Birgens H.,Copenhagen University |
Frederiksen H.,University of Southern Denmark |
Hasselbalch H.C.,Roskilde University |
Rasmussen I.H.,University of Aalborg |
And 9 more authors.
British Journal of Haematology | Year: 2013
The impact of first-line treatment with the anti-CD 20 chimeric monoclonal antibody rituximab in patients with warm-antibody reactive autoimmune haemolytic anaemia (WAIHA) is unknown. We report the first randomized study of 64 patients with newly diagnosed WAIHA who received prednisolone and rituximab combined (N = 32) or prednisolone monotherapy (N = 32). After 12 months, a satisfactory response was observed in 75% of the patients treated with rituximab and prednisolone but in a significantly smaller proportion (36%) of those given prednisolone alone (P = 0·003). Furthermore, relapse-free survival was significantly better after the combined therapy than after prednisolone monotherapy (P = 0·02). After 36 months, about 70% of the patients were still in remission in the rituximab-prednisolone group, whereas only about 45% were still in complete or partial remission in the prednisolone group. There was no significant difference between the two groups regarding adverse reactions to the studied medications. Likewise, serious adverse events were equally distributed, and no allergic reactions to rituximab were recorded. In conclusion, our data show that using rituximab and prednisolone combined rather than prednisolone alone as first-line treatment in WAIHA increases both the rate and the duration of the response. © 2013 John Wiley & Sons Ltd.
Nielsen J.C.,Aarhus University Hospital |
Thomsen P.E.B.,Copenhagen University |
Hojberg S.,Bispebjerg Hospital |
Moller M.,University of Southern Denmark |
And 14 more authors.
European Heart Journal | Year: 2011
Aim s In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any difference between single-lead atrial pacing (AAIR) and dual-chamber pacing (DDDR).Methods and resultsWe randomly assigned 1415 patients referred for first pacemaker implantation to AAIR (n 707) or DDDR (n 708) pacing and followed them for a mean of 5.4 ± 2.6 years. The primary outcome was death from any cause. Secondary outcomes included paroxysmal and chronic atrial fibrillation, stroke, heart failure, and need for pacemaker reoperation. In the AAIR group, 209 patients (29.6) died during follow-up vs. 193 patients (27.3) in the DDDR group, hazard ratio (HR) 1.06, 95 confidence interval (CI) 0.881.29, P 0.53. Paroxysmal atrial fibrillation was observed in 201 patients (28.4) in the AAIR group vs. 163 patients (23.0) in the DDDR group, HR 1.27, 95 CI 1.031.56, P 0.024. A total of 240 patients underwent one or more pacemaker reoperations during follow-up, 156 (22.1) in the AAIR group vs. 84 (11.9) in the DDDR group (HR 1.99, 95 CI 1.532.59, P < 0.001). The incidence of chronic atrial fibrillation, stroke, and heart failure did not differ between treatment groups.Conclusion In patients with sick sinus syndrome, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients. Clinical Trial Registration: URL http://www.clinicaltrials.gov. Unique identifier: NCT00236158. © 2010 The Author.
Schmitz M.L.,Aarhus University Hospital |
Simonsen C.Z.,Aarhus University Hospital |
Hundborg H.,Aarhus University Hospital |
Christensen H.,Bispebjerg Hospital |
And 8 more authors.
Stroke | Year: 2014
BACKGROUND AND PURPOSE -: Data on long-term outcome after intravenous tissue-type plasminogen activator (tPA) in ischemic stroke are limited. We examined the risk of long-term mortality, recurrent ischemic stroke, and major bleeding, including intracranial and gastrointestinal bleeding, in intravenous tPA-treated patients when compared with intravenous tPA eligible but nontreated patients with ischemic stroke. METHODS -: We conducted a register-based nationwide propensity score-matched follow-up study among patients with ischemic stroke in Denmark (2004-2011). Cox regression analysis was used to compute adjusted hazard ratios for all outcomes. RESULTS -: Among 4292 ischemic strokes (2146 intravenous tPA-treated and 2146 propensity score-matched nonintravenous tPA-treated patients), with a follow-up for a median of 1.4 years, treatment with intravenous tPA was associated with a lower risk of long-term mortality (adjusted hazard ratio, 0.66; 95% confidence interval, 0.49-0.88). The long-term risk of recurrent ischemic stroke (adjusted hazard ratio, 1.05; 95% confidence interval, 0.68-1.64) and major bleeding (adjusted hazard ratio, 0.59; 95% confidence interval, 0.24-1.47) did not differ significantly between the intravenous tPA-treated and nontreated patients. CONCLUSIONS -: Treatment with intravenous tPA in patients with ischemic stroke was associated with improved long-term survival. © 2014 American Heart Association, Inc.
