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Sökning: WFRF:(Tone M)

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1.
  • 2017
  • swepub:Mat__t
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3.
  • Abdellaoui, G., et al. (författare)
  • Meteor studies in the framework of the JEM-EUSO program
  • 2017
  • Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255
  • Tidskriftsartikel (refereegranskat)abstract
    • We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
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4.
  • Namkoong, H, et al. (författare)
  • DOCK2 is involved in the host genetics and biology of severe COVID-19
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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5.
  • Wang, QBS, et al. (författare)
  • The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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7.
  • Abdellaoui, G., et al. (författare)
  • First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere
  • 2018
  • Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221 .- 1748-0221. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
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8.
  • Abdollahi, S., et al. (författare)
  • Fermi Large Area Telescope Fourth Source Catalog
  • 2020
  • Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 247:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the fourth Fermi Large Area Telescope catalog (4FGL) of gamma-ray sources. Based on the first eight years of science data from the Fermi Gamma-ray Space Telescope mission in the energy range from 50 MeV to 1 TeV, it is the deepest yet in this energy range. Relative to the 3FGL catalog, the 4FGL catalog has twice as much exposure as well as a number of analysis improvements, including an updated model for the Galactic diffuse gamma-ray emission, and two sets of light curves (one-year and two-month intervals). The 4FGL catalog includes 5064 sources above 4 sigma significance, for which we provide localization and spectral properties. Seventy-five sources are modeled explicitly as spatially extended, and overall, 358 sources are considered as identified based on angular extent, periodicity, or correlated variability observed at other wavelengths. For 1336 sources, we have not found plausible counterparts at other wavelengths. More than 3130 of the identified or associated sources are active galaxies of the blazar class, and 239 are pulsars.
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9.
  • Stanaway, Jeffrey D., et al. (författare)
  • Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
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11.
  • Griswold, Max G., et al. (författare)
  • Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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12.
  • Culina, Antica, et al. (författare)
  • Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub
  • 2021
  • Ingår i: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160
  • Tidskriftsartikel (refereegranskat)abstract
    • The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.
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13.
  • Johansson, Henrik J., et al. (författare)
  • Breast cancer quantitative proteome and proteogenomic landscape
  • 2019
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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14.
  • Keogan, Katharine, et al. (författare)
  • Global phenological insensitivity to shifting ocean temperatures among seabirds
  • 2018
  • Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:4, s. 313-318
  • Tidskriftsartikel (refereegranskat)abstract
    • Reproductive timing in many taxa plays a key role in determining breeding productivity(1), and is often sensitive to climatic conditions(2). Current climate change may alter the timing of breeding at different rates across trophic levels, potentially resulting in temporal mismatch between the resource requirements of predators and their prey(3). This is of particular concern for higher-trophic-level organisms, whose longer generation times confer a lower rate of evolutionary rescue than primary producers or consumers(4). However, the disconnection between studies of ecological change in marine systems makes it difficult to detect general changes in the timing of reproduction(5). Here, we use a comprehensive meta-analysis of 209 phenological time series from 145 breeding populations to show that, on average, seabird populations worldwide have not adjusted their breeding seasons over time (-0.020 days yr(-1)) or in response to sea surface temperature (SST) (-0.272 days degrees C-1) between 1952 and 2015. However, marked between-year variation in timing observed in resident species and some Pelecaniformes and Suliformes (cormorants, gannets and boobies) may imply that timing, in some cases, is affected by unmeasured environmental conditions. This limited temperature-mediated plasticity of reproductive timing in seabirds potentially makes these top predators highly vulnerable to future mismatch with lower-trophic-level resources(2).
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15.
  • van der Valk, Maxime J. M., et al. (författare)
  • Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial
  • 2020
  • Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 147, s. 75-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision is widely accepted as the standard of care for high-risk rectal cancer. Adjuvant chemotherapy is advised in several international guidelines, although the survival benefit remains unclear and compliance is poor. The current multidisciplinary approach has led to major improvements in local control, yet the occurrence of distant metastases has not decreased accordingly. The combination of short-course radiotherapy (SCRT) and chemotherapy in the waiting period before surgery might have several benefits, including higher compliance, downstaging and better effect of systemic therapy. Methods: This is an investigator-initiated, international multicentre randomized phase III trial. High-risk rectal cancer patients were randomized to SCRT followed by chemotherapy (6 cycles CAPOX or alternatively 9 cycles FOLFOX4) and subsequent surgery, or long-course radiotherapy (25-28 x 2-1.8 Gy) with concomitant capecitabine followed by surgery and optional postoperative chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX4) according to local institutions' policy. The primary endpoint is time to disease related treatment failure. Here, we report the compliance, toxicity and postoperative complications in both study groups. Findings: Between June 2011 and June 2016, 920 patients were enrolled. Of these, 901 were evaluable (460 in the experimental arm and 441 in the standard arm). All patients in the experimental arm received 5 x 5 Gy radiotherapy, and 84% of all patients received at least 75% of the prescribed chemotherapy. In the standard arm, the compliance for CRT was 93% and 58% for postoperative chemotherapy. Toxicity >= grade 3 occurred in 48% of patients in the experimental arm, compared to 25% of patients in the standard arm during preoperative treatment and 35% of patients during postoperative chemotherapy. No statistically significant differences in surgical procedures or postoperative complications were observed. Interpretation: High compliance (84%) of preoperative systemic treatment could be achieved with the experimental approach. Although considerable toxicity was observed during preoperative therapy, this did not lead to differences in surgical procedures or postoperative complications. Longer follow-up time is needed to assess the primary endpoint and related outcomes. (c) 2020 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 147 (2020) 75-83
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16.
  • Dahlin, Anna M., 1979-, et al. (författare)
  • A genome-wide association study on medulloblastoma
  • 2020
  • Ingår i: Journal of Neuro-Oncology. - : Springer. - 0167-594X .- 1573-7373. ; 147:2, s. 309-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3).Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.
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17.
