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Sökning: WFRF:(Henriksen M. R.)

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  • Middeldorp, Christel M., et al. (författare)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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  • Barregård, Lars, 1948, et al. (författare)
  • Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
  • 2013
  • Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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  • Signori, A, et al. (författare)
  • Heterogeneity on long-term disability trajectories in patients with secondary progressive MS: a latent class analysis from Big MS Data network
  • 2023
  • Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 94:1, s. 23-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time.MethodsAll patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3–4.ResultsA total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria.ConclusionsContrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.
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  • Muysoms, F. E., et al. (författare)
  • European Hernia Society guidelines on the closure of abdominal wall incisions
  • 2015
  • Ingår i: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 19:1, s. 1-24
  • Forskningsöversikt (refereegranskat)abstract
    • Background The material and the surgical technique used to close an abdominal wall incision are important determinants of the risk of developing an incisional hernia. Optimising closure of abdominal wall incisions holds a potential to prevent patients suffering from incisional hernias and for important costs savings in health care. Methods The European Hernia Society formed a Guidelines Development Group to provide guidelines for all surgical specialists who perform abdominal incisions in adult patients on the materials and methods used to close the abdominal wall. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and methodological guidance was taken from Scottish Intercollegiate Guidelines Network (SIGN). The literature search included publications up to April 2014. The guidelines were written using the AGREE II instrument. An update of these guidelines is planned for 2017. Results For many of the Key Questions that were studied no high quality data was detected. Therefore, some strong recommendations could be made but, for many Key Questions only weak recommendations or no recommendation could be made due to lack of sufficient evidence. Recommendations To decrease the incidence of incisional hernias it is strongly recommended to utilise a non-midline approach to a laparotomy whenever possible. For elective midline incisions, it is strongly recommended to perform a continuous suturing technique and to avoid the use of rapidly absorbable sutures. It is suggested using a slowly absorbable monofilament suture in a single layer aponeurotic closure technique without separate closure of the peritoneum. A small bites technique with a suture to wound length (SL/WL) ratio at least 4/1 is the current recommended method of fascial closure. Currently, no recommendations can be given on the optimal technique to close emergency laparotomy incisions. Prophylactic mesh augmentation appears effective and safe and can be suggested in high-risk patients, like aortic aneurysm surgery and obese patients. For laparoscopic surgery, it is suggested using the smallest trocar size adequate for the procedure and closure of the fascial defect if trocars larger or equal to 10 mm are used. For single incision laparoscopic surgery, we suggest meticulous closure of the fascial incision to avoid an increased risk of incisional hernias.
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  • Svendsen, JI, et al. (författare)
  • Late quaternary ice sheet history of northern Eurasia
  • 2004
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 23:11-13, s. 1229-1271
  • Forskningsöversikt (refereegranskat)abstract
    • The maximum limits of the Eurasian ice sheets during four glaciations have been reconstructed: (1) the Late Saalian (> 140 ka), (2) the Early Weichselian (100-80 ka), (3) the Middle Weichselian (60-50 ka) and (4) the Late Weichselian (25-15 ka). The reconstructed ice limits are based on satellite data and aerial photographs combined with geological field investigations in Russia and Siberia, and with marine seismic- and sediment core data. The Barents-Kara Ice Sheet got progressively smaller during each glaciation, whereas the dimensions of the Scandinavian Ice Sheet increased. During the last Ice Age the Barents-Kara Ice Sheet attained its maximum size as early as 90-80,000 years ago when the ice front reached far onto the continent. A regrowth of the ice sheets occurred during the early Middle Weichselian, culminating about 60-50,000 years ago. During the Late Weichselian the Barents-Kara Ice Sheet did not reach the mainland east of the Kanin Peninsula, with the exception of the NW fringe of Taimyr. A numerical ice-sheet model, forced by global sea level and solar changes, was run through the full Weichselian glacial cycle. The modeling results are roughly compatible with the geological record of ice growth, but the model underpredicts the glaciations in the Eurasian Arctic during the Early and Middle Weichselian. One reason for this is that the climate in the Eurasian Arctic was not as dry then as during the Late Weichselian glacial maximum.
