Waleed Ghanima - Academia.edu (original) (raw)
Papers by Waleed Ghanima
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 4, 2010
Immune thrombocytopenia (ITP) is caused by immune-mediated platelet destruction and reduced plate... more Immune thrombocytopenia (ITP) is caused by immune-mediated platelet destruction and reduced platelet production. The aim of this review article is to provide an updated overview of pathophysiology and new therapeutic modalities in ITP. The article is based on literature identified through a non-systematic search in PubMed and our own clinical experience. ITP is diagnosed in patients with platelet count < 100 × 10(9)/l after excluding other causes of thrombocytopenia. Anti-platelet autoantibodies are important in the platelet destruction mechanism, but other important mechanisms have been identified in recent years. Patients with very low platelet count < 30 × 10(9)/l are particularly susceptible to bleeding complications. The goal of treatment so far has been to increase the platelet count to a level that reduces the risk of serious bleeding. Thrombopoietin receptor agonists are new therapeutic agents that target the thrombopoietin receptor to increase platelet production. The...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 30, 2002
Hairy cell leukaemia is a chronic B-cell disorder that follows an indolent course. Cladribine has... more Hairy cell leukaemia is a chronic B-cell disorder that follows an indolent course. Cladribine has in the last decade emerged as the drug of choice for treating hairy cell leukaemia. We report on the long-term follow-up of 26 patients treated from January 1992 to June 1993 with cladribine administered subcutaneously. 25 patients were evaluable for response. 21 patients (84%) achieved complete remission, three patients (12%) achieved partial remission, and one patient had no response. At a median follow-up of 6.8 years, 24 patients (92%) were still alive. One patient died from infections four months after treatment, while the other patient died from a malignant melanoma 4.4 years after treatment. Relapse assessed by flow cytometry was diagnosed in 95% of the patients. 38% of those in complete and 67% of those in partial remission were treated by a second course of cladribine during the follow-up. Retreatment led to normalisation of peripheral blood count in all patients. Cladribine is...
Seminars in Hematology, 2010
Immune thrombocytopenia (ITP) is a disease characterized by accelerated platelet destruction and ... more Immune thrombocytopenia (ITP) is a disease characterized by accelerated platelet destruction and suboptimal platelet production. The latter concept has led to the exploration of new therapeutic options by focusing on the stimulation of platelet production as opposed to the traditional approach of immune suppression. Thrombopoietic agents act by stimulating the thrombopoietin receptor on the hematopoietic cells leading to stem cell differentiation, megakaryocyte proliferation, and platelet production. The last decade has witnessed the birth of second-generation thrombopoietic agents. Romiplostim and eltrombopag are the two agents that have been recently licensed. In randomized controlled trials, these agents have demonstrated unequivocal superiority over placebo in the treatment of ITP in splenectomized and in nonsplenectomized patients-an effect that seems to be durable while treatment continues and at an acceptable short-/intermediate-term safety profile. These agents represent a new therapeutic option in refractory ITP and in chronic ITP when splenectomy is contraindicated or needs to be deferred. However, the scope of therapeutic indications is expected to expand should long-term safety be confirmed in the ongoing studies. Several other agents are currently being investigated and are in preclinical and clinical development programs.
Thrombosis Research, 2007
Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM... more Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM D-Dimer) based on microparticle enzyme-immunoassay technology by comparing it with three well established D-dimer assays. Patients and methods: The performance of the new assay was evaluated in 280 plasma samples that were collected prospectively from out-patients included in a management study evaluating a decision based algorithm. Results: 58/280 patients (21%) had PE diagnosed by CT. Median values of AxSYM D-dimer in patients with PE were 3689 ng/mL (range 775-9000). Comparison analysis displayed excellent agreement with VIDAS (κ= 0.84) and Asserachrom (κ= 0.81) D-dimer assays. A strong correlation was found between AxSYM and the VIDAS (r= 0.96) and Asserachrom (r= 0.89) D-dimer assays. The highest cut-off value for AxSYM that yielded a sensitivity of 100% was 765 ng/mL with a specificity of 50%. At the cut-off level b500 ng/mL, the sensitivity and specificity of AxSYM D-dimer were 100% and 34%; VIDAS 100% and 42%; Asserachrom 100% and 40%; and STALiatest 100% and 37%, respectively. AxSYM D-dimer was negative in 75 patients (33.8%). None of these had PE at the initial work-up or VTE during the 3-month follow-up. Conclusions: AxSYM D-dimer seems to be safe and effective in ruling out PE in outpatients. The cut-off level can be set at 500 to 750 ng/mL, at which the assay displays a performance that is comparable to that of the ELISA based assays. However, further Thrombosis Research (2007) 120, 471-476 studies are needed to confirm the safety of the assay and to determine the most optimal cut-off level in patients with venous thromboembolism.