  • Lecuona, Oscar, et al. (författare)
  • A Network Analysis of the Fear of COVID-19 Scale (FCV-19S) : A Large-Scale Cross-Cultural Study in Iran, Bangladesh, and Norway
  • 2022
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The rapid spread of the coronavirus disease 2019 (COVID-19) has led to high levels of fear worldwide. Given that fear is an important factor in causing psychological distress and facilitating preventive behaviors, assessing the fear of COVID-19 is important. The seven-item Fear of COVID-19 Scale (FCV-19S) is a widely used psychometric instrument to assess this fear. However, the factor structure of the FCV-19S remains unclear according to the current evidence. Therefore, the present study used a network analysis to provide further empirical evidence for the factor structure of FCV-19S. A total of 24,429 participants from Iran (n = 10,843), Bangladesh (n = 9906), and Norway (n = 3680) completed the FCV-19S in their local language. A network analysis (via regularized partial correlation networks) was applied to investigate the seven FCV-19S items. Moreover, relationships between the FCV-19S items were compared across gender (males vs. females), age groups (18-30 years, 31-50 years, and >50 years), and countries (Iran, Bangladesh, and Norway). A two-factor structure pattern was observed (three items concerning physical factors, including clammy hands, insomnia, and heart palpitations; four items concerning psychosocial factors, including being afraid, uncomfortable, afraid of dying, and anxious about COVID-19 news). Moreover, this pattern was found to be the same among men and women, across age groups and countries. The network analysis used in the present study verified the two-factor structure for the FCV-19S. Future studies may consider using the two-factor structure of FCV-19S to assess the fear of COVID-19 during the COVID-19 era.
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18.
  • Melinder, Annika M. D., et al. (författare)
  • The developmental trajectory of pointing perception in the first year of life
  • 2015
  • Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 233:2, s. 641-647
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study investigated the development of the neural basis of pointing perception in 6-month- and 13-month-old infants. In a spatial-cueing paradigm, infants were presented with a peripheral target followed by a hand pointing toward (congruent condition) or away (incongruent condition) from the previously cued location. EEG responses to the presentation of the hand were measured. Thirteen-month-olds demonstrated larger amplitudes of ERP component P400 to incongruent compared to congruent pointing gestures over posterior temporal areas; 6-month-olds did not show any differential activation. This result suggests that the neural correlates of pointing perception undergo substantial development between 6 and 13 months of age.
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20.
  • Tarpgaard, Line S., et al. (författare)
  • TIMP-1 is under regulation of the EGF signaling axis and promotes an aggressive phenotype in KRAS-mutated colorectal cancer cells : A potential novel approach to the treatment of metastatic colorectal cancer
  • 2016
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:37, s. 59441-59457
  • Tidskriftsartikel (refereegranskat)abstract
    • It is now widely accepted that therapeutic antibodies targeting epidermal growth factor receptor (EGFR) can have efficacy in KRAS wild-type advanced colorectal cancer (CRC) patients. What remains to be ascertained is whether a subgroup of KRAS-mutated CRC patients might not also derive benefit from EGFR inhibitors. Metalloproteinase inhibitor 1 (TIMP-1) is a pleiotropic factor predictive of survival outcome of CRC patients. Levels of TIMP-1 were measured in pre-treatment plasma samples (n = 426) of metastatic CRC patients randomized to Nordic FLOX (5-fluorouracil and oxaliplatin) +/- cetuximab (NORDIC VII study). Multivariate analysis demonstrated a significant interaction between plasma TIMP-1 protein levels, KRAS status and treatment with patients bearing KRAS mutated tumors and high TIMP-1 plasma level (> 3rd quartile) showing a significantly longer overall survival if treated with cetuximab (HR, 0.48; 95% CI, 0.25 to 0.93). To gain mechanistic insights into this association we analyzed a set of five different CRC cell lines. We show here that EGFR signaling induces TIMP-1 expression in CRC cells, and that TIMP-1 promotes a more aggressive behavior, specifically in KRAS mutated cells. The two sets of data, clinical and in vitro, are complementary and support each other, lending strength to our contention that TIMP-1 plasma levels can identify a subset of patients with KRAS-mutated metastatic CRC that will have benefit from EGFR-inhibition therapy.
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21.
  • Ahlborg, Tone, 1950, et al. (författare)
  • Assessing the quality of the dyadic relationship in first-time parents: development of a new instrument.
  • 2005
  • Ingår i: Journal of family nursing. - Thousand Oaks, Calif. : SAGE Publications. - 1074-8407 .- 1552-549X. ; 11:1, s. 19-37
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this research was to psychometrically evaluate the Dyadic Adjustment Scale (DAS), modified for use with new, first-time parents by extending the items of communication, sensuality, and sexuality. A total of 820 Swedish respondents, 6 months after the birth of their first child, participated in the study. Psychometric evaluation was conducted with factor analysis. The obtained factor structure was tested with multitrait analysis program. Thirty-three items were found to fit into a five-factor solution, explaining 50% of the total variance. Descriptive data revealed that most new parents were satisfied with their intimate relationship in general, but dissatisfied with their sexual lives. The modified DAS, now called the Quality of Dyadic Relationship Instrument includes 33 items and seems to be a useful, updated measurement for assessing quality of the intimate relationship in new first-time parents.
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22.
  • Amofah, Hege Andersen, et al. (författare)
  • Octogenarian patients' sleep and delirium experiences in hospital and four years after aortic valve replacement : a qualitative interview study
  • 2021
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesSleep disturbances and delirium are frequently observed complications after surgical aortic valve replacement (SAVR) and transcutaneous aortic valve implantation (TAVI), especially in octogenarian patients. However, a knowledge gap exists on patient experiences of sleep and delirium. In particular, patients' long-term sleep and delirium experiences are unknown. This article explores and describes how octogenarian patients suffering from delirium after aortic valve replacement experience their sleep and delirium situation.DesignAn explorative and descriptive design with a longitudinal qualitative approach was applied. Qualitative content analysis following the recommended steps of Graneheim and Lundman was performed.SettingPatients were included at a tertiary university hospital with 1400 beds. Delirium and insomnia screening was performed at baseline and five postoperative days after aortic valve treatment. For qualitative data, 10 patients were interviewed 6-12 months after treatment with focus on delirium. Five of these patients were reinterviewed 4 years after treatment, with focus on their sleep situation.ParticipantsInclusion criteria; age 80+, treated with SAVR or TAVI and had experienced delirium after treatment.ResultsFor the initial interview, we included five men and five women, four following TAVI and six following SAVR, mean age 83. One overarching theme revealed from the content analyses; Hours in bed represented emotional chaos. Whereas three subthemes described the patients' experiences with sleep and delirium, a cascade of distressful experiences disturbing sleep, the struggle between sleep and activity and elements influencing sleep. Four years after the treatment, sleep disturbances persisted, and patients still remembered strongly the delirium incidences.ConclusionsFor octogenarian patients, sleep disturbances and delirium are long-term burdens and need a greater attention in order to improve patient care.
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23.
