scholarly journals Perceptions of Prognosis Among Patients with Advanced Hematologic Malignancies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4026-4026
Author(s):  
Oreofe O. Odejide ◽  
Scott F. Huntington ◽  
Thomas M. Kuczmarski ◽  
Eleanor Shi ◽  
James A. Tulsky ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Research Funding ◽  
Hematologic Malignancies ◽  
Self Report ◽  
Healthcare Team ◽  
Univariable Analysis ◽  
Eligibility Criteria ◽  
Response Options ◽  
Know How ◽  
Common Diagnosis

Abstract Background: Although accurate prognostic understanding is essential for patients to make informed decisions about their care, little is known regarding understanding of life expectancy among patients with blood cancers approaching end of life. We sought to characterize such perceptions in a cohort of patients with advanced blood cancers. Methods: In October 2020, we began a web-based survey of adult patients with hematologic malignancies recruited from two large cancer centers. Eligibility criteria included: (1) age ≥ 18 years, (2) at least 2 outpatient visits at the study centers, and (3) physician-estimated prognosis of six months or less based on the patient's hematologic oncologist answering "no" to the question: "would you be surprised if this patient died in the next six months?" The 12-month version of this question has been shown to correctly estimate death in 68.3% of patients with blood cancers (Hudson KE, JPM 2018). Among other questions, participants were asked how important it was for them to know how cancer might influence the length of their life, with response options on a 4-point scale ranging from "not important at all," to "very important." We also asked participants if anyone on their healthcare team had ever discussed how long they might expect to live with their cancer, and participants' perception of their life expectancy, with response options of "more than 2 years," "one to two years," "7 to 11 months," "1 to 6 months," and "less than 1 month." We then asked about the most important factor in determining their self-reported prognosis. We summarized responses for prognostic perceptions with relative frequencies (%). We also assessed, in univariable analysis, if patients' reports of prognostic discussion with their healthcare team was associated with self-report of prognosis of "more than 2 years." Results: As of July 2021, 102 patients had completed the survey (response rate: 64.6%). The most common diagnosis was acute leukemia (38.2%), followed by lymphoma (30.4%; Table 1). The median time between diagnosis and completion of survey was 26 months. The majority (91.1%) felt it was "moderately" or "very important" to know how cancer might influence their length of life, but only 47.1% recalled a discussion about life expectancy with their healthcare team. Most respondents (65.7%) felt their life expectancy at the time of the survey exceeded 2 years (Figure). In univariable analysis, patients who reported having had a prognostic discussion with their healthcare team were less likely to estimate their own life expectancy to be greater than 2 years compared to patients who did not (48.9% vs. 81.1%, chi-square p =0.0007). Factors cited to be most important by respondents in estimating their prognosis were their "health/how things had been going with their cancer" (35.3%), "information received from their doctor or healthcare team" (29.4%), "attitude or personal beliefs" (16.7%), "their own research" (9.8%), and "stories they heard from other people" (3.9%). Conclusions: In this cohort of blood cancer patients with a physician-estimated prognosis of ≤ 6 months based on the "surprise question," two-thirds had substantially more optimistic views of their prognosis. Our finding that over 80% of individuals who did not recall a prognostic discussion with their healthcare team thought their own life expectancy to be greater than 2 years suggests that lack of prognostic disclosure contributes to the gap between physician and patient perceptions of prognosis. The fact that almost half of patients who did report having such a discussion had overly optimistic views suggests that additional factors are also putative. Figure 1 Figure 1. Disclosures Huntington: Flatiron Health Inc.: Consultancy; TG Therapeutics: Research Funding; Thyme Inc: Consultancy; Bayer: Honoraria; DTRM Biopharm: Research Funding; SeaGen: Consultancy; AstraZeneca: Consultancy, Honoraria; Novartis: Consultancy; Servier: Consultancy; Genentech: Consultancy; AbbVie: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding.

