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1.
  • Kalkan, Almina, et al. (författare)
  • Increased healthcare utilization costs following initiation of insulin treatment in type 2 diabetes : A long-term follow-up in clinical practice
  • 2017
  • Ingår i: Primary Care Diabetes. - : Elsevier. - 1751-9918 .- 1878-0210. ; 11:2, s. 184-192
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. Methods: Patients newly initiated on insulin (n. =2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. Results: The total mean annual healthcare cost increased from €1656 per patient 2 years before insulin initiation to €3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was €13,823 in the insulin group compared to €9989 in the NIAD group. Conclusions: Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line.
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2.
  • Kolstad, Arne, et al. (författare)
  • Molecular Monitoring after Autologous Stem Cell Transplantation and Preemptive Rituximab Treatment of Molecular Relapse; Results from the Nordic Mantle Cell Lymphoma Studies (MCL2 and MCL3) with Median Follow-Up of 8.5 Years
  • 2017
  • Ingår i: Biology of blood and marrow transplantation. - : ELSEVIER SCIENCE INC. - 1083-8791 .- 1523-6536. ; 23:3, s. 428-435
  • Tidskriftsartikel (refereegranskat)abstract
    • The main objectives of the present study were to monitor minimal residual disease (MRD) in the bone marrow of patients with mantle cell lymphoma (MCL) to predict clinical relapse and guide preemptive treatment with rituximab. Among the patients enrolled in 2 prospective trials by the Nordic Lymphoma Group, 183 who had completed autologous stem cell transplantation (ASCT) and in whom an MRD marker had been obtained were included in our analysis. Fresh samples of bone marrow were analyzed for MRD by a combined standard nested and quantitative real-time PCR assay for Bcl-1/immunoglobulin heavy chain gene (IgH) and clonal IgH rear-rangements. Significantly shorter progression-free survival (PFS) and overall survival (OS) was demonstrated for patients who were MRD positive pre-ASCT (54 patients) or in the first analysis post-ASCT (23 patients). The median PFS was only 20 months in those who were MRD-positive in the first sample post-ASCT, compared with 142 months in the MRD-negative group (P <.0001). OS was 75% at 10 years and median not reached in the MRD-negative group, compared with only 35 months in the MRD-positive group (P <.0001). Of the 86 patients (47%) who remained in continuous molecular remission, 73% were still in clinical remission after 10 years. For all patients, the median time from ASCT to first molecular relapse was 55 months, with a continuous occurrence of late molecular relapses. Fifty-eight patients who experienced MRD relapse received rituximab as preemptive treatment on 1 or more occasions, and in this group, the median time from first molecular relapse to clinical relapse was 55 months. In most cases, rituximab converted patients to MRD negativity (87%), but many patients became MRD-positive again later during follow-up (69%). By multivariate analysis, high-risk Mantle Cell Lymphoma International Prognostic Index score and positive MRD status pre-ASCT predicted early molecular relapse. In conclusion, preemptive rituximab treatment converts patients to MRD negativity and likely postpones clinical relapse. Molecular monitoring offers an opportunity to select some patients for therapeutic intervention and to avoid unnecessary treatment in others. MRD-positive patients in the first analysis post-ASCT have a dismal prognosis and thus are in need of novel strategies.
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3.
  • Back, S E, et al. (författare)
  • Age dependence of renal function: clearance of iohexol and p-amino hippurate in healthy males
  • 1989
  • Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa Healthcare. - 1502-7686. ; 49:7, s. 641-646
  • Tidskriftsartikel (refereegranskat)abstract
    • Iohexol, a newly developed non-ionic contrast agent, has been recently documented as a reliable glomerular filtration marker. This study describes the age dependence of the single injection clearance of iohexol in a sample of healthy male volunteers ranging from 21 to 77 years of age. In parallel, renal plasma flow was studied by measuring the total clearance of p-amino hippuric acid administered as a continuous infusion. In subjects older than 50 years a negative correlation to age was found for both p-amino hippuric acid and iohexol clearance, with a reduction of 52 ml/min and 12 ml/min per decade, respectively, whereas no age dependence was found for younger subjects. Correlation between p-amino hippuric acid and iohexol clearances was 0.81. However, the filtration fraction, defined as the ratio of iohexol to p-amino hippuric acid clearance, was higher in the elderly subjects. A consistent discrepancy was found between total and renal clearances of p-amino hippuric acid, indicating significant renal metabolism. Renal clearance of creatinine was poorly correlated to iohexol clearance and did not show any relationship to age.
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4.
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5.
  • Eskelund, Christian W., et al. (författare)
  • 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2) : prolonged remissions without survival plateau
  • 2016
  • Ingår i: British Journal of Haematology. - : Federation of European Neuroscience Societies and Blackwell Publishing Ltd. - 0007-1048 .- 1365-2141. ; 175:3, s. 410-418
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
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6.