  • Amofah, Hege A., et al. (författare)
  • Sleep in octogenarians during the postoperative phase after transcatheter or surgical aortic valve replacement
  • 2016
  • Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 15:2, s. 168-177
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Octogenarians with aortic stenosis are an increasing population of patients admitted for surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). Although adequate sleep is important after illness and surgery, it has scarcely been studied in the immediate postoperative phase.Aims: To determine and compare the nature of self-reported sleep and insomnia, and recorded sleep–wake patterns in octogenarians during the in-hospital postoperative phase after SAVR or TAVI.Methods: A prospective cohort design was used that included octogenarian patients undergoing SAVR or TAVI at a regional university hospital. Self-reports were used to document sleep and insomnia, and actigraphy was used to record sleep–wake patterns. Data were collected at baseline preoperatively, and then daily for the first five postoperative days.Results: SAVR patients experienced the most insomnia on postoperative nights later in recovery, while TAVI patients experienced the most insomnia on postoperative nights early in recovery. The median total sleep time, as measured by actigraphy, was 6.4 h, and the median sleep efficiency was 79% for the five postoperative nights, but no differences were found between SAVR and TAVI patients on this parameter. All patients slept more during daytime than at night, with SAVR patients having significantly more total sleep hours for all five days than TAVI patients (p < 0.01).Conclusion: Octogenarians with aortic stenosis had disturbed self-reported sleep, increased insomnia, and disturbed sleep–wake patterns postoperatively, resulting in more daytime sleep and inactivity. In patients undergoing SAVR or TAVI, sleep evolves differently during the in-hospital postoperative phase.
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24.
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25.
  • Bahadoer, Renu R., et al. (författare)
  • Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO) : a randomised, open-label, phase 3 trial
  • 2021
  • Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:1, s. 29-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocardnoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within S weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 x 5 Gy over a maximum of 8 days) followed by six cycles of CAPDX chemotherapy (capecitabine 1000 mg/m(2) orally twice daily on days 1-14, oxaliplatin 130 mg/m(2) intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m(2) intravenously on day 1, leucovorin [folinic acid] 200 mg/m 2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m(2) intravenously and fluorouracil 600 mg/m 2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPDX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1.8 Gy up to 50.4 Gy or 25 fractions of 2.0 Gy up to 50.0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m(2) followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPDX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov , NCT01558921, and is now complete. Findings Between June 21,2011, and June 2,2016,920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4.6 years (IQR 3.5-5.5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23.7% (95% CI 19.8-27.6) in the experimental group versus 30.4% (26.1-34.6) in the standard of care group (hazard ratio 0.75, 95% CI 0.60-0-95; p=0-019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer.
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26.
  • Blecken, Godecke-Tobias, et al. (författare)
  • Biofilter treatment of stormwater : temperature influence on the removal of nutrients
  • 2007
  • Ingår i: Techniques et stratégies durables pour la gestion des eaux urbaines par temps de pluie. - Villeurbanne : Graie. - 9782950933775
  • Konferensbidrag (refereegranskat)abstract
    • Nutrients can cause eutrophication of natural water bodies. Thus, urban stormwater which is an important nutrient source has to be treated in order to reduce its nutrient loads. Biofilters which use media, biofilms and plants, are a good treatment option regarding nutrients. This paper presents the results of a biofilter column study in cold temperatures (+2°C, +8°C, control at +20°C) which may cause special problems regarding the biofilter performance. It was shown that particle bound pollutants as TSS and a high fraction of phosphorus were reduced well without being negatively influenced by cold temperatures. Nitrogen, however, was not reduced; especially NOx was produced in the columns which can be explained with both insufficient denitrification and high leaching from the columns.
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27.
  • Blecken, Godecke-Tobias, et al. (författare)
  • The influence of temperature on nutrient treatment efficiency in stormwater biofilter systems
  • 2007
  • Ingår i: Water Science and Technology. - : IWA Publishing. - 0273-1223 .- 1996-9732. ; 56:10, s. 83-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Nutrients can cause eutrophication of natural water bodies. Thus, urban stormwater which is an important nutrient source in urbanised areas has to be treated in order to reduce its nutrient loads. Biofilters which use soil filter media, biofilms and plants, are a good treatment option for nutrients. This paper presents the results of a biofilter column study in cold temperatures (+2 °C, +8 °C, control at +20 °C) which may cause special problems regarding biofilter performance. It was shown that particle-bound pollutants as TSS and a high fraction of phosphorus were reduced well without being negatively influenced by cold temperatures. Nitrogen, however, was not reduced; especially NOx was produced in the columns. This behaviour can be explained with both insufficient denitrification and high leaching from the columns
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28.
  • Borregaard, Britt, et al. (författare)
  • Association between frailty and self-reported health following heart valve surgery
  • 2020
  • Ingår i: IJC Heart & Vasculature. - : ELSEVIER IRELAND LTD. - 2352-9067. ; 31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Knowledge about the association between frailty and self-reported health among patients undergoing heart valve surgery remains sparse. Thus, the objectives were to I) describe changes in self-reported health at different time points according to frailty status, and to II) investigate the association between frailty status at discharge and poor self-reported health four weeks after discharge among patients undergoing heart valve surgery. Methods: In a prospective cohort study, consecutive patients undergoing heart valve surgery, including transapical/transaortic valve procedures were included. Frailty was measured using the Fried score, and self-reported health using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQoL-5 Dimensions 5-Levels Health Status Questionnaire (EQ-5D-5L). To investigate the association between frailty and self-reported health, multivariable logistic regression models were used. Analyses were adjusted for sex, age, surgical risk evaluation (EuroScore) and procedure and presented as odds ratios (OR) with 95% confidence intervals (CI). Results: Frailty was assessed at discharge in 288 patients (median age 71, 69% men); 51 patients (18%) were frail. In the multivariable analyses, frailty at discharge remained significantly associated with poor self-reported health at four weeks, OR (95% CI): EQ-5D-5L Index 3.38 (1.51-7.52), VAS 2.41 (1.13-5.14), and KCCQ 2.84 (1.35-5.97). Conclusion: Frailty is present at discharge in 18% of patients undergoing heart valve surgery, and being frail is associated with poor self-reported health at four weeks of follow-up. This supports a clinical need to address the unique risk of frail patients among heart valve teams broadly, and not only to measure frailty as a marker of operative risk. (C) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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29.
