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Birgegård, Gunnar
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Publications (10 of 61) Show all publications
Birgegård, G., Samuelsson, J., Ahlstrand, E., Ejerblad, E., Enevold, C., Ghanima, W., . . . Andreasson, B. (2019). Inflammatory functional iron deficiency common in myelofibrosis, contributes to anaemia and impairs quality of life. From the Nordic MPN study Group. European Journal of Haematology, 102(3), 235-240
Open this publication in new window or tab >>Inflammatory functional iron deficiency common in myelofibrosis, contributes to anaemia and impairs quality of life. From the Nordic MPN study Group
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2019 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 102, no 3, p. 235-240Article in journal (Refereed) Published
Abstract [en]

Objectives: The study investigates the hypothesis that inflammation in myelofibrosis (MF) like in myeloma and lymphoma, may disturb iron distribution and contribute to anaemia.

Methods: A cross-sectional study of 80 MF and 23 ET patients was performed.

Results: About 35% of anaemic MF patients had functional iron deficiency (FID) with transferrin saturation <20 and normal or elevated S-ferritin (<500 mu g/L). In ET, FID was rare. In MF patients with FID, 70.6% were anaemic, vs 29.4% in patients without FID (P = 0.03). Hepcidin was significantly higher in MF patients with anaemia, including transfusion-dependent patients, 50.6 vs 24.4 mu g/L (P = 0.01). There was a significant negative correlation between Hb and inflammatory markers in all MF patients: IL-2, IL-6 and TNF-alpha, (P < 0.01-0.03), LD (P = 0.004) and hepcidin (P = 0.03). These correlations were also seen in the subgroup of anaemic MF patients (Table ). Tsat correlated negatively with CRP (P < 0.001). Symptom burden was heavier in MF patients with FID, and MPN-SAF quality of life scores correlated with IL-6 and CRP.

Conclusions: The inflammatory state of MF disturbs iron turnover, FID is common and contributes to anaemia development and impairment of QoL. Anaemic MF patients should be screened for FID.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
anaemia of inflammation, cytokines, functional iron deficiency, Myelofibrosis
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-378628 (URN)10.1111/ejh.13198 (DOI)000458535100005 ()30472746 (PubMedID)
Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-03-11Bibliographically approved
Birgegård, G., Folkvaljon, F., Garmo, H., Holmberg, L., Besses, C., Griesshammer, M., . . . Harrison, C. N. (2018). Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study. Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, 74, 105-109
Open this publication in new window or tab >>Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study
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2018 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 74, p. 105-109Article in journal (Refereed) Published
Abstract [en]

EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644)

Keywords
Acute myelogenous leukemia, Malignant transformation, Anagrelide, Hydroxycarbamide
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-369595 (URN)10.1016/j.leukres.2018.10.006 (DOI)000449112000017 ()30368038 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved
Barbuil, T., Tefferi, A., Vannucchi, A. M., Passamonti, F., Silvers, R. T., Hoffman, R., . . . Barosi, G. (2018). Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia, 32(5), 1057-1069
Open this publication in new window or tab >>Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet
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2018 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 32, no 5, p. 1057-1069Article, review/survey (Refereed) Published
Abstract [en]

This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-358109 (URN)10.1038/s41375-018-0077-1 (DOI)000431769800002 ()29515238 (PubMedID)
Available from: 2018-08-24 Created: 2018-08-24 Last updated: 2018-08-24Bibliographically approved
Birgegård, G., Besses, C., Griesshammer, M., Gugliotta, L., Harrison, C. N., Hamdani, M., . . . Kiladjian, J.-J. (2018). Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the Evaluation of Anagrelide Efficacy and Long-term Safety study. Haematologica, 103(1), 51-60
Open this publication in new window or tab >>Treatment of essential thrombocythemia in Europe: a prospective long-term observational study of 3649 high-risk patients in the Evaluation of Anagrelide Efficacy and Long-term Safety study
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2018 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 1, p. 51-60Article in journal (Refereed) Published
Abstract [en]