The Lancet, 2015
Immune thrombocytopenia is characterised by immune-mediated destruction and suboptimum production... more Immune thrombocytopenia is characterised by immune-mediated destruction and suboptimum production of platelets. Despite the absence of supporting evidence, rituximab is frequently used off-label in patients with immune thrombocytopenia. We aimed to assess the efficacy of rituximab as compared with placebo as a splenectomy-sparing treatment in patients who were previously treated with corticosteroids. In this multicentre, randomised, double-masked, placebo-controlled trial, we enrolled corticosteroid unresponsive adult patients (aged ≥18 years) with primary immune thrombocytopenia and a platelet count of less than 30 × 10(9) platelets per L. Patients were randomly assigned (1:1) to four weekly infusions of 375 mg/m(2) rituximab or placebo. Concurrent treatment with corticosteroids only was allowed during the study. The primary endpoint was rate of treatment failure within 78 weeks-a composite of splenectomy or meeting criteria for splenectomy after week 12 if splenectomy was not done, assessed in all patients who received at least one dose of study treatment. Secondary endpoints were response rates, relapse rates, and duration of response. Efficacy endpoints were assessed with the Kaplan-Meier method. Safety endpoints were assessed in all patients who received at least one dose. This trial is registered with ClinicalTrials.gov, number NCT00344149. Between Aug 17, 2006, and June 30, 2011, we enrolled 112 patients. 32 (58%) of 55 patients in the rituximab group and 37 (69%) of 54 patients in the placebo group had treatment failure within 78 weeks (Kaplan-Meier cumulative incidence 46% for rituximab vs 52% for placebo (hazard ratio [HR] 0·89, 95% CI 0·55-1·45; p=0·65). The cumulative incidence of overall response was 81% in the rituximab group versus 73% in the placebo group (p=0·15) and complete response was 58% in the rituximab group versus 50% in the placebo group (p=0·12). Of those achieving an overall response, 68% relapsed in the rituximab group and 78% relapsed in the placebo group, and of those achieving complete response, 50% relapsed in the rituximab group and 62% relapsed in the placebo group. Time to relapse in the rituximab group was longer in patients who achieved overall response (36 vs 7 weeks; p=0·01) but not complete response (76 vs 49 weeks; p=0·19). Rates of bleeding were similar in the two groups (21 [38%] in the rituximab group vs 27 [50%] in the placebo group; p=0·08) as were rates of infection (22 [40%] vs 13 [24%]; p=0·09). Despite no reduction in the rate of long-term treatment failure with rituximab, a small benefit cannot be ruled out, as suggested by an apparently longer duration of response and numerically higher response rates with rituximab. South-East Regional Health Authority and Østfold Hospital, Norway; Roche, France; and Roche, Norway.
Tidsskrift for Den norske legeforening, 2013
Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been ap... more Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs. The review is based on published phase 3 studies, a literature search in PubMed and the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; clinical experience. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.
Thrombosis Research, 2007
Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM... more Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM D-Dimer) based on microparticle enzyme-immunoassay technology by comparing it with three well established D-dimer assays. Patients and methods: The performance of the new assay was evaluated in 280 plasma samples that were collected prospectively from out-patients included in a management study evaluating a decision based algorithm. Results: 58/280 patients (21%) had PE diagnosed by CT. Median values of AxSYM D-dimer in patients with PE were 3689 ng/mL (range 775-9000). Comparison analysis displayed excellent agreement with VIDAS (κ= 0.84) and Asserachrom (κ= 0.81) D-dimer assays. A strong correlation was found between AxSYM and the VIDAS (r= 0.96) and Asserachrom (r= 0.89) D-dimer assays. The highest cut-off value for AxSYM that yielded a sensitivity of 100% was 765 ng/mL with a specificity of 50%. At the cut-off level b500 ng/mL, the sensitivity and specificity of AxSYM D-dimer were 100% and 34%; VIDAS 100% and 42%; Asserachrom 100% and 40%; and STALiatest 100% and 37%, respectively. AxSYM D-dimer was negative in 75 patients (33.8%). None of these had PE at the initial work-up or VTE during the 3-month follow-up. Conclusions: AxSYM D-dimer seems to be safe and effective in ruling out PE in outpatients. The cut-off level can be set at 500 to 750 ng/mL, at which the assay displays a performance that is comparable to that of the ELISA based assays. However, further Thrombosis Research (2007) 120, 471-476 studies are needed to confirm the safety of the assay and to determine the most optimal cut-off level in patients with venous thromboembolism.
