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- Gronberg, B. H., et al.
(author)
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High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial
- 2021
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In: Lancet Oncology. - 1470-2045 .- 1474-5488. ; 22:3, s. 321-331
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Journal article (peer-reviewed)abstract
- Background Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival. Methods This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 ing/m 2 or carboplatin (area under the curve 5-6 mg/mL x min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m 2 on days 1-3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20-28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25-30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov , NCT02041845. Findings Between July 8,2014, and June 6,2018,176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38-56). At 2 years, 66 (74.2% [95% CI 63-8-82.9]) patients in the 60 Gy group were alive, compared with 39 (48.1% 136-9-59.51) patients in the 45 Gy group (odds ratio 3.09 [95% CI 1.62-5-89]; p=0-0005). The most common grade 3-4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 181%1 of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%1), thrombocytopenia (21 [24%] vs 19 125%1), anaemia (14 [16%] vs 15 120%D, and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group). Interpretation The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
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| 10. |
- Killingberg, K. T., et al.
(author)
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Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer
- 2022
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In: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 166, s. 49-57
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Journal article (peer-reviewed)abstract
- Objectives: In a randomized phase II trial, twice daily (BID) thoracic radiotherapy (TRT) of 60 Gy/40 frac-tions improved survival compared with 45 Gy/30 fractions in limited stage small-cell lung cancer (LS SCLC). Notably, the higher dose did not cause more toxicity. Here we present health related quality of life (HRQoL) reported by the trial participants during the first 2 years.& nbsp;Materials and methods: 170 patients were randomized 1:1 to TRT of 45 Gy or 60 Gy concurrently with cisplatin/etoposide chemotherapy. The 150 patients who commenced TRT and completed a minimum of one HRQoL-questionnaire were included in the present study. Patients reported HRQoL on the European Organization for Research and Treatment of Cancer Core 30 and Lung Cancer 13 Quality of Life Questionnaires. Questionnaires were completed weeks 0, 4 (before TRT), 8 (end of TRT), 12 (response evaluation after chemoradiotherapy) and 16 (end of prophylactic cranial irradiation), then every 10 weeks year one, and every 3 months year two. Primary HRQoL endpoints were dysphagia and dyspnea. A difference in mean score of >= 10 was defined as clinically significant.& nbsp;Results: Maximum dysphagia was reported on week 8, with no significant difference between treatment arms (mean scores 45 Gy: 44.2, 60 Gy: 51.1). The 60 Gy arm had more dysphagia in the convalescence period, but dysphagia scores returned to baseline levels at week 16 in both arms. For dyspnea there were no significant changes, or differences between treatment arms, at any timepoint. There were no significant differences between treatment arms for any other HRQoL-scales.& nbsp;Conclusion: TRT of 60 Gy did not cause significantly higher maximum dysphagia, though patients on the 60 Gy arm reported more dysphagia the first 8 weeks of convalescence. The higher dose was well tolerated and is an attractive alternative to current TRT schedules in LS SCLC.& nbsp;
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- Smedsrud, P. H., et al.
(author)
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Kvasir-Capsule, a video capsule endoscopy dataset
- 2021
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 8:1
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Journal article (peer-reviewed)abstract
- Artificial intelligence (AI) is predicted to have profound effects on the future of video capsule endoscopy (VCE) technology. The potential lies in improving anomaly detection while reducing manual labour. Existing work demonstrates the promising benefits of AI-based computer-assisted diagnosis systems for VCE. They also show great potential for improvements to achieve even better results. Also, medical data is often sparse and unavailable to the research community, and qualified medical personnel rarely have time for the tedious labelling work. We present Kvasir-Capsule, a large VCE dataset collected from examinations at a Norwegian Hospital. Kvasir-Capsule consists of 117 videos which can be used to extract a total of 4,741,504 image frames. We have labelled and medically verified 47,238 frames with a bounding box around findings from 14 different classes. In addition to these labelled images, there are 4,694,266 unlabelled frames included in the dataset. The Kvasir-Capsule dataset can play a valuable role in developing better algorithms in order to reach true potential of VCE technology.
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- Kuiper, I. N., et al.
