Search

Introduction: Therapy and immune mediated processes are associated with clonal evolution in multiple myeloma (MM). In this study, we performed whole-exome sequencing (WES) and single cell RNA sequencing (scRNA-seq) on plasma cells (PC) from bone marrow aspirates of the iliac crest (BM) and corresponding osteolytic lesions (OL) to investigate spatial heterogeneity in patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). Next generation flow (NGF) and T-cell receptor sequencing (TCRseq) were performed to investigate the immunogenomic landscape surrounding malignant PC. Methods: In a prospective trial, 18 patients (NDMM: n=10; RRMM: n=8) consented to an imaging-guided biopsy of an OL in addition to the regular BM sampling. At inclusion, 37 different locations were biopsied. Follow-up samples were obtained from 5 patients in remission after therapy. After CD138+ selection, PC were subjected to WES and scRNA-seq (Chromium, 10x genomics). TCRseq was performed using multiplex PCR (ImmunoSEQ, Adaptive biotechnologies) on the CD138- fraction. For scRNA-seq data analyses, Cell Ranger (v3.1.0) and the Seurat R toolkit (v3.1) were used. TCRseq data were analyzed with immunoSEQ ANALYZER (v3.0) and the immunarch R toolkit (v0.6.6.). NGF was performed to study subsets of T-, B-, NK- and dendritic cells (DC). Results: Median PC infiltration was higher in OL compared to random BM (50.0% vs 12.5%, p=0.041). WES revealed more mutations in RRMM compared to NDMM (median; range: 189;120-523 vs 71;23-136, p Conclusion: We report the first prospective clinical trial to investigate spatiotemporal immunogenomic heterogeneity in multiple myeloma as assessed by WES and scRNA-seq of PC and NGF and TCRseq of the non-PC compartment. We demonstrate spatial evolution and reduced TCR diversity especially in patients with RRMM and/or EMD. ScRNA-seq adds another layer of complexity compared to WES and helps identifying how PC create an immune suppressive BM niche. Disclosures Merz: Amgen, BMS, Celgene, Takeda: Honoraria. Block:GlaxoSmithKline LLC: Current Employment. McCarthy:Karyopharm: Consultancy, Honoraria; Magenta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Juno Therapeutics, a Bristol-Myers Squibb Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board , Research Funding is to Roswell Park, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Starton: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory Board; Genentech: Consultancy, Honoraria. Hillengass:Adaptive, Amgen, BMS, Celgene, GSK, Janssen, Oncotracker, Takeda: Honoraria.

To evaluate whether caregiving for older adults is associated with insomnia symptoms and diminished workplace productivity.We analyzed data collected from caregivers to older adults in the US. Participants self-reported awakenings from sleep (caregiving-related or spontaneous) and workplace measures (presenteeism, absenteeism, and productivity impairment). We conduct generalized linear modeling to examine the relationship between awakenings and workplace outcomes, controlling for confounders.Two hundred fifty-eight caregivers to older adults reported current employment and met our inclusion criteria. Adjusted analyses found that reporting caregiving-related awakenings was associated with presenteeism (OR = 1.27, 95%CI: 1.16 to 1.40), absenteeism (OR = 1.10, 95%CI: 1.06 to 1.15), and productivity impairment (OR = 1.41, 95%CI: 1.25 to 1.58). Adjusted analyses found that spontaneous nighttime awakenings were associated with absenteeism (OR = 1.05, 95%CI: 1.01 to 1.08) and productivity impairment (OR = 1.12, 95%CI: 1.02 to 1.124) but not presenteeism.Caregiving-related awakenings are a risk factor for workplace productivity impairment. Future studies should examine means for improving caregiver sleep.

