Comparison of the Myleloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Across Nine Linguistic Translations Among an International Sample of 1,851 Myeloproliferative Neoplasm (MPN) Patients.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2852-2852
Author(s):  
Amylou Constance Dueck ◽  
Robyn M. Emanuel ◽  
Holly Lynn Geyer ◽  
Jean-Jacques Kiladjian ◽  
Stephanie Slot ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Factor Structure ◽  
Internal Consistency ◽  
Research Funding ◽  
Disease Type ◽  
Cronbach’S Alpha ◽  
Advisory Committees ◽  
Cronbach's Alpha ◽  
Language Groups ◽  
And Gender

Abstract Abstract 2852 Background: The 18-item Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF, Scherber et al Blood 2011) given in conjunction with the 9-item Brief Fatigue Inventory (BFI, Mendoza et al Cancer 1999) is a patient-completed questionnaire for assessing symptoms in persons with MPNs. The MPN-SAF has been translated and validated in 9 languages to date. The Total Symptom Score (TSS) is computed from 10 of the most pertinent MPN-SAF items to assess symptom burden in MPN patients and to evaluate response to therapy. Psychometric properties of the TSS have been previously reported (Emanuel et al Blood 2012). The purpose of this analysis is to compare MPN-SAF symptoms and psychometric properties of the TSS across 9 languages in an international sample. Methods: Data were collected in an international cohort of subjects with MPNs. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual problems, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst imaginable) scale. TSS was computed using the published scoring algorithm on a 0 (all symptoms absent) to 100 (all symptoms worst imaginable) scale. Demographic and disease-related data including disease type, gender, and age had to be present to be included in analysis. Demographics were compared across languages groups using ANOVA and chi-squared tests. Symptoms and TSS were compared across language groups using a general linear model adjusting for disease type, age, and gender with post-hoc Tukey pairwise comparisons. Internal consistency and factor structure of the TSS were investigated overall and within language groups using Cronbach's alpha and principal-axis factoring analysis. Results: Subject Demographics and Disease Type: 1,851 subjects with polycythemia vera (PV N=655), essential thrombocythemia (ET N=769) and myelofibrosis (MF N=427; 286 primary MF, 61 PV-MF, 80 ET-MF) were prospectively enrolled and administered the MPN-SAF and BFI in 1 of 9 languages: English [UK] 55, English [US] 102, Italian 186, Swedish 114, German 112, French 457, Spanish 192, Dutch 236, and Chinese 397. Age (median 61, range, 15–94) and gender (55% F) were typical. Disease type and age varied across language groups (both p <0.001). MPN-SAF Symptoms and TSS: Symptom frequencies ranged from 19% (fever) to 88% (fatigue) overall with mean severities ranging from 0.4 (SD=1.3, fever) to 4.3 (SD=2.3, fatigue). Fatigue had the highest mean severity among all symptoms within each language group. Overall, mean TSS was 21.5 (SD=16.7) with the Swedish (mean=18.1, SD=15.2) and Dutch (mean=27.6, SD=17.1) cohorts reporting the lowest and highest unadjusted TSS means, respectively. When comparing symptom items across languages (adjusting for disease type, age, and gender), concentration and sexual problems had the most statistically significant pairwise differences (11 and 10, respectively, out of a possible 36) followed by dizziness and overall quality of life (9 each, out of a possible 36). No statistically significant pairwise differences were observed for abdominal discomfort, headache, extremity tingling, or insomnia. For the TSS, the Dutch cohort appeared to statistically significantly differ (all p <0.05) with all other languages except the English cohorts. All other TSS pairwise comparisons were not statistically significant. TSS Internal Consistency and Factor Structure: The TSS had excellent internal consistency overall (Cronbach's alpha 0.83) as well as within language groups (Cronbach's alpha 0.81–0.86). Overall factor analysis identified a single underlying construct among the 10 TSS items. Factor loadings ranged from 0.41 for fever to 0.73 for inactivity. A single factor solution was appropriate for each language group with factor loadings ranging from 0.18 to 0.85. Conclusion: This analysis suggests that the available translations of the MPN-SAF are generally acceptable for use in a broad context. The TSS demonstrated acceptable internal consistency and similar factor structure across all language groups. Most symptom and TSS comparisons between languages were not statistically significant, but for the few which differed, further studies are needed to evaluate whether these variances are due to disease-related factors or due to linguistic or cultural influences present in the cohorts. Disclosures: Kiladjian: Novartis: Honoraria, Research Funding; Celgene: Research Funding; Shire: Honoraria. Griesshammer:Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Improvements in Skeletal Manifestations in Gaucher Disease Type 1 Patients After 3 Years of Treatment with Oral Eliglustat During a Phase 2 Trial,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3216-3216
Author(s):  
M. Judith Peterschmitt ◽  
Ravi S Kamath ◽  
Elena Lukina ◽  
Nora Watman ◽  
Marta Dragosky ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Disease Type ◽  
Phase 2 ◽  
Z Score ◽  
Advisory Committees ◽  
Lytic Lesions ◽  
Skeletal Complications ◽  
Gaucher Disease Type 1