Defibrotide (DF) in the Treatment of Hepatic Veno-Occlusive Disease (VOD) in Stem Cell Transplant (SCT) and Non-SCT Patients (Pts): Early Intervention Improves Outcome - Updated Results of a Treatment IND Expanded Access Protocol

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 487-487 ◽  
Author(s):  
Paul G. Richardson ◽  
Angela R. Smith ◽  
Stephan A Grupp ◽  
Nancy A. Kernan ◽  
Sally Arai ◽  
...  
Keyword(s):  
Early Intervention ◽  
Board Of Directors ◽  
Research Funding ◽  
Historical Control ◽  
Cell Transplant ◽  
Phase 3 ◽  
Eligibility Criteria ◽  
Advisory Committees ◽  
Common Diagnosis ◽  
Improved Outcome

Abstract Abstract 487FN2 Background: Given the life-threatening nature of severe VOD (sVOD) and multi-organ failure (MOF), DF was made available in the US through a prospective treatment IND protocol (T-IND) to gather additional safety and response data from SCT patients (pts) with sVOD who were not eligible for a pivotal Phase 3 trial. Following completion of this Phase 3 trial, the T-IND protocol has continued and been amended to include pts who would have met eligibility criteria for the completed phase 3 trial, as well as pts with non-severe VOD and non-SCT pts who develop VOD after chemotherapy (chemo). This is the largest prospective evaluation of DF for the treatment of sVOD/MOF post SCT and non-SCT pts to date. Methods: Pts were initially required to have a diagnosis of VOD by Baltimore criteria (total bilirubin > 2.0 mg/dL with > 2 of the following: hepatomegaly, ascites or 5% weight gain) with MOF (either renal and/or pulmonary failure) that followed SCT. Following treatment of 104 pts, an amendment expanded eligibility criteria to include pts with VOD after chemo and pts with non-severe VOD (defined as no MOF). Key exclusion criteria included clinically significant bleeding or >1 pressor to maintain BP. CR was defined as bilirubin < 2 mg/dL + resolution of MOF (if applicable). Mortality was assessed at Day +100 (D+100) in all pts. DF was given at 6.25 mg/kg IV q6h (25 mg/kg/d) with treatment duration recommended for at least 21d. Results: This interim analysis is based on 269 pts enrolled between December 2007 and March 2011 at 67 centers. Nearly all pts (n=251) had undergone SCT (with allogeneic SCT in 225, 90%); 18 developed VOD after chemo alone. Of the 269 cases of VOD, 200 were severe at study entry, with 25% (66/269) of all pts dialysis dependent and 31% (83/269) ventilator dependent. Median age was 16 years (range 0.1 – 70); 55% were male. In the SCT pts, the most common diagnosis was leukemia (29% AML; 22% ALL; CML 3%; 4% other), with conditioning of CY (71%), BU (46%) and TBI (38%) respectively; 18% had undergone multiple SCTs (>1 SCT). Median onset of VOD was 15 d post-SCT. When presenting after chemo alone (n=18), median onset of VOD was 16 d after the first dose, most frequently after CY (61%), cytarabine (44%) and vincristine (39%), and for treatment of leukemia (AML 33%, ALL 33%, other 6%). Overall mean number of days of DF administration in all pts was 22 (range 1–88).Of 269 pts, 32% (85/269) achieved a CR and 50% [ by Kaplan-Meier estimate] survived to D+100. In the subgroup of SCT pts, 31% (78/251) achieved CR and 50% survived to D+100; 134 pts met entry criteria for the original Phase 3 trial and comparison to the Phase 3 historical control showed a statistically improved outcome in CR (30% vs 9%, p=0.0006) and D+100 survival (46% vs 25%; p=0.006). Of 200 pts with sVOD, CR was 28% and D+100 survival was 44%. In the 18 chemo only pts, CR was 39% and D+100 survival was 50%. CR rate and D+100 survival for the 69 pts with non-severe VOD were 42% and 62%, respectively. Delay of >2 d (vs < 2 d) in the start of DF after VOD diagnosis resulted in reduced CR (23% vs 35%, p=0.0339) and survival (37% vs 56%, p=0.01). Children as compared to adults had higher rates in CR (35% vs 29%) and survival (55% vs 43%). Toxicity proved generally manageable: 22% of pts experienced a total of 81 related AEs, primarily consisting of hemorrhage (19%) and hypotension (4%). Hemorrhage included pulmonary bleeding (6%), GI hemorrhage (3%), epistaxis (3%) and hematuria (3%). Similar to the observation of decreased GvHD in other studies, the incidence of all grade GvHD in the allogeneic SCT pts was 8%. Conclusions: In 269 pts with mainly sVOD/MOF, DF therapy achieved significantly improved outcome compared to an untreated historical control. Importantly, CR and survival were improved in pts who were treated within 2d of VOD diagnosis (vs. later) and in pts who had not yet progressed to sVOD. As with prior studies, there was a low incidence of DF-associated toxicities. Interestingly, the incidence of GvHD in allo-SCT pts was low, consistent with the reduction of GvHD seen in the large randomized EBMT pediatric prevention study. These results confirm the findings of previous trials and strongly support early intervention with DF once the diagnosis of VOD is made after SCT, as well as its use in pts who have not progressed to advanced MOF. The use of DF for VOD following intensive chemotherapy without SCT also appears promising, but more research in this patient population is needed. Enrollment to the T-IND study continues. Disclosures: Richardson: Gentium: Membership on an entity's Board of Directors or advisory committees. Arai:Gentium: Research Funding. Symons:Otsuka Pharmaceuticals: Research Funding. Martin:Gentium: Research Funding. Massaro:Gentium: Consultancy. D'Agostino:Gentium: Membership on an entity's Board of Directors or advisory committees. Hannah:Gentium: Consultancy. Tudone:Gentium: Employment. Hume:Gentium: Employment. Iacobelli:Gentium SpA: Employment. Soiffer:Gentium: Honoraria.

