The Relationship between Depression, Anxiety, and Clinical Trial Perceptions Among Patients with Hematologic Cancer

Abstract Introduction. Despite the fact that thousands of cancer clinical trials (CCTs) are available today, engagement remains low, with only 2-7% of patients with cancer participating in CCTs. Research has shown that this may partially be due to fear-based perceptions around CCTs. Unfortunately, depression and anxiety, two psychological factors that are highly prevalent in the cancer space, are known to bias attention in ways that alter perceptions and are specifically known to amplify fear-based perceptions. Thus, the purpose of this exploratory study was to examine the relationship between depression, anxiety, and perceptions of clinical trials among patients with hematologic cancer. Method: In this observational, cross-sectional study, 625 patients with hematologic cancer (46.4% multiple myeloma; 19.5% CLL; 11.4% non-Hodgkin lymphoma; 4.0% AML; 3.5% Hodgkin lymphoma; 3.2% CML; 1.6% ALL; 1.3% MPN; 7.4% other lymphoma; 1.8% other leukemia) completed the Cancer Support Community's online survey, the Cancer Experience Registry®. Participants provided sociodemographic and clinical history information, rated their level of agreement (0 = strongly disagree to 4 = strongly agree) with 8 statements related to beliefs about CCTs, and completed the Anxiety and Depression subscales (4 items each rated 1 = never to 5 = always) from the Patient-Reported Outcomes Measurement Information System (PROMIS-29v2.0). Responses to these 8 PROMIS items were averaged to compute a combined depression and anxiety score on a 5-point Likert scale. To understand the impact of depression and anxiety on perceptions of CCTs, 8 hierarchical regression models were examined; the dependent variable for each model was one of the CCT perception variables. Clinical history (cancer diagnosis, time since diagnosis, type of cancer care facility) and sociodemographic variables (age, gender identity, income, educational attainment, race, ethnicity, geographic area) were controlled for. Results: The sample was 54.9% female, 86.7% Non-Hispanic White, 60.1 years old on average (SD=10.8) and had an average time since diagnosis of 5.3 years (SD=5.3; Median = 3.0 years; IQR = 6 years). 67.7% had a college degree, 20.5% had a gross annual household income of $100,000 or above, 41.4% received cancer treatment at an academic or comprehensive cancer center, and 45.6% lived in a suburban area. Participants' average anxiety and depression score was 1.91 (SD=.93). Hierarchical regression analyses demonstrate that depression and anxiety had a significant effect on 7 of the 8 CCT perceptions assessed, when controlling for sociodemographic and cancer characteristics. Specifically, depression and anxiety were significant predictors of participants' perceptions that, "I would be unable to fulfill trial requirements due to logistical barriers" (ΔR 2=.019, b=.19, p=.003), "I don't trust the medical establishment and fear I will be used as a 'guinea pig'" (ΔR 2=.017, b=.17, p=.006), "I am uncomfortable with being randomly assigned" (ΔR 2=.016, b=.19, p=.01), "I fear receiving a placebo (for example, a sugar pill) in a clinical trial" (ΔR 2=.012, b=.18, p=.024), "I don't understand what clinical trials are" (ΔR 2=.011, b=.13, p=.021), "There are no clinical trials available in my community" (ΔR 2=.010, b=.14, p=.030), and "I fear side effects that might come with treatment on a clinical trial" (ΔR 2=.009, b=.13, p=.047). Thus, depression and anxiety accounted for significant amounts of variance in each of these clinical trial perceptions above and beyond the controls. Depression and anxiety did not have a significant impact on participants' perceptions that their health insurance would not cover a CCT (ΔR 2=.002, b=.05, p=.370). Conclusion. Our findings demonstrate small but significant relationships between depression, anxiety, and perceptions of CCTs among patients with hematologic cancer. While common attempts to alter CCT perceptions often focus on information dissemination, the present study indicates that psychological factors may also need to be considered. While this study is an important first step in considering the relationship between mental health and perceptions of CCT, further longitudinal research is needed to better elucidate these findings. For example, differential analyses should explore if and how these relationships differ among patients with pre-existing clinically-significant levels of depression and anxiety. Disclosures LeBlanc: AbbVie: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Flatiron: Consultancy, Other: Advisory board; AstraZeneca: Consultancy, Honoraria, Other: Advisory board, Research Funding; Daiichi-Sankyo: Consultancy, Honoraria, Other: Advisory board; UpToDate: Patents & Royalties; Pfizer: Consultancy, Other: Advisory Board; CareVive: Consultancy, Other, Research Funding; NINR/NIH: Research Funding; Helsinn: Consultancy, Research Funding; Agios: Consultancy, Honoraria, Other: Advisory board; Travel fees, Speakers Bureau; Astellas: Consultancy, Honoraria, Other: Advisory board; Seattle Genetics: Consultancy, Other: Advisory board, Research Funding; Jazz Pharmaceuticals: Research Funding; Otsuka: Consultancy, Honoraria, Other; BMS/Celgene: Consultancy, Honoraria, Other: Travel fees, Research Funding, Speakers Bureau; Amgen: Consultancy, Other: travel; Heron: Consultancy, Honoraria, Other: advisory board; American Cancer Society: Research Funding; Duke University: Research Funding.