Abstract Abstract 3216 Introduction: In Gaucher disease type 1 (GD1), deficient lysosomal acid β-glucosidase leads to accumulation of undegraded glucosylceramide in lysosomes of tissue macrophages known as Gaucher cells. Skeletal complications are a major cause of morbidity and include bone marrow infiltration by Gaucher cells, osteopenia/osteoporosis, lytic lesions, fractures, avascular necrosis, and bone pain. Eliglustat, a novel, oral inhibitor of glucosylceramide synthase, is under investigation for the treatment of GD1. Objective: To report skeletal changes after 3 years of eliglustat therapy. Methods: This ongoing, open-label, uncontrolled, multicenter, Phase 2 clinical trial enrolled 26 adults with GD1 not on treatment for the previous 12 months, who had splenomegaly with thrombocytopenia and/or anemia. Study entry criteria also required that patients had no new pathologic bone involvement or bone crises within the preceding 12 months and not have used bisphosphonates during the previous 3 months. Changes from baseline were reported for centrally reviewed skeletal x-rays, dual-energy x-ray absorptiometry (DXA) and MRI assessments. Results: Of 26 enrolled patients, 19 completed 3 years of treatment. In 15 patients with evaluable DXA results at baseline and at 1, 2, and 3 years, mean lumbar spine BMD increased by 0.6±0.69 Z-score (baseline, −1.28), with greatest increases seen in osteoporotic patients. Mean femur BMD (T- and Z-score) remained normal through 3 years. Femur dark marrow on MRI, which reflects bone marrow infiltration by Gaucher cells, was reduced in 56% (10/18) or stable in 44% (8/18) of patients with findings at baseline. No bone crises or reductions in mobility occurred. On baseline radiographs, no patients had fractures, 42% (8/19 patients) had femoral lytic lesions, and 37% (7/19 patients) had bone infarcts. After 3 years, the lumbar spine and femurs showed no new lytic lesions, bone infarcts, fractures, or areas of osteonecrosis and no worsening of pre-existing lytic lesions or bone infarcts. One patient had worsening of asymptomatic osteonecrosis after 1 year noted retrospectively at baseline. Eliglustat was well-tolerated. Most adverse events (AEs) were mild and unrelated to treatment; the most common were viral infections (6 patients); urinary and upper respiratory tract infections (4 patients each); and headache, increased blood pressure, abdominal pain, diarrhea (3 patients each). Eight drug-related AEs, all mild, occurred in 6 patients. Conclusions: During 3 years of eliglustat treatment, radiologic monitoring showed improvement or stabilization of GD1 bony manifestations with no noted safety-related trends, suggesting that eliglustat may be a promising treatment for skeletal complications of GD1. Ongoing Phase 3 studies will provide more information on the bone effects of eliglustat. Disclosures: Peterschmitt: Genzyme: Employment. Kamath:Genzyme: Consultancy. Lukina:Genzyme: Honoraria. Watman:Genzyme: Membership on an entity's Board of Directors or advisory committees. Pastores:Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Actelion: Research Funding; Amicus: Research Funding; Biomarin: Research Funding; Shire HGT: Research Funding; Protalix: Research Funding. Arreguin:Genzyme: Research Funding. Aguzzi:Genzyme: Employment. Ross:Genzyme: Employment. Puga:Genzyme: Employment. Rosenthal:Genzyme: Consultancy.

Engage: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center Study To Investigate The Efficacy and Safety Of Eliglustat In Adults With Gaucher Disease Type 1: 9 Month Results

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2275-2275 ◽  
Author(s):  
Suma Shankar ◽  
Elena Lukina ◽  
Dominick J Amato ◽  
Majed Dasouki ◽  
Seymour Packman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Gaucher Disease ◽  
Research Funding ◽  
Liver Volume ◽  
Disease Type ◽  
Spleen Volume ◽  
Advisory Committees ◽  
Gaucher Disease Type 1