The Role and Activities of Board-Certified Chaplains in Advance Care Planning

2021 ◽  
pp. 104990912198999
Author(s):  
Jung Kwak ◽  
Soyeon Cho ◽  
George Handzo ◽  
Brian P. Hughes ◽  
Sami S. Hasan ◽  
...  
Keyword(s):  
Advance Care Planning ◽  
Self Report ◽  
Healthcare Team ◽  
Care Planning ◽  
Cross Sectional ◽  
Team Members ◽  
Roles And Responsibilities ◽  
Healthcare Settings ◽  
Academic Medical ◽  
Advance Care

Background: Healthcare chaplains have key roles in providing palliative support to patients and families, and they are well-suited to facilitate advance care planning (ACP). However, empirical data on the roles and responsibilities of chaplains in facilitating ACP are limited. Objectives: To examine the roles of board-certified healthcare chaplains in ACP in various healthcare settings. Methods: A cross-sectional, web-based self-report survey was conducted with 585 board-certified chaplains recruited from 3 major professional chaplains’ organizations in the U.S. The survey data included chaplains’ demographic and professional characteristics, their roles and responsibilities, and responses regarding communication and participation with other healthcare team members in facilitating ACP, including experienced barriers. Results: More participants worked in community hospital settings (42%) and academic medical centers (19.6%) than in any other setting. Over 90% viewed ACP as an important part of their work, 70% helped patients complete advance directives, and 90% helped patients discuss their preferences about end-of-life treatments. Many chaplains were not consistently included in team discussions regarding decision-making, although most chaplains reported that they could always find ways to communicate with their teams. Conclusion: Professional board-certified chaplains regularly engage in facilitating ACP discussions with patients and families in various healthcare settings. There is a need to recognize and provide systematic support for the role of chaplains in facilitating ACP conversations and to integrate chaplains into routine interdisciplinary team and family meetings.

scholarly journals The Prevalence of Pain in People With Chronic Ankle Instability: A Systematic Review

2019 ◽  
Vol 54 (6) ◽  
pp. 662-670 ◽  
Author(s):  
Saeed Al Adal ◽  
Fereshteh Pourkazemi ◽  
Martin Mackey ◽  
Claire E. Hiller
Keyword(s):  
Physical Examination ◽  
Visual Analog Scale ◽  
Ankle Instability ◽  
Chronic Ankle Instability ◽  
Self Report ◽  
Functional Impairments ◽  
Ankle Pain ◽  
Analog Scale ◽  
Eligibility Criteria ◽  
Prevalence Of Pain

