some countries may deem such studies infeasible. Building on previous studies exploring sample size, we determined the effect of sample size and alternative model specifications on prediction accuracy of modeled coefficients in EQ-5D-5L value set generating regression analyses. Methods. Data sets ( n = 50 to ∼1000) were simulated from 3 valuation studies, resampled at the respondent level and randomly drawn 1000 times with replacement. We estimated utilities for each subsample with leave-one-out at the block level using regression models (8 or 20 parameter; with or without a random intercept; time tradeoff [TTO] data only or TTO + discrete choice experiment [DCE] data). Prediction accuracy, root mean square error (RMSE), was calculated by comparing to censored mean predicted values to the left-out block in the full data set. Linear regression was used to estimate the relative effect of changes in sample size and each model specification. Results. Results showed that doubling the sample size decreased RMSE by on average 0.012. Effects of other model specifications were smaller but can when combined compensate for loss in prediction accuracy from a small sample size. For models using TTO data only, 8-parameter models clearly outperformed 20-parameter models. Adding a random intercept, or including DCE responses, also improved mean RMSE, most prominently for variants of the 20-parameter models. Conclusions. The prediction accuracy impact of further increases in sample size after 300 to 500 were smaller than the impact of combining alternative modeling choices. Hybrid modeling, use of constrained models, and inclusion of random intercepts all substantially improve the expected prediction accuracy. Beyond a minimum of 300 to 500 respondents, the sample size may be better informed by other considerations, such as legitimacy and representativeness, than by the technical prediction accuracy achievable. Highlights Increases in sample size beyond a minimum in the range of 300 to 500 respondents provide smaller gains in expected prediction accuracy than alternative modeling approaches. Constrained, nonlinear models; time tradeoff + discrete choice experiment hybrid modeling; and including a random intercept all improved the prediction accuracy of models estimating values for the EQ-5D-5L based on data from 3 different valuation studies. The tested modeling choices can compensate for smaller sample sizes.

• Tholin, Birgitte; Fiskvik, Hilde; Tveita, Anders Aune; Tsykunova, Galina; Opperud, Helene & Busterud, Kari [Show all 11 contributors for this article] (2022). Thromboembolic complications during and after hospitalization for COVID-19: Incidence, risk factors and thromboprophylaxis. Thrombosis Update. 6, p. 1–6. doi: 10.1016/j.tru.2021.100096. Full text in Research Archive Show summary

  Introduction The incidence of thromboembolism during COVID-19 and the use of thromboprophylaxis vary greatly between studies. Only a few studies have investigated the rate of thromboembolism post-discharge. This study determined the 90-day incidence of venous and arterial thromboembolic complications, risk factors for venous thromboembolic events and characterized the use of thromboprophylaxis during and after hospitalization. Materials and methods We retrospectively reviewed medical records for adult patients hospitalized for >24 h for COVID-19 before May 15, 2020, in ten Norwegian hospitals. We extracted data on demographics, thromboembolic complications, thromboembolic risk factors, and the use of thromboprophylaxis. Cox proportional hazards regression was used to determine risk factors for VTE. Results 550 patients were included. The 90-day incidence of arterial and venous thromboembolism in hospitalized patients was 6.9% (95% CI: 5.1–9.3) overall and 13.8% in the ICU. Male sex (hazard ratio (HR) 7.44, 95% CI 1.73–32.02, p = 0.007) and previous VTE (HR 6.11, 95% CI: 1.74–21.39, p = 0.005) were associated with risk of VTE in multivariable analysis. Thromboprophylaxis was started in 334 patients (61%) with a median duration of 7 days (25th–75th percentile 3–13); in the VTE population 10/23 (43%) started thromboprophylaxis prior to diagnosis. After discharge 20/223 patients received extended thromboprophylaxis and 2/223 (0.7%, 95% CI: 0.3–1.9) had a thromboembolism. Conclusions The 90-day incidence of thromboembolism in COVID-19 patients was 7%, but <1% after discharge. Risk factors were male sex and previous VTE. Most patients received thromboprophylaxis during hospitalization, but only <10% after discharge.

• Garratt, Andrew; Nerheim, Ellen Margrethe; Einvik, Gunnar; Stavem, Knut & Edvardsen, Anne (2022). Evaluation of the Norwegian version of the Dyspnoea-12 questionnaire in patients with COPD. BMJ Open Respiratory Research. 9(1). doi: 10.1136/bmjresp-2022-001262. Full text in Research Archive Show summary

  Background The Dyspnoea-12 (D-12) questionnaire is widely used and tested in patients with breathing difficulties. The objective of this study was to translate and undertake the first evaluation of the measurement properties of the Norwegian version of the D-12 in patients with chronic obstructive pulmonary disease (COPD) attending a 4-week inpatient pulmonary rehabilitation programme. Methods Confirmatory factor analysis was used to assess structural validity. Fit to the Rasch partial credit model and differential item functioning (DIF) were assessed in relation to age, sex and comorbidity. Based on a priori hypotheses, validity was assessed through comparisons with scores for the COPD Assessment Test (CAT), Hospital Anxiety and Depression Scales (HADS) and clinical variables. Results There were 203 (86%) respondents with a mean age (SD) of 65.2 (9.0) years, and 49% were female. The D-12 showed satisfactory structural validity including presence of physical and affective domains. There was acceptable fit to Rasch model including unidimensionality for the two domains, and no evidence of DIF. Correlations with scores for the CAT, HADS and clinical variables were as hypothesised and highest for domains assessing similar aspects of health. Conclusions The Norwegian version of the D-12 showed good evidence for validity and internal consistency in this group of patients with COPD, including support for two separate domains. Further testing for these measurement properties is recommended in other Norwegian patients with dyspnoea.

• Hansen, Tonya Moen; Stavem, Knut & Rand, Kim (2022). Completing the time trade-off with respondents who are older, in poorer health or with an immigrant background in an EQ-5D-5L valuation study. European Journal of Health Economics. ISSN 1618-7598. 24(6), p. 877–884. doi: 10.1007/s10198-022-01517-y. Full text in Research Archive Show summary

  Abstract Objectives To determine the effects of age, immigrant background, and poor self-reported health in a general population sample on the probability of non-completion or slow completion of the time trade-off (TTO). Methods We used data from an interrupted Norwegian EQ-5D-5L valuation study conducted between 2019 and 2020. All participants responded to background items, irrespective of completion. We used mixed effect logistic regression analysis to assess the effect of old age, poor health, and immigrant background on the probability of non-completion of the TTO, and, for those who completed the TTO, of slow completion times. Results First experiences from a Norwegian valuation study were that 29 (5.5%) respondents failed to complete the TTO tasks. For those reporting age over 65 years, poor health, or an immigrant background, 12% failed to complete the TTO. Adjusted odds ratios for predictors of non-completion were statistically significant (age &gt; 65 years, 8.3; EQ-VAS ≤ 50, 3.49; immigrant background, 4.56). Being over 65 years or with an immigrant background also predicted slow completion of both the introduction and TTO tasks. Conclusions High age, poor health, and immigrant status increased the risk of not being able to complete the TTO tasks, and of slow completion. Higher non-completion rates and increased completion times suggest that elements of the TTO may be demanding for some respondent groups, with possible implications for representativeness.

• Stavem, Knut; Einvik, Gunnar & Lundqvist, Christofer (2022). Cognitive Impairment 13 Months After Hospitalization for COVID-19. Open Forum Infectious Diseases. 9(7). doi: 10.1093/ofid/ofac355. Full text in Research Archive Show summary

  Abstract This study assessed cognitive function 13 months after hospital discharge for coronavirus disease 2019 (COVID-19), using computer-based cognitive tests. Compared to population norms, 14%–25% of patients were impaired in each dimension, and 53% had cognitive impairment in 1 or more of 4 tests. There was some association with acute COVID-19 disease severity.

• Stavem, Knut; Einvik, Gunnar; Tholin, Birgitte; Ghanima, Waleed; Hessen, Erik & Lundqvist, Christofer (2022). Cognitive function in non-hospitalized patients 8–13 months after acute COVID-19 infection: A cohort study in Norway. PLOS ONE. 17(8). doi: 10.1371/journal.pone.0273352. Full text in Research Archive Show summary

  Studies have reported reduced cognitive function following COVID-19 illness, mostly from hospital settings with short follow-up times. This study recruited non-hospitalized COVID-19 patients from a general population to study prevalence of late cognitive impairment and associations with initial symptoms. We invited patients with PCR-confirmed COVID-19. A postal questionnaire addressed basic demographics, initial COVID-19 symptoms and co-morbidity about 4 months after diagnosis. About 7 months later, we conducted cognitive tests using the Cambridge Neuropsychological Test Automated Battery, comprising four tests for short-term memory, attention and executive function. We present descriptive statistics using z-scores relative to UK population norms and defined impairment as z-score &lt;-1.5. We used multivariable logistic regression with impairment as outcome. Continuous domain scores were analysed by multiple linear regression. Of the initial 458 participants; 305 were invited, and 234 (77%) completed cognitive testing. At median 11 (range 8–13) months after PCR positivity, cognitive scores for short term memory, visuospatial processing, learning and attention were lower than norms (p≤0.001). In each domain, 4–14% were cognitively impaired; 68/232 (29%) were impaired in ≥ 1 of 4 tests. There was no association between initial symptom severity and impairment. Multivariable linear regression showed association between spatial working memory and initial symptom load (6–9 symptoms vs. 0–5, coef. 4.26, 95% CI: 0.65; 7.86). No other dimension scores were associated with symptom load. At median 11 months after out-of-hospital SARS-Cov-2 infection, minor cognitive impairment was seen with little association between COVID-19 symptom severity and outcome.

• Ruud, Espen Asak; Heck, Sigurd; Stavem, Knut; Søyseth, Vidar; Geitung, Jonn Terje & Ashraf, Haseem (2022). Low diffusion capacity of the lung predicts pneumothorax and chest drainage after CT-guided lung biopsy. BMC Research Notes. 15(1). doi: 10.1186/s13104-022-06234-6. Full text in Research Archive Show summary

  Objectives Complications after CT-guided lung biopsy is a burden both for the individual patient and for the overall healthcare. Pneumothorax is the most common complication. This study determined the association between lung function tests and pneumothorax and chest drainage following CT-guided lung biopsy in consecutive patients in a large university hospital. Results We prospectively registered 875 biopsy procedures from 786 patients in one institution from January 27th 2012 to March 1st 2017 and recorded complications including pneumothorax with or without chest drainage. Lung function data from 637 patients undergoing 710 of the procedures were available. The association of lung function measures with pneumothorax with or without chest drainage was assessed using multivariable logistic regression analyses. Diffusion capacity for carbon monoxide (DLCO) below 4.70 mmol/min/kPa was associated with increased occurrence of pneumothorax and chest drainage after CT guided lung biopsy. We found no association between FEV1, RV and occurrence of pneumothorax and chest drainage. We found low DLCO to be a risk factor of pneumothorax and chest drainage after CT-guided lung biopsy. This should be taken into account in planning and performing the procedure.