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  • Chalise, P., et al. (författare)
  • Addressing Domestic Violence in Antenatal Care Environments in Nepal (ADVANCE) - study protocol for a randomized controlled trial evaluating a video intervention on domestic violence among pregnant women
  • 2023
  • Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDomestic violence (DV) prior to, and during pregnancy is associated with increased risks for morbidity and mortality. As pregnant women routinely attend antenatal care this environment can be used to offer support to women experiencing DV. We have developed a video intervention that focuses on the use of behavioral coping strategies, particularly regarding disclosure of DV experiences. The effectiveness of this intervention will be evaluated through a randomized controlled trial (RCT) and a concurrent process evaluation.MethodsAll pregnant women between 12-22 weeks of gestation attending routine antenatal care at two tertiary level hospitals in Nepal are invited to participate. DV is measured using the Nepalese version of the Abuse Assessment Screen (N-AAS). Additionally, we measure participants' mental health, use of coping strategies, physical activity, and food security through a Color-coded Audio Computer Assisted Self Interview (C-ACASI). Irrespective of DV status, women are randomized into the intervention or control arm using a computer-generated randomization program. The intervention arm views a short video providing information on DV, safety improving actions women can take with an emphasis on disclosing the violence to a trusted person along with utilizing helplines available in Nepal. The control group watches a video on maintaining a healthy pregnancy and when to seek healthcare. The primary outcome is the proportion of women disclosing their DV status to someone. Secondary outcomes are symptoms of anxiety and depression, coping strategies, the use of safety measures and attitudes towards acceptance of abuse. Follow-up is conducted after 32 weeks of gestation, where both the intervention and control group participants view the intervention video after completing the follow-up questionnaire. Additionally, a mixed methods process evaluation of the intervention will be carried out to explore factors influencing the acceptability of the intervention and the disclosure of DV, including a review of project documents, individual interviews, and focus group discussions with members of the research team, healthcare providers, and participants.DiscussionThis study will provide evidence on whether pregnant women attending regular antenatal visits can enhance their safety by disclosing their experiences of violence to a trusted person after receiving a video intervention.Trial registrationThe study is registered in ClinicalTrial.gov with identifier NCT05199935.
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  • Gudbergsen, H., et al. (författare)
  • Weight loss is effective for symptomatic relief in obese subjects with knee osteoarthritis independently of joint damage severity assessed by high-field MRI and radiography
  • 2012
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 20:6, s. 495-502
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: With an increasing prevalence of older and obese citizens, the problems of knee osteoarthritis (KOA) will escalate. Weight loss is recommended for obese KOA patients and in a majority of cases this leads to symptomatic relief. We hypothesized that pre-treatment structural status of the knee joint, assessed by radiographs, 1.5 T magnetic resonance imaging (MRI) and knee-joint alignment, may influence the symptomatic changes following a significant weight reduction. Design: Patients were recruited from a Department of Rheumatology. Eligibility criteria were age above 50 years, body mass index >= 30 kg/m(2), primary KOA diagnosed according to the American College of Rheumatology (ACR) criteria and having verified structural damage. Patients underwent a 16 weeks dietary programme with formula products and counselling. MRI and radiographs of the most symptomatic knee were obtained at baseline and assessed for structural damage using the Boston-Leeds Osteoarthritis of the Knee Score, minimum joint space width and Kellgren Lawrence score. Imaging variables, muscle strength and degree of alignment, were examined as predictors of changes in Knee Osteoarthritis Outcome Score (KOOS) and Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) - Osteoarthritis Research Society International (OARSI) Responder Criterion. Results: Structural damage at baseline assessed by imaging, muscle strength or knee-joint alignment showed no statistically significant association to changes in KOOS pain and function in daily living (r <= 0.13; P > 0.05) or the OMERACT-OARSI Responder Criterion (OR 0.48-1.68; P-values > 0.13). Conclusions: Presence of joint damage did not preclude symptomatic relief following a clinically relevant weight loss in older obese patients with KOA. Neither muscle strength nor knee-joint alignment was associated with the degree of symptomatic relief. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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  • Henriksen, N. A., et al. (författare)
  • EHS and AHS guidelines for treatment of primary ventral hernias in rare locations or special circumstances
  • 2020
  • Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 4:2, s. 342-353
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Rare locations of hernias, as well as primary ventral hernias under certain circumstances (cirrhosis, dialysis, rectus diastasis, subsequent pregnancy), might be technically challenging. The aim was to identify situations where the treatment strategy might deviate from routine management. METHODS: The guideline group consisted of surgeons from the European and Americas Hernia Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in formulating the recommendations. The Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists were used to evaluate the quality of full-text papers. A systematic literature search was performed on 1 May 2018 and updated 1 February 2019. The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was followed. RESULTS: Literature was limited in quantity and quality. A majority of the recommendations were graded as weak, based on low quality of evidence. In patients with cirrhosis or on dialysis, a preperitoneal mesh repair is suggested. Subsequent pregnancy is a risk factor for recurrence. Repair should be postponed until after the last pregnancy. For patients with a concomitant rectus diastasis or those with a Spigelian or lumbar hernia, no recommendation could be made for treatment strategy owing to lack of evidence. CONCLUSION: This is the first European and American guideline on the treatment of umbilical and epigastric hernias in patients with special conditions, including Spigelian and lumbar hernias. All recommendations were weak owing to a lack of evidence. Further studies are needed on patients with rectus diastasis, Spigelian and lumbar hernias.