(author)
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Associations of Preconception Exposure to Air Pollution and Greenness with Offspring Asthma and Hay Fever
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601 .- 1661-7827. ; 17:16
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Journal article (peer-reviewed)abstract
- We investigated if greenness and air pollution exposure in parents' childhood affect offspring asthma and hay fever, and if effects were mediated through parental asthma, pregnancy greenness/pollution exposure, and offspring exposure. We analysed 1106 parents with 1949 offspring (mean age 35 and 6) from the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Mean particulate matter (PM(2.5)and PM10), nitrogen dioxide (NO2), black carbon (BC), ozone (O-3) (mu g/m(3)) and greenness (normalized difference vegetation index (NDVI)) were calculated for parents 0-18 years old and offspring 0-10 years old, and were categorised in tertiles. We performed logistic regression and mediation analyses for two-pollutant models (clustered by family and centre, stratified by parental lines, and adjusted for grandparental asthma and education). Maternal medium PM(2.5)and PM(10)exposure was associated with higher offspring asthma risk (odds ratio (OR) 2.23, 95%CI 1.32-3.78, OR 2.27, 95%CI 1.36-3.80), and paternal high BC exposure with lower asthma risk (OR 0.31, 95%CI 0.11-0.87). Hay fever risk increased for offspring of fathers with medium O(3)exposure (OR 4.15, 95%CI 1.28-13.50) and mothers with high PM(10)exposure (OR 2.66, 95%CI 1.19-5.91). The effect of maternal PM(10)exposure on offspring asthma was direct, while for hay fever, it was mediated through exposures in pregnancy and offspring's own exposures. Paternal O(3)exposure had a direct effect on offspring hay fever. To conclude, parental exposure to air pollution appears to influence the risk of asthma and allergies in future offspring.
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- Nordeide Kuiper, I., et al.
(author)
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Lifelong exposure to air pollution and greenness in relation to asthma, rhinitis and lung function in adulthood
- 2021
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In: Environmental International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
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Journal article (peer-reviewed)abstract
- Objectives: To investigate if air pollution and greenness exposure from birth till adulthood affects adult asthma, rhinitis and lung function. Methods: We analysed data from 3428 participants (mean age 28) in the RHINESSA study in Norway and Sweden. Individual mean annual residential exposures to nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), black carbon (BC), ozone (O3) and greenness (normalized difference vegetation index (NDVI)) were averaged across susceptibility windows (0–10 years, 10–18 years, lifetime, adulthood (year before study participation)) and analysed in relation to physician diagnosed asthma (ever/allergic/non-allergic), asthma attack last 12 months, current rhinitis and low lung function (lower limit of normal (LLN), z-scores of forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC below 1.64). We performed logistic regression for asthma attack, rhinitis and LLN lung function (clustered with family and study centre), and conditional logistic regression with a matched case-control design for ever/allergic/non-allergic asthma. Multivariable models were adjusted for parental asthma and education. Results: Childhood, adolescence and adult exposure to NO2, PM10 and O3 were associated with an increased risk of asthma attacks (ORs between 1.29 and 2.25), but not with physician diagnosed asthma. For rhinitis, adulthood exposures seemed to be most important. Childhood and adolescence exposures to PM2.5 and O3 were associated with lower lung function, in particular FEV1 (range ORs 2.65 to 4.21). No associations between NDVI and asthma or rhinitis were revealed, but increased NDVI was associated with lower FEV1 and FVC in all susceptibility windows (range ORs 1.39 to 1.74). Conclusions: Air pollution exposures in childhood, adolescence and adulthood were associated with increased risk of asthma attacks, rhinitis and low lung function in adulthood. Greenness was not associated with asthma or rhinitis, but was a risk factor for low lung function. © 2020 The Authors
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- Kaastad, T S, et al.