Abstract Background Gaucher disease type 1 is one of the most common lysosomal storage disorders. Deficiency of the lysosomal enzyme acid-β-glucosidase leads to accumulation of glucosylceramide (GL-1) in the spleen, liver, and bone marrow. Enzyme replacement therapy has been the mainstay of therapy for the last 20 years. Substrate reduction therapy is another treatment approach that inhibits GL-1 synthase and ultimately restores the balance between synthesis and degradation of the substrate. Eliglustat is a novel oral substrate reduction therapy that is currently in development for the treatment of Gaucher disease type 1. ENGAGE (NCT00891202) is a randomized, double-blind, placebo-controlled, Phase 3 trial sponsored by Genzyme, a Sanofi company investigating the efficacy and safety of eliglustat in untreated adults with Gaucher disease type 1. Method Forty patients (mean age: 31.8 years; 20 males) with splenomegaly and thrombocytopenia and/or anemia were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg BID depending on plasma levels) or placebo for 9 months. The primary efficacy endpoint was percent change in spleen volume (multiples of normal). Other efficacy measures included hemoglobin, liver volume, and platelets. Bone endpoints included bone marrow burden (BMB) scores and bone mineral density changes (DXA). Quality of life assessments included the Gaucher Disease Severity Scoring System (DS3). Safety monitoring included adverse event reporting, and lab and electrocardiogram evaluations. Results In patients receiving eliglustat vs. placebo, mean spleen volume decreased (-28% vs. +2%, P<0.0001), mean hemoglobin increased (0.69 vs. -0.54 g/dL, P<0.0006), liver volume decreased (-5.20% vs. +1.44%, P<0.0072), and platelets increased (+32% vs. -9.06%, P<0.0001). Significant improvements (eliglustat vs. placebo) were observed for total (-1.1 vs. 0.0, p=0.002), spine (-0.6 vs. 0.1, p=0.002), and femur (-0.5 vs. 0.0, p=0.026) BMB scores. Although patients with symptomatic bone disease were excluded, absolute change in total spine DXA Z-scores approached significance (least square mean treatment difference=0.2, p=0.06). Burden of disease, as measured by the Gaucher DS3, was significantly reduced following treatment with eliglustat vs. placebo (least square mean treatment difference=-0.3, p=0.0452). No patients discontinued due to an adverse event, all of which were classified as mild to moderate, and 39/40 patients transitioned into the ongoing open-label trial. Arthralgia and nasopharyngitis occurred in >10% of eliglustat vs. placebo patients. Conclusion ENGAGE met its primary and secondary efficacy endpoints. Significant effects on bone marrow and a trend toward BMD improvement in spine were observed. Eliglustat treatment was effective and well-tolerated in untreated adults with Gaucher disease type 1. Disclosures: Shankar: Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Lukina:Genzyme, a Sanofi company: Consultancy, Honoraria, Speakers Bureau. Amato:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Packman:Genzyme, a Sanofi company: Consultancy, Research Funding. Pastores:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Balwani:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Mistry:Genzyme, a Sanofi company: Consultancy, Honoraria, Research Funding. Ross:Genzyme, a Sanofi company: Employment. Marulkar:Genzyme, a Sanofi company: Employment. Peterschmitt:Genzyme, a Sanofi company: Employment.

Reliability and Validity of the Center for Epidemiologic Studies Depression Scale in a Population-Based Cohort of Middle-Aged U.S. Adults

2017 ◽  
Vol 25 (3) ◽  
pp. 476-485 ◽  
Author(s):  
Theodore D. Cosco ◽  
Matthew Prina ◽  
Brendon Stubbs ◽  
Yu-Tzu Wu
Keyword(s):  
Factor Structure ◽  
Internal Consistency ◽  
Factor Model ◽  
Depression Scale ◽  
Reliability And Validity ◽  
The United States ◽  
Epidemiological Studies ◽  
Population Based ◽  
Cronbach’S Alpha ◽  
Cronbach's Alpha

Background and Purpose: Globally, depressive symptoms are a leading contributor to years lived with disability. The Center for Epidemiological Studies–Depression (CES-D) scale has been used extensively to quantify depression; yet, its psychometric properties remain contentious. This study examined the reliability and factor structure of the CES-D in the MacArthur Foundation’s Midlife in the United States Study (MIDUS), a nationally representative cohort study of noninstitutionalized, English-speaking adults aged 24–74 years. Methods: Internal consistency (Cronbach’s alpha) and confirmatory factor analysis (CFA) were used to examine the reliability and factor structure of the CES-D. Results: There were 1,233 participants who were included in the analysis (mean age = 57.3 years [SD = 11.5], 56.7% female). Cronbach’s alpha of .90 was observed. The 4-factor model had the best model fit. Conclusions: High internal consistency was demonstrated alongside a replication of the original 4-factor structure. Continued use of the CES-D in noninstitutionalized populations is warranted.

scholarly journals Comorbidities and Complications in Adults with Pyruvate Kinase Deficiency

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2175-2175
Author(s):  
Audra N. Boscoe ◽  
Yan Yan ◽  
Elizabeth Hedgeman ◽  
Eduard J. van Beers ◽  
Hanny Al-Samkari ◽  
...  
Keyword(s):  
Clinical Trial ◽  
General Population ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Board ◽  
Advisory Committees ◽  
Age And Gender ◽  
Look Back ◽  
And Gender ◽  
Transfusion History