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  • Henriksen, N. A., et al. (författare)
  • Guidelines for treatment of umbilical and epigastric hernias from the European Hernia Society and Americas Hernia Society
  • 2020
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 107:3, s. 171-190
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Umbilical and epigastric hernia repairs are frequently performed surgical procedures with an expected low complication rate. Nevertheless, the optimal method of repair with best short- and long-term outcomes remains debatable. The aim was to develop guidelines for the treatment of umbilical and epigastric hernias. Methods: The guideline group consisted of surgeons from Europe and North America including members from the European Hernia Society and the Americas Hernia Society. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, the Scottish Intercollegiate Guidelines Network (SIGN) critical appraisal checklists, and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were used. A systematic literature search was done on 1 May 2018, and updated on 1 February 2019. Results: Literature reporting specifically on umbilical and epigastric hernias was limited in quantity and quality, resulting in a majority of the recommendations being graded as weak, based on low-quality evidence. The main recommendation was to use mesh for repair of umbilical and epigastric hernias to reduce the recurrence rate. Most umbilical and epigastric hernias may be repaired by an open approach with a preperitoneal flat mesh. A laparoscopic approach may be considered if the hernia defect is large, or if the patient has an increased risk of wound morbidity. Conclusion: This is the first European and American guideline on the treatment of umbilical and epigastric hernias. It is recommended that symptomatic umbilical and epigastric hernias are repaired by an open approach with a preperitoneal flat mesh.
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  • Bärebring, Linnea, et al. (författare)
  • Use of bioelectrical impedance analysis to monitor changes in fat-free mass during recovery from colorectal cancer– a validation study
  • 2020
  • Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 40, s. 201-207
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & aims: Although previous research show high correlation between fat-free mass (FFM) measured by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), the validity of BIA to track longitudinal changes in FFM is uncertain. Thus, the aim of this study was to validate the ability of BIA to assess changes in FFM during 6 months of recovery from non-metastatic colorectal cancer (CRC). Methods: A total of 136 women and men (50–80 years) with stage I-III CRC and a wide range of baseline FFM (35.7–73.5 kg) were included in the study. Body composition was measured at study baseline within 2–9 months of surgery and again 6 months later. Whole-body BIA FFM estimates (FFMBIA) were calculated using three different equations (manufacturer's, Schols' and Gray's) before comparison to FFM estimates obtained by DXA (FFMDXA). Results: Correlation between changes in FFMBIA and FFMDXA was intermediate regardless of equation (r ≈ 0.6). The difference in change of FFMBIA was significant compared to FFMDXA, using all three equations and BIA overestimated both loss and gain. However, BIA showed 100% sensitivity and about 90% specificity to identify individuals with ≥5% loss in FFM, using all three equations. Sensitivity of FFMBIA to detect a smaller loss of FFM (60–76%) or a gain in FFM of ≥5% (33–62%) was poor. Conclusion: In a well-nourished population of non-metastatic CRC patients, a single-frequency whole-body BIA device yielded imprecise data on changes in FFM, regardless of equation. BIA is thus not a valid option for quantifying changes in FFM in individuals. However, BIA could be used to identify patients with loss in FFM ≥5% in this population. The validity of BIA to monitor changes in FFM warrants further investigation before implementation in clinical praxis. © 2020 The Author(s)
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  • Flachenecker, P, et al. (författare)
  • Multiple sclerosis registries in Europe - results of a systematic survey
  • 2014
  • Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:11, s. 1523-1532
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. Methods: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries’ leaders, followed by telephone interviews with them. Results: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology ( n=10), long-term therapy outcome ( n=8), healthcare research ( n=9) and support/basis for clinical trials ( n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients’ perspectives were only collected in six registries. Conclusions: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.
