69 results on '"M. Axelsen"'
Search Results
2. Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD—VIVIAD
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K. Kühn-Wache, Philip Scheltens, J. E. Harrison, K. Henriksen, K. Fuchs, T. M. Axelsen, Everard G. B. Vijverberg, P. Alexandersen, A. R. Bihlet, Niels D. Prins, F. Weber, Amsterdam Neuroscience - Neurodegeneration, and Neurology
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Oncology ,medicine.medical_specialty ,Amyloid ,Neurology ,Cognitive Neuroscience ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Placebo ,law.invention ,Double blind ,Double-Blind Method ,Randomized controlled trial ,Alzheimer Disease ,law ,Internal medicine ,medicine ,Humans ,RC346-429 ,Trial methodology ,business.industry ,Research ,Glutaminyl cyclase ,Aminoacyltransferases ,Clinical trial ,Treatment Outcome ,Tolerability ,Clinical trials ,Small molecules ,Puroglutamate ,Alzheimer ,Abeta ,Neurology (clinical) ,Neurology. Diseases of the nervous system ,business ,RC321-571 - Abstract
Background Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD. Methods This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics. Results To be expected early 2023 Conclusion This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta. Trial registration ClinicalTrials.gov Identifier: NCT04498650
- Published
- 2021
3. P22 An exploratory safety and immunogenicity study of human papillomavirus (HPV16+) immunotherapy VB10.16 in women with high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3)
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L Wölber, KU Petry, G Böhmer, Peter Hillemanns, M Jentschke, M Axelsen, I Skjørestad, and A Frederiksen
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Cervical cancer ,Colposcopy ,Oncology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Immunogenicity ,medicine.medical_treatment ,Immunotherapy ,medicine.disease ,female genital diseases and pregnancy complications ,Vaccination ,Regimen ,Cell killing ,Tolerability ,Internal medicine ,Medicine ,business - Abstract
Introduction/Background This was an exploratory, multicenter study of VB10.16 immunotherapy in patients with HPV16+ CIN 2/3. Methodology VB10.16 is a naked DNA plasmid vaccine. It encodes for a recombinant protein consisting of 3 modules: mutation-inactivated HPV16 E7/E6 protein linked to human chemokine MIP-1α via a dimerization module derived from human IgG3. The unique mode of action is that it directly targets APCs, then HPV16+ infected tissue and mediates cell killing. This study with 34 CIN 2/3 patients was divided into a Dosing Phase (two vaccination schedules, 3 injections) and an Expansion Phase (4 vaccinations) to assess safety/tolerability immunogenicity and preliminary signs of efficacy with VB10.16. Patients were followed for 24 weeks by colposcopy, cytology, HPV16+ testing and histology. Immunological testing were IFN-γ ELISpot, IHC, PD-L1. The median age was 29.0 years, 70.6% had CIN 2, 29.4% had CIN 3, all were HPV16 positive (one patient withdrew as she was HPV16 negative), and 44% positive for other HPV types at inclusion. Results Treatment with VB10.16 was well tolerated, and mostly injection site related adverse events were reported. No patients experienced SAEs, or discontinued the study vaccine. The highest grade AEs were Grade 3 in 3 patients. IFN-γ ELISpot data from the Dosing Phase identified the superior dose regimen and suggested a further enhancement with adding a fourth dose. All patients in the Expansion Phase elicited a HPV16-specific T-cell response where 94% showed an increased response after vaccination. Signs of efficacy (CIN regression, HPV16+ clearance, lesion size reduction) correlating with immune responses could be observed. In patients without signs of efficacy, an upregulation of PD-L1 was observed which could have inhibited the T-cells response induced by the vaccine. Conclusion VB10.16 immunotherapy in patients with HPV16+ CIN 2/3 showed promising results. A study for cervical cancer in combination with a checkpoint inhibitor is in Progress. Disclosure Study was supported by VACCIBODY A.S., Oslo, Norway. Agnete Fredriksen and Mads Axelsen are employees and warrant holders of Vaccibody. Dr. Woelber reports personal fees from Medac Oncology, Tesaro, Roche, Pharmamar, GSK, Jenapharm, Merck, grants from Greiner, outside the submitted work.
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- 2019
4. Genome editing of lactic acid bacteria: opportunities for food, feed, pharma and biotech
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Amalie M Axelsen, Elleke Fenna Bosma, Alex Toftgaard Nielsen, Vijayalakshmi Kandasamy, and Rosa Aragão Börner
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Computer science ,Systems biology ,Mini Review ,Microbiology ,GMO regulation ,03 medical and health sciences ,Synthetic biology ,Biotechnology and Synthetic Biology ,Genome editing ,Lactobacillales ,Biotherapeutics ,Cell factory ,phytotherapeutics ,Genetics ,biotherapeutics ,food fermentation ,SDG 2 - Zero Hunger ,Molecular Biology ,030304 developmental biology ,Gene Editing ,0303 health sciences ,030306 microbiology ,GMO ,Genetic tool development ,Phytotherapeutics ,Data science ,Animal Feed ,Workflow ,Food Microbiology ,Food fermentation ,Minireview ,synthetic biology ,genetic tool development ,Biotechnology - Abstract
This mini-review provides a perspective of traditional, emerging and future applications of lactic acid bacteria (LAB) and how genome editing tools can be used to overcome current challenges in all these applications. It also describes available tools and how these can be further developed, and takes current legislation into account. Genome editing tools are necessary for the construction of strains for new applications and products, but can also play a crucial role in traditional ones, such as food and probiotics, as a research tool for gaining mechanistic insights and discovering new properties. Traditionally, recombinant DNA techniques for LAB have strongly focused on being food-grade, but they lack speed and the number of genetically tractable strains is still rather limited. Further tool development will enable rapid construction of multiple mutants or mutant libraries on a genomic level in a wide variety of LAB strains. We also propose an iterative Design–Build–Test–Learn workflow cycle for LAB cell factory development based on systems biology, with ‘cell factory’ expanding beyond its traditional meaning of production strains and making use of genome editing tools to advance LAB understanding, applications and strain development., Traditional, emerging and future applications of lactic acid bacteria can all benefit from genome editing and a proposed Design–Build–Test–Learn workflow cycle for advancement of strain development.
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- 2019
5. Low Mannose-Binding Lectin Concentration Is Associated with Severe Infection in Patients with Hematological Cancer Who Are Undergoing Chemotherapy
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Thierry Calandra, M. Axelsen, S. Costantini, Marcel Vekemans, Oscar Marchetti, Marianne Paesmans, Michel Aoun, Martine Barette, Nathalie Meuleman, Alain Ferrant, Aspasia Georgala, C. Heymans, Jean Klastersky, F. Mathissen, James O. Robinson, Frédérique Muanza, and Françoise Huet
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Adult ,Male ,Microbiology (medical) ,medicine.medical_specialty ,Neutropenia ,Antineoplastic Agents ,chemical and pharmacologic phenomena ,Kaplan-Meier Estimate ,Gastroenterology ,Sepsis ,Risk Factors ,Interquartile range ,Internal medicine ,medicine ,Humans ,Adult Aged Antineoplastic Agents/*adverse effects Disease Susceptibility/*blood/immunology Female Hematologic Neoplasms/complications/drug therapy Humans Kaplan-Meiers Estimate Male Mannose-Binding Lectin/*blood/*deficiency Middle Aged Neutropenia/chemically induced Pneumonia/*blood/immunology Prospective Studies Risk Factors Sepsis/*blood/immunology ,Prospective Studies ,Risk factor ,Aged ,Cancer ,Risk assessment ,Mannose-binding lectin ,Myelosuppressive Chemotherapy ,business.industry ,Pneumonia ,Middle Aged ,medicine.disease ,MBL deficiency ,bacterial infections and mycoses ,Chemotherapy regimen ,Infectious Diseases ,Hematologic Neoplasms ,Immunology ,Female ,Disease Susceptibility ,business ,Immunosuppression ,Febrile neutropenia - Abstract
Background. Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy. Methods. We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables. Results. We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P = .008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P < .001]). Conclusions. MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patients.
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- 2017
6. Effect of Intensive Weight Loss Programs on Diabetes Remission in Newly Diagnosed Patients with Type 2 Diabetes: A Systematic Review
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M, Axelsen, primary, L, Jansson, additional, and L, Svanqvist, additional
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- 2018
- Full Text
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7. EUROSPINE 2015 Copenhagen, Denmark, September 2 - 4 : POSTER PRESENTATIONS
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M. Axelsen, Stig M. Jespersen, Søren Overgaard, and Ming Ding
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chemistry.chemical_classification ,Bone substitute ,business.industry ,medicine.medical_treatment ,Peptide ,Anatomy ,Cell biology ,Bone morphogenetic protein 7 ,Cell binding ,SILK ,chemistry ,Spinal fusion ,Medicine ,Orthopedics and Sports Medicine ,Surgery ,business - Published
- 2015
8. Expression of hemochromatosis in homozygous subjects
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Kim M. Summers, Sonja Webb, June W. Halliday, Phillip G. Board, Elizabeth M. Axelsen, and Lawrie W. Powell
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Proband ,education.field_of_study ,Hepatology ,Population ,Gastroenterology ,Locus (genetics) ,Human leukocyte antigen ,Biology ,medicine.disease ,Genetic linkage ,Genetic marker ,Immunology ,medicine ,Allele ,education ,Hemochromatosis - Abstract
This study looks at expression of genetic hemochromatosis in the homozygous and heterozygous states. Two hundred nine subjects in 40 families with confirmed hemochromatosis and clear evidence of HLA linkage in symptomatic individuals were studied prospectively for up to 24 yr. The study group consisted of 40 probands, 51 subjects sharing two HLA haplotypes with affected relatives (putative homozygotes), 98 putative heterozygotes, and 20 putative normal homozygotes. Forty-eight of 51 subjects predicted to be homozygous showed increased hepatic iron stores as assessed by liver biopsy and quantitative phlebotomy. If not evident initially, this developed in 1-8 yr. In the 3 subjects predicted by HLA typing to be homozygous but in whom there was no progressive iron accumulation, results of studies using another chromosome 6 genetic marker (Factor 13 A subunit) were consistent with chromosomal recombination, presumably separating one hemochromatosis allele from the HLA markers. No heterozygous subject developed overt hemochromatosis during the period of follow-up, although 1 showed evidence of iron overload at initial assessment. Genetic recombination is again thought to have separated the hemochromatosis allele from the HLA markers here. The present findings favor a location of the hemochromatosis locus telomeric to HLA-A. It is concluded that, in this population, hemochromatosis is apparently always HLA linked, and homozygous subjects will develop iron overload in the absence of chromosomal recombination or blood loss.