Introduction: Pyruvate kinase (PK) deficiency causes a defect in the glycolytic pathway, leading to a hereditary hemolytic anemia. Management is supportive and consists of splenectomy, transfusions, and chelation therapy. Aim: To better understand the comorbidity and complication profile of adults with PK deficiency, and the extent to which transfusion frequency contributes, the objectives of this study were to (1) quantify the prevalence of comorbidities and complications according to transfusion history and (2) compare the types and rates of select comorbidities and complications with the general population. Methods: Data were obtained from the enrollment survey of the PK Deficiency Natural History Study (NHS), a longitudinal, retrospective and prospective cohort study in which clinical, laboratory, transfusion, and radiologic data were collected; all participants were confirmed to have 2 mutations in the PKLR gene. Patients (n=122) were eligible for this analysis if they were ≥18 years of age and had sufficient data on transfusion history to enable classification into 1 of 3 cohorts: "Ever Regularly Transfused" (ERT, defined as ≥6 transfusions in any 12-month period), "Never Regularly Transfused" (NRT, defined as having ≥1 lifetime transfusion but never having >4 transfusions in any 12-month period), or "Never Transfused" (NT). To contextualize the findings, the frequencies of select conditions were compared with an age- and gender-matched cohort of individuals from the insured, general US population who did not have any hemolytic anemia diagnoses and had ≥5 years of continuous enrollment in the Truven MarketScan administrative claims database. The NHS reported lifetime prevalence rates, whereas rates obtained from the MarketScan data were based on diagnosis and procedure codes over varying look-back periods; therefore, to minimize bias, we limited PK deficiency vs. general population comparisons to (1) chronic conditions that require lifetime management and would thus still be recorded in claims data years after initial diagnosis, and/or (2) conditions for which a diagnosis/procedure date was available in the NHS and could be matched in time to the average 8-year look-back period for the general population. Frequencies were compared across mutually exclusive cohorts using Fisher's exact 2-tailed tests of significance. Results: ERT (n=65), NRT (n=30), and NT patients (n=27) had a mean age of 34.2, 39.5, and 37.2 years at enrollment, respectively (not significant [ns]), with 46.2%, 56.7%, and 59.3%, respectively, being male (ns). ERT patients trended toward being more likely than NT patients to be Amish and have the homozygous R479H splice variant (30.8% vs 11.1% [p=0.064]) but were significantly less likely to have a missense/missense PKLR genotype (32.3% vs 70.4% [p=0.001]). Compared with the general population, patients with PK deficiency had significantly higher rates of splenectomy, cholecystectomy, osteoporosis, liver cirrhosis, pulmonary hypertension, and current prophylactic antibiotic and anticoagulant use (Table). Rates of splenectomy, cholecystectomy, and osteoporosis were significantly higher in patients with PK deficiency, regardless of transfusion cohort, and both ERT and NRT patients had significantly higher rates of liver cirrhosis than individuals from the general population. A gradient was seen across transfusion cohorts for other conditions. Notably, 83.1% of ERT patients, 50.0% of NRT patients, and 25.9% of NT patients had a history of liver iron overload. ERT patients were also significantly more likely than NRT and NT patients to have had a splenectomy, cholecystectomy, and/or thrombosis, and to currently use prophylactic antibiotics. Findings were consistent when the analysis was restricted to non-Amish patients with PK deficiency. Conclusions: Patients with PK deficiency have higher rates of select comorbidities and complications than age- and gender-matched individuals who do not have PK deficiency. Even patients with PK deficiency who have never been transfused are at increased risk of complications of the disease and its treatment. Disclosures Boscoe: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Yan:Agios Pharmaceuticals, Inc.: Consultancy. Hedgeman:IBM Watson Health: Employment. van Beers:Agios Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Research Funding; RR Mechatronics: Research Funding. Al-Samkari:Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding; Moderna: Consultancy. Barcellini:Incyte: Consultancy; Alexion: Consultancy, Speakers Bureau; Agios Pharmaceuticals, Inc.: Consultancy; Novartis: Speakers Bureau; Apellis: Consultancy; bioverativ: Consultancy. Eber:Agios Pharmaceuticals, Inc.: Consultancy. Glader:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Rothman:Agios: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Kuo:Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy. Kwiatkowski:Agios: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Imara: Consultancy; Apopharma: Research Funding; Novartis: Research Funding; Celgene: Consultancy; Terumo: Research Funding. Ravindranath:Agios Pharmaceuticals, Inc.: Other: I am site PI on several Agios-sponsored studies, Research Funding. Neufeld:Octapharma, Shire Pharmaceuticals (Baxalta), Novo Nordisk, Celgene, NHLBI/NIH: Research Funding; Octapharma, Agios, Acceleron, Grifols, Pfizer, CSL Behring, Shire Pharmaceuticals (Baxalta), Novo Nordisk, ApoPharma, Genentech, Novartis, Bayer Healthcare: Consultancy; Octapharma: Other: study investigator, NuProtect study (Octapharma-sponsored). Holzhauer:Agios Pharmaceuticals, Inc.: Consultancy. Verhovsek:Sickle Cell Disease Association of Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding; Canadian Haemoglobinopathy Association: Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy; Sickle Cell Awareness Group of Ontario: Membership on an entity's Board of Directors or advisory committees. Kunz:Novartis: Membership on an entity's Board of Directors or advisory committees. Sheth:Apopharma: Other: Clinical trial DSMB; Celgene: Consultancy; CRSPR/Vertex: Other: Clinical Trial Steering committee. Despotovic:Novartis: Research Funding; Dova: Honoraria. Grace:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding.

scholarly journals The psychometric properties of the Bergen–Yale Sex Addiction Scale for the Iranian population

2020 ◽  
Author(s):  
Samaneh Youseflu ◽  
Shane W. Kraus ◽  
Fatemeh Razavinia ◽  
Majid Yousefi Afrashteh ◽  
soudabeh niroomand
Keyword(s):  
Psychometric Properties ◽  
Factor Structure ◽  
Internal Consistency ◽  
Content Validity ◽  
Sex Addiction ◽  
Validity And Reliability ◽  
Cronbach’S Alpha ◽  
Structural Validity ◽  
Cronbach's Alpha ◽  
Confirmatory Factor