  • Broekhuizen, Ico, et al. (författare)
  • Urban drainage models for green areas : Structural differences and their effects on simulated runoff
  • 2019
  • Ingår i: Journal of Hydrology X. - : Elsevier. - 2589-9155. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Mathematical stormwater models are often used as tools for planning and analysing urban drainage systems. However, the inherent uncertainties of the models must be properly understood in order to make optimal use of them. One source of uncertainty that has received relatively little attention, particularly for increasingly popular green areas as part of urban drainage systems, is the mathematical model structure. This paper analyses the differences between three different widely-used models (SWMM, MOUSE and Mike SHE) when simulating rainfall runoff from green areas over a 26-year period. Eleven different soil types and six different soil depths were used to investigate the sensitivity of the models to changes in both. Important hydrological factors such as seasonal runoff and evapotranspiration, the number of events that generated runoff, and the initial conditions for rainfall events, varied significantly between the three models. MOUSE generated the highest runoff volumes, while it was rather insensitive to changes in soil type and depth. Mike SHE was mainly sensitive to changes in soil type. SWMM, which generated the least runoff, was sensitive to changes in both soil type and depth. Explanations for the observed differences were found in the descriptions of the mathematical models. The differences in model outputs could significantly impact the conclusions from studies on the design or analysis of urban drainage systems. The amount and frequency of runoff from green areas in all three models indicates that green areas cannot be simply ignored in urban drainage modelling studies.
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30.
  • Brors, Gunhild, et al. (författare)
  • Modes of e-Health delivery in secondary prevention programmes for patients with coronary artery disease : a systematic review
  • 2019
  • Ingår i: BMC Health Services Research. - : BioMed Central. - 1472-6963. ; 19, s. 1-24
  • Forskningsöversikt (refereegranskat)abstract
    • BackgroundElectronic health (e-Health) interventions are emerging as an effective alternative model for improving secondary prevention of coronary artery disease (CAD). The aim of this study was to describe the effectiveness of different modes of delivery and components in e-Health secondary prevention programmes on adherence to treatment, modifiable CAD risk factors and psychosocial outcomes for patients with CAD.MethodA systematic review was carried out based on articles found in MEDLINE, CINAHL, and Embase. Studies evaluating secondary prevention e-Health programmes provided through mobile-Health (m-Health), web-based technology or a combination of m-Health and web-based technology were eligible. The main outcomes measured were adherence to treatment, modifiable CAD risk factors and psychosocial outcomes. The quality appraisal of the studies included was conducted using the Joanna Briggs Institute critical appraisal tool for RCT. The results were synthesised narratively.ResultA total of 4834 titles were identified and 1350 were screened for eligibility. After reviewing 123 articles in full, 24 RCTs including 3654 participants with CAD were included. Eight studies delivered secondary prevention programmes through m-Health, nine through web-based technology, and seven studies used a combination of m-Health and web-based technology. The majority of studies employed two or three secondary prevention components, of which health education was employed in 21 studies. The m-Health programmes reported positive effects on adherence to medication. Most studies evaluating web-based technology programmes alone or in combination with m-Health also utilised traditional CR, and reported improved modifiable CAD risk factors. The quality appraisal showed a moderate methodological quality of the studies.ConclusionEvidence exists that supports the use of e-Health interventions for improving secondary prevention of CAD. However, a comparison across studies highlighted a wide variability of components and outcomes within the different modes of delivery. High quality trials are needed to define the most efficient mode of delivery and components capable of addressing a favourable outcome for patients.Trial registrationNot applicable.
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31.
  • Devik A., Siri, et al. (författare)
  • Variations in drug-related problems detected by multidisciplinary teams in Norwegian nursing homes and home nursing care
  • 2018
  • Ingår i: Scandinavian Journal of Primary Health Care. - : Taylor & Francis Group. - 0281-3432 .- 1502-7724. ; 36:3, s. 291-299
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:Traditionally, nursing homes have been associated with suboptimal drug therapy and drug-related problems (DRPs). In contrast, less is known about drug safety in homecare. The aim of this study was to describe and compare DRPs in older persons across two care settings: nursing homes and home nursing care.DESIGN:Cross-sectional study using descriptive and inferential statistics.SETTING:Nursing homes (n = 5) and home nursing care units (n = 8) across nine municipalities in the middle of Norway.PARTICIPANTS:Multidisciplinary medication reviews for 61 nursing home residents and 93 patients receiving home nursing care performed over the 2013-2014 period, were mapped and examined (N = 154).MAIN OUTCOME MEASURES:DRPs classified by a Norwegian Classification Tool.RESULTS:In all, 740 DRPs were detected in the total sample, 227 in nursing homes and 513 in home nursing care. DRPs were significantly higher among patients receiving home-based care (Mean =5.5) compared to patients in nursing homes (Mean =3.7, p = 0.002). Among the problem categories, the need for additional drug was most frequent in nursing homes (p = 0.001), while documentation discrepancies reached the highest numbers in patients receiving home nursing care (p = 0.000). Additionally, patients in home nursing care had more problems concerning adverse reactions (p = 0.060); however, this was not statistically significant. Differences in DRP categories leading to changes in the patients' medication lists were also discovered.CONCLUSIONS:The frequency of unclear documentation and adverse reactions found in the homecare setting is alarming. This is an important issue given the trend in aged care towards caring people in their own homes. Further research is warranted to explore how different care settings may influence the safety of pharmacotherapy for older persons.Key PointsDrug related problems are a significant cause of concern among patients receiving home nursing care as well as for patients living in nursing homes. The findings of this study showed that:Significantly more DRPs were detected among patients receiving home nursing care than patients living in nursing homes.While patients living in nursing homes were often undermedicated, documentation discrepancies were more frequent in home nursing care.DRP categories leading to changes on the medication lists differed between the settings.
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32.
  • Eide, Leslie S. P., et al. (författare)
  • Anxiety and depression in patients aged 80 years and older following aortic valve therapy. A six-month follow-up study
  • 2023
  • Ingår i: Aging Clinical and Experimental Research. - : Springer. - 1594-0667 .- 1720-8319. ; 35:11, s. 2463-2470
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Little is known about mental health following advanced cardiac procedures in the oldest patients. Aims To study changes in anxiety and depression from baseline to one- and six-month follow-up in older patients following transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). Methods Prospective cohort study of patients >= 80 years undergoing elective TAVI or SAVR in a tertiary university hospital. Anxiety and depression were assessed with the Hospital Anxiety and Depression Scale. Differences between TAVI/SAVR were analyzed using Welch's t test or chi-squared. Changes over time and group differences were established with longitudinal models using generalized least squares. Results In 143 patients (83.5 +/- 2.7 years), 46% (n = 65) received TAVI. Anxiety was identified in 11% of TAVI patients at baseline. One- and six-months later, percentages were 8% and 9%. In SAVR patients, 18% had baseline scores indicating anxiety. One and six-months later, percentages were 11% and 9%. Depression was identified in 15% of TAVI patients. One- and six-months later, percentages were 11% and 17%. At baseline, 11% of SAVR patients had scores indicating depression. One- and six-months after SAVR, percentages were 15% and 12%. Longitudinal analyses showed reductions (P < 0.001) in anxiety from baseline to one-month, and stable scores between one- and six-months for both treatment groups. There was no change over time for depression among treatment groups (P = 0.21). Discussion and conclusions SAVR or TAVI in patients >= 80 years was associated with anxiety reduction between baseline and follow-up. For depression, there was no evidence of change over time in either treatment group.