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Characterizing Inclusion and Exclusion Criteria in Clinical Trials for CAR-T Cellular Therapy Among Adults with Hematologic Malignancies

Blood ◽

10.1182/blood-2019-131504 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5819-5819

Author(s):

Jordon Jaggers ◽

Heidi D. Klepin ◽

Tanya M. Wildes ◽

Rebecca L. Olin ◽

Andrew S. Artz ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Research Funding ◽

Cellular Therapy ◽

Phase 1 ◽

Hematologic Malignancies ◽

Advisory Board ◽

Exclusion Criteria ◽

Car T ◽

History Of

Introduction: Clinical trial development and enrollment are pivotal to advancing cancer outcomes. Novel treatment modalities such as Chimeric Antigen Receptor (CAR) T-cell therapy is an intensive therapy that has altered the landscape of hematologic malignancy therapies, with several FDA approvals based on Phase I-II studies. Strict eligibility criteria are implemented to ensure safety of trial participants; however, these criteria can lead to barriers to patient enrollment, hinder the generalizability of the study, and result in a population of participants not representative of those who would benefit from therapy. The aim of this proposal is to characterize inclusion and exclusion criteria in clinical trials for CAR-T cellular therapy in adults with hematologic malignancies. Methods: The U.S. National Library of Medicine's Clinical Trial database of privately and publicly funded clinical studies was accessed June 2019 to assemble a list of studies with the following filters applied: hematologic, recruiting, not yet recruiting, not recruiting, active, completed, suspended, terminated studies, interventional studies, CAR, CAR T, chimeric antigen receptor, CAR NK, adult, older adult, early phase 1, phase 1, phase 2, phase 3. From this, 95 studies populated, 84 were utilized in this study and 11 studies excluded due to non-hematologic malignancy. Results: We analyzed 84 CAR-T clinical trials targeting multiple diseases (Table 1) including; acute lymphoblastic (n=7) and myeloid leukemia (n=2); lymphoma (n=6); multiple myeloma (n=40); multiple hematologic malignancies (n=27) and other (n=2). The majority of studies were phase 1 (n=47) or phase 1/2 (n=28). Upper age limit restrictions were in place for 53/84 (63%) of trials. Trials included the AYA population (n=5), ≤ age 65 (n=1), ≤ age 70 or 73 (n=26), ≤ age 75 or 78 (n=12), ≤ age 80 or 85 (n=9). Of the 84 trials, 65 (77%) had performance status inclusion criteria, most commonly was status ECOG 0-2 (n=23) and ECOG 0-1 (n=24). Patients were excluded for a history of a separate or concurrent malignancy in 52/84 (62%) trials, CNS disease was excluded in 45/84 (54%) trials and 70/84 (83%) clinical trials excluded infectious diseases; HIV (n=69) and Hepatitis B/C (n=64). Many studies had restrictions for impairment in organ function; renal impairment (n=66), cardiac deficits (n=67), and abnormal pulmonary function (n=44). Unique to CAR-T trials, 27/84 had restrictions in place for neurological disorders: epilepsy (n=15), history of brain injury (n=10), dementia (n=8), coordination/movement disorder (n=6), cerebellar disease (n=8), psychosis (n=7), paresis (n=6), history of stroke/aphasia (n=21), and active autoimmune or inflammatory disease of the central nervous system (n=3). Conclusion: CAR-T cellular therapy is a tremendous therapeutic advancement in the medical community. This study emphasizes, in detail, highly variable cross-study inclusion/exclusion criteria for early phase CAR-T studies. This new and promising therapy is actively being studied in a highly select group of patients and may not be generalizable to the older adult with hematologic malignancies due to non-uniform trial criteria. The applicability of this modality should be tempered by the understanding that CAR-T trials have overt age caps, ambiguous performance and comorbidity exclusions, and neurologic exclusions and play a role in limiting patient accessibility to novel clinical trial therapy. Confirmatory prospective and observational studies of CAR-T therapy in representative populations are a high priority. 1. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. 2016 127:3321-3330. Doi: 10.1182/blood-2016-04-703751 2. Kim ES, Bruinooge SS, Roberts S, et al. Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement. J Clin Oncol. 2017;35(33):3737-3744. doi:10.1200/JCO.2017.73.7916 3. Unger JM, Cook E, Tai E, and Bleyer A. The Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies. American Society of Clinical Oncology Educational Book. 2016; 36:185-198. Doi:10.1200/EDBK\_156686 Disclosures Wildes: Janssen: Research Funding; Carevive: Consultancy. Olin:Spectrum: Research Funding; Novartis: Research Funding. Artz:Miltenyi: Research Funding. Jaglowski:Unum Therapeutics Inc.: Research Funding; Kite: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Novartis: Consultancy, Other: advisory board, Research Funding. William:Guidepoint Global: Consultancy; Defined Health: Consultancy; Techspert: Consultancy; Celgene Corporation: Consultancy; Kyowa Kirin, Inc.: Consultancy. Rosko:Vyxeos: Other: Travel support.