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  • Henriksen, M., et al. (författare)
  • Is increased joint loading detrimental to obese patients with knee osteoarthritis? A secondary data analysis from a randomized trial
  • 2013
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:12, s. 1865-1875
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA). Methods: Data from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into 'Unloaders' (participants that reduced joint loads) and 'Loaders' (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period. Results: 157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: 2.4 KOOS points [95% CI 6.8:1.91) and cartilage loss (group difference: 0.06 BLOKS points [95% CI 0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders. Conclusion: For obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads. Clinicaltrials.gov: NCT00655941. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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  • Iaffaldano, P, et al. (författare)
  • Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network
  • 2021
  • Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 27:10, s. 1543-1555
  • Tidskriftsartikel (refereegranskat)abstract
    • The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined. Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network. Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference. Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( p < 0.0004) for the first quintile patients’ group. Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
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  • Jorgensen, A. A., et al. (författare)
  • Petabit-per-second data transmission using a chip-scale microcomb ring resonator source
  • 2022
  • Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 16:11, s. 798-802
  • Tidskriftsartikel (refereegranskat)abstract
    • Optical fibre communication is the backbone of the internet. As essential core technologies are approaching their limits of size, speed and energy-efficiency, there is a need for new technologies that offer further scaling of data transmission capacity. Here we show that a single optical frequency-comb source based on a silicon nitride ring resonator supports data capacities in the petabit-per-second regime. We experimentally demonstrate transmission of 1.84 Pbit s–1 over a 37-core, 7.9-km-long fibre using 223 wavelength channels derived from a single microcomb ring resonator producing a stabilized dark-pulse Kerr frequency comb. We also present a theoretical analysis that indicates that a single, chip-scale light source should be able to support 100 Pbit s–1 in massively parallel space-and-wavelength multiplexed data transmission systems. Our findings could mark a shift in the design of future communication systems, targeting device-efficient transmitters and receivers.
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22.
  • Kong, D., et al. (författare)
  • Single Dark-Pulse Kerr Comb Supporting 1.84 Pbit/s Transmission over 37-Core Fiber
  • 2020
  • Ingår i: Conference Proceedings - Lasers and Electro-Optics Society Annual Meeting-LEOS. - 1092-8081. ; 2020-May
  • Konferensbidrag (refereegranskat)abstract
    • We show that a single dark-pulse Kerr comb can generate high enough OSNR to carry 1.84 Pbit/s data, achieved by 223 WDM spectral lines modulated with 32-Gbaud, SNR-adapted probabilistically shaped DP-QAM, over a 37-core fiber.
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  • Pålhagen, Sven, et al. (författare)
  • Rufinamide : A double-blind, placebo-controlled proof of principle trial in patients with epilepsy
  • 2001
  • Ingår i: Epilepsy Research. - 0920-1211 .- 1872-6844. ; 43:2, s. 115-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. Methods: Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures were enrolled in this 28-day double-blind, placebo-controlled, weekly rising dose (400-1600 mg/day) trial. PK profiles were obtained after administration of single-dose rufinamide prior to and after the Double-blind phase. Results: In the evaluable patient population, seizure frequency decreased by 41% in the rufinamide group and increased by 52% in the placebo group (P = 0.040). Thirty-nine percent (39%) of rufinamide-treated and 16% of placebo-treated patients experienced reduction in seizure frequency of at least 50% relative to baseline (P = 0.096). Safety: Treatment-emergent adverse events (AEs) consisted mainly of neurologic signs and symptoms commonly associated with antiepileptic drugs (AEDs). Pharmacokinetics: At steady state, rufinamide reached a peak plasma concentration with a mean time (Tmax) of 3.4 h and a mean half-life (t1/2) of 7.3 h. No autoinduction of rufinamide metabolism occurred. Rufinamide did not influence the plasma concentration of carbamazepine, phenytoin or valproate when added to these single AED regimens. Conclusion: Rufinamide has been shown, in this proof of principle trial, to be safe and effective in reducing seizure frequency in epileptic patients with no relevant influence on the metabolism of other AEDs. © 2001 Elsevier Science B.V.
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  • Christensen, Robin, et al. (författare)
  • Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve-Month Randomized Controlled Trial 1
  • 2015
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 67:5, s. 640-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or "no attention" (C; control group). Methods. We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. Results. Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). Conclusion. A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.