PurposeThe purpose of this study is to understand how majority employee-owned firms responded to the pandemic compared to firms that were not majority employee-owned. The Employee Ownership Foundation partnered with Rutgers University and the SSRS survey firm to survey ESOP and non-ESOP firms about their responses to the COVID-19 pandemic. A key purpose of the survey was to estimate firm-level changes in employment from mid-January to August (current employment figures were adjusted to August 5 using BLS industry employment trends). The survey also looked at other forms of adjustment and responses to the pandemic as reviewed below. The focus in this study is on the differences between firms that are majority owned by ESOPs and those that are not.Design/methodology/approachThe survey included 247 executives from ESOP Association member companies and 500 executives from an SSRS business panel constructed to be representative of US companies with 50 or more employees. The survey started on August 5 and ended on September 23, 2020.Findings(1) Majority ESOP firms had employment declines from January to August that were on average only one-fourth as large as for other firms. The difference is maintained when controlling for industry membership. (2) Majority ESOP firms were more likely to be declared “essential,” but the lower employment cutbacks among majority ESOP firms remain among essential and non-essential businesses. As essential businesses, majority ESOP firms were more likely receive Paycheck Protection Program or other government pandemic assistance, but both assistance recipients and non-recipients had lower employment cutbacks among majority ESOP firms. (3) The extent of employment cutbacks was higher for non-managers than for managers, but the manager/non-manager gap was higher among other firms than among majority ESOP firms.Research limitations/implicationsThis study supports empirical findings done previously.Practical implicationsThis study suggests to non-EO firms what they can do.Social implicationsThis study suggests strengths of EO firms.Originality/valueA very original and one-of-a-kind dataset.

Background Although two thirds of tobacco users express interest in quitting, few pharmacists address tobacco use as part of routine practice. Historically, pharmacy schools provided inadequate tobacco cessation training for students. To address this educational gap, train-the-trainer workshops were conducted between 2003 and 2005 to train pharmacy faculty (n = 191) to teach a shared, national tobacco cessation curriculum at their academic institutions. Objective To characterize faculty perceptions of the train-the-trainer workshops and estimate the long-term reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of the shared curriculum at pharmacy schools. Methods This study is the second phase of a sequential mixed methods study. Results from Phase 1, a qualitative study, informed the development of survey items for Phase 2. Applying the RE-AIM framework, a web-based survey was developed and administered to train-the-trainer participants. Results Of 191 trainees, 137 were locatable; of these, 111 completed a survey (81.0%). Most (n = 87; 78.4%) reported current employment in academia. The most highly rated reason for attending a workshop was to improve teaching of tobacco cessation content, and 98.1% reported moderate or high confidence for teaching tobacco cessation. Among those who practice in a clinical setting, 70.6% reported asking their patients about tobacco use all or almost all the time. Just over three fourths of faculty respondents who work in academia believe that shared curricula should be more broadly considered for use in pharmacy schools, and 79.0% agreed that shared curricula are a cost-effective approach to teaching. Conclusion Evidence is provided for long-term reach, effectiveness, adoption, implementation, and maintenance of the Rx for Change shared tobacco cessation training program. Participants perceived that the workshop resulted in long-term, positive effects on their careers as well as their teaching and clinical practice.

This descriptive type of cross-sectional study was conducted with an objective to find out the present employment and academic status of recent dental graduates in Dhaka city. The study was conducted for one year from July 2019 to June 2020 at different work places of recent dental graduates and residence of unemployed dental graduates in Dhaka city. A total of 414 recent dental graduates were the respondents of the study. Study revealed that 212 (51.2%) of the respondents were male and 202 (48.8%) of the respondents were female. With regards to employment, it was revealed that 340 (82.1%) of the respondents were employed as dental surgeon and 57 (13.8%) of the respondents were yet to get formal employment. Among the employed dental graduates, 203 (57%) were full-time employee and 154 (47%) were part-time. Only 55 (15.4%) dental surgeons among them were working in government sector and rest were non-government employee or self-employed. Self-employment as a dental surgeon was the main source of income for 179 (43.2%) of total respondents. Regarding the job satisfaction, 139 (33.6%) were moderately satisfied and 182 (44%) were not satisfied with their pay standard. With regards to further academic engagement, 88 (21.2%) respondents were enrolled in different postgraduation courses whereas 205 (49.5%) of the respondents were also engaged in learning activities to get admitted into postgraduation courses. Study recommended that newly graduated dental surgeons could be utilized by engaging into both urban and rural areas by creating scope in both government and nongovernment sectors. Further academic engagement may be ensured by initiating new courses of dentistry and by increasing number of affiliated institutes for post-graduation. Bangladesh Journal of Medical Education Vol.12(2) July 2021: 10-17