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Aggressive Smoldering Curative Approach Evaluating Novel Therapies (ASCENT): A Phase 2 Trial of Induction, Consolidation and Maintenance in Subjects with High Risk Smoldering Multiple Myeloma (SMM): Initial Analysis of Safety Data

Blood ◽

10.1182/blood-2020-142584 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 35-36

Author(s):

Shaji K. Kumar ◽

Al-Ola Abdallah ◽

Ashraf Z. Badros ◽

Betsy Laplant ◽

Binod Dhakal ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

High Risk ◽

Research Funding ◽

Advisory Board ◽

Phase 2 ◽

Phase 3 ◽

Phase 2 Trial ◽

Risk Of Progression ◽

M Spike

Background: Smoldering multiple myeloma (SMM) represents an intermediate stage between monoclonal gammopathy of undetermined significance and active myeloma with a high risk of progression to active MM, especially during the initial years after diagnosis. Available clinical risk factors have enabled development of risk stratification systems that allow for identification of patients at the highest risk of progression, opening opportunities for early intervention. Two phase 3 trials using lenalidomide with dexamethasone or lenalidomide alone have both shown benefit for early intervention by decreasing the risk of progression and improving the overall survival in the former. It remains unknown if an approach using a single active drug to delay progression, or one that uses therapies like active myeloma, represent a better approach; both are being studied in phase 3 trials. We designed this phase 2 trial to examine if an intense but limited duration therapy can possibly provide a significant elimination of the tumour burden that can potentially lead to long term responses. Patients and Methods: Patients with SMM (per updated IMWG definition of SMM) with high risk disease (defined by the IMWG updated risk stratification criteria- presence of any two of the following: Serum M spike > 2 gm/dL OR an involved to uninvolved FLC ratio > 20 OR bone marrow PC% > 20%) or a score of ≥9 using the risk scoring system using FLC ratio, serum M spike, marrow plasma cell% and presence of high risk FISH were enrolled provided they had adequate marrow and organ function. Patients with significant comorbidities such as heart disease were excluded from the trial. Treatment consisted of three phases: induction, consolidation and maintenance. Patients received carfilzomib (36 mg/m2 twice weekly or as per updated protocol 56mg/m2 weekly for 2 weeks), lenalidomide (25 mg daily for three weeks), daratumumab (weekly for 8 doses, every other week for 16 weeks) and dexamethasone 40 mg weekly, in 4 week cycles for 6 cycles as part of induction, the same regimen was administered with daratumumab every 4 weeks and dexamethasone 20 mg weekly for another 6 cycles for consolidation. This was followed by 12 cycles of maintenance therapy with lenalidomide (10 mg daily for three weeks), daratumumab (day 1 every other cycle) of a 4-week cycle. Appropriate antiviral, and thrombosis prophylaxis were mandated. The primary endpoint of this trial is the rate of confirmed sCR as best response across all cycles of treatment. We plan to accrue 83 patients to this trial with one-stage binomial trial design to test the null hypothesis that the true success (sCR) proportion is at most 65% and the alternate hypothesis of 80%. Results: Forty-six patients have been accrued to the trial as of July 14, 2020. The median age of the study population is 63 years (range 47 - 76); 70% are male. Overall, 2% have completed the maintenance, 50% have completed the consolidation, 80% have completed the induction and 15% are in the induction phase; only two patients have gone off treatment. The reasons for going off treatment were patient preference. At least one patient needed a dose modification for each drug; 17%, 2%, 13% and 7% required dose reductions for carfilzomib, daratumumab, lenalidomide and dexamethasone respectively. The relative median dose intensity for the drugs were 85%, 92%, 80% and 98% for carfilzomib, daratumumab, lenalidomide and dexamethasone respectively across the delivered cycles. The adverse events seen in at least 5% of the patients are as shown in the figure. A grade 3 or higher AE was seen in 52% of patients. There were no treatment related deaths observed. Response rate and depth have been as expected for this regimen in myeloma and analysis is pending completed accrual. Figure 1 Disclosures Kumar: Adaptive Biotechnologies: Consultancy; Sanofi: Research Funding; Cellectar: Other; Genecentrix: Consultancy; Novartis: Research Funding; Dr. Reddy's Laboratories: Honoraria; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Tenebio: Other, Research Funding; Merck: Consultancy, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Kite Pharma: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; MedImmune: Research Funding; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Carsgen: Other, Research Funding. Badros:Amgen: Consultancy; University of Maryland: Current Employment. Dhakal:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Other: AdvIsory Board, Research Funding; Janssen: Consultancy, Other: Advisory Board, Research Funding; Takeda: Consultancy, Other: Advisory Board; GSK: Consultancy, Research Funding, Speakers Bureau; Sanofi: Research Funding. Abonour:Celgene: Consultancy; Janssen: Honoraria, Research Funding; Takeda: Consultancy; BMS: Consultancy, Research Funding. Rosenbaum:Celgene: Honoraria; Akcea: Honoraria; Amgen: Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding. Bensinger:GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Regeneron: Consultancy, Honoraria, Research Funding, Speakers Bureau. Bhutani:Prothena: Other: Clinical Trial Funding to Institute; Sanofi Genzyme: Consultancy; Janssen: Other: Clinical Trial Funding to Institute; BMS: Other: Clinical trial funding to institute, Speakers Bureau; Amgen: Speakers Bureau; MedImmune: Other: Clinical Trial Funding to Institute; Takeda: Other: Clinical trial funding to institute, Speakers Bureau. Jakubowiak:AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive, Juno: Consultancy, Honoraria. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