ObjectiveTo identify the prevalence of pain in people with chronic ankle instability (CAI) and how pain is related to the impairments of CAI.Data SourcesWe searched the databases of AMED, CINAHL, EMBASE, MEDLINE, PubMed, Scopus, SPORTDiscus, and Web of Science from inception to March 2017.Study SelectionEligible studies were peer-reviewed research in which investigators reported the presence of ankle pain or assessed the effects of pain on impairments in participants with CAI. Age and language were not restricted. Studies that included only surgical interventions were excluded.Data ExtractionStudies identified by the search strategy were screened according to the eligibility criteria, and 2 independent reviewers extracted the data. Outcome measurements were (1) pain ratings using measures such as a visual analog scale and (2) other residual impairments, such as feelings of weakness, giving way, or deficits in functional performance.Data SynthesisOf the 5907 records identified through the database search, 14 studies were included in this review. All authors assessed ankle pain by self-report questionnaires or physical examination, or both. Pain was self-reported by 23% to 79% of participants and present on physical examination in 25% to 75% of participants, depending on the test applied. Among these studies, the highest reported pain level was 4.9 on the 11-point visual analog scale. Studies were heterogeneous for pain measures, participant groups, interventions, and follow-up periods. The relationship between pain and the structural and functional impairments associated with CAI was not investigated in the included studies.ConclusionsPain was present in a large proportion of people who had CAI, but pain levels were low. Information about the effects of pain was not reported, so researchers should examine the association between pain and function, balance, or other activities in people with CAI.

scholarly journals Psychometric validation and refinement of the Interoception Sensory Questionnaire (ISQ) in adolescents and adults on the autism spectrum

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Evan Suzman ◽  
Zachary J. Williams ◽  
Jacob I. Feldman ◽  
Michelle Failla ◽  
Carissa J. Cascio ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
The Body ◽  
Self Report ◽  
Psychometric Validation ◽  
Response Scale ◽  
Response Options ◽  
Response Choice ◽  
Autistic People ◽  
Adolescents And Adults ◽  
Sensory Questionnaire

Abstract Background Individuals on the autism spectrum are reported to display alterations in interoception, the sense of the internal state of the body. The Interoception Sensory Questionnaire (ISQ) is a 20-item self-report measure of interoception specifically intended to measure this construct in autistic people. The psychometrics of the ISQ, however, have not previously been evaluated in a large sample of autistic individuals. Methods Using confirmatory factor analysis, we evaluated the latent structure of the ISQ in a large online sample of adults on the autism spectrum and found that the unidimensional model fit the data poorly. Using misspecification analysis to identify areas of local misfit and item response theory to investigate the appropriateness of the seven-point response scale, we removed redundant items and collapsed the response options to put forth a novel eight-item, five-response choice ISQ. Results The revised, five-response choice ISQ (ISQ-8) showed much improved fit while maintaining high internal reliability. Differential item functioning (DIF) analyses indicated that the items of the ISQ-8 were answered in comparable ways by autistic adolescents and adults and across multiple other sociodemographic groups. Limitations Our results were limited by the fact that we did not collect data for typically developing controls, preventing the analysis of DIF by diagnostic status. Additionally, while this study proposes a new 5-response scale for the ISQ-8, our data were not collected using this method; thus, the psychometric properties for the revised version of this instrument require further investigation. Conclusion The ISQ-8 shows promise as a reliable and valid measure of interoception in adolescents and adults on the autism spectrum, but additional work is needed to examine its psychometrics in this population. A free online score calculator has been created to facilitate the use of ISQ-8 latent trait scores for further studies of autistic adolescents and adults (available at https://asdmeasures.shinyapps.io/ISQ_score/).

scholarly journals COMPREHENSIVE MEDICATION MANAGEMENT SERVICES IN A BRAZILIAN SPECIALITY PHARMACY: A QUALITATIVE ASSESSMENT

2017 ◽  
Vol 9 (3) ◽  
pp. 227 ◽  
Author(s):  
Kirla Barbosa Detoni ◽  
Mariana Martins Gonzaga Do Nascimento ◽  
Isabela Viana Oliveira ◽  
Mateus Rodrigues Alves ◽  
Manoel Machuca GonzÁles ◽  
...  
Keyword(s):  
Participant Observation ◽  
Patient Flow ◽  
Medication Management ◽  
Implementation Process ◽  
Ethnographic Study ◽  
Qualitative Assessment ◽  
Healthcare Team ◽  
Structured Interviews ◽  
Eligibility Criteria ◽  
Manager Support