Journal of Internal Medicine, 2010
Risk stratification in pulmonary embolism (PE) may be helpful not only for selecting the appropri... more Risk stratification in pulmonary embolism (PE) may be helpful not only for selecting the appropriate initial therapy but also for planning long-term management. Although several means for risk stratification have been validated during the last years, echocardiography still remains the most important modality for risk stratification in normotensive patients . Recently, we reported an association between the most proximal level of the clot and the severity of PE determined by clinical parameters, computed tomography (CT) radiological markers (pulmonary artery obstruction index, RV ⁄ LV diameter ratio) and cardiac biomarker (cardiac troponin-T) . Based on these findings we proposed a new CT-based score, which we believe can easily be implemented in clinical practice.
British Journal of Haematology, 2012
Blood, 2012
The paradigm for managing primary immune thrombocytopenia (ITP) in adults has changed with the ad... more The paradigm for managing primary immune thrombocytopenia (ITP) in adults has changed with the advent of rituximab and thrombopoietin receptor agonists (TPO-RAs) as options for second-line therapy. Splenectomy continues to provide the highest cure rate (60-70% at 5+ years). Nonetheless, splenectomy is invasive, irreversible, associated with post-operative complications, and its outcome is currently unpredictable, leading some physicians and patients towards postponement and use of alternative approaches.
European Journal of Haematology, 2016
Polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are clonal disorder... more Polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are clonal disorders collectively named myeloproliferative neoplasms (MPN). Published data on epidemiology of MPN after the discovery of the JAK2 mutation and the 2008 WHO classifications, are scarce. We aimed to study the incidence rates, prevalence and survival of MPN in Norway during the period 1993-2012. We identified 2453 persons diagnosed with MPN from the Cancer Registry of Norway between 1993 and 2012. We report age-adjusted incidence rates, prevalence, relative survival and standardized mortality rates. The overall age-adjusted yearly incidence rate of PV increased from 0.4/10⁵ to 0.7/10⁵, ET increased from 0.3/10⁵ to 1.0/10⁵ and MF from 0.2/10⁵ to 0.5/10⁵. Prevalence of PV, ET and MF was 9.2, 8.6 and 3.0 per 10⁵ inhabitants, respectively. The 5-year relative survival (RS) of ET and PV was slightly reduced with no improvement. The 5-year RS of MF was 58.1% (2008-2012). Standardized mortality rate (SMR), was 1.9 (95% CI 1.2 - 2.7). The incidence rates of ET, PV, and MF doubled to tripled during the years 2007-2012 as compared to 1995-2006. This increment in incidence rates may be related to identification of the JAK2 mutation and the derived 2008 WHO-guidelines for MPN. The RS was only slightly reduced in PV and ET, but was substantially reduced in MF. This article is protected by copyright. All rights reserved.
Leukemia & Lymphoma, 2016
In this study with prolonged follow up, we compared clinical outcome, including cause of death an... more In this study with prolonged follow up, we compared clinical outcome, including cause of death and incidence of second cancer, for patients with early stage extranodal marginal zone lymphoma (EMZL, 49 patients), nodal marginal zone lymphoma (NMZL, nine patients) and mantle cell lymphoma (MCL, 42 patients) with emphasis on potential benefit of radiotherapy. Radiotherapy was given to 40 patients with EMZL (nine had surgery only) and all NMZL patients. MCL patients received radiotherapy (17 patients), chemotherapy followed by radiotherapy (13 patients) or chemotherapy alone (12 patients). Compared to a matched control population no increased risk of second cancer or cardiovascular disease was observed. Radiotherapy alone was effective in EMZL and NMZL with low-relapse rates (20% and 33%) and a 10-year overall survival of 78% and 56%, respectively. High-relapse rate and inferior OS in MCL underline the need for extended staging with endoscopy and PET/CT and possibly for novel strategies.