Abstract Introduction Background: The assessment of sex addiction among different populations requires a valid and reliable tool. Since the Bergen–Yale Sex Addiction Scale (BYSAS) was not available in Iran, this study aimed to evaluate the validity and reliability of the Persian version of the BYSAS. Method: After translation/back-translation procedure, a total of 756 Iranian men and women completed the BYSAS. The structural validity of this tool was evaluated by exploratory and confirmatory factor analyses. An expert panel review also examined content validity of the items. Psychometric properties of the scale including validity, reliability (internal consistency [Cronbach’s alpha]) and test-retest) and factor structure were assessed. Results: Content Validity Index (CVI) and Content Validity Ratio (CVR) scores for the BYSAS were 0.75 and 0.62, respectively. In the measure's structural validity, the results of exploratory and confirmatory factor analysis supported the One-factor structure. Data analysis demonstrated satisfactory internal consistency (Cronbach’s alpha ranging from 0.88 to 0.89). Discussion: Study findings suggest that the BYSAS is a valid and reliable instrument for assessing sex addiction among Persian speaking adults. Replication of research findings is needed to expand the BYSAS for clinical and non-clinical Iranian populations.

scholarly journals Splenomegaly Study (SMS): Which Etiologies for Unexplained Splenomegalies?

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2991-2991
Author(s):  
Guillaume Denis ◽  
Louis Terriou ◽  
Thomas Séné ◽  
Regis Costello ◽  
Martin Michaud ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Gaucher Disease ◽  
Research Funding ◽  
Disease Type ◽  
Malignant Diseases ◽  
Type B ◽  
Advisory Committees ◽  
Niemann Pick Disease ◽  
Niemann Pick ◽  
Pick Disease

Abstract The most prevalent etiologies of splenomegaly (SM) are easily detected in routine clinical practice. However, after these first-line diagnoses have been ruled out, many cases remain unexplained. Frequently, signs and symptoms are non-specific hiding rare etiologies such as Lysosomal Storage Diseases (LSD) (e.g., Gaucher disease (GD), Niemann-Pick disease type B). SplenoMegaly Study (SMS) aims to estimate the prevalence of different etiologies in unexplained SM and to describe their diagnostic work-up. We present here the final results of the study. SMS is a prospective, observational, multi-center, longitudinal study performed in France. All patients with unexplained SM, aged ≥15 years, consulting to the French hematology or internal medicine departments were invited to take part of the study. SM was confirmed by echography or CT-scan with a craniocaudal length ≥13 cm; unexplained was defined as negative clinical and biological routine workup. All conducted exams and tests for diagnosis purpose were under each physician's responsibility. For each patient, last visit took place when an etiology was identified or up to 12 months after inclusion. From Sept-2015 to Apr-2020, 505 patients were enrolled by 87 centers (secondary centers [71.3%] and tertiary centers [28.7%]). Physicians were mainly internists (52.9%) or hematologists (46.0%). Patients characteristics at inclusion were as follows: male gender, 61.2%; median age, 51.0 years old (16-94 years old); median spleen length, 15.0 cm (13-30 cm); heterogeneous spleen structure, 11.1%. A total of 501 patients completed the study. After a median duration of 6.6 months, 232 patients (46.3%) received a diagnosis. When compared to patients without diagnosis, patients with diagnosis were older (median age 59.5 vs 45.0; p&lt;0.001), had more often a massive SM (≥18 cm) (25.2% vs 10.7%; p&lt;0.001) and heterogeneous spleen structure (15.9% vs 6.6%; p=0.002). Their biological test results (hemoglobin, leucocytes, CRP, albumin) were also significantly altered and they showed more constitutional (48.3% vs 37.3%) and digestive symptoms (41.9% vs 28.4%) compared to patients without diagnosis. The proportion of diagnosed patients was higher in tertiary than secondary centers (55.2% vs 32.6%). Hematological (lymphoid and myeloid) malignancies represented only 38.7% (n=87) of established diagnoses (Figure 1). Non-malignant diseases, accounted for 61.3% of diagnosis, were: autoimmune disorders (20.0%, n=45), portal hypertension (12.0%, n=27), infectious diseases (11.6%, n=26), LSD (4.4% [n=10], including type 1 Gaucher Disease (GD1) [n=4]; Niemann-Pick disease type B [n=3] and type C [n=2]; and Fabry disease [n=1]), other disorders (13.3%, n=30) and non-specified (3%, n=7). Hematological malignancies were more common in elderly patients (median age 66.0, p&lt;0.001) with massive SM (p&lt;0.001). Compared to other diagnoses, a large proportion of patients diagnosed with portal hypertension were obese (51.9%) and had ongoing metabolism or nutrition disorders (40.7%). Patients with autoimmune disorders had higher CRP levels (median value, 11.5 mg/L) and showed more osteoarticular symptoms (34.8%). All 4 GD1 patients had thrombocytopenia (≤100G/L platelets). Among the tests contributing to diagnosis, biopsies were performed in 34.3% (n=172) of patients, mainly bone marrow trephine biopsy (BMTB) (20.8%, n=104). Half of patients with BMTB received a diagnosis. Splenectomy was performed in 19 patients (4.0%) and was conclusive in 14 of them. β-Glucocerebrosidase activity assay to test for GD was performed in 79.8% of patients. Among patients without diagnosis, 22.7% of them were not tested for GD. In SMS, patients at inclusion had unexplained SM despite routine clinical and biologic analysis. The diagnostic yield improved after further medical evaluations reaching an etiologic diagnosis in 46% of patients. Patients with an established diagnosis were older, had a larger spleen and altered biological parameters compared to patients without diagnosis. Interestingly, non-malignant diseases accounted for 61.3% of diagnoses. It is noteworthy the diversity of LSD etiologies obtained: 10 patients (4%) were diagnosed with LSD, including 4 GD1 patients. This study provides useful new information to optimize the diagnostic strategy of splenomegaly poorly explained by routine workup. SMS is sponsored by Sanofi-Genzyme. Figure 1 Figure 1. Disclosures Denis: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Séné: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Costello: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Michaud: Sanofi: Honoraria, Research Funding. Hellé: Sanofi: Current Employment. Lagadec: Sanofi: Current Employment. Bauduer: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Sanhes: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Urbanski: Sanofi: Honoraria, Research Funding. Berger: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Risk Factors for Early Sudden Cardiac Death in Patients with Systemic Light-Chain Amyloidosis on Treatment