- Published
- 1990
9. Attitudes and barriers to dietary advice aimed at reducing risk of type 2 diabetes in first-degree relatives of patients with type 2 diabetes
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M. Axelsen, Hilde Kristin Brekke, A. Sunesson, and Ragnhild Arvidsson Lenner
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Adult ,Male ,Health Knowledge, Attitudes, Practice ,Cross-sectional study ,Nutritional Sciences ,Medicine (miscellaneous) ,Type 2 diabetes ,Disease ,law.invention ,Randomized controlled trial ,Patient Education as Topic ,law ,Risk Factors ,Environmental health ,Diabetes mellitus ,Surveys and Questionnaires ,Vegetables ,Medicine ,Humans ,Genetic Predisposition to Disease ,First-degree relatives ,Risk factor ,Life Style ,Nutrition and Dietetics ,business.industry ,Feeding Behavior ,Middle Aged ,medicine.disease ,Dietary Fats ,Glycemic index ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Food ,Glycemic Index ,Fruit ,Patient Compliance ,Female ,business ,Attitude to Health - Abstract
Objective To evaluate the attitudes to and adoption of dietary advice in nondiabetic first-degree relatives of patients with type 2 diabetes and to examine barriers to adherence. Design One-year controlled intervention study, where treatment group (n ¼ 73) received lifestyle education. Attitudes towards dietary advice, change in dietary habits and importance of potential barriers to adherence were evaluated by questionnaires. Nondiabetic relatives (25–55 years; males and females) of individuals with type 2 diabetes were recruited. Education was based on current nutrition recommendations and aimed at improving dietary fat quality, increasing intake of fruit and vegetables, with additional advice to reduce dietary glycaemic index (GI). Main outcome measures Attitudes and importance of barriers were classified by the intervened subjects into four categories ranging from ‘No problem’ to ‘Yes, definitely a problem’. Dietary adherence was monitored by food frequency questionnaire at baseline and after 1 year. Results Participants were generally in favour of advice aimed at improving dietary fat quality. Attitudes towards advice to reduce GI varied widely. Food selection changed in accordance with predefined dietary goals. ‘Forgetfulness’, ‘low availability in lunch restaurant’ and ‘lack of ideas for cooking’ were barriers to adherence. Conclusions Dietary advice aimed at reducing risk of type 2 diabetes was generally positively received and adopted in subjects with heredity for the disease. The most prevalent barriers reported are potentially modifiable.
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- 2004
10. PO-0945 USING A SATELLITE CLINIC AS A PILOT SITE FOR DEVELOPING AND IMPLEMENTING ADVANCED RADIOTHERAPY TECHNIQUES
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B.V. Offersen, N. Rubaek, M.S. Thomsen, and M. Axelsen
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medicine.medical_specialty ,biology ,business.industry ,medicine.medical_treatment ,Hematology ,biology.organism_classification ,Radiation therapy ,Oncology ,Physical therapy ,Medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Satellite (biology) ,business - Published
- 2012
11. Comparison of the soluble basal insulin analog insulin detemir with NPH insulin: a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy
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K, Hermansen, S, Madsbad, H, Perrild, A, Kristensen, and M, Axelsen
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Adult ,Blood Glucose ,Cross-Over Studies ,Adolescent ,Insulin, Isophane ,Middle Aged ,Hypoglycemia ,Insulin, Long-Acting ,Kinetics ,Diabetes Mellitus, Type 1 ,Insulin Detemir ,Solubility ,Humans ,Insulin ,Carrier Proteins - Abstract
Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety.This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin.The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049).Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.
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- 2001
12. RECOMBINANT FACTOR VIIa (NOVOSEVEN®) AS ADJUNCTIVE THERAPY FOR BLEEDING CONTROL IN TRAUMA - A RANDOMIZED, PLACEBOCONTROLLED TRIAL
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B. Warren, Rolf Rossaint, Carl J. Hauser, B. Riou, M. Axelsen, Sandro Rizoli, Yoram Kluger, Kenneth D. Boffard, and P. Iau
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Bleeding control ,biology ,business.industry ,Recombinant factor VIIa ,Anesthesia ,Emergency Medicine ,biology.protein ,Medicine ,Critical Care and Intensive Care Medicine ,business - Published
- 2004
13. Midwifery in Denmark
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M, Axelsen
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Job Description ,Nurse Midwives ,Denmark ,Humans - Published
- 1995
14. Extracorporeal dialysis: techniques and adequacy
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C. Donadio, A. Kanaki, A. Martin-Gomez, S. Garcia, M. Palacios-Gomez, D. Calia, E. Colombini, F. DI Francesco, S. Ghimenti, M. Onor, D. Tognotti, R. Fuoco, E. Marka-Castro, M. I. Torres Zamora, J. Giron-Mino, M. A. Jaime-Solis, L. M. Arteaga, H. Romero, A. Akonur, K. Leypoldt, M. Asola, B. Culleton, S. Eloot, G. Glorieux, N. Nathalie, R. Vanholder, A. Perez de Jose, U. Verdalles Guzman, S. Abad Esttebanez, A. Vega Martinez, D. Barraca, C. Yuste, L. Bucalo, A. Rincon, J. M. Lopez-Gomez, P. Bataille, P. Celine, A. Raymond, G. Francois, L. Herve, D. Michel, R. Jean Louis, F. Zhu, P. Kotanko, S. Thijssen, N. W. Levin, N. Papamichail, M. Bougiakli, C. Gouva, S. Antoniou, S. Gianitsi, A. Vlachopanou, S. Chachalos, K. Naka, D. Kaarsavvidou, K. Katopodis, L. Michalis, K. Sasaki, K. Yasuda, M. Yamato, A. Surace, P. Rovatti, D. Steckiph, R. Bandini, S. Severi, A. Dellacasa Bellingegni, A. Santoro, M. Arias, A. Sentis, N. Perez, N. Fontsere, M. Vera, N. Rodriguez, C. Arcal, N. Ortega, F. Uriza, A. Cases, F. Maduell, S. R. Abbas, P. Georgianos, P. Sarafidis, P. Nikolaidis, A. Lasaridis, A. Ahmed, H. Kaoutar, B. Mohammed, O. Zouhir, P. Balter, N. Ginsberg, P. Taylor, T. Sullivan, L. A. Usvyat, P. Zabetakis, U. Moissl, M. Ferrario, F. Garzotto, P. Wabel, D. Cruz, C. Tetta, M. G. Signorini, S. Cerutti, A. Brendolan, C. Ronco, J. Heaf, M. Axelsen, R. S. Pedersen, H. Amine, Z. Oualim, A. L. Ammirati, N. K. Guimaraes de Souza, T. Nemoto Matsui, M. Luiz Vieira, W. A. Alves de Oliveira, C. H. Fischer, F. Dias Carneiro, I. J. Iizuka, M. Aparecida de Souza, A. C. Mallet, M. C. Cruz Andreoli, B. F. Cardoso Dos Santos, L. Rosales, Y. Dou, M. Carter, A. Testa, L. Sottini, B. Giacon, E. Prati, C. Loschiavo, M. Brognoli, C. Marseglia, A. Tommasi, L. Sereni, G. Palladino, S. Bove, G. Bosticardo, E. Schillaci, P. Detoma, R. Bergia, J. W. Park, S. J. Moon, H. Y. Choi, S. K. Ha, H.-C. Park, Y. Liao, L. Zhang, P. Fu, H. Igarashi, N. Suzuki, S. Esashi, I. Masakane, V. Panichi, G. De Ferrari, S. Saffiotti, A. Sidoti, M. Biagioli, S. Bianchi, P. Imperiali, C. Gabrielli, P. Conti, P. Patrone, G. Rombola, V. Falqui, C. Mura, A. Icardi, A. Rosati, F. Santori, A. Mannarino, A. Bertucci, J. Jeong, O. K. Kim, N. H. Kim, M. Bots, C. Den Hoedt, M. P. Grooteman, N. C. Van der Weerd, A. H. A. Mazairac, R. Levesque, P. M. Ter Wee, M. J. Nube, P. Blankestijn, M. A. Van den Dorpel, Y. Park, J. Jeon, N. Tessitore, V. Bedogna, D. Girelli, L. Corazza, P. Jacky, Q. Guillaume, B. Julien, W. Marcinkowski, M. Drozdz, A. Milkowski, T. Rydzynska, T. Prystacki, R. August, E. Benedyk-Lorens, K. Bladek, J. Cina, G. Janiszewska, A. Kaczmarek, T. Lewinska, M. Mendel, M. Paszkot, E. Trafidlo, M. Trzciniecka-Kloczkowska, A. Vasilevsky, G. Konoplev, O. Lopatenko, A. Komashnya, K. Visnevsky, R. Gerasimchuk, I. Neivelt, A. Frorip, M. Vostry, J. Racek, D. Rajdl, J. Eiselt, L. Malanova, U. Pechter, A. Selart, M. Ots-Rosenberg, D. H. Krieter, S. Seidel, K. Merget, H.-D. Lemke, C. Wanner, B. Canaud, A. Rodriguez, A. Morgenroth, K. Von Appen, G.-P. Dragoun, R. Fluck, D. Fouque, R. Lockridge, Y. Motomiya, Y. Uji, T. Hiramatsu, Y. Ando, M. Furuta, T. Kuragano, A. Kida, M. Yahiro, Y. Otaki, Y. Hasuike, H. Nonoguchi, T. Nakanishi, M. Sain, V. Kovacic, D. Ljutic, J. Radic, I. Jelicic, S. F. Yalin, S. Trabulus, A. S. Yalin, M. R. Altiparmak, K. Serdengecti, A. Ohtsuka, K. Fukami, K. Ishikawa, R. Ando, Y. Kaida, T. Adachi, K. Sugi, S. Okuda, O. B. Nesterova, E. D. Suglobova, R. V. Golubev, A. N. Vasiliev, V. A. Lazeba, A. V. Smirnov, K. Arita, E. Kihara, K. Maeda, H. Oda, S. Doi, T. Masaki, S. Hidaka, K. Ishioka, M. Oka, H. Moriya, T. Ohtake, S. Nomura, S. Kobayashi, S. Wagner, A. Gmerek, J. Wagner, V. Wizemann, N. Eftimovska - Otovic, K. Spaseska-Gjurovska, S. Bogdanovska, E. Babalj - Banskolieva, M. Milovanceva, R. Grozdanovski, A. Pisani, E. Riccio, A. Mancini, P. Ambuhl, S. Astrid, P. Ivana, H. Martin, K. Thomas, R. Hans-Rudolf, A. Daniel, K. Denes, M. Marco, R. P. Wuthrich, S. Andreas, S. Andrulli, P. Altieri, G. Sau, P. Bolasco, L. A. Pedrini, C. Basile, S. David, M. Feriani, P. E. Nebiolo, R. Ferrara, D. Casu, F. Logias, R. Tarchini, F. Cadinu, M. Passaghe, G. Fundoni, G. Villa, B. R. DI Iorio, C. Zoccali, F. Locatelli, M. Hamamoto, D.-Y. Lee, B. Kim, K. H. Moon, Z. LI, P. Ahrenholz, R. E. Winkler, G. Waitz, H. Wolf, G. Grundstrom, M. Alquist, M. Holmquist, A. Christensson, P. Bjork, M. Abdgawad, L. Ekholm, M. Segelmark, C. Corsi, J. De Bie, E. Mambelli, D. Mortara, D. Arroyo, N. Panizo, B. Quiroga, J. Reque, R. Melero, M. Rodriguez-Ferrero, P. Rodriguez-Benitez, F. Anaya, J. Luno, A. Ragon, A. James, P. Brunet, S. Ribeiro, M. S. Faria, S. Rocha, S. Rodrigues, C. Catarino, F. Reis, H. Nascimento, J. Fernandes, V. Miranda, A. Quintanilha, L. Belo, E. Costa, A. Santos-Silva, J. Arund, R. Tanner, I. Fridolin, M. Luman, C. Clajus, J. T. Kielstein, H. Haller, P. Libutti, P. Lisi, L. Vernaglione, F. Casucci, N. Losurdo, A. Teutonico, C. Lomonte, C. Krisp, D. A. Wolters, M. Matsuyama, T. Tomo, K. Ishida, K. Matsuyama, T. Nakata, J. Kadota, M. Caiazzo, E. Monari, A. Cuoghi, E. Bellei, S. Bergamini, A. Tomasi, T. Baranger, P. Seniuta, F. Berge, V. Drouillat, C. Frangie, E. Rosier, W. Labonia, A. Lescano, D. Rubio, N. Von der Lippe, J. A. Jorgensen, T. B. Osthus, B. Waldum, I. Os, M. Bossola, E. DI Stasio, M. Antocicco, L. Tazza, I. Griveas, A. Karameris, P. Pasadakis, V. Savica, D. Santoro, S. Saitta, V. Tigano, G. Bellinghieri, S. Gangemi, R. Daniela, I. A. Checherita, A. Ciocalteu, I. A. Vacaroiu, A. Niculae, E. Stefaniak, I. Pietrzak, D. Krupa, L. Garred, E. Mancini, L. Corrazza, M. Atti, B. Afsar, D. Stamopoulos, N. Mpakirtzi, B. Gogola, M. Zeibekis, D. Stivarou, M. Panagiotou, E. Grapsa, O. Vega Vega, D. Barraca Nunez, M. Fernandez-Lucas, A. Gomis, J. L. Teruel, S. Elias, C. Quereda, L. Hignell, S. Humphrey, N. Pacy, and N. Afentakis