Objective: To understand and describe the implementation process of a comprehensive medication management (CMM) service in a public speciality pharmacy in Brazil.Methods: Ethnographic study conducted over 17 mo (September 2014 to February 2016) in a public speciality pharmacy. Semi-structured interviews were conducted with twelve participants. Notes on field journals, resulting from participant observation conducted by the two pharmacists directly responsible for the service implementation, were also used as a source of data.Results: Ten important conditions to improve the success of CMM service implementation were identified: manager support; evaluation of physical and material resources; evaluation of human resources practitioners’ characteristics and knowledge about the theoretical framework of CMM services; time dedicated to CMM services; redefining the work process; defining patient eligibility criteria to CMM service; defining patient flow to CMM service; communication with healthcare team; integration with the staff; and marketing the service internally.Conclusion: The results unveiled by this article can be used by pharmacists and managers as a tool to optimize the implementation of CMM services in different healthcare settings. These conditions do not consist the only aspects necessary to ensure the success of the service; however, they can contribute to optimize the implementation process of the practice

scholarly journals Autoantibody Inhibitor Eradication In Acquired Hemophilia Associated with Cancer: a Retrospective Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1418-1418 ◽  
Author(s):  
Khendi T White ◽  
Anita Aggarwal ◽  
Marisanta Napolitano ◽  
Craig M. Kessler
Keyword(s):  
B Cell ◽  
Solid Tumor ◽  
Research Funding ◽  
Hematologic Malignancies ◽  
Acquired Hemophilia ◽  
Term Survival ◽  
Fviii Inhibitor ◽  
Underlying Malignancy ◽  
Fviii Activity

Abstract Abstract 1418 Introduction: Acquired hemophilia (AH), a rare autoimmune disorder primarily of adults, is typically characterized by the presence of IgG oligoclonal antibodies to the clotting factor VIII protein (FVIII). About 10–15% of patients with AH have an underlying malignancy, but the etiologic relationship of cancer to formation of FVIII inhibitor is yet to be determined. To date, there have been no published, comprehensive reviews on the efficacy of various treatments for AH in the context of either solid tumor or hematologic malignancies. Therefore, we have systematically reviewed 86 patients with cancer-associated AH from our own cancer center and from the published literature. Methods: The literature search for this systematic review was performed using PubMed MEDLINE, Ovid MEDLINE, CINAHL, SCOPUS, and Embase. The search terms included various combinations of “acquired”, “cancer”, “factor VIII”, “hemophilia A”, “autoantibodies”, and “treatment.” The major criterion for inclusion was a diagnosis of cancer before or within three months after appearance of acquired inhibitor. Both solid and hematologic malignancies were included. Any report that did not document a FVIII inhibitor titer and/or FVIII activity was excluded. Success in inhibitor eradication has been defined as undetectable inhibitor and normalization of FVIII activity. All articles with an abstract in English published in the period from January 1985 to July 2010 were considered. Results: 86 cases of AH were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age is 67.8 years. 74% of patients were of Caucasian or European background, 8% were of Asian descent, and 2% were of African descent. AH was associated with solid malignancy in 50 cases (58%) and hematologic malignancy in 36 cases (42%). Among all AH cases, 15% and 14% of patients had lymphoma and CLL, respectively. Of the solid tumors, lung and prostate carcinoma (each 12%) occurred with the greatest frequency followed by colorectal (9%) and bladder (5%). Not all patients had treatment for their underlying cancer, bleeding and/or inhibitor. Complete eradication (CE) of inhibitor was achieved in 48 patients (56%), no eradication (NE) in 22 (26%), and 16 (18%) had unknown status. Of the 73% of patients with CE, 22 were treated with chemotherapy, 10 were treated with surgery, and 1 with both (Table 1). In this series, there was a trend towards successful inhibitor eradication with treatment of B-cell lymphoproliferative malignancies as well as lung and prostate cancer. Long term survival was best achieved when successful CE and treatment of underlying malignancy occurred concurrently. Conclusions: This literature and case series suggests that AH is associated almost equally with hematological and solid tumor malignancies. These retrospective data suggest that treatment of the cancer with chemotherapy or surgery is very likely to induce eradication of the autoantibody inhibitor. There is a trend for increased success in CE in B-cell lymphoproliferative malignancies and selected solid tumors. Long term survival appears dependent on concurrent CE and treatment of the cancer. Disclosures: Kessler: Grifols S.A.: Research Funding; Baxter-Immuno: Research Funding; NovoNordisk: Research Funding.