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32.
  • Odin, Per, et al. (författare)
  • Viewpoint and practical recommendations from a movement disorder specialist panel on objective measurement in the clinical management of Parkinson's disease
  • 2018
  • Ingår i: Npj Parkinson's Disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Motor aspects of Parkinson's disease, such as fluctuations and dyskinesia, can be reliably evaluated using a variety of "wearable" technologies, but practical guidance on objective measurement (OM) and the optimum use of these devices is lacking. Therefore, as a first step, a panel of movement disorder specialists met to provide guidance on how OM could be assessed and incorporated into clinical guidelines. A key aspect of the incorporation of OM into the management of Parkinson's disease (PD) is defining cutoff values that separate "controlled" from "uncontrolled" symptoms that can be modified by therapy and that relate to an outcome that is relevant to the person with PD (such as quality of life). Defining cutoffs by consensus, which can be subsequently tested and refined, is the first step to optimizing OM in the management of PD. OM should be used by all clinicians that treat people with PD but the least experienced may find the most value, but this requires guidance from experts to allow non-experts to apply guidelines. While evidence is gained for devices that produce OM, expert opinion is needed to supplement the evidence base.
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33.
  • Oskarsson, T., et al. (författare)
  • Osteoporotic Fractures in Childhood Cancer Survivors - ALICCS Cohort Study
  • 2018
  • Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:Suppl.2, s. S693-S694
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background/Objectives: Children and adolescents undergoing treatment for cancer are exposed to multiple factors that impact the development of peak bone mass and bone quality. The aims of this study were to examine the risks and cumulative incidence of osteoporotic fractures in childhood cancer survivors and identify subgroups at higher risk.Design/Methods: In the national cancer registries of Denmark, Finland, Iceland and Sweden we identified patients diagnosed with cancer before 20 years of age from the start of registration in the 1940s and 1950s through 2008. We compared 26.334 one‐year survivors with a cohort of 162.372 age‐ and sex‐matched population comparison subjects selected from the national population registries. With data derived from national hospital registries we estimated the standardized hospitalization rate ratios (SHRR) and the mean cumulative count (MCC) of hospital admissions for osteoporotic fractures. To identify subgroups at risk we used Cox regression models to generate hazard ratios (HR) for osteoporotic fractures. Death and new cancer were treated as competing risks.Results: The estimated SHRR for the first osteoporotic fracture was 1.41 (95% CI; 1.27‐1.58) but the MCC for recurrent osteoporotic fractures did not differ between the survivors and the comparison group. The SHRR for isolated hip fractures was 2.90 (2.32‐3.63). The adjusted HR for osteoporotic fracture as the first event was 1.53 (1.09‐2.16) if cancer was diagnosed 15‐19 years and 2.10 (1.48‐2.98) for long‐term survivors of CNS tumors. Survivors 15‐19 years at cancer diagnosis and long‐term survivors of CNS tumors were also at higher risk of experiencing a second fracture, HR 3.29 (1.65‐6.55) and HR 2.71 (1.45‐5.05), respectively.Conclusions: Childhood cancer survivors are at higher risk of being hospitalized for osteoporotic fractures but the burden of recurrent fractures is not higher. For subgroups at risk, surveillance of bone health and measures to increase bone strength and prevent fractures should be encouraged.
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34.
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35.
  • Sorensen, PS, et al. (författare)
  • Occurrence of antibodies against natalizumab in relapsing multiple sclerosis patients treated with natalizumab
  • 2011
  • Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 17:9, s. 1074-1078
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In the clinical trials about 9% of natalizumab treated multiple sclerosis (MS) patients generated anti-natalizumab antibodies, of which 6% were persistent and 3% transient. The occurrence of antibodies reduced serum levels of natalizumab, decreased bio-efficacy, and abrogated the therapeutic efficacy. Objective: The objective was to assess the frequency of anti-natalizumab antibodies in an unselected cohort of patients from four different countries. Methods: We measured anti-natalizumab antibodies in a large cohort of 4881 unselected patients from four MS centres that systematically measured antibodies in patients treated with natalizumab. We applied the same ELISA assay developed by Biogen Idec and used in the pivotal trials of natalizumab. Results: Antibodies occurred in 4.5% (95% confidence interval, CI: 4.0–5.1%) of the patients, and were persistent in 3.5% (95% CI: 3.0–4.0%) and transient in 1.0% (95% CI: 0.7–1.3%) of the patients. The frequencies of permanently antibody positive patients did not show statistically significant differences between the four centres, whereas the frequencies of transiently antibody positive patients showed some variations. Conclusion: The frequencies of antibodies appeared to be of the same magnitude in the four centres, but might be less than in the pivotal studies of natalizumab.