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33.
  • Eide, Leslie S. P., et al. (författare)
  • Delirium as a predictor of physical and cognitive function in individuals aged 80 and older after transcatheter aortic valve implantation or surgical aortic valve replacement
  • 2016
  • Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 64:6, s. 1178-1186
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To determine how development of delirium after surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) could predict activity of daily living (ADL) and instrumental ADLs (IADL) disability, cognitive function, and self-reported health in individuals aged 80 and older.Design: Prospective cohort study. Setting: Tertiary university hospital.Participants: Individuals aged 80 and older undergoing elective SAVR or TAVI (N = 136).Measurements: Delirium was assessed for 5 days using the Confusion Assessment Method. The Barthel Index, Nottingham Extended ADL Scale, and SF-12 were used to determine ADL and IADL ability and self-reported health at baseline and 1- and 6-month follow-up. Cognition was assessed using the Mini-Mental State Examination at baseline and 6-month follow-up.Results: Participants had lower IADL scores 1 month after SAVR than at baseline (baseline 58, 1 month: delirium 42, no delirium 50, P ≤.02), but scores had returned to baseline levels at 6 months. The Medical Outcomes Study 12-item Short-Form Health Survey (SF-12) Physical Component Summary (PCS) score was higher at 6-month follow-up (48) than at baseline (39), especially in participants who did not develop delirium (P <.001). No differences in other outcomes were found. Regression models suggest that delirium may help predict IADL disability 1 month after baseline (P ≤.07) but does not predict large differences in ADL disability, cognitive function, or SF-12-scores. Individuals who underwent TAVI and developed delirium had lower ADL (baseline 19, 1-month 16, P <.001) and IADL (baseline 49, 1-month 40, P =.003) scores at 1-month follow-up. SF-12 PCS score (baseline 30) increased from baseline to 1- (35, P =.04) and 6- (35, P =.02) month follow-up in individuals who underwent TAVI and did not develop delirium. Delirium after TAVI predicted greater ADL and IADL disability at 1-month but not at 6-month follow-up.Conclusion: Individuals who develop delirium after SAVR and TAVI have poorer short-term IADL function but do not seem to have long-term reductions in physical, mental, or self-reported health.
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34.
  • Eide, Leslie S. P., et al. (författare)
  • Readmissions and mortality in delirious versus non-delirious octogenarian patients after aortic valve therapy : A prospective cohort study
  • 2016
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 6:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To determine whether postoperative delirium predicts first-time readmissions and mortality in octogenarian patients within 180 days after aortic valve therapy with surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI), and to determine the most common diagnoses at readmission.Design: Prospective cohort study of patients undergoing elective SAVR or TAVI.Setting: Tertiary university hospital that performs all SAVRs and TAVIs in Western Norway.Participants: Patients 80+ years scheduled for SAVR or TAVI and willing to participate in the study were eligible. Those unable to speak Norwegian were excluded. Overall, 143 patients were included, and data from 136 are presented. Primary and secondary outcome measures: The primary outcome was a composite variable of time from discharge to first all-cause readmission or death. Secondary outcomes were all-cause first readmission alone and mortality within 180 days after discharge, and the primary diagnosis at discharge from first-time readmission. Delirium was assessed with the confusion assessment method. First-time readmissions, diagnoses and mortality were identified in hospital information registries.Results: Delirium was identified in 56% of patients. The effect of delirium on readmissions and mortality was greatest during the first 2 months after discharge (adjusted HR 2.9 (95% CI 1.5 to 5.7)). Of 30 first-time readmissions occurring within 30 days, 24 (80%) were patients who experienced delirium. 1 patient (nondelirium group) died within 30 days after therapy. Delirious patients comprised 35 (64%) of 55 first-time readmissions occurring within 180 days. Circulatory system diseases and injuries were common causes of first-time readmissions within 180 days in delirious patients. 8 patients died 180 days after the procedure; 6 (75%) of them experienced delirium. Conclusions: Delirium in octogenarians after aortic valve therapy might be a serious risk factor for postoperative morbidity and mortality. Cardiovascular disorders and injuries were associated with first-time readmissions in these patients.
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35.
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36.
  • Frantzen, Astri Tafjord, et al. (författare)
  • Frailty Status and Patient-Reported Outcomes in Octogenarians Following Transcatheter or Surgical Aortic Valve Replacement
  • 2021
  • Ingår i: Heart, Lung and Circulation. - : Elsevier. - 1443-9506 .- 1444-2892. ; 30:8, s. 1221-1231
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundFrailty status and patient-reported outcomes are especially pertinent in octogenarians following transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) to guide treatment decisions and promote patient-centred care.AimWe aimed to determine if frailty changed 6 months after aortic valve replacement (AVR) in octogenarians, and to describe changes in self-rated health according to frailty status in patients who underwent TAVI or SAVR.MethodIn a prospective cohort study, frailty and self-rated health were measured one day prior to and 6 months after AVR. Frailty status was measured with the Study of Osteoporotic Fracture index. Self-rated health was measured comprehensively with the disease-specific Minnesota Living with Heart Failure Questionnaire, the generic Medical Outcomes Study Short Form-12 questionnaire (SF-12), and two global questions from The World Health Organization Quality of Life Instrument Abbreviated.ResultsData were available for 143 consecutive patients (mean age 83 +/- 2.7 years, 57% women; 45% underwent TAVI). At baseline, 34% were robust, 27% prefrail, and 39% frail. Overall, there was no change in the distribution of frailty status 6 months after baseline (p=0.13). However, on an individual level 65 patients changed frailty status after AVR (40 patients improved and 25 declined). Improvement in frailty status was common in prefrail (33%; n=13) and frail patients (48%; n=27). Patients had improved self-rated health after AVR, with significant differences between frailty states both at baseline (SF-12 physical: 37.4 [robust], 33.1 [prefrail], 31.6 [frail], p=0.03); SF-12 mental: 51.9 [robust], 50.8 [prefrail], 44.5 [frail], p<0.001); and at the 6-month follow-up (SF-12 physical: 45.4 [robust], 38.3 [prefrail], 32.1 [frail], p<0.001); SF-12 mental: 54.9 [robust], 49.6 [prefrail], 46.8 [frail], p=0.002).ConclusionsAdvanced treatment performed in a high-risk population allowed people to improve their self-rated health. Although frailty is associated with poor self-rated health, frailty status does not equal negative outcomes. The frail patients were those who improved most in self-rated physical and mental health. They had the lowest baseline self-rated health scores and had therefore the most to gain.