- Subjects
Transplantation ,medicine.medical_specialty ,Extracorporeal Dialysis ,Nephrology ,business.industry ,Uremic toxins ,Medicine ,Identification (biology) ,business ,Intensive care medicine ,Microbiology - Published
- 2011
15. [Laser therapy of ankle sprain]
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S M, Axelsen and T, Bjerno
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Adult ,Male ,Adolescent ,Double-Blind Method ,Lasers ,Sprains and Strains ,Humans ,Female ,Ankle Injuries ,Laser Therapy ,Middle Aged - Abstract
The effect of low-power laser therapy on acute ankle sprains was evaluated in a double-blind randomised clinical study consisting of 40 patients from the casualty ward. All patients received treatment until their ankle joint was painless. No statistically significant differences regarding discolouring, pain, oedema, and use of analgetics were observed between patients treated with laser and placebo. The patients treated with active laser had a significantly longer sick leave.
- Published
- 1993
16. [Second extrauterine pregnancy after laparoscopic sterilization]
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S M, Axelsen
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Adult ,Pregnancy ,Sterilization, Tubal ,Humans ,Female ,Laparoscopy ,Pregnancy, Ectopic - Abstract
A case is presented where a woman had a second ectopic pregnancy after laparoscopic sterilization. The causes of the condition are discussed together with possible methods of prevention.
- Published
- 1992
17. More predictable fasting blood glucose with the new soluble basal insulin analogue, insulin detemir: A comparison with NPH in type I diabetic patients
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M. Axelsen, M. Palmér, A. Kristensen, K. Hermansen, and Sten Madsbad
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medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Basal insulin ,General Medicine ,medicine.disease ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,business ,Insulin detemir ,medicine.drug - Published
- 2000
18. Is all genetic (hereditary) hemochromatosis HLA-associated
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Janez Ferluga, Elizabeth M. Axelsen, Mark L Bassett, L. W. Powell, and J. W. Halliday
- Subjects
Genetic Markers ,Linkage disequilibrium ,Alcohol Drinking ,Genetic Linkage ,Genes, Recessive ,Human leukocyte antigen ,Biology ,HLA-A3 Antigen ,General Biochemistry, Genetics and Molecular Biology ,Pathogenesis ,History and Philosophy of Science ,Antigen ,HLA Antigens ,medicine ,Humans ,Gene ,Hemochromatosis ,Alleles ,Genetics ,General Neuroscience ,Haplotype ,Australia ,medicine.disease ,Pedigree ,Hereditary hemochromatosis ,Immunology ,Disease Susceptibility - Abstract
1. GH in Australia is significantly associated with the HLA-A3 antigen, which is the only independent marker for the disease (B7 in linkage disequilibrium with A3). 2. The haplotype A3, B7, DR2 is the only one with increased prevalence in this disease, presumably due to its being the predominant haplotype among early immigrants. 3. Exceptions to HLA association in GH are rare and can be explained by: (1) incorrect HLA serotyping, (2) chromosomal recombination, or (3) rare homozygous-homozygous mating. 4. These data are consistent with GH being due to a mutant gene or genes in close proximity to HLA-A. 5. Heavy alcohol ingestion does not lead to expression of hemochromatosis in heterozygous subjects.
- Published
- 1988
19. Cohort study of internal malignancy in genetic hemochromatosis and other chronic nonalcoholic liver diseases
- Author
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R A, Bradbear, C, Bain, V, Siskind, F D, Schofield, S, Webb, E M, Axelsen, J W, Halliday, M L, Bassett, and L W, Powell
- Subjects
Adult ,Male ,Risk ,Carcinoma, Hepatocellular ,Adolescent ,Liver Diseases ,Liver Neoplasms ,Australia ,Middle Aged ,Neoplasms ,Humans ,Female ,Hemochromatosis ,Prospective Studies ,Aged - Abstract
The risk of hepatocellular carcinoma (HCC) and other internal malignancies was examined in patients with genetic hemochromatosis (GH) by following 208 patients from the time of diagnosis to June 1983 and by comparing the numbers of cancers they developed with expected values constructed from cancer registry incidence data by means of actuarial methods. In addition, cancers occurring in a comparison group of 148 subjects with other chronic nonalcoholic liver diseases (CLD) were determined. Among the GH group, 16 new cases of HCC occurred subsequent to the diagnosis of GH, together with 8 other malignancies. The 16 cases of HCC reflect a 200-fold excess risk, which from all indications represents the first quantitation of the risk of this tumor in GH. There appears to be no increased risk of other malignancies in this disease. Among the CLD group only 1 HCC and 1 other malignancy occurred.
- Published
- 1985
20. Cohort Study of Internal Malignancy in Genetic Hemochromatosis and Other Chronic Nonalcoholic Liver Diseases<xref ref-type='fn' rid='FN2'>2</xref>
- Author
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Chris Bain, Mark L. Bassett, Robin A. Bradbear, June W. Halliday, Elizabeth M. Axelsen, Victor Siskind, Francis D. Schofield, Sonja Webb, and Lawrie W. Powell
- Subjects
Cancer Research ,medicine.medical_specialty ,business.industry ,Cancer ,medicine.disease ,Malignancy ,Gastroenterology ,digestive system diseases ,Cancer registry ,Oncology ,Hepatocellular carcinoma ,Internal medicine ,medicine ,Risk factor ,Prospective cohort study ,business ,Hemochromatosis ,Cohort study - Abstract
The risk of hepatocellular carcinoma (HCC) and other internal malignancies was examined in patients with genetic hemochromatosis (GH) by following 208 patients from the time of diagnosis to June 1983 and by comparing the numbers of cancers they developed with expected values constructed from cancer registry incidence data by means of actuarial methods. In addition, cancers occurring in a comparison group of 148 subjects with other chronic nonalcoholic liver diseases (CLD) were determined. Among the GH group, 16 new cases of HCC occurred subsequent to the diagnosis of GH, together with 8 other malignancies. The 16 cases of HCC reflect a 200-fold excess risk, which from all indications represents the first quantitation of the risk of this tumor in GH. There appears to be no increased risk of other malignancies in this disease. Among the CLD group only 1 HCC and 1 other malignancy occurred.
- Published
- 1985
21. Effectiveness of a bandage to prevent re-dislocation after total hip arthroplasty in patients with a previous hip dislocation. A randomized controlled trial with 12-week follow-up.
- Author
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Mechlenburg I, Knak J, Mosegaard SB, Axelsen M, Krarup Jensen N, Hansen TB, and Stilling M
- Subjects
- Bandages, Female, Follow-Up Studies, Humans, Male, Quality of Life, Retrospective Studies, Arthroplasty, Replacement, Hip adverse effects, Hip Dislocation etiology, Hip Dislocation prevention & control, Hip Dislocation surgery, Hip Prosthesis
- Abstract
Objective: To investigate if using a hip bandage is more effective than standard care in the prevention of total hip arthroplasty re-dislocation in patients with a previous total hip arthroplasty dislocation., Design: randomized controlled trial., Setting: Holstebro Regional Hospital and Viborg Regional Hospital., Subjects: A total of 99 patients, 51 women, mean 70.7 (SD 9.9) years were enrolled in an un-blinded, clinical randomized controlled trial., Interventions: Participants with at least one previous total hip arthroplasty dislocation were randomized to either wearing a bandage reducing flexion, adduction, and internal rotation of the hip (intervention group) or to standard care (control group). The participants were followed for 12 weeks. Main follow-up measures were as follows: number of re-dislocations (primary outcome), hip disability measured with the Oxford Hip Score (0-48, 48 best), quality of life measured with the 36-Item Short Form Survey (0-100, 100 best), satisfaction with treatment and serious adverse events. Statistical analyses followed the intention-to-treat principle., Results: No significant group differences were observed for the primary outcome re-dislocations (9 versus 15, P = 0.143) or for disability (11.3 versus 14.4, P = 0.161), quality of life (57.7 versus 48.3, P = 0.050) or satisfaction with treatment ( P = 0.562). There were 3 serious adverse events leading to total hip arthroplasty revision in the intervention group and 4 in the control group., Conclusion: We found that a hip bandage is not superior to standard care in the prevention of total hip arthroplasty re-dislocation in those with a previous total hip arthroplasty dislocation.