Evaluation of Anagrelide (Xagrid (R)) Efficacy and Long-term Safety, a phase IV, prospective, non-interventional study performed in 13 European countries enrolled high-risk essential thrombocythemia patients treated with cytoreductive therapy. The primary objectives were safety and pregnancy outcomes. Of 3721 registered patients, 3649 received cytoreductive therapy. At registration, 3611 were receiving: anagrelide (Xagrid (R)) (n=804), other cytoreductive therapy (n=2666), or anagrelide + other cytoreductive therapy (n=141). The median age was 56 vs. 70 years for anagrelide vs. other cytoreductive therapy. Event rates (patients with events/100 patient-years) were 1.62 vs. 2.06 for total thrombosis and 0.15 vs. 0.53 for venous thrombosis. Anagrelide was more commonly associated with hemorrhage (0.89 vs. 0.43), especially with anti-aggregatory therapy (1.35 vs. 0.33) and myelofibrosis (1.04 vs. 0.30). Other cytoreductive therapies were more associated with acute leukemia (0.28 vs. 0.07) and other malignancies (1.29 vs. 0.44). Post hoc multivariate analyses identified increased risk for thrombosis with prior thrombohemorrhagic events, age >= 65, cardiovascular risk factors, or hypertension. Risk factors for transformation were prior thrombohemorrhagic events, age >= 65, time since diagnosis, and platelet count increase. Safety analysis reflected published data, and no new safety concerns for anagrelide were found. Live births occurred in 41/54 pregnancies (76%).

Place, publisher, year, edition, pages
Ferrata Storti Foundation, 2018
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-343029 (URN)10.3324/haematol.2017.174672 (DOI)000418944500019 ()29079600 (PubMedID)
Available from: 2018-02-25 Created: 2018-02-25 Last updated: 2019-06-27Bibliographically approved
Birgegård, G., Folkvaljon, Y., Garmo, H., Holmberg, L., Besses, C., Griesshammer, M., . . . Harrison, C. N. (2017). LEUKEMIC TRANSFORMATION AND SECOND CANCERS IN 3649 HIGH RISK ET PATIENTS IN THE EXELS STUDY. Paper presented at 22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN. Haematologica, 102(Suppl. 2), 282-282, Article ID P704.
Open this publication in new window or tab >>LEUKEMIC TRANSFORMATION AND SECOND CANCERS IN 3649 HIGH RISK ET PATIENTS IN THE EXELS STUDY
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2017 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no Suppl. 2, p. 282-282, article id P704Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
FERRATA STORTI FOUNDATION, 2017
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-377417 (URN)000404127002194 ()
Conference
22nd Congress of the European-Hematology-Association, JUN 22-25, 2017, Madrid, SPAIN
Available from: 2019-02-20 Created: 2019-02-20 Last updated: 2019-02-20Bibliographically approved
Scotch, A. H., Kosiorek, H., Scherber, R., Dueck, A. C., Slot, S., Zweegman, S., . . . Geyer, H. L. (2017). Symptom burden profile in myelofibrosis patients with thrombocytopenia: Lessons and unmet needs. Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, 63, 34-40
Open this publication in new window or tab >>Symptom burden profile in myelofibrosis patients with thrombocytopenia: Lessons and unmet needs
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2017 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 63, p. 34-40Article in journal (Refereed) Published
Abstract [en]