(author)
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Vitamin D deficiency and ovariectomy reduced the strength of the femoral neck in rats
- 2001
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In: Calcified Tissue International. - : Springer Science and Business Media LLC. - 1432-0827 .- 0171-967X. ; 69:2, s. 102-108
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Journal article (peer-reviewed)abstract
- Vitamin D (vit D) deficiency is common in the elderly, and the aim of this study was to investigate whether vit D deprivation in ovariectomized (ovx) and normal rats would reduce fracture strength. Forty mature female Wistar rats were randomized into four groups: two were ovariectomized (ovx) and two were sham-operated (sham). One ovx and one sham group were fed a vit D-deficient diet (Ovx-D and Sham-D), and the control groups were fed normal rat chow (Ovx and Sham) for 12 weeks. Vit D deficiency was substantiated after 12 weeks by undetectable serum concentrations of 25OHD in the Sham-D and Ovx-D groups. 85Sr activity was lower in Sham-D than in the other groups (P < 0.005). Tibial and femoral weights and lengths showed no differences. Distal tibial trabecular bone volume was reduced in both ovx groups compare with sham (P < 0.005). Bone mineral density (BMD) was higher in sham than in Sham-D and both ovx groups (P < 0.005). Femoral area moment of inertia increased and ultimate stress decreased in Ovx-D compared with ovx (P < 0.05). Other biomechanical properties of the femoral shafts did not differ significantly. The femoral neck was significantly weaker in Ovx-D than in the other groups. In conclusion, ovx decreased tibial trabecular bone volume and both ovx and vit D depletion reduced femoral BMD in rats. Vit D depletion reduced the ultimate stress in the femoral shaft, and the combined depletion of estrogen and vit D significantly reduced the fracture strength in the femoral neck. This fits well with clinical evidence of how postmenopausal status combined with vit D deficiency lead to an increased risk of hip fractures, making this animal model a possible tool for investigating measures to prevent such fractures.
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- Ratajczak-Tretel, B., et al.
(author)
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Atrial fibrillation in cryptogenic stroke and TIA patients in the nordic atrial fibrillation and stroke The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study : Main results
- 2023
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In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 8:1, s. 148-156
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Journal article (peer-reviewed)abstract
- Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA₂DS₂-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.
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| 26. |
- Ratajczak-Tretel, B, et al.
(author)
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Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke : results from the NOR-FIB Study
- 2023
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In: Journal of Neurology. - 1432-1459. ; 270:8, s. 4049-4059
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Journal article (peer-reviewed)abstract
- BACKGROUND: Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study.METHOD: The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA 2DS 2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. RESULTS: In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7.CONCLUSION: Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units.
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| 27. |
- Ratajczak-Tretel, B, et al.
(author)
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Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study : the importance of comprehensive clinical evaluation
- 2023
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In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 23:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management.METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis.RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA 2DS 2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal.TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.
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| 29. |
- Strom, NI, et al.
(author)
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Polygenic Heterogeneity Across Obsessive-Compulsive Disorder Subgroups Defined by a Comorbid Diagnosis
- 2021
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In: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 12, s. 711624-
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Journal article (peer-reviewed)abstract
- Among patients with obsessive-compulsive disorder (OCD), 65–85% manifest another psychiatric disorder concomitantly or at some other time point during their life. OCD is highly heritable, as are many of its comorbidities. A possible genetic heterogeneity of OCD in relation to its comorbid conditions, however, has not yet been exhaustively explored. We used a framework of different approaches to study the genetic relationship of OCD with three commonly observed comorbidities, namely major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). First, using publicly available summary statistics from large-scale genome-wide association studies, we compared genetic correlation patterns for OCD, MDD, ADHD, and ASD with 861 somatic and mental health phenotypes. Secondly, we examined how polygenic risk scores (PRS) of eight traits that showed heterogeneous correlation patterns with OCD, MDD, ADHD, and ASD partitioned across comorbid subgroups in OCD using independent unpublished data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The comorbid subgroups comprised of patients with only OCD (N = 366), OCD and MDD (N = 1,052), OCD and ADHD (N = 443), OCD and ASD (N = 388), and OCD with more than 1 comorbidity (N = 429). We found that PRS of all traits but BMI were significantly associated with OCD across all subgroups (neuroticism: p = 1.19 × 10−32, bipolar disorder: p = 7.51 × 10−8, anorexia nervosa: p = 3.52 × 10−20, age at first birth: p = 9.38 × 10−5, educational attainment: p = 1.56 × 10−4, OCD: p = 1.87 × 10−6, insomnia: p = 2.61 × 10−5, BMI: p = 0.15). For age at first birth, educational attainment, and insomnia PRS estimates significantly differed across comorbid subgroups (p = 2.29 × 10−4, p = 1.63 × 10−4, and p = 0.045, respectively). Especially for anorexia nervosa, age at first birth, educational attainment, insomnia, and neuroticism the correlation patterns that emerged from genetic correlation analysis of OCD, MDD, ADHD, and ASD were mirrored in the PRS associations with the respective comorbid OCD groups. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across OCD comorbid subgroups.
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