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- 2022
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22. External validation of an artificial intelligence tool for radiographic knee osteoarthritis severity classification.
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Brejnebøl MW, Hansen P, Nybing JU, Bachmann R, Ratjen U, Hansen IV, Lenskjold A, Axelsen M, Lundemann M, and Boesen M
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- Artificial Intelligence, Humans, Knee, Radiography, Retrospective Studies, Osteoarthritis, Knee diagnostic imaging
- Abstract
Purpose: To externally validate an artificial intelligence (AI) tool for radiographic knee osteoarthritis severity classification on a clinical dataset., Method: This retrospective, consecutive patient sample, external validation study used weight-bearing, non-fixed-flexion posterior-anterior knee radiographs from a clinical production PACS. The index test was ordinal Kellgren-Lawrence grading by an AI tool, two musculoskeletal radiology consultants, two reporting technologists, and two resident radiologists. Grading was repeated by all readers after at least four weeks. Reference test was the consensus of the two consultants. The primary outcome was quadratic weighted kappa. Secondary outcomes were ordinal weighted accuracy, multiclass accuracy and F1-score., Results: 50 consecutive patients between September 24, 2019 and October 22, 2019 were retrospectively included (3 excluded) totaling 99 knees (1 excluded). Quadratic weighted kappa for the AI tool and the consultant consensus was 0.88 CI95% (0.82-0.92). Agreement between the consultants was 0.89 CI95% (0.85-0.93). Intra-rater agreements for the consultants were 0.96 CI95% (0.94-0.98) and 0.94 CI95% (0.91-0.96) respectively. For the AI tool it was 1 CI95% (1-1). For the AI tool, ordinal weighted accuracy was 97.8% CI95% (96.9-98.6 %). Average multiclass accuracy and F1-score were 84% (83/99) CI95% (77-91%) and 0.67 CI95% (0.51-0.81)., Conclusions: The AI tool achieved the same good-to-excellent agreement with the radiology consultant consensus for radiographic knee osteoarthritis severity classification as the consultants did with each other., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
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23. Effects of nutrition education using a food-based approach, carbohydrate counting or routine care in type 1 diabetes: 12 months prospective randomized trial.
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Sterner Isaksson S, Bensow Bacos M, Eliasson B, Thors Adolfsson E, Rawshani A, Lindblad U, Jendle J, Berglund A, Lind M, and Axelsen M
- Subjects
- Adult, Blood Glucose, Dietary Carbohydrates, Female, Humans, Male, Middle Aged, Prospective Studies, Quality of Life, Diabetes Mellitus, Type 1 therapy
- Abstract
Introduction: Evidence on the effects of structured nutrition education is weak in adults with type 1 diabetes mellitus (T1D) with moderately impaired glycemic control. Objective was to compare the effects of different types of nutrition education programs on glycemic control, cardiovascular risk factors, quality of life, diet quality and food choices in T1D., Research Design and Methods: A 12 months randomized controlled study conducted at nine diabetes specialist centers with three parallel arms: (i) a food-based approach (FBA) including foods with low glycemic index or (ii) carbohydrate counting (CC) according to today's standard practice or (iii) individual sessions according to routine care (RC). The primary end point was difference in glycated hemoglobin A1c (HbA1c) between groups at 12 months., Results: 159 patients were randomized (FBA: 51; CC: 52; RC: 55). Mean (SD) age 48.6 (12.0) years, 57.9% females and mean (SD) HbA1c level 63.9 (7.9) mmol/mol, 8% (0.7%). After 3 months, HbA1c improved in both FBA and CC compared with RC. However, there were no significant differences at 12 months in HbA1c; FBA versus RC (-0.4 mmol/mol (1.3), 0.04% (0.1%)), CC versus RC (-0.8 mmol/mol (1.2), 0.1% (0.1%)), FBA versus CC (0.4 mmol/mol (0.3), 0.04% (0.01%)). At 12 months, intake of legumes, nuts and vegetables was improved in FBA versus CC and RC. FBA also reported higher intake of monounsaturated and polyunsaturated fats compared with RC, and dietary fiber, monounsaturated and polyunsaturated fats compared with CC (all p values <0.05). There were no differences in blood pressure levels, lipids, body weight or quality of life., Conclusions: Nutrition education using an FBA, CC or RC is equivalent in terms of HbA1c and cardiovascular risk factors in persons with T1D with moderately impaired glycemic control. An FBA had benefits regarding food choices compared with CC and RC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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24. Sociodemographic determinants and health outcome variation in individuals with type 1 diabetes mellitus: A register-based study.
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Willers C, Iderberg H, Axelsen M, Dahlström T, Julin B, Leksell J, Lindberg A, Lindgren P, Looström Muth K, Svensson AM, and Lilja M
- Subjects
- Adult, Aged, Diabetes Mellitus, Type 1 blood, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Sex Factors, Socioeconomic Factors, Sweden epidemiology, Delivery of Health Care, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 therapy, Quality of Health Care, Registries
- Abstract
Background: Socioeconomic status, origin or demographic attributes shall not determine the quality of healthcare delivery, according to e.g. United Nations and European Union rules. Health equity has been defined as the absence of systematic disparities and unwarranted differences between groups defined by differences in social advantages. A study was performed to investigate whether this was applicable to type 1 diabetes mellitus (T1D) care in a setting with universal, tax-funded healthcare., Methods: This retrospective registry-study was based on patient-level data from individuals diagnosed with T1D during 2010-2011 (n = 16,367) in any of seven Swedish county councils (covering ~65% of the Swedish population). Health equity in T1D care was analysed through multivariate regression analyses on absolute HbA1c level at one-year follow-up, one-year change in estimated glomerular filtration rate (eGFR) and one-year change in cardiovascular risk score, using selected sociodemographic dimensions as case-mix factors., Results: Higher educational level was consistently associated with lower levels of HbA1c, and so was being married. Never married was associated with worse eGFR development, and lower educational level was associated with higher cardiovascular risk. Women had higher HbA1c levels than men, and glucose control was significantly worse in patients below the age of 25., Conclusion: Patients' sociodemographic profile was strongly associated with absolute levels of risk factor control in T1D, but also with an increased annual deterioration in eGFR. Whether these systematic differences stem from patient-related problems or healthcare organisational shortcomings is a matter for further research. The results, though, highlight the need for intensified diabetes management education and secondary prevention directed towards T1D patients, taking sociodemographic characteristics into account., Competing Interests: CW, HI and BJ are employed by Ivbar Institute, a research company specialized in health care governance and analysis of health care data. The other authors state no disclosures.
- Published
- 2018
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25. Tele-Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial.
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de Thurah A, Stengaard-Pedersen K, Axelsen M, Fredberg U, Schougaard LMV, Hjollund NHI, Pfeiffer-Jensen M, Laurberg TB, Tarp U, Lomborg K, and Maribo T
- Subjects
- Aged, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid physiopathology, Arthritis, Rheumatoid psychology, Denmark, Female, Health Status, Humans, Male, Middle Aged, Nurses, Patient Reported Outcome Measures, Quality of Life, Remission Induction, Rheumatologists, Self Efficacy, Severity of Illness Index, Time Factors, Treatment Outcome, Aftercare methods, Arthritis, Rheumatoid therapy, Telemedicine methods
- Abstract
Objective: To test the effect of patient-reported outcome (PRO)-based tele-health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele-health followup performed by rheumatologists or rheumatology nurses., Methods: A total of 294 patients were randomized (1:1:1) to either PRO-based tele-health followup carried out by a nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self-efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent-to-treat (ITT), and multivariate imputation analysis., Results: Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO-TR versus control were -0.10 (90% confidence interval [90% CI] -0.30, 0.13) and -0.19 (90% CI -0.41, 0.02) between PRO-TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO-TN had mean ± SD 1.72 ± 1.03 visits/year, PRO-TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare., Conclusion: Among RA patients with low disease activity or remission, a PRO-based tele-health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses., (© 2017, American College of Rheumatology.)
- Published
- 2018
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26. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.
- Author
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Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, and Hjerpsted JB
- Subjects
- Adult, Appetite Depressants administration & dosage, Appetite Depressants adverse effects, Basal Metabolism drug effects, Body Mass Index, Cross-Over Studies, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Feeding Behavior drug effects, Female, Food Preferences drug effects, Glucagon-Like Peptide-1 Receptor metabolism, Glucagon-Like Peptides administration & dosage, Glucagon-Like Peptides adverse effects, Humans, Injections, Subcutaneous, Male, Middle Aged, Obesity metabolism, Self Report, Weight Loss drug effects, Adiposity drug effects, Appetite Depressants therapeutic use, Appetite Regulation drug effects, Energy Intake drug effects, Glucagon-Like Peptide-1 Receptor agonists, Glucagon-Like Peptides therapeutic use, Obesity drug therapy
- Abstract
Aim: The aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide., Materials and Methods: This randomised, double-blind, placebo-controlled, two-period crossover trial investigated the effects of 12 weeks of treatment with once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well-being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed., Results: After a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (-1255 kJ; P < .0001) and during the subsequent evening meal ( P = .0401) and snacks ( P = .0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (-3036 kJ; P < .0001). Fasting overall appetite suppression scores were improved with semaglutide vs placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high-fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass., Conclusion: After 12 weeks of treatment, ad libitum energy intake was substantially lower with semaglutide vs placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide-induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy-dense foods., (© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
- Published
- 2017
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27. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial.