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Investigation of the role of anxiety and depression on the formation of phantom vibration and ringing syndrome induced by working stress during medical internship (Preprint)

10.2196/preprints.16705 ◽

2019 ◽

Author(s):

Yu-Hsuan Lin ◽

Kuan-I Lin ◽

Yuan-Chien Pan ◽

Sheng-Hsuan Lin

Keyword(s):

Anxiety And Depression ◽

Depression And Anxiety ◽

Prospective Longitudinal Study ◽

Work Related ◽

Working Stress ◽

Causal Mediation Analysis ◽

Accompanying Symptoms ◽

Prospective Longitudinal ◽

The Relationship

BACKGROUND Phantom vibrations syndrome (PVS) and phantom ringing syndrome (PRS) are prevalent hallucinations during medical internship. Depression and anxiety are probably understudied risk factors of PVS and PRS. OBJECTIVE The aim of this study was to investigate the role of anxiety and depression on the relationship between working stress during medical internship and PVS and PRS. METHODS A prospective longitudinal study of 74 medical interns was carried out using repeated investigations of the severity of phantom vibrations and ringing, as well as accompanying symptoms of anxiety and depression as measured by Beck Anxiety Inventory and the Beck Depression Inventory before, at the 3rd, 6th, and 12th month during internship, and 2 weeks after internship. We conducted a causal mediation analysis to investigate the role of depression and anxiety in the mechanism of working stress during medical internship inducing PVS and PRS. RESULTS The results showed that depression explained 21.9% and 8.4% for stress-induced PRS and PVS, respectively. In addition, anxiety explained 15.0% and 7.8% for stress-induced PRS and PVS, respectively. CONCLUSIONS Our findings showed both depression and anxiety can explain a portion of stress-induced PVS and PRS during medical internship and might be more important in clinical practice and benefit to prevention of work-related burnout.

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Childhood Material Hardship and Adolescent Mental Health

Youth & Society ◽

10.1177/0044118x211001896 ◽

2021 ◽

pp. 0044118X2110018

Author(s):

Chrisse Edmunds ◽

Melissa Alcaraz

Keyword(s):

Mental Health ◽

Adolescent Depression ◽

Adolescent Mental Health ◽

Anxiety And Depression ◽

Fragile Families ◽

Depression Symptoms ◽

Depression And Anxiety ◽

Material Hardship ◽

Critical Age ◽

The Relationship

Adolescent mental health has implications for current and future wellbeing. While a link exists between poverty and mental health, little is known about how experiencing material hardship, such as insecurity of food, housing, utilities, and medical care, throughout early childhood affects adolescent mental health. We examine the relationship between material hardship in childhood and adolescent mental health. We use Poisson regression to examine the effect of material hardship experienced at different stages of childhood on adolescent depression and anxiety outcomes at age 15. We use longitudinal data from the Fragile Families and Child Wellbeing Study ( N = 3,222). We find that recently experiencing material hardship during childhood is positively and significantly associated with anxiety and depression symptoms at age 15, even when controlling for material hardship at age 15. Additionally, we find that insecurity during mid-childhood and the stress of lacking basic needs during a critical age may influence mental health in adolescence.