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37.
  • Fritz, Josef, et al. (författare)
  • Body mass index, triglyceride-glucose index, and prostate cancer death : a mediation analysis in eight European cohorts
  • 2024
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 130, s. 308-316
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited.Methods: We included 259,884 men from eight European cohorts, with 11,760 incident PCa’s and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index.Results: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01–1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14–1.35, of which 28%; 4%–52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death.Conclusions: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.
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38.
  • Fritz, Josef, et al. (författare)
  • Body mass index, triglyceride-glucose index, and prostate cancer death : a mediation analysis in eight European cohorts
  • 2024
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 130:2, s. 308-316
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited.METHODS: We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index.RESULTS: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death.CONCLUSIONS: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.
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39.
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40.
  • Fålun, Nina, et al. (författare)
  • Patients’ goals, resources, and barriers to future change : A qualitative study of patient reflections at hospital discharge after myocardial infarction
  • 2016
  • Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press (OUP). - 1474-5151 .- 1873-1953. ; 15:7, s. 495-503
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial infarction (MI) patients may find it challenging to adhere to lifestyle advice and medications. Understanding motivational factors and barriers to change is crucial. However, empirical evidence on patients’ ability to effect lifestyle changes at the time of discharge is limited.Aim: The aim of this study was to identify at the time of hospital discharge the goals, resources, and barriers to future change in MI patients.Methods: We conducted a qualitative interview study with a purposive sample of 20 MI patients (eight women) in a cardiac department at a university hospital in Norway. All interviews were conducted before hospital discharge, transcribed verbatim, and analysed using qualitative content analysis.Findings: Three themes suggested that, at the time of discharge, patients’ views of their MI were complex and diverse. Patients were motivated to change their lifestyle and contemplated taking their life in new directions, adopting a change of life perspective. Frequently, patients struggled to understand the context of living with an MI, manage symptoms, and understand the precipitating causes of MI. There were also patients who wanted to maintain their present lifestyle and live as normal as possible. They just wanted to keep going.Conclusions and implications: There is a need for a different approach to communicating with MI patients at the time of discharge. Person-centred care that allows personal narratives to emerge may enable health-care professionals to offer more individualised guidance to MI patients that will help them cope with the everyday challenges they experience after discharge.
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41.
  • Fålun, Nina, et al. (författare)
  • Patients' reflections on prehospital symptom recognition and timely treatment of myocardial infarction
  • 2021
  • Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press. - 1474-5151 .- 1873-1953. ; 20:6, s. 526-533
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsEarly treatment is crucial to successful therapy in patients with acute myocardial infarction (MI). Prehospital delay is associated with increased morbidity and mortality. There is little empirical evidence of patients' reflections on prehospital symptoms of MI and timely treatment at the time of discharge from hospital. To explore patients' reflections on prehospital symptoms of MI and their experiences of interaction with local hospitals, general practitioners, and laypersons.Methods and resultsAn inductive explorative design with a qualitative method approach was used to conduct in-depth interviews of patients after confirmed MI. Twenty patients were purposefully selected based on age and gender. Face-to-face, semi-structured interviews were conducted prior to hospital discharge. The interviews were organized around a set of predetermined, open-ended questions, transcribed verbatim and analysed using qualitative content analysis. There were patients who acted upon severe symptoms of MI by seeking medical assistance. Patients commonly experienced that the time from the onset of symptoms to treatment posed a transitional challenge. They did not take subtle signs of MI seriously; they underestimated symptoms of MI and delayed seeking medical assistance. Patients frequently experienced that healthcare professionals did not take them seriously, as they struggled to gain access to healthcare services.ConclusionThis study highlights patients' unique experiences of the pathway from symptom onset to confirmed MI. Severe chest pain is associated with MI and triggers an immediate need for care. However, patients often underestimated moderate chest pain or subtle signs and symptoms of MI. Existing knowledge gaps concerning the misinterpretation of symptoms in primary care need to be addressed in order to reduce this clinical challenge.
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42.
  • Gullvåg, Marianne, et al. (författare)
  • Sleepless nights and sleepy days : a qualitative study exploring the experiences of patients with chronic heart failure and newly verified sleep-disordered breathing.
  • 2019
  • Ingår i: Scandinavian Journal of Caring Sciences. - : John Wiley & Sons. - 0283-9318 .- 1471-6712. ; 33:3, s. 750-759
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Sleep-disordered breathing, including obstructive sleep apnoea and central sleep apnoea, is a common disorder among patients with chronic heart failure. Obstructive sleep apnoea is often treated with continuous positive airway pressure, but central sleep apnoea lacks a clear treatment option. Knowledge of how sleep-disordered breathing is experienced (e.g. difficulties and care needs) and handled (e.g. self-care actions) by the patients is limited, but needed, to provide patient-centred care.AIM: To explore how newly verified sleep-disordered breathing is experienced by patients with chronic heart failure.METHODS: Data were collected through semi-structured interviews and analysed with qualitative content analysis. Seventeen participants (14 men, three women), mean age 60 years (range 41-80) diagnosed with chronic heart failure and objectively verified sleep-disordered breathing (nine obstructive, seven central and one mixed) were strategically selected from heart failure outpatient clinics at two Norwegian university hospitals.RESULTS: Patients with chronic heart failure and newly verified sleep-disordered breathing (SDB) described experiences of poor sleep that had consequences for their daily life and their partners. Different self-care strategies were revealed, but they were based on 'common sense' and were not evidence-based. The awareness of having SDB was varied; for some, it gave an explanation to their trouble while others were surprised by the finding.CONCLUSION: Patients with chronic heart failure and sleep-disordered breathing experienced reduced sleep quality, influencing their daily life. Possible underlying causes of disrupted sleep, such as sleep-disordered breathing, should be identified to establish proper patient-centred treatment strategies. There is a need for new strategies to approach patients with chronic heart failure (i.e. those with central sleep apnoea) who are not subject to continuous positive airway pressure treatment for their sleep-disordered breathing.