- Author
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Aroda VR, Bain SC, Cariou B, Piletič M, Rose L, Axelsen M, Rowe E, and DeVries JH
- Subjects
- Aged, Drug Therapy, Combination, Female, Glucagon-Like Peptides adverse effects, Humans, Hypoglycemic Agents adverse effects, Insulin Glargine adverse effects, Male, Metformin therapeutic use, Middle Aged, Diabetes Mellitus, Type 2 drug therapy, Glucagon-Like Peptides administration & dosage, Hypoglycemic Agents administration & dosage, Insulin Glargine administration & dosage
- Abstract
Background: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas)., Methods: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries. Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea. We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose target of 4·0-5·5 mmol/L [72-99 mg/dL]) for 30 weeks. In all treatment groups, previous background metformin and sulfonylurea treatment was continued throughout the trial. We did the randomisation using an interactive voice or web response system. The primary endpoint was change in mean HbA
1c from baseline to week 30 and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30. We assessed efficacy and safety in the modified intention-to-treat population (mITT; all randomly assigned participants who were exposed to at least one dose of study drug) and used a margin of 0·3% to establish non-inferiority in HbA1c reduction. This trial is registered with ClinicalTrials.gov, number NCT02128932., Findings: Between Aug 4, 2014, and Sept 3, 2015, we randomly assigned 1089 participants to treatment; the mITT population consisted of 362 participants assigned to 0·5 mg semaglutide, 360 to 1·0 mg semaglutide, and 360 to insulin glargine. 49 (14%) participants assigned to 0·5 mg semaglutide discontinued treatment prematurely, compared with 55 (15%) assigned to 1·0 mg semaglutide, and 26 (7%) assigned to insulin glargine. Most discontinuations were due to adverse events-mostly gastrointestinal with semaglutide, and others such as skin and subcutaneous tissue disorders (eg, rash, pruritus, and urticaria) with insulin glargine. From a mean baseline HbA1c of 8·17% (SD 0·89), at week 30, 0·5 and 1·0 mg semaglutide achieved reductions of 1·21% (95% CI 1·10-1·31) and 1·64% (1·54-1·74), respectively, versus 0·83% (0·73-0·93) with insulin glargine; estimated treatment difference versus insulin glargine -0·38% (95% CI -0·52 to -0·24) with 0·5 mg semaglutide and -0·81% (-0·96 to -0·67) with 1·0 mg semaglutide (both p<0·0001). Mean bodyweight at baseline was 93·45 kg (SD 21·79); at week 30, 0·5 and 1·0 mg semaglutide achieved weight losses of 3·47 kg (95% CI 3·00-3·93) and 5·17 kg (4·71-5·66), respectively, versus a weight gain of 1·15 kg (0·70-1·61) with insulin glargine; estimated treatment difference versus insulin glargine -4·62 kg (95% CI -5·27 to -3·96) with 0·5 mg semaglutide and -6·33 kg (-6·99 to -5·67) with 1·0 mg semaglutide (both p<0·0001). Severe or blood glucose-confirmed hypoglycaemia was reported by 16 (4%) participants with 0·5 mg semaglutide and 20 (6%) with 1·0 mg semaglutide versus 38 (11%) with insulin glargine (p=0·0021 and p=0·0202 for 0·5 mg and 1·0 mg semaglutide vs insulin glargine, respectively). Severe hypoglycaemia was reported by two (<1%) participants with 0·5 mg semaglutide, five (1%) with 1·0 mg semaglutide, and five (1%) with insulin glargine. Six deaths were reported: four (1%) in the 0·5 mg semaglutide group (three cardiovascular deaths, one pancreatic carcinoma, which was assessed as being possibly related to study medication) and two (<1%) in the insulin glargine group (both cardiovascular death). The most frequently reported adverse events were nausea with semaglutide, reported in 77 (21%) patients with 0·5 mg and in 80 (22%) with 1·0 mg, and nasopharyngitis reported in 44 (12%) patients with insulin glargine., Interpretation: Compared with insulin glargine, semaglutide resulted in greater reductions in HbA1c and weight, with fewer hypoglycaemic episodes, and was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists., Funding: Novo Nordisk A/S., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2017
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28. Cephalic phase of insulin secretion in response to a meal is unrelated to family history of type 2 diabetes.
- Author
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Eliasson B, Rawshani A, Axelsen M, Hammarstedt A, and Smith U
- Subjects
- Adult, C-Peptide metabolism, Case-Control Studies, Eating, Fasting physiology, Glucose Intolerance, Glucose Tolerance Test, Humans, Insulin Secretion, Male, Meals, Middle Aged, Pedigree, Diabetes Mellitus, Type 2, Insulin metabolism
- Abstract
The pre-absorptive cephalic phase of insulin secretion is elicited during the first ten min of a meal and before glucose levels rise. Its importance for insulin release during the post-absorptive phase has been well documented in animals but its presence or importance in man has become increasingly controversial. We here examined the presence of an early cephalic phase of insulin release in 31 well matched individuals without (n = 15) or with (n = 16) a known family history of type 2 diabetes (first-degree relatives; FDR). We also examined the potential differences in individuals with or without impaired fasting (IFG) and impaired glucose tolerance (IGT). We here demonstrate that a cephalic phase of insulin secretion was present in all individuals examined and without any differences between control persons and FDR or IFG/IGT. However, the overall importance of the cephalic phase is conjectural since it was unrelated to the subsequent post-absorptive insulin release or glucose tolerance. One of the best predictors of the incremental cephalic phase of insulin release was fasting insulin level and, thus, a relation to degree of insulin sensitivity is likely. In conclusion, an early pre-absorptive and cephalic phase of insulin release is robustly present in man. However, we could not document any relation to family history of Type 2 diabetes nor to the post-absorptive phase and, thus, confirm its importance for subsequent degree of insulin release or glucose tolerance.
- Published
- 2017
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29. Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis.
- Author
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Carlson N, Mortensen OH, Axelsen M, Pedersen RS, and Heaf JG
- Subjects
- Adaptor Proteins, Signal Transducing, Aged, Female, Fibroblast Growth Factor-23, Genetic Markers, Humans, Male, Middle Aged, Bone Morphogenetic Proteins blood, Fibroblast Growth Factors blood, Kidney Failure, Chronic blood, Kidney Failure, Chronic therapy, Osteocalcin blood, Osteoprotegerin blood, Renal Dialysis methods
- Abstract
Introduction: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed., Methods: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23, sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance., Results: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed., Conclusions: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged., (© 2017 S. Karger AG, Basel.)
- Published
- 2017
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30. Protein-bound solute removal during extended multipass versus standard hemodialysis.
- Author
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Eloot S, Van Biesen W, Axelsen M, Glorieux G, Pedersen RS, and Heaf JG
- Subjects
- Aged, Cross-Over Studies, Female, Humans, Kidney Failure, Chronic diagnosis, Male, Middle Aged, Prognosis, Renal Dialysis methods, Time Factors, Treatment Outcome, Ultrafiltration methods, Ultrafiltration standards, Urea analysis, Uric Acid analysis, Appointments and Schedules, Hemodialysis Solutions, Kidney Failure, Chronic therapy, Proteins, Renal Dialysis standards
- Abstract
Background: Multipass hemodialysis (MPHD) is a recently described dialysis modality, involving the use of small volumes of dialysate which are repetitively recycled. Dialysis regimes of 8 hours for six days a week using this device result in an increased removal of small water soluble solutes and middle molecules compared to standard hemodialysis (SHD). Since protein-bound solutes (PBS) exert important pathophysiological effects, we investigated whether MPHD results in improved removal of PBS as well., Methods: A cross-over study (Clinical Trial NCT01267760) was performed in nine stable HD patients. At midweek a single dialysis session was performed with either 4 hours SHD using a dialysate flow of 500 mL/min or 8 hours MPHD with a dialysate volume of 50% of estimated body water volume. Blood and dialysate samples were taken every hour to determine concentrations of p-cresylglucuronide (PCG), hippuric acid (HA), indole acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (PCS). Dialyser extraction ratio, reduction ratio, and solute removal were calculated for these solutes., Results: Already at 60 min after dialysis start, the extraction ratio in the hemodialyser was a factor 1.4-4 lower with MPHD versus SHD, resulting in significantly smaller reduction ratios and lower solute removal within a single session. Even when extrapolating our findings to 3 times 4 h SHD and 6 times 8 h MPHD per week, the latter modality was at best similar in terms of total solute removal for most protein-bound solutes, and worse for the highly protein-bound solutes IS and PCS. When efficiency was calculated as solute removal/litre of dialysate used, MPHD was found superior to SHD., Conclusion: When high water consumption is a concern, a treatment regimen of 6 times/week 8 h MPHD might be an alternative for 3 times/week 4 h SHD, but at the expense of a lower total solute removal of highly protein-bound solutes.
- Published
- 2015
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31. Childhood-onset schizophrenia case with 2.2 Mb deletion at chromosome 3p12.2-p12.1 and two large chromosomal abnormalities at 16q22.3-q24.3 and Xq23-q28.
- Author
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Rudd D, Axelsen M, Epping EA, Andreasen N, and Wassink T
- Abstract
Childhood-onset schizophrenia is rare, comprising 1% of known schizophrenia cases. Here, we report a patient with childhood-onset schizophrenia who has three large chromosomal abnormalities: an inherited 2.2 Mb deletion of chromosome 3p12.2-p12.1, a de novo 16.7 Mb duplication of 16q22.3-24.3, and a de novo 43 Mb deletion of Xq23-q28.
- Published
- 2015
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32. Influence of field strength, coil type and image resolution on assessment of synovitis by unenhanced MRI--a comparison with contrast-enhanced MRI.
- Author
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Eshed I, Krabbe S, Østergaard M, Bøyesen P, Møller JM, Therkildsen F, Madsen OR, Axelsen M, and Pedersen SJ
- Subjects
- Adolescent, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Reproducibility of Results, Young Adult, Contrast Media, Image Enhancement, Magnetic Resonance Imaging methods, Synovitis diagnosis
- Abstract
Objectives: To explore if the reliability of synovitis assessment by unenhanced MRI is influenced by different MRI field-strengths, coil types and image resolutions in RA patients., Methods: Forty-one RA patients and 12 healthy controls underwent hand MRI (wrist and 2(nd)--5(th) metacarpophalangeal joints) at 4 different field-strengths (0.23 T/0.6 T/1.5 T/3.0 T) on the same day. Seven protocols using a STIR sequence with different field-strengths, coils (flex coils/dedicated phased-array extremity coils) and resolution were applied and scored blindly for synovitis (OMERACT-RAMRIS method). A 1.5 T post-contrast T1-weighted sequence was used as gold standard reference., Results: Fair-good agreement (ICC=0.38--0.72) between the standard reference and the different STIR protocols (best agreement with extremity coil and small voxel size at 1.5 T). The accuracy for presence/absence of synovitis was very high per person (0.80--1.0), and moderate-high per joint (0.63--0.85), whereas exact agreements on scores were moderate (0.50--0.66). The intrareader agreement (15 patients and 3 controls) on presence/absence of synovitis was very high (0.87--1.0)., Conclusions: Unenhanced MRI using STIR sequence is only moderately reliable for assessing hand synovitis in RA, when contrast-enhanced MRI is considered the gold standard reference. Contrast injection, field strength and coil type influence synovitis assessment, and should be considered before performing MRI in clinical trials and practice., Key Points: • STIR is only moderately reliable for synovitis assessment, compared with post-contrast-T1-w. • Contrast injection, field strength, and coil type influence synovitis assessment. • Contrast injection is recommended for reliable and reproducible hand synovitis assessment.