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3756-3756
Author(s):  
Cherng-Horng Wu ◽  
Philip Tracy ◽  
Denis Toskic ◽  
Raymond Comenzo
Keyword(s):  
Clin Oncol ◽  
Board Of Directors ◽  
Autonomic Dysfunction ◽  
Research Funding ◽  
Troponin I ◽  
Nyha Class ◽  
Al Amyloidosis ◽  
Advisory Committees ◽  
Age And Gender ◽  
And Gender

Abstract Introduction: Despite advances in therapy for patients with light-chain (AL) amyloidosis, mortality remains high in the first 6 months after diagnosis in those on treatment (Blood 2017;129:2111). The early deaths are usually sudden cardiac deaths (SCD); a prior study showed that troponin I level and lack of response to therapy influenced survival (Br J Haematol 2008;143:369). In January 2021 at the approval of daratumumab with cyclophosphamide, bortezomib and dexamethasone for AL (Dara/CyBorD), the FDA label warned that patients with higher cardiac staging may be at risk for fatal cardiac events. We sought to analyze risk factors for SCD in patients on treatment, defining SCD as a sudden unexpected death caused by loss of cardiovascular function (Arrhythm Electrophysiol Rev 2016;5:177). Methods: From a database of 398 patients with AL amyloidosis collected from 2005-2019, we identified patients who suffered out-patient SCD on treatment within 180 days of diagnosis. We recorded baseline age, gender, systolic BP, presence of syncope, LVEF, FLC, cardiac biomarkers, NYHA class, cycles of treatment with bortezomib, and data on SCD. For comparison we identified an age and gender matched group who achieved complete or very good partial responses (CR or VGPR) based on standard criteria and recorded that group's data (J Clin Oncol 2012;30:4541). We compared these datasets by two-tailed Mann-Whitney and where appropriate by contingency table analysis. We computed the medians of the involved FLC, BNP and troponin for all the cases to determine the frequency with which patients in either group had baseline values above or below those medians. Results: Comparative results are shown in Table 1. We identified 13 SCD and 74 age and gender matched CR/VGPR patients. Compared with the CR/VGPR group, both hypotension and exertional syncope were significantly more common in the SCD group, indicating the presence of autonomic dysfunction. NYHA class 3 or 4 status was also more common in the SCD group (40% and 13% vs 26% and 13% in the CR/VGPR group). In addition, more SCD patients were Mayo cardiac stage III (80% vs 46% in the CR/VGPR group) (Blood 2004;104:1881; J Clin Oncol 2004;22:3751). The SCD patients had significantly lower LVEF and higher iFLC and were significantly more likely to have iFLC values above the median. Similarly they had significantly higher BNP and troponin-I levels and were more likely to have values above the medians. The causes of death were unclear in 9 cases but were described by witnesses as due to syncopal events associated with micturition, climbing stairs, or light exertion. In 4 cases seen in emergency rooms, PEA was documented in 3 and septic shock in 1. The SCD patients had a median of 1 cycle of subcutaneous bortezomib-based therapy (CyBorD) (range, 1-5). Three patients received daratumumab subcutaneously with CyBorD. The median starting dose of bortezomib was 1.3mg/m2 (0.7-1.5) usually on a weekly schedule; 2 patients initiated therapy at 1.5mg/m2 weekly, one of whom had had progression of disease (POD) after 2 cycles of oral melphalan and dexamethasone and then had further progression despite completing 3 cycles of CyBorD (POD=1). Eight patients were inevaluable for hematologic response (NR=8), 2 achieved PR after 2 and 4 cycles of CyBorD (PR=2), and of the 3 who got Dara/CyBorD, 1 was inevaluable, 1 achieved VGPR after C1 and 1 CR in C2 (CR/VGPR=2), before having SCD. Conclusion: These findings indicate the contribution that the presence of autonomic dysfunction makes in this population of AL patients with advanced cardiac disease and high levels of iFLC, key variables in the revised Mayo staging system (J Clin Oncol 2012;30:989). The potential pre-morbid significance of exertional syncope has been identified previously (Am J Cardiol 1997;80:1242). In conclusion, this case series suggests that compared with AL amyloid patients who achieve CR or VGPR with treatment, patients who suffer early SCD on treatment have symptoms indicative of autonomic dysfunction and may benefit from in-patient initiation of treatment and from obtaining insurance approval for Dara/CyBorD but starting therapy with weekly subcutaneous daratumumab and dexamethasone, adding cyclophosphamide and bortezomib at a later timepoint based on hematologic response. Moreover, weekly assessment of FLC response is reasonable in these patients in order to guide therapy and adjust supportive care. Figure 1 Figure 1. Disclosures Comenzo: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Prothena Biosciences: Consultancy, Research Funding; Caelum: Consultancy, Research Funding; Takeda: Research Funding; Karyopharm: Research Funding; Janssen: Patents & Royalties: WO2016187546A1, Research Funding; Unum: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Patient Reported Financial Toxicity in Myeloproliferative Neoplasms