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Investigation of the role of anxiety and depression on the formation of phantom vibration and ringing syndrome caused by working stress during medical internship (Preprint)

10.2196/preprints.23858 ◽

2020 ◽

Author(s):

Yu-Hsuan Lin ◽

Kuan-I Lin ◽

Yuan-Chien Pan ◽

Sheng-Hsuan Lin

Keyword(s):

Anxiety And Depression ◽

Depression And Anxiety ◽

Prospective Longitudinal Study ◽

Work Related ◽

Working Stress ◽

Causal Mediation Analysis ◽

Accompanying Symptoms ◽

Prospective Longitudinal ◽

The Relationship

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Northstar-2: Updated Safety and Efficacy Analysis of Lentiglobin Gene Therapy in Patients with Transfusion-Dependent β-Thalassemia and Non-β0/β0 Genotypes

Blood ◽

10.1182/blood-2019-126046 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3543-3543 ◽

Cited By ~ 1

Author(s):

Alexis A. Thompson ◽

Mark C. Walters ◽

Janet L. Kwiatkowski ◽

Suradej Hongeng ◽

John B. Porter ◽

...

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Board Of Directors ◽

Research Funding ◽

Advisory Board ◽

Adult Patients ◽

Employment Equity ◽

Advisory Committees ◽

Transfusion Independence ◽

Equity Ownership

Background Transfusion-dependent β-thalassemia (TDT) is treated with regular, lifelong red blood cell (RBC) transfusions and despite iron-chelating therapy, carries a risk of serious organ damage from iron overload and other complications. Transplantation with autologous CD34+ cells encoding a βA-T87Q-globin gene (LentiGlobin for β-thalassemia) is being evaluated in patients with TDT. Interim results are presented here from the ongoing, international, single-arm, phase 3 Northstar-2 study (HGB-207; NCT02906202) of LentiGlobin gene therapy in pediatric, adolescent, and adult patients with TDT (defined by receiving ≥100 mL/kg/yr of RBCs or ≥8 RBC transfusions/yr) and non-β0/β0 genotypes. Methods Patients undergo hematopoietic stem cell (HSC) mobilization with G-CSF and plerixafor. Following apheresis, CD34+ cells are transduced with BB305 lentiviral vector and infused into patients after pharmacokinetic-adjusted, single-agent busulfan myeloablation. The primary efficacy endpoint is transfusion independence (TI; weighted average hemoglobin [Hb] ≥9 g/dL without RBC transfusions for ≥12 months). HSC engraftment, βA-T87Q-globin expression, Hb levels, detection of replication competent lentivirus (RCL), and adverse events (AE) are also assessed. Patients are followed for 2 years and offered participation in a long-term follow-up study. Summary statistics are presented as median (min - max). Results Twenty patients were treated in Northstar-2 as of 13 December 2018 and have been followed for a median of 8.1 (0.5 - 22.2) months. At enrollment, median age was 16 (8 - 34) years; 5 patients were <12 years of age. Median drug product cell dose was 8.0 (5.0 - 19.9) x106 cells/kg and vector copy number was 3.2 (1.9 - 5.6) copies/diploid genome. Time to neutrophil and platelet engraftment in the 18/20 and 15/20 evaluable patients was 22.5 (13 - 32) and 45 (20 - 84) days, respectively. Non-hematologic grade ≥3 AEs in ≥3 patients after LentiGlobin infusion included stomatitis (n=12), febrile neutropenia (n=6), pyrexia (n=4), epistaxis (n=3), and veno-occlusive liver disease (n=3). One serious AE of grade 3 thrombocytopenia was considered possibly related to LentiGlobin. No patient died, had graft failure, or had detection of RCL. No insertional oncogenesis has been observed. Gene therapy-derived HbAT87Q stabilized approximately 6 months after infusion. In adolescent and adult patients treated with LentiGlobin, median HbAT87Q at Months 6, 12 and 18 was 9.5 (n=11), 9.2 (n=8), and 9.5 (n=3) g/dL, respectively. The median total Hb without transfusions at Months 6, 12, and 18 were 11.9 (n=11), 12.4 (n=8), 12.3 (n=2) g/dL, respectively. At Month 6, 91% (10/11) of patients had total Hb of >11 g/dL without transfusions. Five adolescent and adult patients were evaluable for the primary endpoint of transfusion independence, 4 (80%) of whom achieved TI. The median weighted average Hb during TI was 12.4 (11.5 - 12.6) g/dL which compared favorably to pre-transfusion nadir Hb levels before enrollment (median 9.1 g/dL [7.5 - 10.0 g/dL]). At time of analysis, the median duration of TI was 13.6 (12.0 - 18.2) months. One patient who did not achieve TI stopped transfusions for 11.4 months but resumed transfusions due to recurrent anemia. This patient had a 71.4% reduction in RBC transfusion volume from Month 6 to Month 18 compared to baseline. Marrow cellularity and myeloid:erythroid (M:E) ratios were evaluated in 8 adolescent and adult patients with ≥12 months follow-up to assess the effect of LentiGlobin treatment on dyserythropoiesis. Seven of 8 patients had improved marrow M:E ratios at Month 12 (0.63 - 1.90) compared with baseline (0.14 - 0.48). In patients who stopped transfusions, soluble transferrin receptor levels were reduced by a median of 72% (58% - 78%) at Month 12 (n=6). Updated outcomes in adolescents and adults and outcomes in pediatric patients will be reported. Summary In this update of the Northstar-2 study of LentiGlobin gene therapy in patients with TDT and non-β0/β0 genotypes, transfusion independence was observed in 4/5 evaluable adolescent and adults and 10/11 treated patients had total Hb of >11 g/dL without transfusion support 6 months after LentiGlobin infusion. HbAT87Q stabilized approximately 6 months after treatment and patients who stopped RBC transfusions had improved erythropoiesis. A safety profile consistent with busulfan conditioning was observed after LentiGlobin gene therapy. Disclosures Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Walters:TruCode: Consultancy; AllCells, Inc: Consultancy; Editas Medicine: Consultancy. Kwiatkowski:bluebird bio, Inc.: Consultancy, Research Funding; Terumo: Research Funding; Celgene: Consultancy; Agios: Consultancy; Imara: Consultancy; Apopharma: Research Funding; Novartis: Research Funding. Porter:Protagonism: Honoraria; Celgene: Consultancy, Honoraria; Bluebird bio: Consultancy, Honoraria; Agios: Consultancy, Honoraria; La Jolla: Honoraria; Vifor: Honoraria; Silence therapeutics: Honoraria. Thrasher:Rocket Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orchard Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Generation Bio: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; 4BIOCapital: Membership on an entity's Board of Directors or advisory committees. Thuret:BlueBird bio: Other: investigators for clinical trials, participation on scientific/medical advisory board; Celgene: Other: investigators for clinical trials, participation on scientific/medical advisory board; Novartis: Other: investigators for clinical trials, participation on scientific/medical advisory board; Apopharma: Consultancy. Elliot:bluebird bio, Inc.: Employment, Equity Ownership. Tao:bluebird bio, Inc.: Employment, Equity Ownership. Colvin:bluebird bio, Inc.: Employment, Equity Ownership. Locatelli:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Miltenyi: Honoraria.