• Stavem, Knut; Schirmer, Henrik & Gulsvik, Amund (2022). Respiratory symptoms and cardiovascular causes of deaths: A population-based study with 45 years of follow-up. PLOS ONE. 17(10). doi: 10.1371/journal.pone.0276560. Full text in Research Archive Show summary

  This study determined the association between respiratory symptoms and death from cardiovascular (CV) diseases during 45 years in a pooled sample of four cohorts of random samples of the Norwegian population with 95,704 participants. Respiratory symptoms were assessed using a modification of the MRC questionnaire on chronic bronchitis. We analyzed the association between respiratory symptoms and specific cardiovascular deaths by using Cox regression analysis with age as the time variable, accounting for cluster-specific random effects using shared frailty for study cohort. Hazard ratios (HR) for death were adjusted for sex, highest attained education, smoking habits, occupational air pollution, and birth cohort. Overall, 12,491 (13%) of participants died from CV diseases: 4,123 (33%) acute myocardial infarction, 2,326 (18%) other ischemic heart disease, 2,246 (18%) other heart diseases, 2,553 (20%) cerebrovascular diseases, and 1,120 (9%) other vascular diseases. The adjusted HR (95% confidence interval) for CV deaths was 1.9 (1.7–2.1) in men and 1.5 (1.2–1.9) in women for “yes” to the question “Are you breathless when you walk on level ground at an ordinary pace?”. The same item response showed an adjusted HR for death from acute myocardial infarction of 1.8 (1.5–2.1), other ischemic heart disease 2.2 (1.8–2.7), other heart diseases 1.5 (1.1–1.9), cerebrovascular disease 1.8 (1.5–2.3), and other circulatory diseases 1.7 (1.2–2.4). The adjusted HR for CV death was 1.3 (1.2–1.4) when answering positive to the question” Are you more breathless than people of your own age when walking uphill?”. However, positive answers to questions on cough, phlegm, wheezing and attacks of breathlessness were after adjustments not associated with early CV deaths. The associations between CV deaths and breathlessness were also present in never smokers. Self-reported breathlessness was associated with CV deaths and could be an early marker of CV deaths.

• Ingul, Charlotte Bjørk; Edvardsen, Anne; Follestad, Turid; Trebinjac, Divna; Ankerstjerne, Odd Andre Wathne & Brønstad, Eivind [Show all 14 contributors for this article] (2022). Changes in cardiopulmonary exercise capacity and limitations 3-12 months after COVID-19. European Respiratory Journal. ISSN 0903-1936. 61(2). doi: 10.1183/13993003.00745-2022. Full text in Research Archive Show summary

  Rationale: To describe cardiopulmonary function during exercise 12 months after hospital discharge for coronavirus disease 2019 (COVID-19), assess the change from 3 to 12 months, and compare the results with matched controls without COVID-19. Methods: In this prospective, longitudinal, multicentre cohort study, hospitalised COVID-19 patients were examined using a cardiopulmonary exercise test (CPET) 3 and 12 months after discharge. At 3 months, 180 performed a successful CPET, and 177 did so at 12 months (mean age 59.3 years, 85 females). The COVID-19 patients were compared with controls without COVID-19 matched for age, sex, body mass index and comorbidity. Main outcome was peak oxygen uptake (V′O2 peak). Results: Exercise intolerance (V′O2 peak <80% predicted) was observed in 23% of patients at 12 months, related to circulatory (28%), ventilatory (17%) and other limitations including deconditioning and dysfunctional breathing (55%). Estimated mean difference between 3 and 12 months showed significant increases in V′O2 peak % pred (5.0 percentage points (pp), 95% CI 3.1–6.9 pp; p<0.001), V′O2 peak·kg−1 % pred (3.4 pp, 95% CI 1.6–5.1 pp; p<0.001) and oxygen pulse % pred (4.6 pp, 95% CI 2.5–6.8 pp; p<0.001). V′O2 peak was 2440 mL·min−1 in COVID-19 patients compared to 2972 mL·min−1 in matched controls. Conclusions: 1 year after hospital discharge for COVID-19, the majority (77%), had normal exercise capacity. Only every fourth had exercise intolerance and in these circulatory limiting factors were more common than ventilator factors. Deconditioning was common. V′O2 peak and oxygen pulse improved significantly from 3 months.

• Garratt, Andrew & Stavem, Knut (2022). Comparison of EQ-5D-3L and 5L versions following operative fixation of closed ankle fractures. Quality of Life Research. ISSN 0962-9343. 31(7), p. 2071–2082. doi: 10.1007/s11136-022-03105-2. Full text in Research Archive Show summary

  Abstract Purpose To undertake the first testing and comparison of measurement properties for the EuroQol EQ-5D-3L and 5L in patients with ankle problems. Methods The cross-sectional postal survey of 959 patients aged ≥ 18 years, who underwent surgical treatment (ORIF) for unstable and closed ankle fractures in Eastern Norway. Both the EQ-5D-3L and 5L were included in a postal questionnaire in 2015, 3–6 years post surgery. Missing data, floor and ceiling effects, and response consistency were assessed. Tests of validity included comparisons with scores for the SF-36 and widely used ankle-specific instruments. The 5L version was assessed for test–retest reliability. Results There were 567 (59%) respondents; 501 completed both versions and 182 (61%) the 5L retest questionnaire. The 5L outperformed the 3L in tests of data quality and classification efficiency. Correlations with scores for other instruments largely met expectations, those for the 5L being slightly higher. All 5L scores had acceptable levels of reliability. For the 5L index, the smallest detectable differences for group and individual comparisons were 0.02 and 0.20, respectively. Conclusion The 5L outperformed the 3L in terms of data quality, number of health states assessed and tests of validity. The 5L is recommended in research and other applications following surgery for ankle fracture but further testing including responsiveness to change is recommended at clinically relevant follow-up periods.

• Cestelli, Lucia; Johannessen, Ane; Stavem, Knut; Gulsvik, Amund & Nielsen, Rune (2022). Period and cohort effects: consequences on spirometric lung function in Norway during the 20th century. European Respiratory Journal Open Research (ERJ Open Research). 8(4), p. 1–11. doi: 10.1183/23120541.00302-2022. Full text in Research Archive Show summary

  Background and aim Several factors can influence measured lung function over time. The aim of this study was to investigate period and cohort effects on spirometric measures in a large general population sample in Norway during the 20th century, using Global Lung Function Initiative (GLI-2012) equations as a reference. Methods 36 466 subjects (born 1894–1969) from four cross-sectional surveys conducted between 1965 and 1999 were included, with harmonised data on smoking habits, respiratory symptoms, lung diseases, education and spirometry. Changes in forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) z-scores in healthy subjects across surveys were explored to investigate period effects. Linear mixed-effects models of FEV1 and FVC z-scores on birth cohort, with survey as random effect, were used to investigate cohort effects, both in subjects of the total population and in healthy ones. Results Relatively higher FEV1 and FVC z-scores in healthy subjects were found in the first survey (1965–1970) compared to the more recent ones (1988–1999), suggesting period effects. FEV1 and FVC z-scores increased significantly with birth cohort from 1894 to 1935, after adjustment for covariates. A more stable trend of FEV1 and FVC z-scores with birth cohort was evidenced for subjects born more recently (1945–1969). Conclusions An increase of lung function with year of birth was observed in Norwegian subjects during the first half of the 20th century. The impact of period effects on lung function decreased from 1965 to 1999.

• Ingul, Charlotte Ingeborg Björk; Grimsmo, Jostein; Mecinaj, Albulena; Trebinjac, Divna; Nossen, Magnus Berger & Andrup, Simon [Show all 14 contributors for this article] (2022). Cardiac Dysfunction and Arrhythmias 3 Months After Hospitalization for COVID-19. Journal of the American Heart Association (JAHA). 11(3). doi: 10.1161/JAHA.121.023473. Full text in Research Archive Show summary

  Background - The extent of cardiac dysfunction post‐COVID‐19 varies, and there is a lack of data on arrhythmic burden. Methods and Results - This was a combined multicenter prospective cohort study and cross‐sectional case‐control study. Cardiac function assessed by echocardiography in patients with COVID‐19 3 to 4 months after hospital discharge was compared with matched controls. The 24‐hour ECGs were recorded in patients with COVID‐19. A total of 204 patients with COVID‐19 consented to participate (mean age, 58.5 years; 44% women), and 204 controls were included (mean age, 58.4 years; 44% women). Patients with COVID‐19 had worse right ventricle free wall longitudinal strain (adjusted estimated mean difference, 1.5 percentage points; 95% CI, −2.6 to −0.5; P=0.005) and lower tricuspid annular plane systolic excursion (−0.10 cm; 95% CI, −0.14 to −0.05; P<0.001) and cardiac index (−0.26 L/min per m2; 95% CI, −0.40 to −0.12; P<0.001), but slightly better left ventricle global strain (−0.8 percentage points; 95% CI, 0.2–1.3; P=0.008) compared with controls. Reduced diastolic function was twice as common compared with controls (60 [30%] versus 29 [15%], respectively; odds ratio, 2.4; P=0.001). Having dyspnea or fatigue were not associated with cardiac function. Right ventricle free wall longitudinal strain was worse after intensive care treatment. Arrhythmias were found in 27% of the patients, mainly premature ventricular contractions and nonsustained ventricular tachycardia (18% and 5%, respectively). Conclusions - At 3 months after hospital discharge with COVID‐19, right ventricular function was mildly impaired, and diastolic dysfunction was twice as common compared with controls. There was little evidence for an association between cardiac function and intensive care treatment, dyspnea, or fatigue. Ventricular arrhythmias were common, but the clinical importance is unknown.

• Tran, Thien Trung; Kristiansen, Cathrine Helgestad; Thomas, Owen Matthew Truscott; Roy, Sumit K; Haidl, Frans Felxi & Ashraf, Haseem [Show all 9 contributors for this article] (2022). Indirect CT venography of the lower extremities: impact of scan delay and patient factors on contrast enhancement and examination quality. European Radiology. ISSN 0938-7994. 32(11), p. 7946–7955. doi: 10.1007/s00330-022-08841-0. Full text in Research Archive Show summary

  Objectives Indirect computed tomography venography (CTV) is often the next imaging modality for deep vein thrombosis (DVT) when sonography is inconclusive. Our aim was to investigate the impact of scan delay and patient factors on contrast enhancement (CE) and examination quality in CTV. Methods Patients with clinical suspicion or clinical mimics of DVT in one large hospital were enrolled. Age, sex, body weight, height, heart rate, systolic blood pressure and cardiac output were registered. CTV of the popliteal veins was obtained at 30 s intervals at 30–210 s delays. The proportions of examinations with CE exceeding predefined cut-offs were estimated and subjective examination quality was rated. Changes in CE with time, and associations between patient factors and time to peak contrast enhancement (TPCE) were modelled with mixed effects non-linear and linear regression, respectively. Results The CE increased with increasing scan delay and reached a plateau from 120 to 210 s. The percentages of examinations achieving enhancement above cut-offs across all thresholds from 70 to 100 HU were higher at 120 s compared to 90 s (p < 0.001). After 120 s, there were no differences across scan delays for any thresholds. No patient factors showed a significant effect on TPCE. The percentage of examinations rated as acceptable was higher at 120 s compared to 90 s (p < 0.001). After 120 s, there were no statistically significant differences across scan delays. Conclusions No patient factors were associated with TPCE in CTV. A fixed scan delay of 120–210 s yielded the best examination quality.