Data Revues 00028703 V154i5 S0002870307005935, Aug 16, 2011
The Lancet Haematology, 2016
Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT)... more Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT) and is associated with reduced quality of life and a substantial cost burden. In the 2-year results of the CaVenT study, additional catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life. In this study we report results at the 5-year follow-up, aiming to assess whether findings for post-thrombotic syndrome and quality of life have persisted. Between Jan 3, 2006, and Dec 22, 2009, we recruited patients aged 18-75 years with a first-time high proximal leg DVT from 20 hospitals in the Norwegian southeastern health region. With sealed envelopes, participants were randomly assigned (1:1) to standard treatment with compression stockings and anticoagulants (control group) or to standard treatment plus catheter-directed thrombolysis with alteplase within 21 days from symptom onset. Pre-specified outcomes in this analysis were post-thrombotic syndrome at 5 years as assessed with the Villalta score and scores for quality of life at 5 years with EQ-5D and the disease-specific VEINES-QOL/Sym. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00251771. At 5 year follow-up (last date Oct 14, 2014), data were available for 176 patients (84% of the 209 patients originally randomised)-87 originally assigned to catheter-directed thrombolysis and 89 originally assigned to the control group. 37 patients (43%; 95% CI 33-53) allocated to catheter-directed thrombolysis developed post-thrombotic syndrome, compared with 63 (71%; 95% CI 61-79) allocated to the control group (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·0001), corresponding to an absolute risk reduction of 28% (95% CI 14-42) and a number needed to treat of 4 (95% CI 2-7). Four (5%) patients assigned to catheter-directed thrombolysis and one (1%) to standard treatment had severe post-thrombotic syndrome (Villalta score ≥15 or presence of an ulcer). Quality-of-life scores with either assessment scale did not differ between the treatment groups. Additional catheter-directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter-directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life. The optimal endovascular thrombolytic approach needs further investigation. Southeastern Norway Regional Health Authority, the Research Council of Norway, University of Oslo, Oslo University Hospital.
Thrombosis and Haemostasis, 2015
Post-thrombotic syndrome (PTS) is a long-term complication of deep-vein thrombosis (DVT). The Vil... more Post-thrombotic syndrome (PTS) is a long-term complication of deep-vein thrombosis (DVT). The Villalta scale is the recommended tool for diagnosing PTS, but requires a clinician&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s assessment in addition to patient self-assessment. In the present study, we validated a self-administered tool for patient reporting of leg symptoms and signs as a mean to assess PTS. We first validated a form for patient self-reported Villalta (PRV1), then developed and validated a visually assisted form (PRV2). The validity of PRV1 and PRV2 was assessed in patients diagnosed with DVT between 2004 and 2012. Median time from DVT to inclusion was 5.1 and 3.5 years for PRV1 (n=162) and PRV2 (n=94), respectively. Patients were requested to complete the PRV form before a scheduled visit. PTS diagnosed by the original Villalta scale during the visit served as the reference method. PRV1 showed only moderate agreement for diagnosing PTS compared with the original Villalta scale (kappa agreement 0.60, 95 % CI 0.48-0.72), whereas PRV2 showed very good agreement (0.82, 95 % CI 0.71-0.94). In the validation of PRV2, PTS was diagnosed in 54 (57 %) patients according to the original Villalta scale and in 60 (64 %) by PRV2. The sensitivity of PRV2 to detect PTS was 98 % and the specificity was 83 %. We conclude that the visually assisted form for PRV is a valid and sensitive tool for diagnosing PTS. Such a tool could be applied in further clinical studies of PTS, making studies less resource demanding by reducing the need for in-person clinic visits.
British journal of haematology, Jan 12, 2015
British Journal of Haematology, 2015
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2015
The aim of the current study was to translate and test the psychometrical properties of the disea... more The aim of the current study was to translate and test the psychometrical properties of the disease-specific pulmonary embolism quality-of-life questionnaire (PEmb-QoL). Patients with a prior history of pulmonary embolism (PE) were identified from the thrombosis registry at Østfold Hospital Trust, Fredrikstad, Norway. All eligible patients were asked to complete the generic EuroQol 5-dimension (EQ-5D) QoL questionnaire as well as the disease-specific PEmb-QoL at baseline and after 2 weeks. Construct validity was tested using principal component factor analysis. Criterion validity was tested using Spearman's correlation coefficients (rho) between EQ-5D and PEmb-QoL. Internal consistency reliability was calculated using Cronbach's alpha coefficient, while test-retest reliability was calculated using the intra-class correlation coefficients (ICC). A total of 213 participants had complete datasets and were included in further analyses. Factor analysis with varimax rotation yield...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 4, 2010
Immune thrombocytopenia (ITP) is caused by immune-mediated platelet destruction and reduced plate... more Immune thrombocytopenia (ITP) is caused by immune-mediated platelet destruction and reduced platelet production. The aim of this review article is to provide an updated overview of pathophysiology and new therapeutic modalities in ITP. The article is based on literature identified through a non-systematic search in PubMed and our own clinical experience. ITP is diagnosed in patients with platelet count < 100 × 10(9)/l after excluding other causes of thrombocytopenia. Anti-platelet autoantibodies are important in the platelet destruction mechanism, but other important mechanisms have been identified in recent years. Patients with very low platelet count < 30 × 10(9)/l are particularly susceptible to bleeding complications. The goal of treatment so far has been to increase the platelet count to a level that reduces the risk of serious bleeding. Thrombopoietin receptor agonists are new therapeutic agents that target the thrombopoietin receptor to increase platelet production. The...