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- 2015
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33. A genome-wide CNV analysis of schizophrenia reveals a potential role for a multiple-hit model.
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Rudd DS, Axelsen M, Epping EA, Andreasen NC, and Wassink TH
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- Adolescent, Adult, Female, Genome-Wide Association Study methods, Humans, Male, Middle Aged, Models, Genetic, Sequence Deletion genetics, Young Adult, DNA Copy Number Variations genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics, Schizophrenia genetics
- Abstract
Schizophrenia is a chronic and severe psychiatric disorder that is highly heritable. While both common and rare genetic variants contribute to disease risk, many questions still remain about disease etiology. We performed a genome-wide analysis of copy number variants (CNVs) in 166 schizophrenia subjects and 52 psychiatrically healthy controls. First, overall CNV characteristics were compared between cases and controls. The only statistically significant finding was that deletions comprised a greater proportion of CNVs in cases. High interest CNVs were then identified as conservative using the following filtering criteria: (i) known deleterious CNVs; (ii) CNVs > 1 Mb that were novel (not found in a database of control individuals); and (iii) CNVs < 1 Mb that were novel and that overlapped the coding region of a gene of interest. Cases did not harbor a higher proportion of conservative CNVs in comparison to controls. However, similar to previous reports, cases had a slightly higher proportion of individuals with clinically significant CNVs (known deleterious or conservative CNVs > 1 Mb) or with multiple conservative CNVs. Two case individuals with the highest burden of conservative CNVs also share a recurrent 15q11.2 BP1-2 deletion, indicating a role for a potential multiple-hit CNV model for schizophrenia. In total, we report three 15q11.2 BP1-2 deletion individuals with schizophrenia, adding to a growing body of evidence that this CNV is involved in disease etiology., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
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34. Children under the age of seven with diabetes are increasing their cardiovascular risk by their food choices.
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Sundberg F, Augustsson M, Forsander G, Cederholm U, and Axelsen M
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- Case-Control Studies, Child, Preschool, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, Humans, Infant, Male, Risk Factors, Cardiovascular Diseases epidemiology, Choice Behavior, Feeding Behavior, Food
- Abstract
Aim: Early-onset diabetes increases the risk of cardiovascular disease. This study examined the eating habits of children under 7 years of age with diabetes to see whether their diet increased that risk even further., Methods: A total of 24 children with type 1 diabetes (mean age 4.5 years) and 27 healthy controls (mean age 4.6 years) participated in this cross-sectional study. Food intake was assessed by two 4-day food records., Results: Children with type 1 diabetes had a higher energy intake from protein (18 vs 15%, p < 0.05) and fat (35 vs 31%, p < 0.05) but lower intake from carbohydrates (47 vs 54%, p < 0.05), than the healthy control group. Intake of saturated fat was higher than recommended in both groups, and consumption of fruit and vegetables was lower than recommended, but similar, in both the diabetes and control groups (191 vs 207 g per day). Total intake of fat was negatively correlated with intake of fruit and vegetables (r = -0.74 p < 0.05) in children with type 1 diabetes., Conclusion: Children under 7 years of age with type 1 diabetes eat too much saturated fat and not enough fruit and vegetables. Their diet should be improved to reduce their cardiovascular risk., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)
- Published
- 2014
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35. Mesangioproliferative glomerulonephritis: a 30-year prognosis study.
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Axelsen M, Smith Pedersen R, Heaf JG, and Ellingsen T
- Abstract
Background: Diffuse mesangioproliferative glomerulonephritis (MesP) is the most commonly diagnosed type of glomerulonephritis (GN) in Denmark, with an incidence of 10.8 million per year. In the present study, the 30-year renal survival was estimated., Methods: A retrospective cohort investigation of 140 patients with biopsy-proven MesP was performed between the period 1967-2006. Factors influencing renal survival were investigated using Cox regression analysis., Results: Renal survival at 5, 10, 20 and 30 years was 87, 78, 59 and 50%, respectively. Female survival after 30 years was significantly better than male survival (70 vs. 40%, p = 0.049). Multivariate analysis, adjusted for age, estimated glomerular filtration rate (GFR) and nephrotic syndrome (NS) was performed for each sex individually. An increase in GFR was associated with a hazard risk (HR) of 0.98 (p = 0.02) in women and 0.99 (p = 0.006) in men. Older age was associated with a HR of 1.04 (p = 0.02) in women and 1.03 (p = 0.004) in men. NS had a poorer prognosis in men (HR 2.53, p = 0.01), but not in women (HR 0.54, p = 0.38)., Conclusion: Increasing age and decreasing GFR were adversely associated with renal death. Renal prognosis was better for women after 30 years, and NS resulted in a poorer prognosis in men. This suggests that disease course and prognosis are different between men and women.
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- 2014
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36. Multipass haemodialysis: a novel dialysis modality.
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Heaf JG, Axelsen M, and Pedersen RS
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- Adolescent, Adult, Creatinine analysis, Female, Follow-Up Studies, Humans, Kidney Failure, Chronic complications, Male, Middle Aged, Models, Theoretical, Phosphates analysis, Prognosis, Ultrafiltration, Urea analysis, Uric Acid analysis, Young Adult, Biomarkers analysis, Dialysis Solutions, Kidney Failure, Chronic therapy, Renal Dialysis
- Abstract
Introduction: Most home haemodialysis (HD) modalities are limited to home use since they are based on a single-pass (SP) technique, which requires preparation of large amounts of dialysate. We present a new dialysis method, which requires minimal dialysate volumes, continuously recycled during treatment [multipass HD (MPHD)]. Theoretical calculations suggest that MPHD performed six times weekly for 8 h/night, using a dialysate bath containing 50% of the calculated body water, will achieve urea clearances equivalent to conventional HD 4 h thrice weekly, and a substantial clearance of higher middle molecules., Methods: Ten stable HD patients were dialyzed for 4 h using standard SPHD (dialysate flow 500 mL/min). Used dialysate was collected. One week later, an 8-h MPHD was performed. The dialysate volume was 50% of the calculated water volume, the dialysate inflow 500 mL/min-0.5 × ultrafiltration/min and the outflow 500 mL/min + 0.5 × ultrafiltration/min. Elimination rates of urea, creatinine, uric acid, phosphate and β2-microglobulin (B2M) and dialysate saturation were determined hourly., Results: Three hours of MPHD removed 49, 54, 50, 51 and 57%, respectively, of the amounts of urea, creatinine, uric acid, phosphate and B2M that were removed by 4 h conventional HD. The corresponding figures after 8 h MPHD were 63, 78, 74, 78 and 111%., Conclusions: Clearance of small molecules using MPHD 6 × 8 h/week will exceed traditional HD 3 × 4 h/week. Similarly, clearance of large molecules will significantly exceed traditional HD and HD 5 × 2.5 h/week. This modality will increase patients' freedom of movement compared with traditional home HD. The new method can also be used in the intensive care unit and for automated peritoneal dialysis.
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- 2013
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37. Eating habits and physical activity: Health in Sweden: The National Public Health Report 2012. Chapter 8.
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Axelsen M, Danielsson M, Norberg M, and Sjöberg A
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Overweight epidemiology, Sex Factors, Socioeconomic Factors, Sweden epidemiology, Young Adult, Feeding Behavior, Health Status, Motor Activity, Public Health statistics & numerical data
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- 2012
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38. Warts in a cohort of Danish kidney transplanted patients: impact on quality of life.
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Zachariae C, Sand C, Hansen JM, Sørensen SS, Koch K, Villumsen J, and Axelsen M
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- Adult, Aged, Cost of Illness, Denmark epidemiology, Female, Health Status, Humans, Incidence, Kidney Transplantation adverse effects, Kidney Transplantation immunology, Linear Models, Logistic Models, Male, Middle Aged, Skin Neoplasms epidemiology, Skin Neoplasms immunology, Surveys and Questionnaires, Time Factors, Warts epidemiology, Warts immunology, Kidney Transplantation psychology, Quality of Life, Skin Neoplasms psychology, Warts psychology
- Abstract
There are no published clinical studies evaluating the impact of warts on quality of life after transplantation. The aim of this study was to determine the frequency of self-reported skin warts and skin cancer and their impact on quality of life in kidney transplanted patients, as measured with the Dermatology Life Quality Index (DLQI). Of 740 patients with a functioning renal allograft and were free of dialysis who were surveyed, 568 returned the questionnaires. Patients were asked about general health issues, with a focus on transplantation history, cutaneous warts and whether they had ever had cutaneous cancer. A total of 285 (52%) patients replied that they had warts, and these increased with time since last transplantation, with a p-value < 0.0001. A total of 101 patients (18%) reported that they had ever had skin cancer. The median DLQI was 0 for patients not having warts, 1 for patients with warts, and 2 for patients having warts and skin cancer. In conclusion, renal transplant recipients experience increasing numbers of warts and skin cancer over time, and having skin cancer impairs patients' quality of life to a greater degree than warts.
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- 2012
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39. Influence of ZNF804a on brain structure volumes and symptom severity in individuals with schizophrenia.