• Stavem, Knut; Heir, Trond; Dammen, Toril; Brønstad, Eivind; Lerum, Tøri Vigeland & Durheim, Michael Thomas [Show all 9 contributors for this article] (2022). The course and determinants of post-traumatic stress over 12 months after hospitalization for COVID-19. Frontiers in Psychiatry. 13. doi: 10.3389/fpsyt.2022.931349. Full text in Research Archive Show summary

  Objective: To assess the trajectory of symptoms and symptom-defined post-traumatic stress disorder (PTSD) from 1.5 to 12 months after hospitalization for COVID-19 and determine risk factors for persistent symptoms and PTSD. Methods: This was a prospective cohort study of consecutive patients discharged after hospitalization for COVID-19 before 1 June 2020 in six hospitals in Southern Norway. Symptom-defined PTSD was assessed by the post-traumatic stress disorder (PTSD) checklist for DSM-5 (PCL-5) at 1.5, 3 and/or 12 months after hospitalization, using DSM-5 criteria. Changes in PCL-5 symptom score and the prevalence of PTSD were analyzed with multivariable mixed models. Results: In total, 388 patients were discharged alive, and 251 (65%) participated. Respondents had a mean (SD) age of 58.4 (14.2) years, and 142 (57%) were males. The prevalence of symptom-defined PTSD was 14, 8, and 9% at 1.5, 3, and 12 months, respectively. WHO disease severity for COVID-19 was not associated with PCL-5 scores. Female sex, lower age and non-Norwegian origin were associated with higher PCL-5 scores. The odds ratio (OR) (95%CI) for PTSD was 0.32 (0.12 to 0.83, p = 0.019) at 3 months and 0.38 (0.15 to 0.95, p = 0.039) at 12 months compared to 1.5 months. There was no association between PTSD and WHO severity rating. Conclusions: The level of PTSD symptoms decreased from 1.5 to 3 months after hospitalization, but did not decrease further to 12 months, and there was no association between PTSD symptoms and COVID-19 disease severity.

• Hansen, Tonya Moen; Stavem, Knut & Rand, Kim (2021). Time trade-off with someone to live for: impact of having significant others on time trade-off valuations of hypothetical health states. Quality of Life Research. ISSN 0962-9343. doi: 10.1007/s11136-021-03026-6. Full text in Research Archive Show summary

  Abstract Background The TTO task involves giving up life years, i.e. living a shorter life, to avoid an undesirable health state. Despite being a hypothetical task, some respondents take other life factors into account when completing the task. This study explored the effect of having children and/or a partner on TTO valuations of hypothetical EQ-5D-5L health states in a valuation study of the general population. Methods The study used TTO data collected in a Norwegian EQ-5D-5L valuation study in 2019–2020, by one-to-one pc-assisted interviews following the EQ-VT protocol. We used regression modelling to determine the effect of significant others (having children or a partner) on disutility per health state from the TTO valuations. Results 430 respondents were included [mean age 43.8 (SD 15.9) years, 58% female, 48% with children, 68% with a partner, 25% with neither children nor partner]. Having children and/or a partner was associated with lowered willingness to trade life years translating to higher elicited health state utilities ( p  &lt; 0.01). Conclusion Having significant others, or the lack of having significant others, was associated with respondents’ valuation of hypothetical health states using TTO, more so than traditional sampling variables such as age and sex. Inadequate representativeness in terms of having significant others could bias health state preference values in valuation studies.

• Stavem, Knut; Johannessen, Ane; Nielsen, Rune & Gulsvik, Amund (2021). Respiratory symptoms and respiratory deaths: A multi-cohort study with 45 years observation time. PLOS ONE. 16(11), p. 1–14. doi: 10.1371/journal.pone.0260416. Full text in Research Archive Show summary

  This study determined the association between respiratory symptoms and death from respiratory causes over a period of 45 years. In four cohorts of random samples of Norwegian populations with 103,881 participants, 43,731 persons had died per 31 December 2016. In total, 5,949 (14%) had died from respiratory diseases; 2,442 (41%) from lung cancer, 1,717 (29%) chronic obstructive pulmonary disease (COPD), 1,348 (23%) pneumonia, 119 (2%) asthma, 147 (2%) interstitial lung disease and 176 (3%) other pulmonary diseases. Compared with persons without respiratory symptoms the multivariable adjusted hazard ratio (HR) for lung cancer deaths increased with score of breathlessness on effort and cough and phlegm, being 2.6 (95% CI 2.1–3.2) for breathlessness score 3 and 2.1 (95% CI 1.7–2.5) for cough and phlegm score 5. The HR of COPD death was 6.4 (95% CI 5.4–7.7) for breathlessness score 3 and 3.0 (2.4–3.6) for cough and phlegm score 5. Attacks of breathlessness and wheeze score 2 had a HR of 1.6 (1.4–1.9) for COPD death. The risk of pneumonia deaths increased also with higher breathlessness on effort score, but not with higher cough and phlegm score, except for score 2 with HR 1.5 (1.2–1.8). In this study with >2.4 million person-years at risk, a positive association was observed between scores of respiratory symptoms and deaths due to COPD and lung cancer. Respiratory symptoms are thus important risk factors, which should be followed thoroughly by health care practitioners for the benefit of public health.

• Chaibi, Aleksander; Stavem, Knut & Russell, Michael Bjørn (2021). Spinal manipulative therapy for acute neck pain: A systematic review and meta-analysis of randomised controlled trials. Journal of Clinical Medicine. 10(21). doi: 10.3390/jcm10215011. Full text in Research Archive Show summary

  (1) Background: Acute neck pain is common and usually managed by medication and/or manual therapy. General practitioners (GPs) hesitate to refer to manual therapy due to uncertainty about the effectiveness and adverse events (AEs); (2) Method: To review original randomized controlled trials (RCTs) assessing the effect of spinal manipulative therapy (SMT) for acute neck pain. Data extraction was done in duplicate and formulated in tables. Quality and evidence were assessed using the Cochrane Back and Neck (CBN) Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria, respectively; (3) Results: Six studies were included. The overall pooled effect size for neck pain was very large −1.37 (95% CI, −2.41, −0.34), favouring treatments with SMT compared with controls. A single study that showed that SMT was statistically significantly better than medicine (30 mg ketorolac im.) one day post-treatment, ((−2.8 (46%) (95% CI, −2.1, −3.4) vs. −1.7 (30%) (95% CI, −1.1, −2.3), respectively; p = 0.02)). Minor transient AEs reported included increased pain and headache, while no serious AEs were reported; (4) Conclusions: SMT alone or in combination with other modalities was effective for patients with acute neck pain. However, limited quantity and quality, pragmatic design, and high heterogeneity limit our findings.

• Stavem, Knut (2021). Switching from one reference biological to another in stable patients for non-medical reasons: a literature search and brief review. Journal of Market Access & Health Policy. 9(1). doi: 10.1080/20016689.2021.1964792. Full text in Research Archive Show summary

  Background: The practice of non-medical switch (NMS) from a reference biological (originator) to a biosimilar is widely accepted in some countries. However, there is little documentation on the impact of NMS from one originator to another originator. Objectives: To assess the consequences for patients of NMS from one biological originator to another, based on existing literature. The focus was on efficacy and cost of treatment with TNF-α-inhibitors in three disease areas. Methods: A literature search was conducted in Ovid (PubMed, EMBASE) and abstracts from meetings in key therapeutic areas, to identify studies reporting efficacy, safety or costs by switching between originator biologics. Results: 167 references were identified and abstracts screened; 36 papers reviewed in full text, and 6 fulfilled the inclusion criteria. Three clinical studies of NMS had very small sample sizes, but suggested that NMS is beneficial. The remaining three studies used administrative data with little clinical information, indicating that NMS was disadvantageous and associated with increased health care utilization and costs. Conclusions: There is very limited documentation on NMS from one originator biological to another, and the literature suffers from methodological limitations. The results are mixed and preclude drawing an overriding conclusion. Future studies, are warranted.

• Wimmer, Rolf Henning; Lundqvist, Christofer; Benth, Jurate Saltyte; Stavem, Knut; Andersen, Geir Øystein & Henriksen, Julia [Show all 9 contributors for this article] (2021). Health-related quality of life after out-of-hospital cardiac arrest – a five-year follow-up study. Resuscitation. ISSN 0300-9572. 162, p. 372–380. doi: 10.1016/j.resuscitation.2021.01.036. Full text in Research Archive Show summary

  Background Health-related quality of life (HRQoL) is affected after out-of-hospital cardiac arrest (OHCA), but data several years after the arrest are lacking. We assessed long-term HRQoL in OHCA survivors and how known outcome predictors impact HRQoL. Methods In adult OHCA survivors, HRQoL was assessed five years post arrest using Short-form 36 (SF-36), EQ-5D-3 L (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) among others. Results were compared to the next of kins’ estimates and to a Norwegian reference population. Results Altogether 96 survivors were included mean 5.3 (range 3.6–7.2) years after OHCA. HRQoL compared well to the reference population, except for lower score for general health with 67.2 (95%CI (62.1; 72.3) vs. 72.9 (71.9; 74.0)), p = 0.03. Younger (≤58 years) vs. older survivors scored lower for general health with mean (SD) of 62.1 (27.5) vs. 73.0 (19.5), p = 0.03, vitality (55.2 (20.5) vs. 64.6 (17.3), p = 0.02, social functioning (75.3 (28.7) vs. 94.1 (13.5), p < 0.001 and mental component summary (49.0 (9.9) vs. 55.8 (6.7), p < 0.001. They scored higher for HADS-anxiety (4.8 (3.6 vs. 2.7 (2.5), p = 0.001, and had lower EQ-5D index (0.72 (0.34) vs. 0.84 (0.19), p = 0.04. Early vs. late awakeners had higher EQ-5D index (0.82 (0.23) vs. 0.71 (0.35), p = 0.04 and lower HADS-depression scores (2.5 (2.9) vs. 3.8 (2.3), p = 0.04. Next of kin estimated HRQoL similar to the survivors’ own estimates. Conclusions HRQoL five years after OHCA was good and mainly comparable to a matched reference population. Stratified analyses revealed impaired HRQoL among younger survivors and those awakening late, mainly for mental domains.

• Skjørten, Ingunn; Ankerstjerne, Odd Andre Wathne; Trebinjac, Divna; Brønstad, Eivind; Rasch-Halvorsen, Øystein & Einvik, Gunnar [Show all 10 contributors for this article] (2021). Cardiopulmonary exercise capacity and limitations 3 months after COVID-19 hospitalisation. European Respiratory Journal. ISSN 0903-1936. 58(2). doi: 10.1183/13993003.00996-2021. Full text in Research Archive Show summary

  Background This study aimed to describe cardiopulmonary function during exercise 3 months after hospital discharge for COVID-19 and compare groups according to dyspnoea and intensive care unit (ICU) stay. Methods Participants with COVID-19 discharged from five large Norwegian hospitals were consecutively invited to a multicentre, prospective cohort study. In total, 156 participants (mean age 56.2 years, 60 females) were examined with a cardiopulmonary exercise test (CPET) 3 months after discharge and compared with a reference population. Dyspnoea was assessed using the modified Medical Research Council (mMRC) dyspnoea scale. Results Peak oxygen uptake (V′O2 peak) <80% predicted was observed in 31% (n=49). Ventilatory efficiency was reduced in 15% (n=24), while breathing reserve <15% was observed in 16% (n=25). Oxygen pulse <80% predicted was found in 18% (n=28). Dyspnoea (mMRC ≥1) was reported by 47% (n=59). These participants had similar V′O2 peak (p=0.10) but lower mean±sd V′O2 peak·kg−1 % predicted compared with participants without dyspnoea (mMRC 0) (76±16% versus 89±18%; p=0.009) due to higher body mass index (p=0.03). For ICU- versus non-ICU-treated participants, mean±sd V′O2 peak % predicted was 82±15% and 90±17% (p=0.004), respectively. Ventilation, breathing reserve and ventilatory efficiency were similar between the ICU and non-ICU groups. Conclusions One-third of participants experienced V′O2 peak <80% predicted 3 months after hospital discharge for COVID-19. Dyspnoeic participants were characterised by lower exercise capacity due to obesity and lower ventilatory efficiency. Ventilation and ventilatory efficiency were similar between ICU- and non-ICU-treated participants.