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36.
  • Tegner, H., et al. (författare)
  • The effect of graded activity and pain education (GAPE): an early post-surgical rehabilitation programme after lumbar spinal fusion-study protocol for a randomized controlled trial
  • 2020
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPatients with chronic low back pain undergoing lumbar spinal fusion (LSF) are physically inactive and thereby at risk of poor health. Barriers to being physically active need to be acknowledged in post-surgical rehabilitation. The primary objective of this randomized controlled trial (RCT) is to examine the effect of an early active intervention consisting of graded activity and pain education (GAPE) on sedentary behaviour in a population of patients undergoing LSF. The secondary objective is to examine the effect of GAPE on disability, pain, fear of movement, self-efficacy for exercise, and health-related quality of life.MethodsThe study is an RCT planned to include 144 patients undergoing LSF at 1-2 levels for low back pain caused by degeneration of the lumbar spine. The patients will be randomly assigned to receive either usual care or usual care plus GAPE. GAPE consists of nine individual physiotherapist-guided sessions over a 10-week period. The overall purpose is to reduce sedentary behaviour, by educating the patient about pain and, based on a cognitive behavioural perspective, gradually strengthen the patient's self-efficacy to be physically active and reduce fear of movement. The physiotherapist will plan the intervention in collaboration with the patient. Based on a semi-structured interview and observations of the patient in their home, they will set individually functional goals. The primary outcome will be a reduction in sedentary behaviour, measured by an accelerometer at baseline (pre-surgery) and at 3 and 12months post-surgery. Secondary outcomes will include disability, pain, fear of movement, self-efficacy for exercise, and quality of life. Secondary outcome data will be collected at baseline (pre-surgery) and at 3, 6 and 12months post-surgery.DiscussionWe hypothesize that, compared with the "usual care group", GAPE will primarily lead to a significant reduction in sedentary behaviour, and secondarily a reduction in disability, pain intensity, and fear of movement; further, it will increase the patient's self-efficacy for exercise and quality of life.Trial registrationwww.clinicaltrials.gov NCT04103970, Registered on 24 September 2019
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37.
  • Wagner, A. M., et al. (författare)
  • Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?
  • 2007
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:3, s. 676-681
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis Post-translational modifications, such as isomerisation of native proteins, may create new antigenic epitopes and play a role in the development of the autoimmune response. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT), encoded by the gene PCMT1, is an enzyme that recognises and repairs isomerised Asn and Asp residues in proteins. The aim of this study was to assess the role of PIMT in the development of type 1 diabetes. Materials and methods Immunohistochemical analysis of 59 normal human tissues was performed with a monoclonal PIMT antibody. CGP3466B, which induces expression of Pcmt1, was tested on MIN6 and INS1 cells, to assess its effect on Pcmt1 mRNA and PIMT levels (RT-PCR and western blot) and apoptosis. Forty-five diabetes-prone BioBreeding (BB) Ottawa Karlsburg (OK) rats were randomised to receive 0, 14 or 500 mu g/kg (denoted as the control, low-dose and high-dose group, respectively) of CGP3466B from week 5 to week 20. Results A high level of PIMT protein was detected in beta cells. CGP3466B induced a two- to threefold increase in Pcmt1 mRNA levels and reduced apoptosis by 10% in MIN6 cells. No significant effect was seen on cytokine-induced apoptosis or PIMT protein levels in INS1 cells. The onset of diabetes in the BB/OK rats was significantly delayed (85.6 +/- 9.0 vs 84.3 +/- 6.8 vs 106.6 +/- 13.5 days, respectively; p < 0.01 for high-dose vs low-dose and control groups), the severity of the disease was reduced (glucose 22.2 +/- 3.2 vs 16.9 +/- 2.6 vs 15.8 +/- 2.7 mmol; p < 0.01 for high- and low-dose groups vs control group) and residual beta cells were more frequently identified (43% vs 71% vs 86%; p < 0.05 for high-dose vs control group) in the treated animals. Conclusions/interpretation The results support a role for post-translational modifications and PIMT in the development of type 1 diabetes in the diabetes-prone BB rat, and perhaps also in humans.
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