Sorensen P.S.,Copenhagen University |
Lycke J.,Sahlgrenska University Hospital |
Eralinna J.-P.,Suomen Terveystalo Clinical Research |
Edland A.,Buskerud Hospital |
And 9 more authors.
The Lancet Neurology | Year: 2011
Treatment of relapsing-remitting multiple sclerosis with interferon beta is only partly effective. We aimed to establish whether add-on of simvastatin, a statin with anti-inflammatory properties, improves this efficacy. Methods: We enrolled treatment-naive patients with relapsing-remitting multiple sclerosis in a multicentre, placebo-controlled, double-blind, randomised, parallel-group trial of simvastatin (80 mg daily) as add-on treatment to intramuscular interferon beta-1a (30 μg weekly). After starting treatment with interferon beta, patients were randomly assigned (in computer-generated blocks of four patients) to simvastatin 80 mg per day or placebo for 1-3 years. Patients and treating and evaluating physicians were masked to treatment allocation. The primary outcome measure was annual rate of documented relapses; analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00492765. Findings: We randomly assigned 307 patients to interferon beta plus simvastatin (n=151) or plus placebo (n=156). Annual rate of documented relapses was 0·19 (95% CI 0·13 to 0·28) in the simvastatin group and 0·14 (95% CI 0·09 to 0·23) in the placebo group (absolute difference 0·059, 95% CI -0·21 to 0·09; p=0·35). Time to first documented relapse (20th percentile) was 18·1 months in patients on simvastatin and 21·5 months in those on placebo (hazard ratio 1·21, 95% CI 0·74 to 1·99; p=0·51). Mean number of new or enlarging T2 lesions was 2·96 in the simvastatin group and 2·52 in the placebo group (ratio of new lesions, 1·17, 95% CI 8·89 to 1·55; p=0·25). Eight (6%) patients on simvastatin and 17 (13%) on placebo had no disease activity (odds ratio 0·42, 95% CI 0·17 to 1·00; p=0·05). No unexpected adverse events were seen. Generally, adverse events were mild and there were no group differences in infections or musculoskeletal disorders, including myalgia (five [3%] patients on simvastatin and nine [6%] on placebo). Rhabdomyolysis and myoglobinuria were not reported and there were no differences in serum creatine phosphokinase. Interpretation: We found no beneficial effect of simvastatin as add-on therapy to interferon beta-1a. Although unlikely, we can not exclude that combination of other statins with other disease-modifying drugs still could be beneficial. Funding: Biogen Idec. © 2011 Elsevier Ltd.
Gang A.O.,Herlev Hospital |
Strom C.,Rigshospitalet |
Pedersen M.,Herlev Hospital |
d'Amore F.,Arhus Hospital |
And 10 more authors.