• Ruud, Espen Asak; Stavem, Knut; Geitung, Jonn Terje; Borthne, Arne Sigmund; Søyseth, Vidar & Ashraf, Haseem (2021). Predictors of pneumothorax and chest drainage after percutaneous CT-guided lung biopsy: A prospective study. European Radiology. ISSN 0938-7994. doi: 10.1007/s00330-020-07449-6. Full text in Research Archive
• Tran, Thien Trung; Bjarnason, Haraldur; Mcdonald, Jennifer Rebecca; Skaga, Nils Oddvar; Houghton, Damon E & Kim, Brian [Show all 8 contributors for this article] (2021). Prophylactic placement of inferior vena cava filters and the risk of death or venous thromboembolism in severe trauma patients: a retrospective study comparing two hospitals with different approaches. Acta Radiologica Open. 10(3), p. 1–8. doi: 10.1177/2058460121999345. Full text in Research Archive
• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Johannessen, Hege Hølmo; Gleditsch, Jostein; Stavem, Knut & Steine, Kjetil [Show all 11 contributors for this article] (2021). Pulmonary rehabilitation to improve physical capacity, dyspnea, and quality of life following pulmonary embolism (the PeRehab study): study protocol for a two-center randomized controlled trial. Trials. 22, p. 1–9. doi: 10.1186/s13063-020-04940-9. Full text in Research Archive Show summary

  Background Recently, a large group of patients with persistent dyspnea, poor physical capacity, and reduced health-related quality of life (HRQoL) following pulmonary embolism (PE) has been identified and clustered under the name “post pulmonary embolism syndrome” (PPS). These patients seem good candidates for pulmonary rehabilitation. The aim of the study is to explore whether a pulmonary rehabilitation program can improve physical capacity, dyspnea, and HRQoL in PPS patients. Methods A two-center randomized controlled trial (RCT) is being performed at Østfold Hospital and Akershus University Hospital in Norway. Patients with PPS are 1:1 randomized into an intervention or a control group. The intervention consists of a supervised, outpatient rehabilitation program twice weekly (1 h) for 8 weeks provided by experienced physiotherapists. The intervention involves individually adapted exercises based on existing pulmonary rehabilitation programs (relaxation, interval, and resistance training), and an educational session including topics such as normal anatomy and physiology of the respiratory and circulatory system, information on PE/PPS, breathing strategies, and benefits of exercise/physical activity. Patients randomized to the control group receive usual care without specific instructions to exercise. Participants in the intervention and control groups will be compared based on assessments conducted at baseline, 12 weeks, and 36 weeks after inclusion using the incremental shuttle walk test (primary outcome) and endurance shuttle walk test (exercise capacity), Sensewear activity monitor (daily physical activity), the modified Medical Research Council scale, the Shortness of Breath Questionnaire (dyspnea), and EQ-5D-5L and the Pulmonary Embolism Quality of Life Questionnaire (HRQoL). Recruitment of 190 patients is currently ongoing. Discussion Results from this study may provide a currently untreated group of PPS patients with an effective treatment resulting in reduced symptoms of dyspnea, improved exercise capacity, and better HRQoL following PE. Trial registration Clinical Trials NCT03405480 . Registered prospectively on September 2017. Protocol version 1 (from original protocol September 2017). The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 1).

• Tholin, Birgitte; Ghanima, Waleed Khalid; Einvik, Gunnar; Aarli, Bernt Bøgvald; Brønstad, Eivind & Skjønsberg, Ole Henning [Show all 7 contributors for this article] (2021). Incidence of thrombotic complications in hospitalised and non-hospitalised patients after COVID-19 diagnosis. British Journal of Haematology. ISSN 0007-1048. 194(3), p. 542–546. doi: 10.1111/bjh.17522. Full text in Research Archive Show summary

  Infection with coronavirus disease-2019 (COVID-19) may predispose for venous thromboembolism (VTE). There is wide variation in reported incidence rates of VTE in COVID-19, ranging from 3% to 85%. Therefore, the true incidence of thrombotic complications in COVID-19 is uncertain. Here we present data on the incidence of VTE in both hospitalised and non-hospitalised patients from two ongoing prospective cohort studies. The incidence of VTE after diagnosis of COVID-19 was 3·9% [95% confidence interval (CI): 2·1–7·2] during hospitalisation, 0·9% (95% CI: 0·2–3·1) in the three months after discharge and 0·2% (95% CI: 0·00–1·25) in non-hospitalised patients, suggesting an incidence rate at the lower end of that in previous reports.

• Stavem, Knut; Ghanima, Waleed Khalid; Olsen, Magnus Kringstad; Gilboe, Hanne M. & Einvik, Gunnar (2021). Prevalence and determinants of fatigue after covid-19 in non-hospitalized subjects: A population-based study. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 18(4), p. 1–11. doi: 10.3390/ijerph18042030. Full text in Research Archive Show summary

  This study assessed the prevalence and determinants of fatigue in a population-based cohort of non-hospitalized subjects 1.5–6 months after COVID-19. It was a mixed postal/web survey of all non-hospitalized patients ≥18 years with a positive PCR for SARS-CoV-2 until 1 June 2020 in a geographically defined area. In total, 938 subjects received a questionnaire including the Chalder fatigue scale (CFQ-11) and the energy/fatigue scale of the RAND-36 questionnaire. We estimated z scores for comparison with general population norms. Determinants were analyzed using multivariable logistic and linear regression analysis. In total, 458 subjects (49%) responded to the survey at median 117.5 days after COVID-19 onset, and 46% reported fatigue. The mean z scores of the CFQ-11 total was 0.70 (95% CI 0.58 to 0.82), CFQ-11 physical 0.66 (0.55 to 0.78), CFQ-11 mental 0.47 (0.35 to 0.59) and RAND-36 energy/fatigue −0.20 (−0.31 to −0.1); all CFQ-11 scores differed from those of the norm population (p &lt; 0.001). Female sex, single/divorced/widowed, short time since symptom debut, high symptom load, and confusion during acute COVID-19 were associated with higher multivariable odds of fatigue. In conclusion, the burden of post-viral fatigue following COVID-19 was high, and higher than in a general norm population. Symptoms of fatigue were most prevalent among women, those having a high symptom load, or confusion during the acute phase.

• Einvik, Gunnar; Dammen, Toril; Ghanima, Waleed Khalid; Heir, Trond & Stavem, Knut (2021). Prevalence and risk factors for post-traumatic stress in hospitalized and non-hospitalized COVID-19 patients. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 18(4), p. 1–12. doi: 10.3390/ijerph18042079. Full text in Research Archive Show summary

  This population-based study assessed the prevalence and determinants of symptom-defined post-traumatic stress disorder (PTSD) in a cohort of hospitalized and non-hospitalized patients about 1.5–6 months after their COVID-19 onset. The data were acquired from two mixed postal/web surveys in June–September 2020 from patients all aged ≥18 years with a positive polymerase chain reaction for severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) until 1 June 2020, comprising both hospitalized and non-hospitalized subjects. The catchment areas of the two included hospitals covers about 17% of the population of Norway. In total, 211 hospitalized and 938 non-hospitalized subjects received invitation. The prevalence of symptom-defined PTSD was assessed using the PTSD checklist for DSM-5 (PCL-5). Determinants of symptom-defined PTSD and PTSD symptoms were analyzed using multivariable logistic and linear regression analysis. In total, 583 (51%) subjects responded at median 116 (range 41–200) days after COVID-19 onset. The prevalence of symptom-defined PTSD was 9.5% in hospitalized and 7.0% in non-hospitalized subjects (p = 0.80). Female sex, born outside of Norway, and dyspnea during COVID-19 were risk factors for persistent PTSD symptoms. In non-hospitalized subjects, previous depression and COVID-19 symptom load were also associated with persistent PTSD symptoms. In conclusion, COVID-19 symptom load, but not hospitalization, was associated with symptom-defined PTSD and PTSD symptom severity.

• Garratt, Andrew; Hansen, Tonya Moen; Augestad, Liv Ariane; Rand, Kim & Stavem, Knut (2021). Norwegian population norms for the EQ-5D-5L: results from a general population survey. Quality of Life Research. ISSN 0962-9343. doi: 10.1007/s11136-021-02938-7. Full text in Research Archive Show summary

  Abstract Purpose To provide the first Norwegian EQ-5D-5L and EQ VAS population norms for the adult general population. Methods Postal survey of a random sample of 12,790 Norwegians identified through the National Registry of the Norwegian Tax Administration. Norms, weighted for Norwegian general population characteristics, are shown for the five EQ-5D-5L dimensions, EQ-5D index, and EQ VAS scores for seven age categories, females, males, and education level. Results There were 3200 (25.9%) respondents to 12,263 correctly addressed questionnaires. The EQ-5D-5L dimensions, EQ VAS, and background questions were completed by 3120 (24.6%) respondents. The mean age (SD) was 50.9 (21.7) and range was 18–97 years. The youngest age group of 18–29 years and oldest of 80 years and over had the highest ( n  = 691) and lowest ( n  = 239) number of respondents, respectively. Compared to the general population, the respondents comprised a greater number of females, younger and older ages, and had a higher education level. 32% of respondents reported no health problems on the EQ-5D-5L. From the youngest to oldest age groups, there was a general decline in health as assessed by the EQ-5D-5L. The exception was for anxiety/depression, where the youngest age groups had the poorest health. Apart from self-care, women reported poorer health than men, as assessed by the EQ-5D-5L; EQ VAS scores were similar for men and women. Higher levels of health (EQ-5D index, EQ VAS scores) were found with increasing levels of education. Conclusion The population norms will improve interpretation of EQ-5D-5L and EQ VAS scores in Norwegian applications including clinical practice, clinical and health services research, and national quality registers where EQ-5D-5L is the most widely used patient-reported instrument.

• Astrup, Guro Lindviksmoen; Rohde, Gudrun E.; Rimehaug, Stein Arne; Andersen, Marit Helen; Bernklev, Tomm & Bjordal, Kristin [Show all 11 contributors for this article] (2021). Comparing the use of patient-reported outcomes in clinical studies in Europe in 2008 and 2018: a literature review. Quality of Life Research. ISSN 0962-9343. 31. doi: 10.1007/s11136-021-02946-7. Full text in Research Archive Show summary

  Purpose Several guidelines for the use of patient-reported outcomes (PROs) in clinical studies have been published in the past decade. This review primarily aimed to compare the number and compliance with selected PRO-specifc criteria for reporting of clinical studies in Europe using PROs published in 2008 and 2018. Secondarily, to describe the study designs, PRO instruments used, patient groups studied, and countries where the clinical studies were conducted. Methods A literature search was conducted in MEDLINE to identify eligible publications. To assess the number of publications, all abstracts were screened for eligibility by pairs of reviewers. Compliance with PRO-specifc criteria and other key characteristics was assessed in a random sample of 150 eligible full-text publications from each year. Randomized controlled trials (RCTs) were assessed according to the full CONSORT-PRO checklist. Results The search identifed 1692 publications in 2008 and 4290 in 2018. After screening of abstracts, 1240 from 2008 and 2869 from 2018 were clinical studies using PROs. By full-text review, the proportion of studies discussing PRO-specifc limitations and implications was higher in 2018 than in 2008, but there were no diferences in the other selected PRO-specifc criteria. In 2018, a higher proportion of studies were longitudinal/cohort studies, included≥300 patients, and used electronic administration of PRO than in 2008. The most common patient groups studied were those with cancer or diseases of the musculoskeletal system or connective tissue. Conclusion The number of clinical studies from Europe using PROs was higher in 2018 than in 2008, but there was little diference in compliance with the PRO-specifc criteria. The studies varied in terms of study design and PRO instruments used in both publication years.