  • Geisler, Christian H., et al. (författare)
  • Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group
  • 2008
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:7, s. 2687-2693
  • Tidskriftsartikel (refereegranskat)abstract
    • Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + highdose cytarabine. Responders received highdose chemotherapy with BEAM or BEAC carmustine, etoposide, cytarabine, and melphalan/ cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL- 1 trial, the event- free, overall, and progression- free survival, the duration of molecular remission, and the proportion of PCR- negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression- free survival of MCL and perhaps cure. Registered at www. isrctn. org as # ISRCTN 87866680.
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7.
  • Geisler, Christian H., et al. (författare)
  • Nordic MCL2 trial update: six-year follow-up after intensive immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or BEAC plus autologous stem-cell support: still very long survival but late relapses do occur
  • 2012
  • Ingår i: British Journal of Haematology. - : Federation of European Neuroscience Societies and Blackwell Publishing Ltd. - 0007-1048 .- 1365-2141. ; 158:3, s. 355-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Mantle cell lymphoma (MCL) is a heterogenic non-Hodgkin lymphoma entity, with a median survival of about 5 years. In 2008 we reported the early based on the median observation time of 4 years results of the Nordic Lymphoma Group MCL2 study of frontline intensive induction immunochemotherapy and autologous stem cell transplantation (ASCT), with more than 60% event-free survival at 5 years, and no subsequent relapses reported. Here we present an update after a median observation time of 6.5 years. The overall results are still excellent, with median overall survival and response duration longer than 10 years, and a median event-free survival of 7.4 years. However, six patients have now progressed later than 5 years after end of treatment. The international MCL Prognostic Index (MIPI) and Ki-67-expression were the only independent prognostic factors. Subdivided by the MIPI-Biological Index (MIPI + Ki-67, MIPI-B), more than 70% of patients with low-intermediate MIPI-B were alive at 10 years, but only 23% of the patients with high MIPI-B. These results, although highly encouraging regarding the majority of the patients, underline the need of a risk-adapted treatment strategy for MCL. The study was registered at as ISRCTN 87866680.
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8.
  • Geisler, Christian H., et al. (författare)
  • The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the International Prognostic Index (IPI) in predicting survival following intensive first-line immunochemotherapy and autologous stem cell transplantation (ASCT)
  • 2010
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:8, s. 1530-1533
  • Tidskriftsartikel (refereegranskat)abstract
    • Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the survival of MCL better than the International Prognostic Index in MCL patients treated with conventional chemotherapy, but its validity in MCL treated with more intensive immunochemotherapy has been questioned. Applied here to 158 patients of the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation, the MIPI and the simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI mainly identified 2 risk groups, low and intermediate versus high risk, with the more easily applied s-MIPI being just as powerful as the MIPI. The MIPI(B) (biological), incorporating Ki-67 expression, identified almost half of the patients as high risk. We suggest that also a simplified MIPI(B) is feasible.
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9.
  • Kolstad, Arne, et al. (författare)
  • Nordic MCL3 study: Y-90-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma
  • 2014
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020. ; 123:19, s. 2953-2959
  • Tidskriftsartikel (refereegranskat)abstract
    • The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding 90 Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475.
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10.
  • Nilsson, Peter, et al. (författare)
  • Effects of smoking cessation on insulin and cardiovascular risk factors--a controlled study of 4 months' duration
  • 1996
  • Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 1365-2796. ; 240:4, s. 189-194
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate the effects on serum lipids, plasma fibrinogen, plasma insulin, plasma C-peptide and blood glucose, of smoking cessation after 4 months. To develop a group-based smoking intervention programme in primary health care. SETTING: Twenty health centres in primary health care in southern Sweden. SUBJECTS: Four hundred habitual smokers (> 10 cigarettes per day-1, > 10 years), recruited by advertisement in local papers. INTERVENTION: The smokers were randomized, after stratification for age and sex, to one intervention group (n = 200) and one control group (n = 200). The intervention group was offered supportive group sessions and free nicotine supplementation (patches, chewing gum). MAIN OUTCOME MEASURES: All participants were investigated at the start and after 4 months (medical history, physical examination, laboratory evaluation). Blood samples were drawn for determination of glucose, insulin and C-peptide, both in the fasting state and during an oral glucose tolerance test (OGTT), and for measurement of lipoproteins, fibrinogen, nicotine and cotinine. RESULTS: In the intervention group 98 of the subjects (48%) had quit smoking after 4 months. They were compared with the 156 subjects in the control group (91%) who were still daily smokers during the whole period. There were no significant differences in any variable between the two (total) experimental groups at baseline. Plasma nicotine and cotinine decreased (P < 0.001) in the intervention group following smoking cessation, and weight increased by 2.7 kg. In the intervention group HDL-cholesterol increased by 11% (P < 0.001), whereas HbA1c increased by 2% (P < 0.05) only in the control group. No changes occurred in levels of glucose, insulin, C-peptide and fibrinogen. CONCLUSION: The smoking cessation programme had a success rate of almost 50% over 4 months. Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance. A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism.
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