scholarly journals A scoping review protocol to map the evidence on the use of action research methodology by healthcare professionals and in healthcare team settings

2021 ◽  
Vol 4 ◽  
pp. 68
Author(s):  
Kinley Roberts ◽  
Mary Casey ◽  
David Coghlan ◽  
Catherine Cornall ◽  
Clare Hudson ◽  
...  
Keyword(s):  
Action Research ◽  
Scoping Review ◽  
Healthcare Professionals ◽  
Scientific Journal ◽  
Social Situation ◽  
Healthcare Team ◽  
Transformative Change ◽  
Eligibility Criteria ◽  
Process Stage ◽  
Stage 1

Background: Action research (AR) starts with an existing practical situation with which there is a concern or potential for improvement. It seeks transformative change through the simultaneous process of doing research and undertaking actions, both of which are linked together by a critical reflective process. It simultaneously allows one to systematically investigate a given social situation while promoting democratic change and collaborative participation. AR approaches have been used for many years in business management and education. More recently, AR has become an increasingly popular method of inquiry in healthcare, particularly in nursing, to investigate professional practice while simultaneously; introducing innovations; planning and undertaking action; and evaluating new ideas. The overall goal is to augment collaboration whilst improving the patient experience and outcomes. Methods: The Arksey and O'Malley methodology framework will be used to guide this scoping review process: stage 1 will identify the research questions; the eligibility criteria and search strategy will be defined in stage 2; studies will then be selected in stage 3; data will be extracted and charted from these included studies in stage 4; stage 5 involves aggregating and summarising these results along with criteria relevant for health professionals and policy-makers. An optional consultation (stage 6) exercise may potentially be included. Conclusion: This scoping review will comprehensively map the evidence on the use of AR methodology by healthcare professionals and in healthcare team settings. It is predicted that the findings will inform researchers in carrying out future AR and highlight gaps in the literature. An article reporting the results of the completed scoping review will be submitted for publication to a scientific journal and presented at relevant national and international conferences.

Evaluation of Eligibility for CAR-T Cell Therapy in a Population-Based Cohort of 3550 Patients with Incident Diffuse Large B-Cell Lymphoma (DLBCL) in Sweden

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Karin Ekstroem Smedby ◽  
Sara Harrysson ◽  
Sara Ekberg ◽  
Mats Jerkeman ◽  
Per-Ola Andersson ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Research Funding ◽  
Eligibility Criteria ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Line Therapy ◽  
Car T Cell Therapy ◽  
Car T ◽  
First Relapse