• Falk, Ragnhild Sørum; Mariampillai, Julian Eek; Prestgaard, Erik Edvard; Heir, Trond; Bodegard, Johan & Robsahm, Trude Eid [Show all 18 contributors for this article] (2021). The Oslo Ischaemia Study: cohort profile. BMJ Open. 11(10). doi: 10.1136/bmjopen-2021-049111. Full text in Research Archive Show summary

  Abstract Purpose The Oslo Ischaemia Study was designed to investigate the prevalence and predictors of silent coronary disease in Norwegian middle-aged men, specifically validating exercise electrocardiography (ECG) findings compared with angiography. The study has been important in investigating long-term predictors of cardiovascular morbidity and mortality, as well as investigating a broad spectrum of epidemiological and public health perspectives. Participants In 1972–1975, 2014 healthy men, 40–59 years old, were enrolled in the study. Comprehensive clinical examination included an ECG-monitored exercise test at baseline and follow-ups. The cohort has been re-examined four times during 20 years. Linkage to health records and national health registries has ensured complete endpoint registration of morbidity until the end of 2006, and cancer and mortality until the end of 2017. Findings to date The early study results provided new evidence, as many participants with a positive exercise ECG, but no chest pain (‘silent ischaemia’), did not have significant coronary artery stenosis after all. Still, they were over-represented with coronary disease after years of follow-up. Furthermore, participants with the highest physical fitness had lower risk of cardiovascular disease, and the magnitude of blood pressure responses to moderate exercise was shown to influence the risk of cardiovascular disease and mortality. With time, follow-up data allowed the scope of research to expand into other fields of medicine, with the aim of investigating predictors and the importance of lifestyle and risk factors. Future plans Recently, the Oslo Ischaemia Study has been found worthy, as the first scientific study, to be preserved by The National Archives of Norway. All the study material will be digitised, free to use and accessible for all. In 2030, the Oslo Ischaemia Study will be linked to the Norwegian Cause of Death Registry to obtain complete follow-up to death. Thus, a broad spectrum of additional opportunities opens.

• Jervan, Øyvind; Gleditsch, Jostein; Tavoly, Mazdak; Klok, Frederikus A.; Rashid, Diyar Nori Mohamad & Holst, René [Show all 9 contributors for this article] (2021). Pulmonary and cardiac variables associated with persistent dyspnea after pulmonary embolism. Thrombosis Research. ISSN 0049-3848. 201, p. 90–99. doi: 10.1016/j.thromres.2021.02.014. Full text in Research Archive Show summary

  Introduction Persistent dyspnea is common in follow-up after pulmonary embolism (PE), but the underlying mechanisms are poorly understood. Material and methods This cross-sectional study included subjects aged 18–75 years with confirmed PE by computed tomography pulmonary angiography (CTPA) 6–72 months earlier. A total of 180 participants underwent clinical examination, incremental shuttle walk test, laboratory tests, transthoracic echocardiography, pulmonary function tests and ventilation/perfusion scintigraphy. In further analysis, we divided participants into two groups; “dyspnea” or “no dyspnea”, based on interview and questionnaires at inclusion. The association of cardiac and pulmonary variables with persistent dyspnea was assessed using multiple logistic regression analysis. Results In total, 44% (95% CI: 39%–51%) of the participants reported persistent dyspnea after PE. Age (adjusted odds ratio (aOR) 0.93 per year, 95% CI: 0.90–0.97, P = 0.001), body mass index (BMI) (aOR 1.14 per kg/m2, 95% CI: 1.04–1.25, P = 0.004), recurrent venous thromboembolism (VTE) (aOR 3.69, 95% CI: 1.45–9.38, P = 0.006) and diffusion capacity of the lung for carbon monoxide (DLCO) (aOR 0.95 per increase of 1%, 95% CI: 0.92–0.98, P = 0.001) were independently associated with persistent dyspnea. Conclusions Persistent dyspnea was prevalent after PE. Age, BMI and recurrent VTE were independently associated with dyspnea. Apart from reduced DLCO, no other cardiac or pulmonary variables were associated with persistent dyspnea.

• Aalberg, Karoline; Stavem, Knut; Norheim, Frode Amador; Russell, Michael Bjørn & Chaibi, Aleksander (2021). Effect of oral and transdermal oestrogen therapy on bone mineral density in functional hypothalamic amenorrhoea: A systematic review and meta-analysis. BMJ Open sport & exercise medicine. 7(3). doi: 10.1136/bmjsem-2021-001112. Full text in Research Archive Show summary

  Background Female athletes might develop reduced bone mineral density (BMD) and amenorrhoea due to low energy intake. Objective To systematically review the literature of randomised controlled trials (RCTs) assessing the effect of oestrogen oral contraceptives (OCP), conjugated oestrogens (CE) and transdermal estradiol (TE) on BMD in premenopausal women with functional hypothalamic amenorrhoea (FHA) due to weight loss, vigorous exercise and/or stress. Methods A comprehensive literature search in PubMed, MEDLINE, Cochrane Library, Ovid and CINAHL from inception to 1 October 2020. Data extraction and synthesis Two authors independently extracted data. When possible, the data were pooled in a random-effects meta-analysis. Main outcomes Difference in BMD (g/cm 2 ) at the lumbar spine. Results Nine RCTs comprising 770 participants met the inclusion criteria; five studies applied OCP, two CE and two TE. Four RCTs (two OCP, two TE) found an increased BMD in premenopausal women with FHA, and five (three OCP, two CE) found a decreased BMD compared with controls. A meta-analysis showed no difference in BMD between the treatment and control groups, (standardised mean difference (SMD) 0.30, 95% CI −0.12 to 0.73). A secondary analysis for change scores from baseline to first assessment point, showed a similar overall result (SMD 0.17, 95% CI −0.16 to 0.51). No serious adverse events were reported. Conclusion The literature suggests that TE might increase lumbar BMD in premenopausal women with FHA, but pooled results revealed no effect of the intervention. The findings do not support oestrogen therapy to improve BMD in these patient groups.

• Tran, Thien Trung; Bjarnason, Haraldur; McDonald, Jennifer; Gross, Brian; Kim, Brian & Houghton, Damon E. [Show all 8 contributors for this article] (2020). Does prophylactic inferior vena cava filter reduce the hazard of pulmonary embolism and mortality in severe trauma? A single center retrospective comparative study. European Journal of Radiology Open (EJR Open). 8:100299, p. 1–6. doi: 10.1016/j.ejro.2020.100299. Full text in Research Archive Show summary

  Objectives Use of inferior vena cava (IVC) filters in patients following severe trauma without recent history of venous thromboembolism (VTE) is controversial. Our objective was to determine if IVC filter placement in the setting of severe trauma effects the hazard of in-hospital pulmonary embolism (PE), deep venous thrombosis (DVT) and mortality. Methods This retrospective study recruited patients from a single Level I Trauma Center between 1/2008 and 12/2013. Inclusion criteria were age>15 years, Injury Severity Score (ISS)>15 and survival>24 h after hospital admission. Patients with VTE diagnosed prior to IVC filter placement were excluded. A Cox proportional hazards regression model was used, adjusting for immortal time bias with landmark analysis at predefined time after injury. Differences between IVC filter and non-IVC filter groups were adjusted using propensity score. Results In total 1451 patients were reviewed; 282 patients received an IVC filter and 1169 patients had no IVC filter placed. The mean age was 45.9 vs. 56.9 years and the mean ISS was 29.8 vs. 22.6 in the IVC filter and the non-IVC filter group, respectively. IVC filter placement was not associated with the hazard of PE (HR = 0.46; 95 % CI, 0.12,1.70; P = 0.24) or mortality (HR = 1.02; 95 % CI 0.60,1.75; P = 0.93). However, IVC filter placement was associated with the hazard of DVT (HR = 2.73; 95 % CI, 1.28,5.85; P = 0.01). Conclusions In patients with severe trauma, those with prophylactic IVC filter placement did not have a reduced hazard of PE or mortality, but an increased hazard of DVT was observed.

• Fredriksen, Mats; Golparian, Neshat; Beiske, Kornelia Katalin & Stavem, Knut (2020). Impact of methylphenidate on sleep problems in adults with ADHD: a pilot polysomnography study. Nordic Journal of Psychiatry. ISSN 0803-9488. 75(3), p. 234–238. doi: 10.1080/08039488.2020.1833984. Full text in Research Archive Show summary

  Background: Attention-deficit hyperactivity disorder (ADHD) is associated with disrupted sleep and circadian rhythm. Medication for ADHD may have side effects aggravating sleep-disturbances, however beneficial effects on ADHD may contribute to improve sleep. Aims: This pilot study aims to examine outcomes of first time stimulant treatment on objective and subjective sleep characteristics, and psychiatric symptoms, in adult ADHD patients with pretreatment sleep problems, but without any primary sleep disorder. Methods: In total, 9 previously unmedicated adult ADHD subjects who reported pretreatment sleep problems, completed polysomnography (PSG) and questionnaires on subjective sleep disturbances and psychiatric symptoms. Data was collected before and after 6 weeks on first time medication with immediate-release methylphenidate (MPH-IR), mean daily dose 43mg. Results: Subjects on-medication showed an increased percentage of Stage 2 sleep compared to their non-treated baseline (46.6% versus 55.2%, p¼.011). Otherwise, there were no significant changes in PSG variables. There were no firm changes in daytime sleepiness or symptoms of sleep disturbances. Conclusions: These findings should be interpreted cautiously given the open-label design and small sample size, and should be examined in larger studies with more rigorous study designs.

• Stavem, Knut; Ghanima, Waleed Khalid; Olsen, Magnus Kringstad; Gilboe, Hanne Margrethe & Einvik, Gunnar (2020). Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: A population-based cohort study. Thorax. ISSN 0040-6376. doi: 10.1136/thoraxjnl-2020-216377. Full text in Research Archive Show summary

  This study assessed symptoms and their determinants 1.5–6 months after symptom onset in non-hospitalised subjects with confirmed COVID-19 until 1 June 2020, in a geographically defined area. We invited 938 subjects; 451 (48%) responded. They reported less symptoms after 1.5–6 months than during COVID-19; median (IQR) 0 (0–2) versus 8 (6–11), respectively (p&lt;0.001); 53% of women and 67% of men were symptom free, while 16% reported dyspnoea, 12% loss/disturbance of smell, and 10% loss/disturbance of taste. In multivariable analysis, having persistent symptoms was associated with the number of comorbidities and number of symptoms during the acute COVID-19 phase.