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 30, 2002
Hairy cell leukaemia is a chronic B-cell disorder that follows an indolent course. Cladribine has... more Hairy cell leukaemia is a chronic B-cell disorder that follows an indolent course. Cladribine has in the last decade emerged as the drug of choice for treating hairy cell leukaemia. We report on the long-term follow-up of 26 patients treated from January 1992 to June 1993 with cladribine administered subcutaneously. 25 patients were evaluable for response. 21 patients (84%) achieved complete remission, three patients (12%) achieved partial remission, and one patient had no response. At a median follow-up of 6.8 years, 24 patients (92%) were still alive. One patient died from infections four months after treatment, while the other patient died from a malignant melanoma 4.4 years after treatment. Relapse assessed by flow cytometry was diagnosed in 95% of the patients. 38% of those in complete and 67% of those in partial remission were treated by a second course of cladribine during the follow-up. Retreatment led to normalisation of peripheral blood count in all patients. Cladribine is...
Seminars in Hematology, 2010
Immune thrombocytopenia (ITP) is a disease characterized by accelerated platelet destruction and ... more Immune thrombocytopenia (ITP) is a disease characterized by accelerated platelet destruction and suboptimal platelet production. The latter concept has led to the exploration of new therapeutic options by focusing on the stimulation of platelet production as opposed to the traditional approach of immune suppression. Thrombopoietic agents act by stimulating the thrombopoietin receptor on the hematopoietic cells leading to stem cell differentiation, megakaryocyte proliferation, and platelet production. The last decade has witnessed the birth of second-generation thrombopoietic agents. Romiplostim and eltrombopag are the two agents that have been recently licensed. In randomized controlled trials, these agents have demonstrated unequivocal superiority over placebo in the treatment of ITP in splenectomized and in nonsplenectomized patients-an effect that seems to be durable while treatment continues and at an acceptable short-/intermediate-term safety profile. These agents represent a new therapeutic option in refractory ITP and in chronic ITP when splenectomy is contraindicated or needs to be deferred. However, the scope of therapeutic indications is expected to expand should long-term safety be confirmed in the ongoing studies. Several other agents are currently being investigated and are in preclinical and clinical development programs.
Thrombosis Research, 2007
Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM... more Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM D-Dimer) based on microparticle enzyme-immunoassay technology by comparing it with three well established D-dimer assays. Patients and methods: The performance of the new assay was evaluated in 280 plasma samples that were collected prospectively from out-patients included in a management study evaluating a decision based algorithm. Results: 58/280 patients (21%) had PE diagnosed by CT. Median values of AxSYM D-dimer in patients with PE were 3689 ng/mL (range 775-9000). Comparison analysis displayed excellent agreement with VIDAS (κ= 0.84) and Asserachrom (κ= 0.81) D-dimer assays. A strong correlation was found between AxSYM and the VIDAS (r= 0.96) and Asserachrom (r= 0.89) D-dimer assays. The highest cut-off value for AxSYM that yielded a sensitivity of 100% was 765 ng/mL with a specificity of 50%. At the cut-off level b500 ng/mL, the sensitivity and specificity of AxSYM D-dimer were 100% and 34%; VIDAS 100% and 42%; Asserachrom 100% and 40%; and STALiatest 100% and 37%, respectively. AxSYM D-dimer was negative in 75 patients (33.8%). None of these had PE at the initial work-up or VTE during the 3-month follow-up. Conclusions: AxSYM D-dimer seems to be safe and effective in ruling out PE in outpatients. The cut-off level can be set at 500 to 750 ng/mL, at which the assay displays a performance that is comparable to that of the ELISA based assays. However, further Thrombosis Research (2007) 120, 471-476 studies are needed to confirm the safety of the assay and to determine the most optimal cut-off level in patients with venous thromboembolism.