Myelofibrosis is a myeloproliferative neoplasm associated with progressive cytopenias and high symptom burden. MF patients with thrombocytopenia have poor prognosis but the presence of thrombocytopenia frequently precludes the use of JAK2 inhibitors. In this study, we assessed quality of life and symptom burden in 418 MF patients with (n = 89) and without (n = 329) thrombocytopenia using prospective data from the MPN-QOL study group database, including the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and Total Symptom Score (MPN10). Thrombocytopenia, defined as platelet count < 100 x10(9)/L (moderate 51-100 x 10(9)/L; severe <= 50 x10(9)/L), was associated with anemia (76% vs. 45%, p < 0.001), leukopenia (29% vs. 11%, p < 0.001), and need for red blood cell transfusion (35% vs. 19%, p = 0.002). Thrombocytopenic patients had more fatigue, early satiety, inactivity, dizziness, sad mood, cough, night sweats, itching, fever, and weight loss; total symptom scores were also higher (33 vs. 24, p < 0.001). Patients with severe thrombocytopenia were more likely to have anemia (86% vs. 67%, p = 0.04), leukopenia (40% vs. 20%, p = 0.04), and transfusion requirements (51% vs. 20%, p = 0.002) but few differences in symptoms when compared to patients with moderate thrombocytopenia. These results suggest that MF patients with thrombocytopenia experience greater symptomatic burden than MF patients without thrombocytopenia and may benefit from additional therapies.

Keywords
Myelofibrosis, Myeloproliferative neoplasm, Quality of life, Symptomatology, Thrombocytopenia
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-343027 (URN)10.1016/j.leukres.2017.10.002 (DOI)000416744700006 ()29096334 (PubMedID)
Available from: 2018-02-25 Created: 2018-02-25 Last updated: 2018-03-01Bibliographically approved
Marchetti, M., Barosi, G., Cervantes, F., Birgegård, G., Griesshammer, M., Harrison, C., . . . Barbui, T. (2017). Which patients with myelofibrosis should receive ruxolitinib therapy?: ELN-SIE evidence-based recommendations. Leukemia, 31(4), 882-888
Open this publication in new window or tab >>Which patients with myelofibrosis should receive ruxolitinib therapy?: ELN-SIE evidence-based recommendations
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2017 (English)In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 4, p. 882-888Article in journal (Refereed) Published
Abstract [en]

Ruxolitinib is an oral Janus-activated kinase 1 (JAK1)/JAK2 inhibitor approved for the treatment of patients with myelofibrosis based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of the three clinical outcomes: (a) splenomegaly, (b) disease-related symptoms, and (c) survival. Ruxolitinib was strongly recommended for improving symptomatic or severe (415 cm below the costal margin) splenomegaly in patients with an International Prognostic Scoring System (IPSS)/dynamic IPSS risk intermediate 2 or high. Ruxolitinib was also strongly recommended for improving systemic symptoms in patients with an MPN10 score 444, refractory severe itching, unintended weight loss not attributable to other causes or unexplained fever. Because of weak evidence, the panel does not recommend ruxolitinib therapy for improving survival. Also, the recommendations given above do not necessarily apply to patients who are candidates for allogeneic stem cell transplant.

National Category
Hematology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-320640 (URN)10.1038/leu.2016.283 (DOI)000398261800012 ()27740634 (PubMedID)
Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2018-02-25Bibliographically approved
Birgegård, G., Henry, D., Glaspy, J., Chopra, R., Thomsen, L. L. & Auerbach, M. (2016). A Randomized Noninferiority Trial of Intravenous Iron Isomaltoside versus Oral Iron Sulfate in Patients with Nonmyeloid Malignancies and Anemia Receiving Chemotherapy: The PROFOUND Trial. Pharmacotherapy, 36(4), 402-414
Open this publication in new window or tab >>A Randomized Noninferiority Trial of Intravenous Iron Isomaltoside versus Oral Iron Sulfate in Patients with Nonmyeloid Malignancies and Anemia Receiving Chemotherapy: The PROFOUND Trial
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2016 (English)In: Pharmacotherapy, ISSN 0277-0008, E-ISSN 1875-9114, Vol. 36, no 4, p. 402-414Article in journal (Refereed) Published
Abstract [en]