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2099-2099
Author(s):  
Thomas G. Knight ◽  
Myra Robinson ◽  
Jing Ai ◽  
Brittany K Ragon ◽  
Rhonda Davis ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Disease Type ◽  
Morbidity And Mortality ◽  
Financial Toxicity ◽  
Advisory Committees ◽  
Patient Reported ◽  
The Cost ◽  
Disease Specific

Background: Financial Toxicity (FT) is increasingly recognized as a major contributor to morbidity and mortality in a variety of cancers. Previous research has demonstrated patients with myeloproliferative neoplasms (MPNs) exhibit a substantial comorbidity burden and have an increased risk of mortality. The purpose of this study was to define rates of FT and the implications on morbidity and mortality in this population using patient reported data. Methods: All patients seen at the Levine Cancer Institute, a tertiary hospital-based specialty practice, were surveyed prior to their visit over a six-month period. All patients were aged ≥18 years and diagnosed with Philadelphia chromosome−negative classical MPNs including myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). The survey consisted of the PROMIS Global-10 measure and two questions from the COST measure. FT was defined as scoring 4 or less (maximum: 10) in agreement with the COST questions: "I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment" and "I am satisfied with my current financial situation." Patient disease and treatment characteristics were summarized with frequencies and proportions for categorical variables and medians and ranges for continuous variables. Correlation of numerical FT scores with PROMIS scores was assessed with Pearson correlation coefficients and ANOVA regression. Additionally, model selection was carried out using logistic regression to identify factors impacting the incidence of financial toxicity (where FT score <=4). Kaplan Meier methods were used to estimate overall survival distributions and log rank tests were used to compare between groups. Results: A total of 51 patients were surveyed. Disease type consisted of 45.1% MF, 31.4% PV, and 23.5% ET. Median age was 62 years. Most patients were high risk by disease specific scoring systems (58.8%), Caucasian (82.4%), and had commercial insurance (56.9%). Median distance from the clinic was 21 miles and median time from diagnosis was 2.2 years. Of the 51 patients surveyed, 20 (39.2%) met the predefined definition of exhibiting severe FT. Lower FT scores (indicating a higher degree of FT) were associated with lower global physical (p < .001) and mental (p < .002) scores by the PROMIS measures (Figure 1). There was no statistically significant difference in survival between patients with FT scores >4 compared to patients with FT scores <=4; however, there was a trend toward decreased survival in those with lower FT scores. The rate of mortality in those with FT score ≤4 was 15.0% compared to 3.2% in those with FT score >4 (p =.287). There also appeared to be a separation of the survival curves when looking at both time from diagnosis and time from survey administration (Figures 2 and 3). Age, race, gender, insurance type, distance from the hospital, disease type, disease specific risk classification, medications utilized, and history of blood/marrow transplant were not found to be significantly different in the two groups. Conclusions: Patients with myeloproliferative neoplasms represent an extremely vulnerable population for financial toxicity with quantifiably increased distress related to this toxicity increasing morbidity and potentially mortality. These findings should be validated in a larger patient cohort and interventions devised to reduce financial distress. Disclosures Knight: Foundation for Financial Planning: Research Funding. Ai:InCyte: Speakers Bureau; Amgen: Speakers Bureau. Trivedi:Incyte: Speakers Bureau. Avalos:Best Practice-Br Med J: Patents & Royalties: receives royalties from a coauthored article on evaluation of neutropenia; Juno: Membership on an entity's Board of Directors or advisory committees. Symanowski:Boston Biomedical: Membership on an entity's Board of Directors or advisory committees; Carsgen Therapeutics: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; Immatics: Membership on an entity's Board of Directors or advisory committees. Grunwald:Amgen: Consultancy; Novartis: Research Funding; Genentech/Roche: Research Funding; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Agios: Consultancy; Incyte: Consultancy, Research Funding; Cardinal Health: Consultancy; Forma Therapeutics: Research Funding; Abbvie: Consultancy; Celgene: Consultancy; Merck: Consultancy; Medtronic: Equity Ownership; Janssen: Research Funding.

scholarly journals The psychometric properties of the Bergen–Yale Sex Addiction Scale for the Iranian population

2020 ◽  
Author(s):  
Samaneh Youseflu ◽  
Shane W. Kraus ◽  
Fatemeh Razavinia ◽  
Majid Yousefi Afrashteh ◽  
Soudabeh Niroomand
Keyword(s):  
Psychometric Properties ◽  
Factor Structure ◽  
Internal Consistency ◽  
Content Validity ◽  
Sex Addiction ◽  
Validity And Reliability ◽  
Cronbach’S Alpha ◽  
Structural Validity ◽  
Cronbach's Alpha ◽  
Confirmatory Factor