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A-121 Functional Outcomes in Bilingual Persons with Traumatic Brain: The Role of Mood

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.139 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1171-1171

Author(s):

Winter Olmos ◽

Daniel W Lopez-Hernandez ◽

Isabel Munoz ◽

Laura Schierholz ◽

Rachel A Rugh-Fraser ◽

...

Keyword(s):

Depressive Symptoms ◽

Functional Outcomes ◽

Depression Scale ◽

Anxiety And Depression ◽

Depression And Anxiety ◽

Hospital Anxiety ◽

Anxiety Levels ◽

The Relationship ◽

Pearson Correlations

Abstract Introduction We examined the relationship between depression and anxiety, language, and functional outcomes in persons with traumatic brain injury (TBI). Methods The sample consisted of 48 acute TBI (ATBI: 23 Spanish-English Bilinguals; 25 English monolinguals), 30 chronic TBI (CTBI: 17 Spanish English Bilinguals; 12 English monolinguals), and 47 healthy comparison (HC: 29 Spanish-English Bilinguals; 18 English monolinguals) participants. The Hospital Anxiety and Depression Scale was used to measure depression (HADS-D) and anxiety (HADS-A). The Mayo Portland Adaptability Inventory-4 (MPAI-4) was used to measure functional outcomes (ability, adjustment, participation). Results An ANCOVA, controlling for age, revealed the ATBI group reported lower anxiety levels compared to the CTBI group, p = 0.034 np2 = 0.06. HC participants demonstrated significantly higher functional ability compared to both TBI groups, p < 0.05, np2 = 0.08–0.19. The ATBI group demonstrated worse participation scores compared to the CTBI and HC groups, p = 0.001, np2 = 0.11. Pearson correlations revealed mood was related to functional status in ATBI monolinguals (HADS-A: r = 0.29–0.64; HADS-D, r = 0.49–0.62). Monolingual participants with ATBI demonstrated correlations between depressive symptoms and functional adjustment (r = 0.57, p = 0.005) and ability (r = 0.44, p = 0.034). For monolinguals with CTBI, HADS-A correlated with functional outcomes, r = 0.60–0.66, p < 0.05. For bilinguals with CTBI, functional outcomes correlated with HADS-A, r = 0.53–0.66, p < 0.05, and HADS-D, r = 0.54–0.66, p < 0.05. For HC monolinguals, functional outcomes correlated with HADS-A, r = 0.53–0.70, p < 0.05, and HADS-D, r = 0.50–0.72, p < 0.05. Finally, for HC bilinguals, functional outcomes correlated with HADS-A, r = 0.59–0.68, p < 0.05. Conclusion Our results suggest that a relationship between anxiety and depressive symptoms is related more to functional outcomes in monolingual TBI survivors compared to bilingual TBI survivors.