Annals of Oncology | Year: 2012
Background: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18-60 years with two or more risk factors (stage III-IV, elevated lactate dehydrogenase levels, performance status 2-4). To our knowledge, this is the first study comparing these two regimens in this patient group. Methods: We obtained data for the period 2004-2009 from the Danish Lymphoma Database. One hundred and fiftynine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety. Results: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P = 0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P = 0.02). Conclusion: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
Pedersen R.S.,Herning Hospital |
Bayat A.,Esbjerg Hospital |
Steen N.P.,Vejle Hospital |
Jacobsson M.-L.B.,Hillerod Hospital
Danish Medical Journal | Year: 2013
INTRODUCTION: Pain and distress during minor hospital-related procedures is a familiar problem in many children. Inadequate relief of children's procedural pain and distress not only affects the experience of the children and their parents, but also adversely impacts procedural success. We aimed to review the safety and efficacy of nitrous oxide during brief, but painful paediatric procedures and to compare nitrous oxide with some of the commonly used pharmacological and non-pharmacological treatments for relieving anxiety and mild to moderate pain in Denmark. METHOD: We searched MEDLINE (PubMed) and the Cochrane Database of Systematic Reviews with the MeSH term nitrous oxide combined with midazolam, surgical procedures minor, analgesia or conscious sedation. The references in the articles acquired that were not found in the MEDLINE search were further investigated. Only articles written in English and published after 1980 were included to ensure optimal data collection. RESULTS: Nitrous oxide is an effective sedative/analgesic for mildly to moderately painful paediatric procedures. Furthermore, it is safely administrated, particularly for short procedures (< 15 min.). Serious and potentially serious adverse events are rare and occur in less than 0.5% of cases, while minor events typically occur amongst 4-8% of patients. CONCLUSION: Nitrous oxide is a safe and effective method to achieve analgesia and sedation during minor, but painful procedures. It can be safely administered by a dedicated staff member. This helpful method is still underused in Denmark, and we believe that it could be an alternative or the first choice of treatment in emergency and paediatric departments.
Glintborg B.,Gentofte University Hospital |
Ostergaard M.,Copenhagen University |
Krogh N.S.,Zitelab Aps |
Tarp U.,Aarhus University Hospital |
And 13 more authors.
Annals of the Rheumatic Diseases | Year: 2013
Objective: To investigate frequencies and reasons for switching, treatment responses and drug survival in patients with ankylosing spondylitis (AS) switching tumour-necrosis-factor-α inhibitor (TNFi) treatment in routine clinical care. Methods: AS patients were identified in the Danish nationwide DANBIO registry. Disease activity, treatment responses (50% or 20 mm reduction in Bath AS Disease Activity Index (BASDAI)), duration and rates of drug survival and predictors thereof were studied in patients receiving ≥2 different biological drugs. Results: Of 1436 AS patients starting TNFi treatment, 432 patients (30%) switched to a second and 137 (10%) to a third biological drug. Compared with non-switchers, switchers were more frequently women (33%/22%), had shorter disease duration (3 years/5 years) and higher BASDAI (62(52-76) mm/56(43-69) mm (median (interquartile-range))), Bath AS Functional Index (BASFI) (54(39-71) mm/47(31-65) mm) and visual-analoguescale (VAS) global, pain and fatigue scores when they started the first TNFi (all p<0.01). Main reason for switching was lack of response (56%). During the first, second and third treatment BAS- and VAS scores had decreased after 6 months' treatment (all p<0.05). Median drug survivals were 3.1, 1.6 and 1.8 years respectively ( p<0.001). After 2 years of treatment 52% of switchers and 63% of non-switchers had achieved response (number needed to treat 1.9 and 1.6, respectively, p=0.01). Drug survivals were similar regardless of the reason for switching. Male gender and low BASFI predicted drug survival of the second TNFi. Conclusions: Nearly one-third of AS patients in clinical practice switched biological treatment. Response rates and drug survivals were lower among switchers, however, half of switchers achieved treatment response.
Hoffmann-Petersen B.,University of Southern Denmark |
Host A.,University of Southern Denmark |
Toksvig Larsen K.,Sonderborg Hospital |
Ryttov Bergstein K.,Esbjerg Hospital |
And 3 more authors.