Higher Education Institutions (HEIs) are responsible for supplying the labor market with professionals that not only possess knowledge, but also the competencies and skills demanded by the workplace. In order to evaluate the relevance of their program offerings to the demand of the labor market, colleges and universities, like the Nueva Ecija University of Science and Technology (NEUST), conduct tracer studies on the employability of their graduates. With this, the researchers conducted this tracer study to determine the employability of the teacher education graduates of NEUST, San Isidro Campus from 2016 to 2020. It further aimed to trace their employment and the skills or competencies that they have acquired from the university which proved to be useful in their current employment, as well as their correlation with each other. It used descriptive-correlation method. The findings revealed that there is positive correlation between the graduates’ select profile variables and their employment and their perceived useful competencies and skills. There was also a direct correlation between their employment and their perceived useful competencies and skills. Recommendations for future tracer study initiatives were also made.

Injurious falls, especially those leading to bone fracture are major causes of death and disability among older people. The aim was to identify the factors and conditions associated with falls leading to fracture (FLF) among older adults in a developing country. The data was collected in 2019 and analyzed in 2020. In total, 300 patients and 590 age- and sex-matched controls were selected from two referral hospitals, and the eligible older individuals who were under the same family physicians of the patients respectively. Significant and direct associations observed between the risk of FLF and cardiovascular diseases, hobby during leisure time, current employment, vertigo, history of falling during the past five years and smoking (P

El objetivo de la presente investigación consistió en analizar las condiciones laborales de universidades peruanas, ante la virtualidad de la educación en el contexto de la pandemia COVID-19. La metodología utilizada se desarrolló desde el enfoque cuantitativo, diseño no experimental, tipo descriptivo, paradigma positivista y método analítico. El instrumento fue aplicado a 235 docentes con vínculo laboral vigente en universidades peruanas. Los resultados expresan que a partir de los indicadores virtualidad de la enseñanza, ciberconviencia, competencias digitales y derechos laborales podría ser factible establecer nuevas condiciones laborales derivadas de la contratación docente en el actual contexto. Se concluyó que los docentes universitarios peruanos contratados que interactúan por la virtualidad de la educación conservan las condiciones laborales existentes antes la pandemia vigente, situación debe ser actualizada.

Our objective was to associate characteristics of pediatric critical care medicine (PCCM) fellowship training programs with career outcomes of PCCM physicians, including research publication productivity and employment characteristics. This is a descriptive study using publicly available data from 2557 PCCM physicians from the National Provider Index registry. We analyzed data on a systematic sample of 690 PCCM physicians representing 62 fellowship programs. There was substantial diversity in the characteristics of fellowship training programs in terms of fellowship size, intensive care unit (ICU) bed numbers, age of program, location, research rank of affiliated medical school, and academic metrics based on publication productivity of their graduates standardized over time. The clinical and academic attributes of fellowship training programs were associated with publication success and characteristics of their graduates' employment hospital. Programs with greater publication rate per graduate had more ICU beds and were associated with higher ranked medical schools. At the physician level, training program attributes including larger size, older program, and higher academic metrics were associated with graduates with greater publication productivity. There were varied characteristics of current employment hospitals, with graduates from larger, more academic fellowship training programs more likely to work in larger pediatric intensive care units (24 [interquartile range, IQR: 16–35] vs. 19 [IQR: 12–24] beds; p