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Wassink TH, Epping EA, Rudd D, Axelsen M, Ziebell S, Fleming FW, Monson E, Ho BC, and Andreasen NC
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- Adult, Case-Control Studies, Cerebral Cortex pathology, Female, Gene Frequency genetics, Genetic Carrier Screening, Genetic Predisposition to Disease genetics, Genotype, Homozygote, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Organ Size physiology, Phenotype, Psychiatric Status Rating Scales, Reference Values, Schizophrenia diagnosis, Young Adult, Alleles, Kruppel-Like Transcription Factors genetics, Polymorphism, Single Nucleotide genetics, Schizophrenia genetics, Schizophrenic Psychology
- Abstract
CONTEXT The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and with quantitative phenotypic features, including brain structure volume and the core symptoms of schizophrenia. OBJECTIVE To evaluate associations of rs1344706 with brain structure and the core symptoms of schizophrenia. DESIGN Case-control analysis of covariance. SETTING University-based research hospital. PARTICIPANTS Volunteer sample of 335 individuals with schizophrenia spectrum disorders (306 with core schizophrenia) and 198 healthy volunteers. MAIN OUTCOME MEASURES Cerebral cortical gray matter and white matter (WM) volumes (total and frontal, parietal, temporal, and occipital lobes), lateral ventricular cerebrospinal fluid volume, and symptom severity from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms divided into 3 domains: psychotic, negative, and disorganized. RESULTS The rs1344706 genotype produced significant main effects on total, frontal, and parietal lobe WM volumes (F = 3.98, P = .02; F = 4.95, P = .007; and F = 3.08, P = .05, respectively). In the schizophrenia group, rs1344706 produced significant simple effects on total (F = 3.93, P = .02) and frontal WM volumes (F = 7.16, P < .001) and on psychotic symptom severity (F = 6.07, P = .003); the pattern of effects was concordant with risk allele carriers having larger volumes and more severe symptoms of disease than nonrisk homozygotes. In the healthy volunteer group, risk allele homozygotes had increased total WM volume compared with nonrisk allele carriers (F = 4.61, P = .03), replicating a previously reported association. CONCLUSIONS A growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. Our study supports this assertion by finding that specific genotypes of the polymorphism are associated with brain structure volumes in individuals with schizophrenia and healthy volunteers and with symptom severity in schizophrenia.
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- 2012
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40. Estimating risk of pulmonary neoplastic embolism during vertebroplasty.
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Axelsen M, Thomassen LD, Bünger C, Bendtsen M, Zou X, Flo C, Wang Y, and Rehling M
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- Animals, Bone Cements adverse effects, Neoplasm Invasiveness diagnostic imaging, Radiography, Spinal Fractures diagnostic imaging, Spinal Fractures surgery, Spinal Neoplasms diagnostic imaging, Swine, Neoplasm Invasiveness prevention & control, Risk, Spinal Neoplasms surgery, Vertebroplasty adverse effects
- Abstract
Study Design: Vertebroplasty was simulated on a pig model., Objective: To evaluate the risk of neoplastic tissue migration into lungs during vertebroplasty., Summary of Background Data: The application of vertebroplasty in spinal metastasis is not well documented. The risk of neoplastic tissue migration into the lungs during vertebroplasty remains unknown., Methods: A cancer model was built in 11 Landrace pigs (50 kg) by injecting 99mTc-labeled albumin macroaggregates into the center of L5 and L6 prior to vertebroplasty. Continuous scintigraphic imaging was performed with 1-minute frames over the lungs and vertebrae before and after injection to ensure steady state and baseline. We surveyed free TcO4- in thyroid. Twenty minutes after the 99mTc injection, 2-level vertebroplasty was performed at L5 and L6 with 3 Jamshidi needles in each vertebra. Into each vertebra, on average, 2.8 ± 1.1 mL of poly(methyl methacrylate) cement (Depuy CMW, Blackpool, UK) was injected. Quantitative scintigrams were obtained within 90 minutes after vertebroplasty. X-rays and quantitative computed tomography scans quantified cement distribution. Means of 99mTc activity before and after vertebroplasty were compared in a paired t test., Results: In this cancer model, we found an 80% risk of tissue migration to the lungs when performing vertebroplasty. In average, the study showed a significant amount of macroaggregate migration of 1.87% total range from 0% to 8% (CI: 0.05%-0.37%) with P = 0.045. There was no free TcO4- in the thyroid. Despite the standardized procedure, we found a large interindividual variation of pulmonary embolism., Conclusion: It is demonstrated that there exists a significant risk of exporting neoplastic disease or fatty tissue to the lungs when performing vertebroplasty. A similar adverse effect can be expected with balloon kyphoplasty. In patients with metastatic disease, vertebroplasty should be limited to those with short life expectancy.
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- 2012
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41. Efficacy of recombinant human mannose binding lectin alone and in combination with itraconazole against murine Candida albicans vaginitis.
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Clemons KV, Martinez M, Axelsen M, Thiel S, and Stevens DA
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- Administration, Intravaginal, Administration, Oral, Animals, Body Fluids metabolism, Candidiasis, Vulvovaginal microbiology, Disease Models, Animal, Drug Therapy, Combination, Female, Humans, Injections, Intravenous, Itraconazole administration & dosage, Mannose-Binding Lectin administration & dosage, Mannose-Binding Lectin blood, Mannose-Binding Lectin genetics, Mannose-Binding Lectin metabolism, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Recombinant Proteins administration & dosage, Recombinant Proteins blood, Recombinant Proteins metabolism, Treatment Outcome, Vagina metabolism, Vagina microbiology, Vaginal Creams, Foams, and Jellies administration & dosage, Vaginal Douching, Candida albicans isolation & purification, Candidiasis, Vulvovaginal drug therapy, Itraconazole therapeutic use, Mannose-Binding Lectin therapeutic use, Recombinant Proteins therapeutic use
- Abstract
Mannan binding lectin (MBL) deficiency has been associated with increased susceptibility to vaginitis in humans due to Candida albicans. In these studies we assessed the utility of recombinant human MBL (rhMBL) as a therapeutic against experimental C. albicans vaginitis. After intravenous treatment of uninfected mice with 75 μg of rhMBL, rhMBL was detected in the serum and peritoneal lavage fluid; rhMBL was detected in the serum of infected mice 2 and 24 hours post-dose, and at very low concentrations in vaginal lavage fluid. Intravenous treatment with rhMBL alone or in combination with oral itraconazole enhanced the clearance of C. albicans from the vagina of wild-type or MBL gene knockout (KO) mice; rhMBL was modestly effective alone. However, rhMBL in combination with itraconazole was not better than itraconazole alone. Topical administration of rhMBL in a cream appeared more effective than rhMBL in a gel and both were inferior to commercial clotrimazole cream. Topical rhMBL cream in combination with itraconazole resulted in a 3-fold improvement in clearance of the yeast compared with sole itraconazole therapy. Overall, these data indicate that rhMBL may have utility in the treatment of candidal vaginitis when used as an adjunctive therapy.
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- 2011
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42. Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin.
- Author
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Fosgerau K, Ristagno G, Jayatissa M, Axelsen M, Gotfredsen JW, Weber UJ, Køber L, Torp-Pedersen C, and Videbaek C
- Subjects
- Animals, Arrhythmias, Cardiac, Capsaicin administration & dosage, Capsaicin adverse effects, Capsaicin pharmacology, Cardiac Output, Low, Disease Models, Animal, Electric Countershock, Heart Arrest physiopathology, Humans, Infusions, Intravenous, Male, Rats, Rats, Sprague-Dawley, TRPV Cation Channels agonists, Transient Receptor Potential Channels agonists, Capsaicin analogs & derivatives, Heart Arrest drug therapy, Resuscitation
- Abstract
Background: Survivors of a cardiac arrest often have persistent cardiovascular derangements following cardiopulmonary resuscitation including decreased cardiac output, arrhythmias and morphological myocardial damage. These cardiovascular derangements may lead to an increased susceptibility towards the external and internal environment of the cardiovascular system as compared to the healthy situation., Methods: Here we tested the hypothesis that the cardiovascular system in healthy rats and rats resuscitated from a cardiac arrest may be differentially affected by a transient receptor potential vanilloid type 1 agonist, by continuous intravenous infusion of dihydrocapsaicin (DHC)., Results: Compared to baseline, infusion of DHC caused an initial increase in mean arterial blood pressure in both healthy and resuscitated rats of 25% and 10%, respectively. Also, we observed an initial response of tachycardia in both healthy and resuscitated rats of 30% and 20%, respectively. Then, at high levels of DHC infusion (> 2.0 mg/kg/hr) we observed two single episodes of transient bradycardia and hypotension in 33% of the healthy rats, which was consistent with a TRPV1 agonist induced Bezold-Jarisch reflex. In contrast, in resuscitated rats we observed multiple episodes of bradycardia/hypotension in 100% of the rats and at a dose of DHC of 0.65 mg/kg/hr. Notably, this DHC effect could be completely blocked in the resuscitated rats by pre-treatment with atropine, a muscarinic acetylcholine antagonist., Conclusions: Our results indicate that the susceptibility of the rats towards TRPV1 agonist induced Bezold-Jarisch reflex is increased in those resuscitated from cardiac arrest compared to the healthy situation.
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- 2010
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43. Measuring the glycemic index of foods: interlaboratory study.
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Wolever TM, Brand-Miller JC, Abernethy J, Astrup A, Atkinson F, Axelsen M, Björck I, Brighenti F, Brown R, Brynes A, Casiraghi MC, Cazaubiel M, Dahlqvist L, Delport E, Denyer GS, Erba D, Frost G, Granfeldt Y, Hampton S, Hart VA, Hätönen KA, Henry CJ, Hertzler S, Hull S, Jerling J, Johnston KL, Lightowler H, Mann N, Morgan L, Panlasigui LN, Pelkman C, Perry T, Pfeiffer AF, Pieters M, Ramdath DD, Ramsingh RT, Robert SD, Robinson C, Sarkkinen E, Scazzina F, Sison DC, Sloth B, Staniforth J, Tapola N, Valsta LM, Verkooijen I, Weickert MO, Weseler AR, Wilkie P, and Zhang J
- Subjects
- Adolescent, Adult, Aged, Area Under Curve, Blood Glucose metabolism, Cross-Over Studies, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, Reference Values, Reproducibility of Results, Sensitivity and Specificity, Clinical Laboratory Techniques standards, Dietary Carbohydrates metabolism, Food classification, Food Analysis standards, Glycemic Index
- Abstract
Background: Many laboratories offer glycemic index (GI) services., Objective: We assessed the performance of the method used to measure GI., Design: The GI of cheese-puffs and fruit-leather (centrally provided) was measured in 28 laboratories (n=311 subjects) by using the FAO/WHO method. The laboratories reported the results of their calculations and sent the raw data for recalculation centrally., Results: Values for the incremental area under the curve (AUC) reported by 54% of the laboratories differed from central calculations. Because of this and other differences in data analysis, 19% of reported food GI values differed by >5 units from those calculated centrally. GI values in individual subjects were unrelated to age, sex, ethnicity, body mass index, or AUC but were negatively related to within-individual variation (P=0.033) expressed as the CV of the AUC for repeated reference food tests (refCV). The between-laboratory GI values (mean+/-SD) for cheese-puffs and fruit-leather were 74.3+/-10.5 and 33.2+/-7.2, respectively. The mean laboratory GI was related to refCV (P=0.003) and the type of restrictions on alcohol consumption before the test (P=0.006, r2=0.509 for model). The within-laboratory SD of GI was related to refCV (P<0.001), the glucose analysis method (P=0.010), whether glucose measures were duplicated (P=0.008), and restrictions on dinner the night before (P=0.013, r2=0.810 for model)., Conclusions: The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.