Pediatric Allergy and Immunology | Year: 2013
Objective: The aim of this article was to estimate the prevalence of IgE sensitization in Danish children with suspected asthma and to characterize the pattern of sensitization. Study design: We performed a cross-sectional study including 1744 children from 0 to 15 yr suspected of asthma who were referred to pediatric outpatient clinics in the region of southern Denmark from 2003 to 2005. The children were subjected to an extensive questionnaire-based interview, clinical examination, and both skin prick testing (SPT) and IgE measurements for 17 allergens. Results: Asthma was confirmed in 1024 of the 1744 children. Among the children in whom the asthma diagnosis was confirmed, sensitization to one or more of the 17 allergens tested was found in 67.5% by either SPT or s-IgE ≥ class 2. Sensitization to any food allergen was found in 31.1%, to any outdoor allergen in 36.2%, and to any indoor allergen in 51.8%. Sensitization to cockroach and latex was rare. We found a weak correlation between SPT and s-IgE among food allergens and a more distinct correlation among inhalant allergens. Surprisingly, 30.1% of children in whom the asthma diagnosis was disproven used inhaled corticosteroids (ICS). On the contrary, 32.5% of the children for whom the asthma diagnosis was verified were not treated with ICS. Conclusion: We have found a high prevalence of sensitization among children with verified asthma. Our study supports relevant allergy testing in all children with verified asthma and emphasizes the importance of a thorough asthma diagnosis before prescribing continuous inhaled corticosteroids to children. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kristensen T.,University of Southern Denmark |
Moller M.B.,University of Southern Denmark |
Friis L.,University of Southern Denmark |
Bergmann O.J.,Esbjerg Hospital |
Preiss B.,University of Southern Denmark
European Journal of Haematology | Year: 2011
Mutation in the NPM1 gene occurs in 60% of acute myeloid leukaemia (AML) patients with normal karyotype. NPM1 mutation is potentially a superior minimal residual disease (MRD) marker compared to WT1 gene overexpression by being specific to the malignant clone, although experimental evidence published so far includes very limited numbers of relapsed cases. Also, the stability of the NPM1 mutation has been questioned by reports of the mutation being lost at relapse. In the present study we compared NPM1 mutation and WT1 overexpression as MRD markers in 20 cases of relapsed AML. The 20 patients experienced a total of 28 morphological relapses. Karyotypic evolution was detected in 56% of relapses. All relapses were accompanied by high levels of NPM1 mutation, along with high WT1 mRNA levels, thus demonstrating complete stability of both markers during relapse. Detectable NPM1 mutation following a period of morphological remission was accompanied by a morphological relapse in all cases. In contrast, WT1 expression was detected in 33% of the NPM1 mutation negative samples. This background WT1 expression produced by non-leukaemia cells was highly variable, both between and within patients, and limited the de facto sensitivity of the WT1 expression analysis. The present study therefore provides important experimental evidence demonstrating that NPM1 mutation is superior to WT1 overexpression as marker of MRD in NPM1-mutated AML, even in the presence of extensive karyotypic evolution. © 2011 John Wiley & Sons A/S.
Tumer Z.,Center for Applied Human Molecular Genetics |
Tumer Z.,Copenhagen University |
Bertelsen B.,Center for Applied Human Molecular Genetics |
Gredal O.,The Rehabilitation Center for Neuromuscular Diseases |
And 6 more authors.
Neurobiology of Aging | Year: 2012
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. About 10% of ALS cases are familial (FALS) and the genetic defect is known only in approximately 20%-30% of these cases. The most common genetic cause of ALS is SOD1 (superoxide dismutase 1) mutation. Very recently, mutations of the optineurin gene (OPTN), which is involved in open-angle glaucoma, were identified in 3 Japanese patients/families with ALS, and subsequently in a few FALS patients of European descent. We found a heterozygous nonsense mutation (c.493C>T, p.Gln165X, exon 6) in the OPTN gene in a Danish patient with ALS, and the mutation segregated from his affected father. The p.Gln165X mutation could not be detected in 1070 healthy Danish controls, in 1000 Danish individuals with metabolic phenotypes or in 64 sporadic ALS (SALS) cases. The p.Gln165X mutation described in this study is the first mutation reported in a Danish family and is likely involved in disease pathogenesis. Until now, only few OPTN mutations have been associated with ALS. As the underlying genetic defect is known only in approximately 20%-30% of FALS families, further screening of these cases is necessary for establishing the contribution of OPTN mutations in disease pathogenesis. © 2012 Elsevier Inc.