The Lancet, 2015
Immune thrombocytopenia is characterised by immune-mediated destruction and suboptimum production... more Immune thrombocytopenia is characterised by immune-mediated destruction and suboptimum production of platelets. Despite the absence of supporting evidence, rituximab is frequently used off-label in patients with immune thrombocytopenia. We aimed to assess the efficacy of rituximab as compared with placebo as a splenectomy-sparing treatment in patients who were previously treated with corticosteroids. In this multicentre, randomised, double-masked, placebo-controlled trial, we enrolled corticosteroid unresponsive adult patients (aged ≥18 years) with primary immune thrombocytopenia and a platelet count of less than 30 × 10(9) platelets per L. Patients were randomly assigned (1:1) to four weekly infusions of 375 mg/m(2) rituximab or placebo. Concurrent treatment with corticosteroids only was allowed during the study. The primary endpoint was rate of treatment failure within 78 weeks-a composite of splenectomy or meeting criteria for splenectomy after week 12 if splenectomy was not done, assessed in all patients who received at least one dose of study treatment. Secondary endpoints were response rates, relapse rates, and duration of response. Efficacy endpoints were assessed with the Kaplan-Meier method. Safety endpoints were assessed in all patients who received at least one dose. This trial is registered with ClinicalTrials.gov, number NCT00344149. Between Aug 17, 2006, and June 30, 2011, we enrolled 112 patients. 32 (58%) of 55 patients in the rituximab group and 37 (69%) of 54 patients in the placebo group had treatment failure within 78 weeks (Kaplan-Meier cumulative incidence 46% for rituximab vs 52% for placebo (hazard ratio [HR] 0·89, 95% CI 0·55-1·45; p=0·65). The cumulative incidence of overall response was 81% in the rituximab group versus 73% in the placebo group (p=0·15) and complete response was 58% in the rituximab group versus 50% in the placebo group (p=0·12). Of those achieving an overall response, 68% relapsed in the rituximab group and 78% relapsed in the placebo group, and of those achieving complete response, 50% relapsed in the rituximab group and 62% relapsed in the placebo group. Time to relapse in the rituximab group was longer in patients who achieved overall response (36 vs 7 weeks; p=0·01) but not complete response (76 vs 49 weeks; p=0·19). Rates of bleeding were similar in the two groups (21 [38%] in the rituximab group vs 27 [50%] in the placebo group; p=0·08) as were rates of infection (22 [40%] vs 13 [24%]; p=0·09). Despite no reduction in the rate of long-term treatment failure with rituximab, a small benefit cannot be ruled out, as suggested by an apparently longer duration of response and numerically higher response rates with rituximab. South-East Regional Health Authority and Østfold Hospital, Norway; Roche, France; and Roche, Norway.
Tidsskrift for Den norske legeforening, 2013
Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been ap... more Dabigatran, rivaroxaban and apixaban are three new oral anticoagulants that have recently been approved in Norway. The aim of this article is to provide an overview of the mechanisms of action, the most important indications and practical advice on the use of these drugs. The review is based on published phase 3 studies, a literature search in PubMed and the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; clinical experience. Indications for use of the new anticoagulants include thromboprophylaxis after total hip and knee replacement surgery (all three), prevention of stroke and systemic embolism in non-valvular atrial fibrillation (all three), treatment of acute venous thrombosis and secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For the aforementioned indications, these drugs have proven to be non-inferior to standard established anticoagulation therapy. For atrial fibrillation, all three drugs have also shown a lower incidence of intracranial bleeding compared with standard treatment. It is important to limit the use of these drugs to approved indications, to select patients who show good compliance, to rule out contraindications and to identify drug interactions. Monitoring of coagulation is not required, but patients should be followed up regularly to detect conditions that may lead to changes in the expected efficacy or safety.
Thrombosis Research, 2007
Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM... more Objectives: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM D-Dimer) based on microparticle enzyme-immunoassay technology by comparing it with three well established D-dimer assays. Patients and methods: The performance of the new assay was evaluated in 280 plasma samples that were collected prospectively from out-patients included in a management study evaluating a decision based algorithm. Results: 58/280 patients (21%) had PE diagnosed by CT. Median values of AxSYM D-dimer in patients with PE were 3689 ng/mL (range 775-9000). Comparison analysis displayed excellent agreement with VIDAS (κ= 0.84) and Asserachrom (κ= 0.81) D-dimer assays. A strong correlation was found between AxSYM and the VIDAS (r= 0.96) and Asserachrom (r= 0.89) D-dimer assays. The highest cut-off value for AxSYM that yielded a sensitivity of 100% was 765 ng/mL with a specificity of 50%. At the cut-off level b500 ng/mL, the sensitivity and specificity of AxSYM D-dimer were 100% and 34%; VIDAS 100% and 42%; Asserachrom 100% and 40%; and STALiatest 100% and 37%, respectively. AxSYM D-dimer was negative in 75 patients (33.8%). None of these had PE at the initial work-up or VTE during the 3-month follow-up. Conclusions: AxSYM D-dimer seems to be safe and effective in ruling out PE in outpatients. The cut-off level can be set at 500 to 750 ng/mL, at which the assay displays a performance that is comparable to that of the ELISA based assays. However, further Thrombosis Research (2007) 120, 471-476 studies are needed to confirm the safety of the assay and to determine the most optimal cut-off level in patients with venous thromboembolism.