• Noone, John Christopher; Stegger, Marc; Lilje, Berit; Stavem, Knut; Helmersen, Karin & Skråmm, Inge [Show all 7 contributors for this article] (2020). Molecular characteristics of Staphylococcus aureus associated prosthetic joint infections after hip fractures treated with hemiarthroplasty: a retrospective genome-wide association study. Scientific Reports. 10:16553, p. 1–8. doi: 10.1038/s41598-020-73736-3. Full text in Research Archive Show summary

  Abstract A retrospective study of Staphylococcus aureus isolates from orthopaedic patients treated between 2000 and 2017 at Akershus University Hospital, Norway was performed using a genome-wide association approach. The aim was to characterize and investigate molecular characteristics unique to S. aureus isolates from HHA associated prosthetic joint infections and potentially explain the HHA patients’ elevated 1-year mortality compared to a non-HHA group. The comparison group consisted of patients with non-HHA lower-extremity implant-related S. aureus infections. S. aureus isolates from diagnostic patient samples were whole-genome sequenced. Univariate and multivariate analyses were performed to detect group-associated genetic signatures. A total of 62 HHA patients and 73 non-HHA patients were included. Median age (81 years vs. 74 years; p  &lt; 0.001) and 1-year mortality (44% vs. 15%, p  &lt; 0.001) were higher in the HHA group. A total of 20 clonal clusters (CCs) were identified; 75% of the isolates consisted of CC45, CC30, CC5, CC15, and CC1. Analyses of core and accessory genome content, including virulence, resistance genes, and k-mer analysis revealed few group-associated variants, none of which could explain the elevated 1-year mortality in HHA patients. Our findings support the premise that all S. aureus can cause invasive infections given the opportunity.

• Lerum, Tøri Vigeland; Aaløkken, Trond M; Brønstad, Eivind; Aarli, Bernt Bøgvald; Ikdahl, Eirik & Lund, Kristine Marie Aarberg [Show all 14 contributors for this article] (2020). Dyspnoea, lung function and CT findings three months after hospital admission for COVID-19. European Respiratory Journal. ISSN 0903-1936. 57. doi: 10.1183/13993003.03448-2020. Full text in Research Archive Show summary

  The long-term pulmonary outcomes of coronavirus disease 2019 (COVID-19) are unknown. We aimed to describe self-reported dyspnoea, quality of life, pulmonary function, and chest CT findings three months following hospital admission for COVID-19. We hypothesised outcomes to be inferior for patients admitted to intensive care units (ICU), compared with non-ICU patients. Discharged COVID-19-patients from six Norwegian hospitals were consecutively enrolled in a prospective cohort study. The current report describes the first 103 participants, including 15 ICU patients. Modified Medical Research Council dyspnoea scale (mMRC), EuroQol Group's Questionnaire, spirometry, diffusion capacity (DLCO), six-minute walk test, pulse oximetry, and low-dose CT scan were performed three months after discharge. mMRC was >0 in 54% and >1 in 19% of the participants. The median (25th–75th percentile) forced vital capacity and forced expiratory volume in one second were 94% (76, 121) and 92% (84, 106) of predicted, respectively. DLCO was below the lower limit of normal in 24%. Ground-glass opacities (GGO) with >10% distribution in ≥1 of 4 pulmonary zones were present in 25%, while 19% had parenchymal bands on chest CT. ICU survivors had similar dyspnoea scores and pulmonary function as non-ICU patients, but higher prevalence of GGO (adjusted odds ratio [95% confidence interval] 4.2 [1.1, 15.6]) and performance in lower usual activities. Three months after admission for COVID-19, one fourth of the participants had chest CT opacities and reduced diffusion capacity. Admission to ICU was associated with pathological CT findings. This was not reflected in increased dyspnoea or impaired lung function.

• Cheng, Socheat; Siddiqui, Tahreem Ghazal; Gossop, Michael; Stavem, Knut; Kristoffersen, Espen Saxhaug & Lundqvist, Christofer (2020). Health-related quality of life in hospitalized older patients with versus without prolonged use of opioid analgesics, benzodiazepines, and z-hypnotics: a cross-sectional study. BMC Geriatrics. 20(425), p. 1–9. doi: 10.1186/s12877-020-01838-8. Full text in Research Archive Show summary

  Background Central nervous system depressant medications (CNSDs) such as opioid analgesics and sedative-hypnotics are commonly prescribed to older patients for the treatment of chronic pain, anxiety and insomnia. Yet, while many studies reported potential harms, it remains unknown whether persistent use of these medications is beneficial for older patients’ self-reported health-related quality of life (HRQoL). The present study clarified this knowledge gap through comparing HRQoL of hospitalized older patients with versus without using CNSD drugs for ≥4 weeks. Moreover, we explored the relationship between such use and HRQoL, adjusting for the effects of polypharmacy, comorbidity burden and other clinically relevant covariates. Methods The study was cross-sectional and included 246 older patients recruited consecutively from somatic departments of a large regional university hospital in Norway. We defined prolonged CNSD use as using opioids, benzodiazepines and/or z-hypnotics for ≥4 weeks. Patients’ self-reported HRQoL were measured with scales of the EuroQol EQ-5D-3L instrument. Data analyses were mainly descriptive statistics and regression models. Results Patients with prolonged use of CNSDs reported lower scores on both EQ-5D index and EQ VAS compared with those without such use (p < 0.001). They had higher odds of having more problems performing usual activities (OR = 3.37, 95% CI: 1.40 to 8.13), pain/discomfort (OR = 2.06, 95% CI: 1.05 to 4.04), and anxiety/depression (OR = 3.77, 95% CI: 1.82 to 7.82). In multivariable regression models, there was no significant association between prolonged CNSD use and HRQoL when including pain as a predictor variable. In models not including pain, CNSD use was strongly associated with HRQoL (adjusted for sociodemographic background, polypharmacy, comorbidity, anxiety and depressive symptoms, regression coefficient − 0.19 (95% CI, − 0.31 to − 0.06). Conclusions Older patients with prolonged CNSD use reported poorer HRQoL. They also had more pain and higher depression scores. Prolonged use of CNSDs was not independently associated with higher HRQoL.

• Hansen, Tonya Moen; Helland, Ylva; Augestad, Liv Ariane; Rand, Kim; Stavem, Knut & Garratt, Andrew Malcolm (2020). Elicitation of Norwegian EQ-5D-5L values for hypothetical and experience-based health states based on the EuroQol Valuation Technology (EQ-VT) protocol. BMJ Open. 10(6). doi: 10.1136/bmjopen-2019-034683. Full text in Research Archive
• Gulsvik, Amund; Bakke, Per; Brøgger, Jan; Nielsen, Rune & Stavem, Knut (2020). Respiratory symptoms and mortality in four general population cohorts over 45 years. Respiratory Medicine. ISSN 0954-6111. 170. doi: 10.1016/j.rmed.2020.106060. Full text in Research Archive Show summary

  Objective: This study assessed the association between respiratory symptoms and mortality in four cohorts of the general population in Norway aged 15–75 years and in selected subgroups in the pooled sample. Methods: The study comprised 158,702 persons, who were drawn randomly from the Norwegian population register. All subjects received a standardized, self-administered questionnaire on 11 respiratory symptoms between 1972 and 1998, with follow-up of death until December 31, 2017. Analyses were performed on 114,380 respondents. Results: The hazard of death was closely associated with sex, age, and education. The hazard ratios (HR) for death and the 95% confidence intervals (CI) by risk factors were similar in the four cohorts. After adjustment for demographic and environmental, modifiable factors, the HR for death was 1.90 (95% CI 1.80–2.00) for breathlessness score 3, 1.28 (1.21–1.37) for cough/phlegm score 5 and 1.09 (1.05–1.14) for attack of breathlessness/wheeze score 2 compared to the referent (no symptom), respectively. The cough/phlegm score was associated with death in current smokers but not in never smokers or ex-smokers. Breathlessness score was associated with death in men and women. Conclusion: Among persons aged 45–75 years, respiratory symptoms were significant predictors of all cause mortality. Education and smoking habits influenced only the associations between coughing and mortality. The associations were independent of study sites.

• Solberg, Ole Geir; Stavem, Knut; Ragnarsson, Asgrimur; Beitnes, Jan Otto; Skårdal, Rita & Seljeflot, Ingebjørg [Show all 10 contributors for this article] (2019). Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study. Catheterization and cardiovascular interventions. ISSN 1522-1946. 94(5), p. 660–668. doi: 10.1002/ccd.28157. Full text in Research Archive Show summary

  <i>Introduction</i> - Many women undergoing coronary angiography for chest pain have no or only minimal coronary artery disease (CAD). However, despite the lack of obstructive CAD, they still have an increased risk of major adverse cardiovascular events. Pleiotropic effects of statins may influence microvascular function, but if statins improve microvascular function in unselected chest pain patients is not well studied. This study assessed microvascular function by using the thermodilution‐derived test “the index of microvascular resistance” (IMR) with the aim of determining the (i) IMR level in women with chest pain and non‐obstructive CAD and if (ii) IMR is modified by high‐dose statin treatment in these patients. Additional objectives were to identify the influence of statins on the health status as assessed with generic health questionnaires and on biomarkers of endothelial activation.<p> <p><i>Materials and methods</i> - The study was a randomized, double‐blind, single‐center trial comparing 6 months of rosuvastatin treatment with placebo. In total, 66 women without obstructive CAD were included. Mean age was 52.7 years and 55.5 years in the placebo and rosuvastatin group, respectively. Microvascular function was assessed using the IMR, health status was assessed using the SF‐36 and EQ‐5D questionnaires, and biochemical values were assessed at baseline and 6 months later.<p> <p><i>Results and conclusions</i> - In the placebo group IMR was 14.6 (<i>SD</i> 5.7) at baseline and 14.4 (<i>SD</i> 6.5) at follow‐up. In the rosuvastatin group IMR was 16.5 (<i>SD</i> 7.5) at baseline and 14.2 (<i>SD</i> 5.8) at follow‐up. IMR did not differ significantly between the two study groups at follow‐up controlled for preintervention values. C‐reactive protein (CRP) was comparable between the groups at baseline, while at follow‐up CRP was significantly lower in the rosuvastatin group compared to placebo [0.6 (±0.5) mg/L vs. 2.6 (±3.0) mg/L; <i>p</i> = 0.002]. Whereas rosuvastatin treatment for 6 months attenuated CRP levels, it did not improve microvascular function as assessed by IMR (Clinical Trials.gov NCT 01582165, EUDRACT 2011‐002630‐39.3tcAZ).

• Kristoffersen, Espen Saxhaug; Stavem, Knut; LUNDQVIST, CHRISTOFER & Russell, Michael Bjørn (2019). The impact of chronic headache on workdays, unemployment and disutility in the general population. Journal of Epidemiology and Community Health. ISSN 0143-005X. doi: 10.1136/jech-2018-211127. Full text in Research Archive
• Utvåg, Stein-Erik; Naumann, Markus George; Sigurdsen, Ulf & Stavem, Knut (2019). Functional outcome 3–6 years after operative treatment of closed Weber B ankle fractures with or without syndesmotic fixation. Foot and Ankle Surgery. ISSN 1268-7731. doi: 10.1016/j.fas.2019.04.013. Full text in Research Archive Show summary

  Background To compare the long-term functional outcomes of patients surgically treated for Weber B ankle fractures with or without syndesmotic fixation. Methods In total, 959 adult patients with previous treatment with open reduction and internal fixation (ORIF) for closed ankle fractures were eligible for inclusion in a cross-sectional postal survey 3–6 years after surgery; 645 had Weber B fractures. The survey assessed functional outcomes with three validated ankle questionnaires. Results In total 365 (57%) patients responded at a median of 4.2 years after the trauma. After adjusting for age, sex, education, smoking status, body mass index, diabetes, physical status before surgery, fracture classification, and duration of surgery, patients with a syndesmotic fixation had no different OMAS score (p = 0.98), LEFS score (p = 0.61), and SEFAS score (p = 0.98) than those without a syndesmotic fixation. Trimalleolar fracture was associated with worse functional outcomes than unimalleolar on two of the scales, the OMAS (p = 0.028) and LEFS (p = 0.046). Conclusions In multivariable analysis, patients with a syndesmotic fixation had no worse long-term functional outcomes than those without syndesmotic fixation.