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The Correlation of the Tinnitus Handicap Inventory with Depression and Anxiety in Veterans with Tinnitus

International Journal of Otolaryngology ◽

10.1155/2015/689375 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Jinwei Hu ◽

Jane Xu ◽

Matthew Streelman ◽

Helen Xu ◽

O’neil Guthrie

Keyword(s):

Anxiety And Depression ◽

Depression And Anxiety ◽

Multidisciplinary Intervention ◽

Tinnitus Handicap Inventory ◽

Hearing Status ◽

Male Veterans ◽

Positive Correlations ◽

Anxiety Depression ◽

The Relationship ◽

Severe Tinnitus

Objective. The mechanisms of tinnitus are known to alter neuronal circuits in the brainstem and cortex, which are common to several comorbid conditions. This study examines the relationship between tinnitus and anxiety/depression.Subjects and Methods. Ninety-one male veterans with subjective tinnitus were enrolled in a Veterans Affairs Tinnitus Clinic. The Tinnitus Handicap Inventory (THI) was used to assess tinnitus severity. ICD-9 codes for anxiety/depression were used to determine their prevalence. Pure tone averages (PTA) were used to assess hearing status.Results. Descriptive analyses revealed that 79.1% of the 91 tinnitus sufferers had a diagnosis of anxiety, 59.3% had depression, and 58.2% suffered from both anxiety/depression. Patients with anxiety had elevated total THI scores as compared to patients without anxiety (p<0.05). Patients with anxiety or depression had significantly increased Functional and Emotional THI scores, but not Catastrophic THI score. Significant positive correlations were illustrated between the degree of tinnitus and anxiety/depression (p<0.05). There were no differences in PTA among groups.Conclusions. A majority of patients with tinnitus exhibited anxiety and depression. These patients suffered more severe tinnitus than did patients without anxiety and depression. The data support the need for multidisciplinary intervention of veterans with tinnitus.

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Examination of Phosphoprotein Targets in Timed Samples from Patients with RAS-Mutated AML during Concurrent Treatment with Alpelisib and Binimetinib on the Phase Ib Clinical Trial CMEK162X2109

Blood ◽

10.1182/blood.v128.22.2749.2749 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2749-2749

Author(s):

Kira Gritsman ◽

Robert P. Hasserjian ◽

Taneisha Sinclair ◽

David M. Weinstock ◽

Britta Will ◽

...

Keyword(s):