Journal of Internal Medicine, 2010
Risk stratification in pulmonary embolism (PE) may be helpful not only for selecting the appropri... more Risk stratification in pulmonary embolism (PE) may be helpful not only for selecting the appropriate initial therapy but also for planning long-term management. Although several means for risk stratification have been validated during the last years, echocardiography still remains the most important modality for risk stratification in normotensive patients . Recently, we reported an association between the most proximal level of the clot and the severity of PE determined by clinical parameters, computed tomography (CT) radiological markers (pulmonary artery obstruction index, RV ⁄ LV diameter ratio) and cardiac biomarker (cardiac troponin-T) . Based on these findings we proposed a new CT-based score, which we believe can easily be implemented in clinical practice.
British Journal of Haematology, 2012
Blood, 2012
The paradigm for managing primary immune thrombocytopenia (ITP) in adults has changed with the ad... more The paradigm for managing primary immune thrombocytopenia (ITP) in adults has changed with the advent of rituximab and thrombopoietin receptor agonists (TPO-RAs) as options for second-line therapy. Splenectomy continues to provide the highest cure rate (60-70% at 5+ years). Nonetheless, splenectomy is invasive, irreversible, associated with post-operative complications, and its outcome is currently unpredictable, leading some physicians and patients towards postponement and use of alternative approaches.
European Journal of Haematology, 2016
Polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are clonal disorder... more Polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are clonal disorders collectively named myeloproliferative neoplasms (MPN). Published data on epidemiology of MPN after the discovery of the JAK2 mutation and the 2008 WHO classifications, are scarce. We aimed to study the incidence rates, prevalence and survival of MPN in Norway during the period 1993-2012. We identified 2453 persons diagnosed with MPN from the Cancer Registry of Norway between 1993 and 2012. We report age-adjusted incidence rates, prevalence, relative survival and standardized mortality rates. The overall age-adjusted yearly incidence rate of PV increased from 0.4/10⁵ to 0.7/10⁵, ET increased from 0.3/10⁵ to 1.0/10⁵ and MF from 0.2/10⁵ to 0.5/10⁵. Prevalence of PV, ET and MF was 9.2, 8.6 and 3.0 per 10⁵ inhabitants, respectively. The 5-year relative survival (RS) of ET and PV was slightly reduced with no improvement. The 5-year RS of MF was 58.1% (2008-2012). Standardized mortality rate (SMR), was 1.9 (95% CI 1.2 - 2.7). The incidence rates of ET, PV, and MF doubled to tripled during the years 2007-2012 as compared to 1995-2006. This increment in incidence rates may be related to identification of the JAK2 mutation and the derived 2008 WHO-guidelines for MPN. The RS was only slightly reduced in PV and ET, but was substantially reduced in MF. This article is protected by copyright. All rights reserved.
Leukemia & Lymphoma, 2016
In this study with prolonged follow up, we compared clinical outcome, including cause of death an... more In this study with prolonged follow up, we compared clinical outcome, including cause of death and incidence of second cancer, for patients with early stage extranodal marginal zone lymphoma (EMZL, 49 patients), nodal marginal zone lymphoma (NMZL, nine patients) and mantle cell lymphoma (MCL, 42 patients) with emphasis on potential benefit of radiotherapy. Radiotherapy was given to 40 patients with EMZL (nine had surgery only) and all NMZL patients. MCL patients received radiotherapy (17 patients), chemotherapy followed by radiotherapy (13 patients) or chemotherapy alone (12 patients). Compared to a matched control population no increased risk of second cancer or cardiovascular disease was observed. Radiotherapy alone was effective in EMZL and NMZL with low-relapse rates (20% and 33%) and a 10-year overall survival of 78% and 56%, respectively. High-relapse rate and inferior OS in MCL underline the need for extended staging with endoscopy and PET/CT and possibly for novel strategies.