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43.
  • Holm, Marianne Saetrang, et al. (författare)
  • The patient experience of in-hospital telemetry monitoring : a qualitative analysis
  • 2024
  • Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press. - 1474-5151 .- 1873-1953. ; 23:3, s. 258-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims In-hospital telemetry monitoring has been an integrated part of arrhythmia monitoring for decades. A substantial proportion of patients require arrhythmia monitoring during stays in non-intensive care units. However, studies exploring patients' experiences of telemetry monitoring are scarce. Therefore, the aim was to explore and describe patients' experiences of in-hospital telemetry monitoring in a non-intensive care setting.Methods and results Twenty face-to-face, semi-structured interviews were conducted. Interviews were conducted before discharge at two university hospitals in Norway. The patients were purposively sampled, resulting in a well-balanced population comprising 11 men and nine women, mean age 62 years (range 25-83). Average monitoring time was 9 days (range 3-14). Data were audiotaped, transcribed verbatim, and coded using NVivo software. Qualitative content analysis using an inductive approach was performed. Patients expressed a need for individualized information during telemetry monitoring. Their feelings of safety were related to responses from nurses from the central monitoring station when alarms from the telemetry were triggered. Despite perceived physical restrictions and psychological limitations associated with telemetry monitoring, they found monitoring to be beneficial because it facilitated the diagnosis of arrhythmia. Moreover, they expressed a need for improvements in wearable monitoring equipment. Patients expressed ambivalent feelings about discontinuing the telemetry and their readiness for discharge.Conclusion Patients need individualized information about the results of their telemetry monitoring in order to better understand the arrhythmia management and to increase their experience of safety after discharge. The limitations patients experienced should be taken into consideration in further upgrades of telemetry monitoring equipment.
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44.
  • Instenes, Irene, et al. (författare)
  • 'I hope you get normal again' : an explorative study on how delirious octogenarian patients experience their interactions with healthcare professionals and relatives after aortic valve therapy
  • 2019
  • Ingår i: European Journal of Cardiovascular Nursing. - : Sage Publications. - 1474-5151 .- 1873-1953. ; 18:3, s. 224-233
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Delirium affects nearly half of octogenarian patients after aortic valve replacement, resulting in impaired cognition, reduced awareness and hallucinations. Although healthcare professionals and relatives are often present during episodes, the nature of interactions with them is scarcely studied, and little is known about their long-term experiences. Purpose: The purpose of this study was to explore and describe how octogenarian patients with post-aortic valve replacement delirium experience interactions with healthcare professionals and relatives within the first year and four years later. Method: An explorative design with qualitative content analysis was used. Delirium was assessed for five consecutive days after aortic valve replacement using the Confusion Assessment Method. Delirious patients (n=10) were interviewed 6-12 months post-discharge and four years later (n=5). We used an inductive approach to identify themes in transcribed interviews. Findings: An overarching theme emerged: 'Healthcare professionals' and relatives' responses made a considerable impact on the delirium experience postoperatively and in a long-term'. Three sub-themes described the patients' experiences: 'the need for close supportive care', 'disrespectful behaviour created a barrier' and 'insensitive comments made lasting impressions'. Having healthcare professionals and relatives nearby made the patients feel secure, while lack of attention elevated patients' emotional distress. Four years later, patients clearly recalled negative comments and unsupportive actions in their delirious state. Conclusions: Healthcare professionals and relatives have an essential role in the aortic valve replacement recovery process. Inconsiderate behaviour directed at older patients in delirium elevates distress and has long-term implications. Supportive care focused on maintaining the patients' dignity and integrity is vital.
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45.
  • Instenes, Irene, et al. (författare)
  • 'When age is not a barrier' : an explorative study of nonagenarian patients' experiences of undergoing percutaneous coronary intervention
  • 2024
  • Ingår i: European Journal of Cardiovascular Nursing. - : Oxford University Press. - 1474-5151 .- 1873-1953.
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The recent rise in the number of nonagenarians (age >= 90 years) undergoing percutaneous coronary intervention (PCI) has revealed gaps in research, in particular on patients' experiences. Therefore, the aim of the study was to explore and describe nonagenarians' internal resources and their experiences of the in-hospital pathway.Methods and results Nineteen nonagenarian patients (women n = 9), mean age 91 years, 9 acutely, and 10 electively treated, were consecutively enrolled from a tertiary university hospital from June 2021 to February 2023. In-depth interviews were conducted during hospitalization, audiotaped and transcribed. The interviews were analysed using qualitative content analysis. Three sub-themes emerged from the nonagenarians' experiences with the PCI treatment trajectory: (i) Taking lifelong responsibility for own physical and mental health describes a population striving to live a healthy life and to stay independent. Physical and mental activities including healthy food choices had been an integral aspect of their lives from early childhood. (ii) Individual internal resources influenced the PCI pathway describes how their internal resources were used, from actively engaging in the decision-making process to withstanding discomfort during the PCI procedure. (iii) The post-PCI pathway was multifaceted describes a short stay at the cardiac ward with individual post-procedural experiences, close monitoring, and preparation for discharge including cardiac rehabilitation.Conclusion Nonagenarians undergoing PCI demonstrated a personal incentive to stay healthy and independent. Their internal resources of independence, stoicism, and resilience were used during their in-hospital stay contributing to a successful PCI procedure. Individual cardiac rehabilitation strategies were highlighted after discharge from hospital. Graphical Abstract
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46.