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- 2008
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44. Low mannose-binding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy.
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Vekemans M, Robinson J, Georgala A, Heymans C, Muanza F, Paesmans M, Klastersky J, Barette M, Meuleman N, Huet F, Calandra T, Costantini S, Ferrant A, Mathissen F, Axelsen M, Marchetti O, and Aoun M
- Subjects
- Adult, Aged, Disease Susceptibility immunology, Female, Hematologic Neoplasms complications, Hematologic Neoplasms drug therapy, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neutropenia chemically induced, Pneumonia immunology, Prospective Studies, Risk Factors, Sepsis immunology, Antineoplastic Agents adverse effects, Disease Susceptibility blood, Mannose-Binding Lectin blood, Mannose-Binding Lectin deficiency, Pneumonia blood, Sepsis blood
- Abstract
Background: Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy., Methods: We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables., Results: We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P=.008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P<.001])., Conclusions: MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patients.
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- 2007
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45. Phase I safety, tolerability, and pharmacokinetic study of recombinant human mannan-binding lectin.
- Author
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Petersen KA, Matthiesen F, Agger T, Kongerslev L, Thiel S, Cornelissen K, and Axelsen M
- Subjects
- Adolescent, Adult, Dose-Response Relationship, Drug, Double-Blind Method, Half-Life, Humans, Male, Mannose-Binding Lectin blood, Middle Aged, Recombinant Proteins, Immunologic Deficiency Syndromes drug therapy, Mannose-Binding Lectin deficiency, Mannose-Binding Lectin pharmacology
- Abstract
Mannan-binding lectin (MBL), a human plasma protein, plays an important role in the innate immune defence. MBL recognizes microorganisms through surface carbohydrate structures. Due to genetic polymorphisms, MBL plasma concentrations range from 5 to 10,000 ng/mL. Approximately 30% of the human population have low levels of MBL (below 500 ng/mL). MBL deficiency is associated with increased susceptibility to infections in immunosuppressed individuals, e.g., during chemotherapeutically induced neutropenia. Replacement therapy with MBL may be beneficial in this patient group, and recombinant human MBL (rhMBL) is in development as a novel therapeutic approach. To assess the safety, tolerability, and pharmacokinetics of rhMBL, a placebo-controlled double-blinded study was performed in MBL-deficient healthy male subjects. rhMBL was administered as both single intravenous (i.v.) infusions (0.01, 0.05, 0.1, and 0.5 mg/kg) and repeated i.v. infusions (0.1 or 0.3 mg/kg given at 3-day intervals). There were no difference in incidence and type of adverse events reported in the study between the groups of subjects receiving rhMBL and the placebo group. All adverse events reported as drug-related were mild and no serious adverse events were recorded. There were no clinically significant changes in laboratory evaluations, ECG or vital signs, and no anti-MBL antibodies were detected following rhMBL administration. After single i.v. doses of rhMBL the maximal plasma levels increased in a dose-dependent manner reaching a geometric mean of 9710 ng/mL+/-10.5% in the highest dose group (0.5 mg/kg), with an elimination half-life of approximately 30 h. No rhMBL accumulation in plasma was observed following repeat dosing. Administration of rhMBL restored the ability to activate the MBL pathway of the complement system without non-specific activation of the complement cascade. In conclusion, no safety or tolerability concern was raised following rhMBL administration no signs of immunogenicity detected, and an rhMBL plasma level judged sufficient to achieve therapeutic benefit (>1000 ng/mL) can be achieved.
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- 2006
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46. Postprandial interstitial insulin concentrations in type 2 diabetes relatives.
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Sandqvist M, Johanson EH, Ahrén B, Axelsen M, Schmelz M, Smith U, and Jansson PA
- Subjects
- Adipose Tissue blood supply, Adult, Anthropometry, Biological Transport physiology, Cyclohexanes, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Insulin Resistance genetics, Insulin Secretion, Lipolysis physiology, Male, Microdialysis methods, Middle Aged, Nateglinide, Phenylalanine analogs & derivatives, Regional Blood Flow, Adipose Tissue metabolism, Diabetes Mellitus, Type 2 genetics, Insulin metabolism, Insulin Resistance physiology, Postprandial Period physiology
- Abstract
Background: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue., Subjects and Methods: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively., Results: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide., Conclusions: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients.
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- 2006
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47. Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects.
- Author
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Ambring A, Johansson M, Axelsen M, Gan L, Strandvik B, and Friberg P
- Subjects
- Adult, C-Reactive Protein analysis, Chemokine CCL2 blood, Cross-Over Studies, Female, Humans, Interleukin-6 blood, Male, Middle Aged, Phospholipids analysis, Phospholipids blood, Diet, Mediterranean, Fatty Acids, Omega-3 blood, Fatty Acids, Omega-6 blood, Leukocyte Count, Platelet Count, Vascular Endothelial Growth Factor A blood
- Abstract
Background: Reduced cardiovascular mortality and morbidity have been shown in persons adhering to Mediterranean-inspired diets (MIDs). Although the underlying mechanisms of this association are poorly understood, the importance of increasing dietary amounts of polyunsaturated fatty acids of the n-3 series has been emphasized., Objective: We investigated whether a MID provided to healthy subjects would affect 1) the inflammatory process and endothelial indexes such as vasoregulation and vascular endothelial growth factor (VEGF) and 2) serum phospholipid fatty acid composition., Design: A total of 22 subjects (10 women) received a MID or an ordinary Swedish diet (OSD) for 4 wk in a crossover fashion. Concentrations of lipids and fatty acids, high-sensitivity C-reactive protein, and interleukin 6, both before and after lipopolysaccharide stimulation; the number of leukocytes and platelets; and VEGF and monocyte chemoattractant protein 1 were analyzed., Results: The plasma ratio of n-6 to n-3 fatty acids was substantially lower after the MID than after the OSD (x +/- SEM: 4.72 +/- 0.19 and 2.60 +/- 0.17, respectively; P < 0.0001). Neither C-reactive protein nor interleukin 6 concentrations changed significantly after the MID compared with the OSD. The total number of leukocytes and platelets was 10% (P < 0.05) and 15% (P < 0.001) lower, respectively, after the MID than after the OSD. Serum VEGF concentrations were lower after the MID than after the OSD (237 +/- 30 and 206 +/- 25 pg/mL, respectively; P = 0.0014)., Conclusions: A MID reduces the number of platelets and leukocytes and VEGF concentrations in healthy subjects. This may be linked to higher serum concentrations of n-3 fatty acids, which promote a favorable composition of phospholipids.
- Published
- 2006
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48. No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes.
- Author
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Johanson EH, Jansson PA, Gustafson B, Sandqvist M, Taskinen MR, Smith U, and Axelsen M
- Subjects
- Blood Glucose metabolism, Body Mass Index, Cholesterol blood, Female, Glucose Tolerance Test, Humans, Male, Middle Aged, Nateglinide, Phenylalanine pharmacology, Risk Factors, Triglycerides blood, Cyclohexanes pharmacology, Diabetes Mellitus, Type 2 epidemiology, Hypoglycemic Agents pharmacology, Lipids blood, Lipoproteins blood, Phenylalanine analogs & derivatives, Postprandial Period
- Abstract
Background: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes., Methods: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1))., Results: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide., Conclusions: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.
- Published
- 2005
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49. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials.
- Author
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Boffard KD, Riou B, Warren B, Choong PI, Rizoli S, Rossaint R, Axelsen M, and Kluger Y
- Subjects
- Adult, Chi-Square Distribution, Double-Blind Method, Erythrocyte Transfusion statistics & numerical data, Female, Hemorrhage etiology, Hemostasis physiology, Humans, Male, Statistics, Nonparametric, Treatment Outcome, Factor VIIa therapeutic use, Hemorrhage prevention & control, Wounds and Injuries complications
- Abstract
Background: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma., Methods: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose., Results: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups., Conclusion: Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.
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- 2005
- Full Text
- View/download PDF
50. Attitudes and barriers to dietary advice aimed at reducing risk of type 2 diabetes in first-degree relatives of patients with type 2 diabetes.
- Author
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Brekke HK, Sunesson A, Axelsen M, and Lenner RA
- Subjects
- Adult, Cross-Sectional Studies, Diabetes Mellitus, Type 2 genetics, Dietary Fats administration & dosage, Feeding Behavior, Female, Food classification, Fruit, Genetic Predisposition to Disease, Glycemic Index, Health Knowledge, Attitudes, Practice, Humans, Life Style, Male, Middle Aged, Patient Education as Topic, Risk Factors, Surveys and Questionnaires, Vegetables, Attitude to Health, Diabetes Mellitus, Type 2 prevention & control, Nutritional Sciences education, Patient Compliance
- Abstract
Objective: To evaluate the attitudes to and adoption of dietary advice in nondiabetic first-degree relatives of patients with type 2 diabetes and to examine barriers to adherence., Design: One-year controlled intervention study, where treatment group (n=73) received lifestyle education. Attitudes towards dietary advice, change in dietary habits and importance of potential barriers to adherence were evaluated by questionnaires. Nondiabetic relatives (25-55 years; males and females) of individuals with type 2 diabetes were recruited. Education was based on current nutrition recommendations and aimed at improving dietary fat quality, increasing intake of fruit and vegetables, with additional advice to reduce dietary glycaemic index (GI)., Main Outcome Measures: Attitudes and importance of barriers were classified by the intervened subjects into four categories ranging from 'No problem' to 'Yes, definitely a problem'. Dietary adherence was monitored by food frequency questionnaire at baseline and after 1 year., Results: Participants were generally in favour of advice aimed at improving dietary fat quality. Attitudes towards advice to reduce GI varied widely. Food selection changed in accordance with predefined dietary goals. 'Forgetfulness', 'low availability in lunch restaurant' and 'lack of ideas for cooking' were barriers to adherence., Conclusions: Dietary advice aimed at reducing risk of type 2 diabetes was generally positively received and adopted in subjects with heredity for the disease. The most prevalent barriers reported are potentially modifiable.
- Published
- 2004
- Full Text
- View/download PDF
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