Data Revues 00028703 V154i5 S0002870307005935, Aug 16, 2011
The Lancet Haematology, 2016
Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT)... more Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT) and is associated with reduced quality of life and a substantial cost burden. In the 2-year results of the CaVenT study, additional catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life. In this study we report results at the 5-year follow-up, aiming to assess whether findings for post-thrombotic syndrome and quality of life have persisted. Between Jan 3, 2006, and Dec 22, 2009, we recruited patients aged 18-75 years with a first-time high proximal leg DVT from 20 hospitals in the Norwegian southeastern health region. With sealed envelopes, participants were randomly assigned (1:1) to standard treatment with compression stockings and anticoagulants (control group) or to standard treatment plus catheter-directed thrombolysis with alteplase within 21 days from symptom onset. Pre-specified outcomes in this analysis were post-thrombotic syndrome at 5 years as assessed with the Villalta score and scores for quality of life at 5 years with EQ-5D and the disease-specific VEINES-QOL/Sym. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00251771. At 5 year follow-up (last date Oct 14, 2014), data were available for 176 patients (84% of the 209 patients originally randomised)-87 originally assigned to catheter-directed thrombolysis and 89 originally assigned to the control group. 37 patients (43%; 95% CI 33-53) allocated to catheter-directed thrombolysis developed post-thrombotic syndrome, compared with 63 (71%; 95% CI 61-79) allocated to the control group (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0·0001), corresponding to an absolute risk reduction of 28% (95% CI 14-42) and a number needed to treat of 4 (95% CI 2-7). Four (5%) patients assigned to catheter-directed thrombolysis and one (1%) to standard treatment had severe post-thrombotic syndrome (Villalta score ≥15 or presence of an ulcer). Quality-of-life scores with either assessment scale did not differ between the treatment groups. Additional catheter-directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter-directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life. The optimal endovascular thrombolytic approach needs further investigation. Southeastern Norway Regional Health Authority, the Research Council of Norway, University of Oslo, Oslo University Hospital.
Thrombosis and Haemostasis, 2015
Post-thrombotic syndrome (PTS) is a long-term complication of deep-vein thrombosis (DVT). The Vil... more Post-thrombotic syndrome (PTS) is a long-term complication of deep-vein thrombosis (DVT). The Villalta scale is the recommended tool for diagnosing PTS, but requires a clinician&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s assessment in addition to patient self-assessment. In the present study, we validated a self-administered tool for patient reporting of leg symptoms and signs as a mean to assess PTS. We first validated a form for patient self-reported Villalta (PRV1), then developed and validated a visually assisted form (PRV2). The validity of PRV1 and PRV2 was assessed in patients diagnosed with DVT between 2004 and 2012. Median time from DVT to inclusion was 5.1 and 3.5 years for PRV1 (n=162) and PRV2 (n=94), respectively. Patients were requested to complete the PRV form before a scheduled visit. PTS diagnosed by the original Villalta scale during the visit served as the reference method. PRV1 showed only moderate agreement for diagnosing PTS compared with the original Villalta scale (kappa agreement 0.60, 95 % CI 0.48-0.72), whereas PRV2 showed very good agreement (0.82, 95 % CI 0.71-0.94). In the validation of PRV2, PTS was diagnosed in 54 (57 %) patients according to the original Villalta scale and in 60 (64 %) by PRV2. The sensitivity of PRV2 to detect PTS was 98 % and the specificity was 83 %. We conclude that the visually assisted form for PRV is a valid and sensitive tool for diagnosing PTS. Such a tool could be applied in further clinical studies of PTS, making studies less resource demanding by reducing the need for in-person clinic visits.
British journal of haematology, Jan 12, 2015
British Journal of Haematology, 2015
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2015
The aim of the current study was to translate and test the psychometrical properties of the disea... more The aim of the current study was to translate and test the psychometrical properties of the disease-specific pulmonary embolism quality-of-life questionnaire (PEmb-QoL). Patients with a prior history of pulmonary embolism (PE) were identified from the thrombosis registry at Østfold Hospital Trust, Fredrikstad, Norway. All eligible patients were asked to complete the generic EuroQol 5-dimension (EQ-5D) QoL questionnaire as well as the disease-specific PEmb-QoL at baseline and after 2 weeks. Construct validity was tested using principal component factor analysis. Criterion validity was tested using Spearman's correlation coefficients (rho) between EQ-5D and PEmb-QoL. Internal consistency reliability was calculated using Cronbach's alpha coefficient, while test-retest reliability was calculated using the intra-class correlation coefficients (ICC). A total of 213 participants had complete datasets and were included in further analyses. Factor analysis with varimax rotation yield...