• Parker, Krystina; Bull-Engelstad, Ingrid; Benth, Jurate Saltyte; Lippe, Nanna von der; Reier-Nilsen, Morten & Os, Ingrid [Show all 7 contributors for this article] (2019). Effectiveness of using STOPP/START criteria to identify potentially inappropriate medication in people aged ≥ 65 years with chronic kidney disease: a randomized clinical trial. European Journal of Clinical Pharmacology. ISSN 0031-6970. doi: 10.1007/s00228-019-02727-9. Full text in Research Archive Show summary

  Purpose Polypharmacy and inappropriate prescribing are common in elderly with chronic kidney disease (CKD). This study identified potentially inappropriate prescriptions (PIPs) and potential prescribing omissions (PPOs) using the Screening Tool of Older Persons’ Prescriptions (STOPP) and the Screening Tool to Alert doctors to the Right Treatment (START) criteria in elderly with advanced CKD and determined the effect of a medication review on medication adherence and health-related quality of life (HRQoL). Methods The intervention consisted of a medication review using STOPP/START criteria with a recommendation to a nephrologist or similar review without a recommendation. End points were prevalence of PIP and PPO, medication adherence, and HRQoL. Group differences in outcomes were assessed using a generalized linear mixed model. The trial was registered under www.clinicaltrial.gov (ID: NCT02424786). Results We randomized 180 patients with advanced CKD (mean age 77 years, 23% female). The prevalence of PIPs and PPOs in the intervention group was 54% and 50%, respectively. The odds of PPOs were lower in the intervention than the control group (OR 0.42, 95% CI 0.19–0.92, p = 0.032), while there was no intergroup difference in the number of PIPs (OR 0.57, CI 0.27–1.20, p = 0.14). There was no difference in changes in medication adherence or HRQoL from baseline to 6 months between the groups. Conclusions The intervention with the STOPP/START criteria identified a high prevalence of inappropriate medications in the elderly with advanced CKD and reduced the number of PPOs. However, there was no detectable impact of the intervention on medication adherence or HRQoL.

• Parker, Krystina; Bull-Engelstad, Ingrid; Aasebø, Willy; Lippe, Nanna von der; Reier-Nilsen, Morten & Os, Ingrid [Show all 7 contributors for this article] (2019). Medication regimen complexity and medication adherence in elderly patients with chronic kidney disease. Hemodialysis International. ISSN 1492-7535. doi: 10.1111/hdi.12739. Full text in Research Archive Show summary

  Introduction: Elderly patients with chronic kidney disease (CKD) stage 5 with or without dialysis treatment usually have concomitant comorbidities, which often result in multiple pharmacological therapies. This study aimed to identify factors associated with medication complexity and medication adherence, as well as the association between medication complexity and medication adherence, in elderly patients with CKD. Methods: This prospective study involved elderly patients with CKD stage 5 (estimated glomerular filtration rate < 15 ml/min/1.73m2) recruited from three Norwegian hospitals. Most of the patients were receiving either hemodialysis or peritoneal dialysis. We used the Medication Regimen Complexity Index (MRCI) to assess the complexity of medication regimens, and the eight‐item Morisky Medication Adherence Scale (MMAS‐8) to assess medication adherence. Factors associated with the MRCI and MMAS‐8 score were determined using either multivariable linear or ordinal logistic regression analysis. Findings: In total, 157 patients aged 76 ± 7.2 years (mean ± SD) were included in the analysis. Their overall MRCI score was 22.8 ± 7.7. In multivariable linear regression analyses, female sex (P = 0.044), Charlson Comorbidity Index of 4 or 5 (P = 0.029) and using several categories of phosphate binders (P < 0.001 to 0.04) were associated with the MRCI. Moderate or high adherence (MMAS‐8 score ≥ 6) was demonstrated by 83% of the patients. The multivariable logistic regression analyses found no association of medication complexity, age or other variables with medication adherence as assessed using the MMAS‐8. Discussion: Female sex, comorbidity and use of phosphate binders were associated with more‐complex medication regimens in this population. No association was found between medication regimen complexity, phosphate binders or age and medication adherence. These findings are based on a homogeneous elderly group, and so future studies should test if they can be generalized to patients of all ages with CKD.

• Stavem, Knut; Skjaker, Stein Arve; Hoel, Henrik; Naumann, Markus George; Sigurdsen, Ulf & Ghanima, Waleed Khalid [Show all 7 contributors for this article] (2019). Risk factors for symptomatic venous thromboembolism following surgery for closed ankle fractures: A case-control study. Foot and Ankle Surgery. ISSN 1268-7731. doi: 10.1016/j.fas.2019.08.006. Full text in Research Archive Show summary

  Background We analyzed risk factors for venous thromboembolism (VTE) within 6 months after surgery for closed ankle fractures. Methods This was a case-control study based on data from chart review in a cohort of patients having open reduction and internal fixation (ORIF) for closed ankle fractures in two large general hospitals 2009–2011. Cases with symptomatic VTE (pulmonary embolism or deep venous thrombosis) were identified in the cohort, and additional cases of VTE were identified by computerized search of discharge diagnoses in the same hospitals in 2004–2008 and 2012–2016. In total, we identified 60 cases with VTE and compared with 240 randomly selected controls among 998 patients without VTE in the cohort. Risk factors were assessed using logistic regression analysis. Results Among cases, 27 (45%) had pulmonary embolism, 33 (55%) deep venous thrombosis. Those with VTE were older, had higher BMI, had more often a family history of VTE, and more often had antibiotic prophylaxis during surgery than controls. In multivariable logistic regression analysis age/10 (OR 25.75, 95%CI 3.52–188.44, p = 0.001), (age/10)2 (OR 0.77, 95%CI 0.65–0.93, p = 0.005), BMI (1.15 per kg/m2, 95%CI 1.07–1.24, p < 0.001) and Charlson comorbidity index ≥2 vs.0 (OR 0.27, 95%CI 0.08–0.92, p = 0.036) and 1 vs. 0 (OR 0.27, 95%CI 0.09–0.86, p = 0.026) were associated with VTE within 6 months of surgery. Conclusions The odds of symptomatic VTE within 6 months of ORIF increased with increasing age and BMI, but were lower with increasing comorbidity.

• Stavem, Knut; Augestad, Liv Ariane; Kristiansen, Ivar Sønbø & Rand, Kim (2018). General population norms for the EQ-5D-3 L in Norway: comparison of postal and web surveys. Health and Quality of Life Outcomes. 16(204), p. 1–10. doi: 10.1186/s12955-018-1029-1. Full text in Research Archive Show summary

  Background The EQ-5D-3 L instrument is a standardized questionnaire which was developed as a simple, generic measure of health for clinical and economic appraisal. To aid in the interpretation, scores are often compared with a normative group. The objectives of this study were 1) to provide population norms for the EQ-5D-3 L for Norway, and 2) to compare scores from postal and web surveys. Methods We conducted two surveys in samples that were aimed to be representative of the Norwegian general population: 1) a postal survey (n = 5000) and 2) a panel study with electronic data collection (n = 1936). For scoring the EQ-5D Index, we used the UK tariff. EQ-5D items were compared using multivariable ordinal logistic regression analysis and EQ-5D Index and EQ VAS scores using multivariable linear regression, adjusting for age, sex and education. Results In total 1131 (22.6%) responded to the postal survey and 977 (50.5%) to the web survey. The odds ratio (OR) for being in a higher score category on the Pain/Discomfort scale in the web survey was 1.25 (95%CI 1.04 to 1.50, p = 0.019) relative to the postal survey. The odds were similar in the other four dimensions. The EQ-5D Index and EQ VAS scores were similar in the postal and web surveys in the various strata according to age, sex and education, except for lower unadjusted and adjusted score for web respondents aged 41–50 years and for those with higher education (≥14 years) than postal respondents. Conclusions The distribution of scores for the EQ-5D descriptive system and its derived utility scores were rather similar in a postal survey and a panel web survey. Hence, these values were combined into a norm set for Norway.

• Farkhooy, Amir; Bodegard, Johan; Erikssen, Jan Emil; Janson, Christer; Hedenström, Hans & Stavem, Knut [Show all 7 contributors for this article] (2018). Cross-sectional and longitudinal analyses of the association between lung function and exercise capacity in healthy Norwegian men. BMC Pulmonary Medicine. 18(118). doi: 10.1186/s12890-018-0655-z. Full text in Research Archive Show summary

  Background It is widely accepted that exercise capacity in healthy individuals is limited by the cardiac function, while the respiratory system is considered oversized. Although there is physiological, age-related decline in both lung function and physical capacity, the association between decline in lung function and decline in exercise capacity is little studied. Therefore, we examined the longitudinal association between lung function indices and exercise capacity, assessed by the total amount of work performed on a standardized incremental test, in a cohort of middle-aged men. Methods A total of 745 men between 40 and 59 years were examined using spirometry and standardized bicycle exercise ECG test within “The Oslo Ischemia Study,” at two time points: once during 1972–1975, and again, approximately 16 years later, during 1989–1990. The subjects exercise capacity was assessed as physical fitness i.e. the total bicycle work (in Joules) at all workloads divided by bodyweight (in kg). Results Higher FEV1, FVC and PEF values related to higher physical fitness at both baseline and follow-up (all p values < 0.05). Higher explanatory values were found at follow-up than baseline for FEV1 (r2 = 0.16 vs. r2 = 0.03), FVC (r2 = 0.14 vs. r2 = 0.03) and PEF (r2 = 0.13 vs. r2 = 0.02). No significant correlations were found between decline in physical fitness and declines in FEV1, FVC or PEF. Conclusions A weak association between lung function indices and exercise capacity, assessed through physical fitness, was found in middle-aged, healthy men. This association was strengthened with increasing age, suggesting a larger role for lung function in limiting exercise capacity among elderly subjects. However, decline in physical fitness over time was not related to decline in lung function.

• Beiske, Kornelia Katalin & Stavem, Knut (2018). Health status in subjects with suspected obstructive sleep apnea and comparison with a general population. Scientific Reports. 8(1). doi: 10.1038/s41598-018-23904-3. Full text in Research Archive Show summary

  The purpose of this study was to assess health status (HS) in patients with clinical suspicion of obstructive sleep apnea (OSA) in order to estimate the dose response relationship between HS and OSA severity, and to compare HS in this clinical cohort with a general population sample (N=5000). Patients referred to an overnight sleep study due to suspected OSA, whom also responded to the SF-36 questionnaire, were included (N=418). Of these, 194 showed normal fndings, while 111, 60 and 53 demonstrated mild, moderate and severe OSA, respectively. Mean age was 47.5 (SD 11.9) and 69% were males. Only the mental health scale (p=0.015) and mental component summary score (p=0.023) were associated with OSA severity. This association, however, disappeared in multivariable analysis. All SF-36 scores in the sleep study group were lower than that of the general population sample, in both unadjusted and multivariable linear regression analysis. In this study, there was a lack of association between OSA severity and general HS. However, as a whole, patients in this clinical population referred to an overnight sleep study due to suspected OSA had impaired HS on all scales compared to a general population, with greatest diferences in the vitality domain.