  • Kitahara, Cari M., et al. (författare)
  • Maternal health, in-utero, and perinatal exposures and risk of thyroid cancer in offspring : a Nordic population-based nested case-control study
  • 2021
  • Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 9:2, s. 94-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Thyroid cancer tends to be diagnosed at a younger age (median age 51 years) compared with most other malignancies (such as breast cancer [62 years] or lung cancer [71 years]). The incidence of thyroid cancer is higher in women than men diagnosed from early adolescence. However, few in-utero and early life risk exposures associated with increased risk of thyroid cancer have been identified. Methods In this population-based nested case-control study we used registry data from four Nordic countries to assess thyroid cancer risk in offspring in relation to maternal medical history, pregnancy complications, and birth characteristics. Patient with thyroid cancer (cases) were individuals born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway, or 1973 to 2014 in Sweden. Each case was matched with up to ten individuals without thyroid cancer (controls) based on birth year, sex, country, and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than non-melanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Cases and matched controls had to reside in the country of birth at the time of thyroid cancer diagnosis. Conditional logistic regression models were used to calculate odds ratios (ORs) with 95% CIs. Findings Of the 2437 cases, 1967 (81.4%) had papillary carcinomas, 1880 (77.1%) were women, and 1384 (56.7%) were diagnosed before age 30 years (range 0-48). Higher birth weight (OR per kg 1.14 [95% CI 1.05-1.23]) and congenital hypothyroidism (4.55 [1.58-13.08]); maternal diabetes before pregnancy (OR 1.69 [0.98-2.93]) and postpartum haemorrhage (OR 1.28 [1.06-1.55]); and (from registry data in Denmark) maternal hypothyroidism (18.12 [10.52-31.20]), hyperthyroidism (11.91 [6.77-20.94]), goiter (67.36 [39.89-113.76]), and benign thyroid neoplasms (22.50 [6.93-73.06]) were each associated with an increased risk of thyroid cancer in offspring. Interpretation In-utero exposures, particularly those related to maternal thyroid disorders, might have a long-term influence on thyroid cancer risk in offspring. 
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47.
  • Kitahara, Cari M., et al. (författare)
  • Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk : A Nordic Population-Based Registry Study
  • 2023
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 192:1, s. 70-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer >= 2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.
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48.
  • Kjersem, Janne B, et al. (författare)
  • Let-7 miRNA-binding site polymorphism in the KRAS 3`UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/- cetuximab.
  • 2012
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 12:1, s. 534-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Recent studies have reported associations between a variant allele in a let-7 microRNA complementary site (LCS6) within the 3 untranslated region (3 UTR) of KRAS (rs61764370) and clinical outcome in metastatic colorectal cancer (mCRC) patients receiving cetuximab. The variant allele has also been associated with increased cancer risk. We aimed to reveal the incidence of the variant allele in a colorectal cancer screening population and to investigate the clinical relevance of the variant allele in mCRC patients treated with 1st line 5-fluorouracil-oxaliplatin (Nordic FLOX) +/- cetuximab.METHODS: The feasibility of the variant allele as a risk factor for CRC was investigated by comparing the LCS6 gene frequencies in 197 CRC patients, 1060 individuals with colorectal polyps, and 358 healthy controls. The relationship between clinical outcome and LCS6 genotype was analyzed in 180 mCRC patients receiving Nordic FLOX and 355 patients receiving Nordic FLOX + cetuximab in the NORDIC-VII trial (NCT00145314). RESULTS: LCS6 frequencies did not vary between CRC patients (23%), individuals with polyps (20%), and healthy controls (20%) (P=0.50). No statistically significant differences were demonstrated in the NORDIC-VII cohort even if numerically increased progression-free survival (PFS) and overall survival (OS) were found in patients with the LCS6 variant allele (8.5 (95% CI: 7.3-9.7 months) versus 7.8 months (95% CI: 7.4-8.3 months), P=0.16 and 23.5 (95% CI: 21.6-25.4 months) versus 19.5 months (95% CI: 17.8-21.2 months), P=0.31, respectively). Addition of cetuximab seemed to improve response rate more in variant carriers than in wild-type carriers (from 35% to 57% versus 44% to 47%), however the difference was not statistically significant (interaction P = 0.16).CONCLUSIONS: The LCS6 variant allele does not seem to be a risk factor for development of colorectal polyps or CRC. No statistically significant effect of the LCS6 variant allele on response rate, PFS or OS was found in mCRC patients treated with 1st line 5-fluorouracil-oxaliplatin +/- cetuximab.
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49.
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50.
  • Løvvik, Tone S., et al. (författare)
  • Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2) : a randomised, double-blind, placebo-controlled trial
  • 2019
  • Ingår i: The Lancet Diabetes and Endocrinology. - : Elsevier. - 2213-8587 .- 2213-8595. ; 7:4, s. 256-266
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy complications. Epi-analysis of two previous randomised controlled trials that compared metformin with placebo during pregnancy in women with PCOS showed a significant reduction in late miscarriages and preterm births in the metformin group. The aim of this third randomised trial (PregMet2) was to test the hypothesis that metformin prevents late miscarriage and preterm birth in women with PCOS.Methods: PregMet2 was a randomised, placebo-controlled, double-blind, multicentre trial done at 14 hospitals in Norway, Sweden, and Iceland. Singleton pregnant women with PCOS aged 18-45 years were eligible for inclusion. After receiving information about the study at their first antenatal visit or from the internet, women signed up individually to participate in the study. Participants were randomly assigned (1: 1) to receive metformin or placebo by computer-generated random numbers. Randomisation was in blocks of ten for each country and centre; the first block had a random size between one and ten to assure masking. Participants were assigned to receive oral metformin 500 mg twice daily or placebo during the first week of treatment, which increased to 1000 mg twice daily or placebo from week 2 until delivery. Placebo tablets and metformin tablets were identical and participants and study personnel were masked to treatment allocation. The primary outcome was the composite incidence of late miscarriage (between week 13 and week 22 and 6 days) and preterm birth (between week 23 and week 36 and 6 days), analysed in the intention-to-treat population. Secondary endpoints included the incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit. We also did a post-hoc individual participant data analysis of pregnancy outcomes, pooling data from the two previous trials with the present study. The study was registered with ClinicalTrials. gov, number NCT01587378, and EudraCT, number 2011-002203-15.Findings: The study took place between Oct 19, 2012, and Sept 1, 2017. We randomly assigned 487 women to metformin (n=244) or placebo (n=243). In the intention-to-treat analysis, our composite primary outcome of late miscarriage and preterm birth occurred in 12 (5%) of 238 women in the metformin group and 23 (10%) of 240 women in the placebo group (odds ratio [OR] 0.50, 95% CI 0.22- 1.08; p = 0.08). We found no significant differences for our secondary endpoints, including incidence of gestational diabetes (60 [25%] of 238 women in the metformin group vs 57 [24%] of 240 women in the placebo group; OR 1.09, 95% CI 0.69-1.66; p=0.75). We noted no substantial between-group differences in serious adverse events in either mothers or offspring, and no serious adverse events were considered drug-related by principal investigators. In the post-hoc pooled analysis of individual participant data from the present trial and two previous trials, 18 (5%) of 397 women had late miscarriage or preterm delivery in the metformin group ]compared with 40 (10%) of 399 women in the placebo group (OR 0.43, 95% CI 0.23-0.79; p=0.004).Interpretation: In pregnant women with PCOS, metformin treatment from the late first trimester until delivery might reduce the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes.
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