Abstract Background: The assessment of sex addiction among different populations requires a valid and reliable tool. Since the Bergen–Yale Sex Addiction Scale (BYSAS) was not available in Iran, this study aimed to evaluate the validity and reliability of the Persian version of the BYSAS. Method: After translation/back-translation procedure, a total of 756 Iranian men and women completed the BYSAS. The structural validity of this tool was evaluated by exploratory and confirmatory factor analyses. An expert panel review also examined content validity of the items. Psychometric properties of the scale including validity, reliability (internal consistency [Cronbach’s alpha]) and test-retest) and factor structure were assessed. Results: Content Validity Index (CVI) and Content Validity Ratio (CVR) scores for the BYSAS were 0.75 and 0.62, respectively. In the measure's structural validity, the results of exploratory and confirmatory factor analysis supported the One-factor structure. Data analysis demonstrated satisfactory internal consistency (Cronbach’s alpha ranging from 0.88 to 0.89). Discussion: Study findings suggest that the BYSAS is a valid and reliable instrument for assessing sex addiction among Persian speaking adults. Replication of research findings is needed to expand the BYSAS for clinical and non-clinical Iranian populations.

Eliglustat, An Investigational Oral Therapy for Gaucher Disease Type 1: Phase 2 Results After 3 Years

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1104-1104
Author(s):  
M. Judith Peterschmitt ◽  
Elena Lukina ◽  
Nora Watman ◽  
Marta Dragosky ◽  
Marcelo Iastrebner ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Disease Type ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Advisory Committees ◽  
Therapeutic Goals ◽  
Gaucher Disease Type 1

Abstract Abstract 1104 Introduction: Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder characterized by deficient activity of the enzyme acid β-glucosidase. This enzymatic deficiency leads to accumulation of undegraded glucosylceramide primarily in tissue macrophages (Gaucher cells) and results in multisystemic manifestations, including thrombocytopenia, anemia, hepatosplenomegaly, and bone disease. The variable clinical course and progression among patients have led to the development of therapeutic goals for the different disease manifestations (Pastores, Semin Hematol. 2004;41(suppl 5):4–14). Eliglustat, a novel, small molecule, specific inhibitor of glucosylceramide synthase, is currently under clinical development as an oral substrate reduction therapy for GD1. Objective: To report long-term efficacy and safety results of eliglustat. Methods: This ongoing, open-label, uncontrolled, multicenter, Phase 2 clinical trial enrolled 26 adults with GD1 not on treatment for the previous 12 months, who had splenomegaly with thrombocytopenia and/or anemia. Efficacy outcomes included changes from baseline in hemoglobin, platelets, spleen and liver volumes, and bone mineral density (mean±SD); biomarker levels (median); and achievement of therapeutic goals for anemia, thrombocytopenia, splenomegaly, and hepatomegaly. Results: Nineteen patients completed 3 years of treatment; 7 patients discontinued the trial. After 3 years, hemoglobin increased by 2.6±1.39 g/dL (from 11.3±1.63 to 13.8±1.37); platelets increased by 91±65.9% (from 70,000±21,700 to 126,800±40,500/mm3); and spleen and liver volumes (multiples of normal, MN) decreased by 61±12.2% (from 16.8±9.5 to 6.2±3.6 MN) and 29±15.8% (from 1.7±0.5 to 1.2±0.3 MN), respectively. Most patients met long-term therapeutic goals for hemoglobin (100%), spleen volume (100%), liver volume (89%), and platelets (63%). All patients met ≥3 therapeutic goals at 3 years. GD1 biomarkers were elevated in most patients pre-treatment. Statistically significant decreases (P<0.0001) following eliglustat treatment were seen in median plasma GL-1 (80%, from 12.15 to 2.70 μg/mL) and GM3 (64%, from 19.25 to 6.60 μg/mL), which normalized; and median chitotriosidase (80%, from 7304 to 1426 nmol/hr/mL) and CCL-18 (73%, from 3560 to 789.3 ng/mL), which both remained above normal. Mean lumbar spine BMD increased by 0.6 Z-score (from −1.3±1.0 to −0.7±1.1). Eliglustat was well tolerated. Most adverse events (AEs) were mild and unrelated to treatment. The most common AEs were viral infections (6 pts); urinary and upper respiratory tract infections (4 pts each); and headache, increased blood pressure, abdominal pain and diarrhea (3 pts each). Eight drug-related AEs, all mild, occurred in 6 patients. Conclusions: Eliglustat has shown promising efficacy and safety, with clinically meaningful hematologic, visceral, and bone improvements. Most patients met long-term therapeutic goals. Eliglustat was well-tolerated through 3 years and continues to have a safety profile that supports clinical investigations in Phase 3 studies. Disclosures: Peterschmitt: Genzyme: Employment. Lukina:Genzyme: Honoraria. Watman:Genzyme: Membership on an entity's Board of Directors or advisory committees. Pastores:Protalix: Research Funding; Shire HGT: Research Funding; Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Research Funding; Actelion: Research Funding; Amicus: Research Funding. Arreguin:Genzyme: Research Funding. Aguzzi:Genzyme: Employment. Ross:Genzyme: Employment. Puga:Genzyme: Employment.

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