• Rønning, Pål Andre; Helseth, Eirik; Skaga, Nils Oddvar; Stavem, Knut & Langmoen, Iver Arne (2018). The effect of ICP monitoring in severe traumatic brain injury: a propensity score-weighted and adjusted regression approach. Journal of Neurosurgery. ISSN 0022-3085. 131(6), p. 1896–1904. doi: 10.3171/2018.7.JNS18270. Full text in Research Archive Show summary

  OBJECTIVE The use of intracranial pressure (ICP) monitoring has been postulated to be beneficial in patients with severe traumatic brain injury (TBI), although studies investigating this hypothesis have reported conflicting results. The objective of this study was to evaluate the effect of inserting an ICP monitor on survival in patients with severe TBI. METHODS The Oslo University Hospital trauma registry was searched for the records of all patients admitted between January 1, 2002, and December 31, 2013, who fulfilled the Brain Trauma Foundation criteria for intracranial hypertension and who survived at least 24 hours after admission. The impact of ICP monitoring was investigated using both a logistic regression model and a multiple imputed, propensity score–weighted logistic regression analysis. RESULTS The study involved 1327 patients, in which 757 patients had an ICP monitor implanted. The use of ICP monitors significantly increased in the study period (p < 0.01). The 30-day overall mortality was 24.3% (322 patients), divided into 35.1% (200 patients, 95% confidence interval [CI] 31.3%–39.1%) in the group without an ICP monitor and 16.1% (122 patients, 95% CI 13.6%–18.9%) in the group with an ICP monitor. The impact of ICP monitors on 30-day mortality was found to be beneficial both in the complete case analysis logistic regression model (odds ratio [OR] 0.23, 95% CI 0.16–0.33) and in the adjusted, aggregated, propensity score–weighted imputed data sets (OR 0.22, 95% CI 0.15–0.35; both p < 0.001). The sensitivity analysis indicated that the findings are robust to unmeasured confounders. CONCLUSIONS The authors found that the use of an ICP monitor is significantly associated with improved survival in patients with severe head injury. https://thejns.org/doi/abs/10.3171/2018.7.JNS18270 KEYWORDS traumatic brain injury; Glasgow Coma Scale; ICP monitoring; intracranial pressure

• Kristoffersen, Espen Saxhaug; Stavem, Knut; LUNDQVIST, CHRISTOFER & Russell, Michael Bjørn (2018). Excessive daytime sleepiness in chronic migraine and chronic tension-type headache from the general population. Cephalalgia. ISSN 0333-1024. 38(5), p. 993–997. doi: 10.1177/0333102417721133. Full text in Research Archive

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• Haukeland-Parker, Stacey; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Hubin, Aliaksandr & Gleditsch, Jostein [Show all 10 contributors for this article] (2026). The effect of exercise-based rehabilitation on objectively measured daily physical activity levels in patients with persistent dyspnoea after pulmonary embolism. Full text in Research Archive
• Haukeland-Parker, Stacey; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Holst, Rene & Gleditsch, Jostein [Show all 13 contributors for this article] (2026). Exercise capacity, dyspnoea and health-related quality of life six months after exercise- based rehabilitation in patients with persistent dyspnea following pulmonary embolism. Full text in Research Archive
• Gulsvik, Amund; Bakke, Per S. & Stavem, Knut (2025). Nordic Respiratory Academy: a historical note and reflection. European Clinical Respiratory Journal. 12(1). doi: 10.1080/20018525.2025.2577531. Full text in Research Archive Show summary

  The first formal meeting of Nordic professors in pulmonary medicine took place in Gothenburg in December 1995. In Reykjavik in June 2003, the laws and statutes of the Nordic Respiratory Academy (NORA) were approved, and the first board was elected. NORA aimed to improve education, research, and clinical practice and became a meeting place for building friendships and exchange of ideas among academic teachers in pulmonary medicine in the Nordic region. The meetings initiated cooperative research among the university departments of respiratory medicine, and NORA reestablished the Nordic chest physicians’ own pulmonary medical journal with roots in the Nordic region. Until 2025, 20 NORA meetings have been held. Its future depends on the perceived need for such a meeting place and academics that are willing to continue organizing and using this institution as a think tank.

• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David GT; Stavem, Knut & Barra, Georg Mathias Honoré (2024). Preferences for extending Lives. Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David GT; Stavem, Knut & Barra, Georg Mathias Honoré (2024). SEVQoL del 2 - Hvem skal få leve litt lengre? Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David GT; Stavem, Knut & Barra, Georg Mathias Honoré (2024). A preference for the better-off? A discrete choice experiment using individually calibrated EQ-5D-5L health state values. Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David GT; Stavem, Knut & Barra, Georg Mathias Honoré (2024). Hvem skal få leve litt lengre? - Foreløpige resultater fra en norsk preferansestudie. Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David GT; Stavem, Knut & Barra, Georg Mathias Honoré (2024). A preference for the better-off? A discrete choice experiment using individually calibrated EQ-5D-5L health state values. Full text in Research Archive
• Haukeland-Parker, Stacey Marie; Jervan, Øyvind; Ghanima, Waleed; Spruit, Martijn A.; Holst, Rene & Gleditsch, Jostein [Show all 8 contributors for this article] (2024). The effect of exercise-based rehabilitation on daily physical activity following pulmonary embolism. Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David GT.; Stavem, Knut & Barra, Mathias (2023). Alvorlighet eller helsegevinst - Hva prioriterer befolkningen? Full text in Research Archive
• Moss, Thomas Totland; Stavem, Knut; Aandahl, Astrid; Gløersen, Anne Siri; Grønberg, Bjørn Henning & Neumann, Kirill [Show all 8 contributors for this article] (2023). Case Report: Limbic encephalitis following treatment with durvalumab for small-cell lung cancer. Frontiers in Immunology. 14. doi: 10.3389/fimmu.2023.1278761. Full text in Research Archive Show summary

  Background: Durvalumab is an immune checkpoint Inhibitor (ICIs) that is used in the treatment of malignant tumors, such as lung cancer and melanoma. ICIs are associated with immune-related adverse events including autoimmune encephalitis, although both paraneoplastic phenomena and ICI treatment may lead to autoimmunity. Case presentation: We describe a 72-year old male patient with small-cell lung cancer, who during adjuvant treatment with Durvalumab developed GABABR1 and GAD65 antibodies and both diabetes and autoimmune limbic encephalitis. Because he was followed prospectively as part of a treatment study, we had access to repeated serum samples and cognitive assessments over time prior to developing encephalitis and diabetes, in addition to later assessments. A high titer of GABABR1 antibodies appeared early, while GAD65 antibodies appeared later with a lower titer in parallel with the development of diabetes. As he subsequently developed clinical signs of encephalitis, verified by EEG and brain MRI, he also had CSF GABABR1 antibodies. Durvalumab was discontinued and steroid treatment with subsequent plasmapheresis were started, resulting in reduction of both CSF and serum antibody levels. Clinical signs of encephalitis gradually improved. Conclusion: This case illustrates the importance of being aware of possible serious autoimmune adverse reactions, including neurological syndromes such as encephalitis, when treating patients with high risk of para-neoplasia with ICIs. In addition, the case shows the development of autoantibodies over time.

• Ho, Ai Phi Thuy; Tjønnfjord, Eirik; Schreiner, Christoffer; Sørensen, Ole Henrik Sellereite; Iqbal, Naveed & Stavem, Knut [Show all 7 contributors for this article] (2023). En kvinne i 50-årene med levercirrhose og stillingsavhengig dyspné. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(14). doi: 10.4045/tidsskr.22.0754. Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Stavem, Knut; Whitehurst, David G T & Barra, Mathias (2023). Alvorlighet og EQ-5D - Hvordan bruke livskvalitetsverktøy til å få nye innsikter om befolkningens intuisjoner rundt prioriteringer i helsevesenet. Full text in Research Archive
• Torjusen, Marius Lamberg; Rand, Kim; Whitehurst, David GT.; Stavem, Knut & Barra, Mathias (2023). SEVQoL, Severity and EQ-5D-5L, An early look. Full text in Research Archive
• Jervan, Øyvind; Haukeland-Parker, Stacey Marie; Gleditsch, Jostein; Tavoly, Mazdak; Klok, Frederikus A. & Steine, Kjetil [Show all 14 contributors for this article] (2023). Rehabilitation to improve exercise capacity and quality of life after pulmonary embolism. Full text in Research Archive
• Verveen, Anouk; Müller, Fabiola; Lloyd, Andrew; Moss-Morris, Rona; Omland, Torbjørn & Penninx, Brenda [Show all 14 contributors for this article] (2022). A research agenda for post-COVID-19 fatigue. Journal of Psychosomatic Research. ISSN 0022-3999. 154. doi: 10.1016/j.jpsychores.2022.110726. Full text in Research Archive
• Chaibi, Aleksander; Stavem, Knut & Russell, Michael Bjørn (2022). Manipulasjonsbehandling mot akutte nakkesmerter? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 142(1), p. 16–17. doi: 10.4045/tidsskr.21.0798. Full text in Research Archive
• Hansen, Tonya Moen; Stavem, Knut & Rand, Kim (2022). Correction to: Time trade‑off with someone to live for: impact of having significant others on time trade‑off valuations of hypothetical health states (Quality of Life Research, (2022), 31, 4, (1199-1207), 10.1007/s11136-021-03026-6). Quality of Life Research. ISSN 0962-9343. 31(10), p. 3087–3087. doi: 10.1007/s11136-022-03160-9. Full text in Research Archive
• Garratt, Andrew Malcolm; Ghanima, Waleed Khalid; Einvik, Gunnar & Stavem, Knut (2021). Quality of life after COVID-19 without hospitalisation: Good overall, but reduced in some dimensions. Journal of Infection. ISSN 0163-4453. 82(5), p. 186–188. doi: 10.1016/j.jinf.2021.01.002. Full text in Research Archive
• Astrup, Guro Lindviksmoen; Rohde, Gudrun E.; Rimehaug, Stein Arne; Andersen, Marit Helen; Bernklev, Tomm & Bjordal, Kristin [Show all 10 contributors for this article] (2020). Comparing the use of patient-reported outcomes in clinical studies in Europe in 2008 and 2018; a literature review. Full text in Research Archive
• Cheng, Socheat; Siddiqui, Tahreem Ghazal; Gossop, Michael; Stavem, Knut; Kristoffersen, Espen Saxhaug & Lundqvist, Christofer (2019). Overuse of opioids and benzidiazepines among elderly patients: Characteristics of at-risk patients and disparities in quality of life. Full text in Research Archive
• Parker, Krystina; Lippe, Nanna von der; Reier-Nilsen, Morten; Os, Ingrid & Stavem, Knut (2018). A prevalence study of potentially inappropriate prescribing in elderly kidney patients. Full text in Research Archive
• Kristoffersen, Espen Saxhaug; Stavem, Knut; LUNDQVIST, CHRISTOFER & Russell, Michael Bjørn (2018). The impact of chronic headache on workdays, unemployment and disutility in the general population. Full text in Research Archive
• Kristoffersen, Espen Saxhaug; Stavem, Knut; LUNDQVIST, CHRISTOFER & Russell, Michael Bjørn (2018). Reply to the letter by Min et al. Cephalalgia. ISSN 0333-1024. 38(10), p. 1701–1702. doi: 10.1177/0333102417747213. Full text in Research Archive

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