Clinical Trial ◽

Bone Marrow ◽

Peripheral Blood ◽

Clinical Benefit ◽

Research Funding ◽

Mapk Signaling ◽

Advisory Board ◽

Post Treatment ◽

Blood Samples ◽

Phase Ib

Abstract Activation of MAPK signaling is characteristic of many cancers, and approximately 15% of AML patients carry activating RAS mutations. The PI3K pathway is also constitutively activated in AML. Both pathways interact with each other extensively and provide compensatory signaling when one pathway is inhibited. It has been demonstrated in vitro that concurrent inhibition of both pathways is effective in blocking the proliferation of AML cell lines through an immediate decrease in pAkt and pErk, leading to inhibition of pS6 (Gritsman et al, J Clin Invest, 2014, 124(4):1794-1809). The combination of alpelisib (BYL-719), which inhibits PI3K (p110alpha), and binimetinib (MEK-162), which inhibits MEK (MAPK pathway), was tested in various tumor types in the Phase Ib Clinical Trial CMEK162x2109. We present here the clinical data and correlative phosphoprotein analysis of 6 patients with relapsed refractory RAS-mutated AML treated at Massachusetts General Hospital on Extension Arm 4A of this trial. Entry to this trial was restricted to adult patients with RAS-mutated AML previously treated with 1 or 2 prior chemotherapy regimens or for whom there was no known effective therapy. Patients received 200mg QD of alpelisib and 45mg BID of binimetinib concurrently and continuously with adjustments for toxicities. Hematologic toxicity could not be determined in these patients with active AML causing myelosuppression. There were responses in blood and/or bone marrow (BM) in 3 patients, but none made partial response criteria by IWG guidelines, mainly due to platelet counts <100,000/ul. Blast clearance from blood in the first month were seen in 2 patients, with a >50% reduction in a third patient. A rise in absolute neutrophil count was seen in 3 patients, 2 from below 100/ul to above 500/ul, and in 1 from 5,320/ul to 12,797/ul during the first month. BM partial responses were seen in 2 patients, with blast percentages dropping from 39% to 10% in 1 patient and from 12% to 5% in another. We analyzed the effects of this drug combination on signaling targets by collecting peripheral blood samples on day 1 pre-treatment and at 6 and 24 hours post-initiation of treatment. In 4 patients, we performed analysis of the phosphorylation of Akt, ribosomal protein S6, Erk, STAT5, and STAT3 on timed peripheral blood samples by immunoblotting. In all 4 cases at baseline, pAkt, pErk, and pS6 were detectable, while pSTAT5 and pSTAT3 levels were variable. In 3 of 4 cases, we observed a transient decrease in pAkt at 6 hours, but then a rebound at 24 hours. In 3 of 4 cases, we observed a lack of sustained pS6 inhibition. We observed sustained pErk inhibition at 24 hours in 2 cases. One patient who had blood blast clearance, improvement in ANC, and a drop in bone marrow blasts, showed strong inhibition of pAkt and pERK at 6 hours, although pS6 did not decrease. In another case we performed phospho-flow cytometry on timed whole blood samples. We observed an increase in pAkt, pS6, and pErk from baseline at 24 hours, both in CD34+38+blasts, and in the primitive CD34+38- cells. This second patient showed no clinical benefit from the treatment in terms of blood blast count, ANC, or platelets. We also performed immunohistochemistry for pS6, pErk, pAkt, pSTAT5, pSTAT3, p-eIF4E, and Caspase 3 on BM sections obtained at diagnosis and at one month and two months post-initiation of treatment, when available. These studies generally showed either persistence or an increase in the pS6 and p-eIF4E signals, both indicators of mTORC1 activity, in post-treatment BM samples. Levels of pAkt, pErk, pSTAT5 and pSTAT3 were highly variable in the post-treatment bone marrow samples. In conclusion, we demonstrated some initial target inhibition with the concurrent use of alpelisib and binimetinib in a subset of patients. However, inhibition of late downstream targets was not sufficiently sustained to achieve consistent clinical benefit in our patients with RAS-mutated AML. While the strategy of concurrent inhibition of various critical signaling pathways remains interesting, sustained inhibition of downstream signaling may require a different dosing schedule of the two drugs. Given the incomplete inhibition of mTORC1 targets pS6 and p-eIF4E in most cases, the addition of a third agent to inhibit pathways causing cross-activation downstream of mTORC1 may be required. Disclosures Weinstock: Novartis: Consultancy, Research Funding. Fathi:Bexalata: Other: Advisory Board participation; Merck: Other: Advisory Board participation; Celgene: Consultancy, Research Funding; Seattle Genetics: Consultancy, Other: Advisory Board participation, Research Funding; Agios Pharmaceuticals: Other: Advisory Board participation.

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The Mediational Effect of Weight Self-Stigma in the Relationship between Blatant and Subtle Discrimination and Depression and Anxiety

The Spanish Journal of Psychology ◽

10.1017/sjp.2017.1 ◽

2017 ◽

Vol 20 ◽

Cited By ~ 9

Author(s):

Alejandro Magallares ◽

Patricia Bolaños-Rios ◽

Inmaculada Ruiz-Prieto ◽

Pilar Benito de Valle ◽

Jose Antonio Irles ◽

...

Keyword(s):

Social Stigma ◽

Depression Scale ◽

Anxiety And Depression ◽

Depression And Anxiety ◽

Hospital Anxiety ◽

Obesity Stigma ◽

Subtle Discrimination ◽

Dependent Variables ◽

Similar Weight ◽

The Relationship

AbstractObesity may be considered a social stigma. In addition, people with obesity are frequently aware of stigma directed at others who have a similar weight and come to think stigmatized thoughts about themselves. Our study focused specifically on how blatant and subtle discrimination and weight self-stigma are related to depression and anxiety in people with obesity. The sample comprised 170 participants from the Clinical Nutrition Unit of the “Hospital de Valme” (Seville, Spain). The Weight Self-Stigma Questionnaire, the Multidimensional Perceived Discrimination Scale, and the Hospital Anxiety and Depression Scale were used. It was found that blatant and subtle discrimination and weight self-stigma were positively related to depression (.31, .38, and .45 respectively) and anxiety (.30, .36, and .49 respectively; all ps < .01). The path analysis conducted showed that there was a mediational effect of weight self-stigma between blatant (β = .36) and subtle discrimination (β = .40) and depression (β = .24) and anxiety (β = .49; all ps < .01). According to these results, it can be said that weight self-stigma was a full mediator in the model found because the relationships between the independent and the dependent variables were non-significant. Finally, results are discussed in the frame of the obesity stigma literature, and some clinical implications of the results of the study are suggested.

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