Study ObjectiveA safe alternative to erythropoiesis-stimulating agents to treat anemia is warranted in patients with cancer and anemia; thus the objective of this trial was to compare the efficacy and safety of intravenous (IV) iron isomaltoside with oral iron in patients with cancer and anemia by testing the noninferiority of IV versus oral iron. DesignPhase III, prospective, open-label, comparative, randomized, noninferiority, multicenter trial. SettingForty-seven hospitals or private cancer clinics in Asia, the United States, and Europe. PatientsA total of 350 patients with cancer and anemia. InterventionPatients were randomized in a 2:1 ratio to either intravenous iron isomaltoside or oral iron sulfate. Patients in the iron isomaltoside group were then randomized into an infusion subgroup (single intravenous infusions of a maximum dose of 1000 mg over 15 min) or a bolus injection subgroup (bolus injections of 500 mg over 2 min). Measurements and Main ResultsThe primary efficacy outcome was change in hemoglobin concentration from baseline to week 4. Changes in other relevant hematology variables, effect on quality of life, and safety outcomes were also assessed. The primary efficacy outcome was tested for noninferiority, whereas the remaining outcomes were tested for superiority. Iron isomaltoside was noninferior to oral iron in change in hemoglobin concentration from baseline to week 4 (difference estimate 0.016, 95% confidence interval -0.26 to 0.29, p<0.001). A faster onset of the hemoglobin response was observed with infusion of iron isomaltoside (superiority test: p=0.03 at week 1), and a sustained effect on hemoglobin level was shown in both the iron isomaltoside and oral iron treatment groups until week 24. A significant mean decrease in fatigue score was observed from baseline to week 12 in the iron isomaltoside group (p<0.001) but not in the oral iron group (p=0.057). A higher proportion of patients treated with oral iron experienced adverse drug reactions (18.8% vs 6.6%, p<0.001) and discontinued the trial due to intolerance (8.0% vs 0.9%, p=0.001). Transient hypophosphatemia (phosphate level less than 2 mg/dl) was reported at similar low frequencies among the groups: 7.1% in the iron isomaltoside infusion subgroup versus 8.5% in the iron isomaltoside bolus injection subgroup versus 5.4% in the oral iron group. ConclusionThis trial demonstrated comparable sustained increases in hemoglobin concentration over time with both iron isomaltoside and oral iron. Iron isomaltoside was better tolerated than oral iron, and fatigue was significantly decreased with iron isomaltoside. Low rates of clinically insignificant hypophosphatemia were reported in patients receiving both treatments.

Keywords
anemia, cancer, iron isomaltoside, iron treatment
National Category
Cancer and Oncology Hematology Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-297135 (URN)10.1002/phar.1729 (DOI)000374696400008 ()26927900 (PubMedID)
Available from: 2016-06-22 Created: 2016-06-21 Last updated: 2018-01-10Bibliographically approved
Geyer, H. L., Kosiorek, H., Dueck, A. C., Scherber, R., Slot, S., Zweegman, S., . . . Mesa, R. A. (2016). Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group. Haematologica, 102(1), 85-93
Open this publication in new window or tab >>Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 1, p. 85-93Article in journal (Refereed) Published
Abstract [en]

The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-316138 (URN)10.3324/haematol.2016.149559 (DOI)000392921800021 ()27540137 (PubMedID)
Available from: 2017-03-03 Created: 2017-03-03 Last updated: 2019-08-27Bibliographically approved
Geyer, H., Kosiorek, H., Dueck, A., Slot, S., Zweegman, S., Kiladjian, J. J., . . . Mesa, R. (2016). Development Of An Mf Patient Reported Outcome (Pro) Tool For Fda Qualification: Comprehensive Literature Search And Physician Cognitive Debriefing Results. Paper presented at 21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK. Haematologica, 101, 564-564
Open this publication in new window or tab >>Development Of An Mf Patient Reported Outcome (Pro) Tool For Fda Qualification: Comprehensive Literature Search And Physician Cognitive Debriefing Results
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2016 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 564-564Article in journal, Meeting abstract (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-301460 (URN)000379484602151 ()
Conference
21st Congress of the European-Hematology-Association, JUN 09-12, 2016, Copenhagen, DENMARK
Available from: 2016-08-23 Created: 2016-08-23 Last updated: 2017-11-28Bibliographically approved
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