Background Today, even though most patients with diffuse large B-cell lymphoma (DLBCL) can be cured with standard immunochemotherapy, 20-30% are refractory to primary therapy or relapse during follow-up with a drastic worsening of the prognosis. In recent years, new promising treatment options including CAR-T cell therapy are becoming available for relapsed/refractory (R/R) DLBCL patients although so far with logistic challenges including disease control and toxicities, and a considerable cost. In view of these challenges, we aimed to estimate the proportion of patients with R/R DLBCL that are likely to be eligible for CAR-T cell therapy in clinical routine, and their expected outcome in the pre-CAR-T era. Methods All patients with DLBCL starting primary therapy with curative intent were identified in the Swedish Lymphoma Register for the period 2007-2014 (N=3550). Primary CNS and primary mediastinal B-cell lymphomas were excluded. Data regarding primary treatment response and relapse was validated through medical chart review in the entire cohort during follow-up until Dec 31st 2017, and information about additional treatment lines including disease characteristics, blood test results, and relapse treatment response was collected. Eligibility for CAR-T cell therapy was estimated retrospectively based on eligibility criteria specified in clinical trials, both at first relapse by applying similar criteria as in the ongoing TRANSFORM, ZUMA-7 or PILOT studies (hereafter termed "CAR-T-2ndline"), and at second relapse applying criteria similar to those specified in the JULIET trial (hereafter termed "CAR-T-3rdline"). Administration of second- and third-line therapies and corresponding response rates were considered as proxies for eligibility and response to bridging therapies. Criteria applied for "CAR-T-2ndline" included R/R DLBCL within 12 months of evaluation date of primary treatment, age 18-75 years, ECOG 0-1, and additional criteria as specified in the TRANSFORM trial (see figure footnote). Criteria applied for "CAR-T-3rdline" included relapse following second-line therapy, age 18-76 years, ECOG 0-1, and additional criteria as in the JULIET trial (see figure footnote). Individuals with missing data on performance status were assumed ineligible. We lacked information about other malignancies in the disease history. Overall survival probabilities were estimated with the Kaplan-Meier method among all R/R DLBCL patients in the trial-specified age intervals and separately among those fulfilling all trial criteria. Results In the cohort of 3550 curatively treated DLBCL patients, 847 (cumulative incidence 23%) experienced R/R disease during a median follow-up of 4.3 years. Median age at first relapse was 71 years (range 18-95 years). Overall, 308 patients ≤75 years experienced progression/relapse within 12 months and were able to start second-line therapy. Of these, 148 patients (17% of all R/R DLBCL patients) fulfilled trial eligibility criteria for "CAR-T-2ndline", of whom 60 responded with at least partial remission (overall response rate, ORR, 41%). At second relapse, 370 patients 76 years or younger received third-line therapy, of whom 55 (6.5% of all R/R DLBCL patients) were deemed eligible for "Car-T-3rdline", and 13 responded (ORR 24%, another 5 patients had SD). Two-year overall survival (OS) among all R/R DLBCL patients ≤75 years receiving second-line therapy was 20% (95% confidence interval, CI, 16-25%) (Fig 1). Among those eligible for "CAR-T-2ndline", 2-year OS was 24% (95% CI 17-31%). Among patients ≤76 years at second relapse, 2-year OS was 18% (95% CI 13-24%), and among those eligible for "CAR-T-3rdline", 21% (95% CI 11-32%). Conclusion In the population-based setting, one in six patients (17%) with R/R DLBCL fitted trial eligibility criteria for CAR-T-cell therapy at first relapse and only one in fifteen patients (6.5%) fitted trial criteria at second relapse at retrospective evaluation. Figures were reduced when adding requirement of response to relapse/bridging therapy. These estimates illustrate to what extent current CAR-T cell therapies may be applied in a routine setting when based on trial criteria, and the need for development of modified and additional therapies in this group. Outcome estimation confirmed a poor outcome in these groups and did not indicate that fulfillment of trial criteria led to selection bias in terms of survival. Disclosures Ekstroem Smedby: Janssen Cilag: Research Funding; Celgene: Other: Advisory Board; Takeda: Research Funding. Harrysson:Janssen Cilag: Research Funding. Jerkeman:Janssen: Research Funding; Roche: Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Gilead: Research Funding. Eloranta:Janssen Cilag: Research Funding.

A Better and Healthier Time to Be Alive than Ever

2021 ◽  
pp. 3-24
Author(s):  
Sandro Galea
Keyword(s):  
Life Expectancy ◽  
Global Development ◽  
Know How ◽  
The World ◽  
The Future ◽  
Over Time ◽  
Hiv Aids

This chapter discusses how the time of the COVID-19 pandemic was also a time when the world, in many respects, had never been better—or healthier. In a number of key areas—from life expectancy, to declines in poverty, to reductions in preventable diseases like HIV/AIDS—it was, and is, a more favorable time to be alive than any other point in recorded history. All these advances was a byproduct of foundational forces unfolding over time, forces like industrialization, global development, urbanization, and political changes. However, the incidental nature of this success has meant that we have yet to fully acknowledge why it occurred, which hinders our ability to advance it in the future. Why do we need to know how we got here? First, our understanding of the causes of health shapes our investment in health. America's investment in healthcare comes at the expense of their investment in the foundational drivers of health. The second reason is that if we do not understand the true causes of health, we will be unable to build a world that is ready for the next pandemic.

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