Introduction A grant-funded faculty development program, From Practice to Preceptor (FP2P), sought to recruit and train diverse general and pediatric dentists to become dental faculty from 2012-2018. This study is an evaluation of this completed initiative and offers an initial review of long-term outcomes of the program. Methods Over 5 entering cohorts, 133 practitioners applied to the program and 45 were accepted. A 2-year training program used classroom and hands-on training to prepare practitioners for the occupational demands of academia. Program participants were offered pre- and post-surveys to evaluate their perceived preparedness in faculty competencies identified by the program. Participants were also sent an alumni survey, and employment was tracked by the host institution. Results Most (43 of 45) participants completed the program. Pre- and post-survey results were received from 24 of 30 (80%) participants in Cohorts 2, 3, and 5, and used for this analysis. The results suggest the program participants' perception of their ability to work effectively as faculty members in administrative, teaching, and clinical arenas increased. Over half of the program completers obtained employment as dental faculty. A majority of (19/26, 73%) program completers who responded to the alumni survey indicated the skills and knowledge gained in the program were useful to their current employment. Conclusion The FP2P program evaluation results indicate a long-term faculty training program may be a useful methodology for recruiting and training current dentists to work in academic dentistry.

This study investigates the relationship between mergers and acquisitions (M&A) and entrepreneurial spawning in labour-intensive service sectors. We discuss two sets of theoretical mechanisms. First, M&As may push employees into entrepreneurship by lowering the average barriers of leaving the current employment (i.e. being associated with general deterioration of working conditions). Second, M&A activities may generate new entrepreneurial opportunities, which are first and foremost accessible by employees directly affected by M&As. Results on entrepreneurial spawning in 3,198 Swedish firms during the time period 2000–2009 confirm that the number of firms spawned from a specific incumbent increases following an M&A. Push-oriented factors are found to contribute to this effect, but a dominating part of the total effect remains in the presence of proxies for push-effects. This suggests that pull-oriented explanations of opportunity creation in the wake of M&As constitute an important avenue for further research on the antecedents of new firm formation.

El propósito de la investigación es conocer la calidad de vida laboral que tiene el trabajador en Latinoamérica. Se realizó una revisión bibliográfica de estudios desarrollados por el Banco Interamericano de Desarrollo, en el que se muestran las dimensiones de calidad y cantidad de las condiciones de empleo actuales para américa latina. Los resultados obtenidos muestran que Uruguay es uno de los países que brinda mejor calidad de vida a sus trabajadores y por otro lado esta Guatemala que no presenta garantías para el desarrollo de un trabajo óptimo.

The traditional theories governing the capital structure decisions completely ignore the human side of the enterprise (e.g. attitude to work). The objective of this paper is to identify the optimal mix of Theory X and Theory Y type employees to be employed by an organization in order to maintain (i.e. unaffected by the type of employees at work) the optimal level of capital structure. The classification of an employee into Theory X and Theory of Y is made based on the organizational contribution conditional on motivation rather than merely considering the attitude to work. Internal motivation of an employee (i.e. inherently likes or dislikes) alone cannot be identified as the criterion of recognizing employees under Theory X and Theory of Y. Level of attainment of needs within the organization, psychological state of mind and cultural dimension (i.e. individualism-collectivism) of the individual attached to the organization are the main behavioural criteria that distinguish between Theory X-type and Theory Y-type employees. This paper shows that the optimal capital structure is unaffected by the employment mix at the optimal level of Theory X and Theory Y type employees employed by an organization. The firms’ managers must therefore consider the behavioral aspects of employees (e.g. attitude to risk) when making organizational decisions such as financial decisions. For example, mismatches in the capital structure can be explained by a careful analysis of behavioral aspects of employees. By making necessary adjustments to the current employment mix, the firm could eliminate the mismatches in the firm’s capital structure.

The purpose of this study was to derive implications for the employment support program for young soldiers through the survey on the perceptions and needs of young soldiers on Activate Youth Recruitment and Start-up Business (SOS project) by the Korean Ministry of Defense as a part of the government’s job creation policy. For this purpose, it investigated the level of recognition of the importance of the current employment support program, along with their satisfaction levels, using the IPA (Importance-Performance Analysis). The result was as follows: First, the perception level was relatively high in certification acquisition, credit recognition system, self-development support, and online education support. Second, the scores of importance perception and satisfaction were measured as 3.69 and 3.13, respectively. Third, the IPA results suggested that it was necessary to maintain the current status of self-development support, certification acquisition and credit recognition, and the reform and expansion of the soldier’s savings due to high scores for both importance and satisfaction, while they differ by group for other programs.

The International Labor Organization (ILO) in the 'Report of the Committee on Employment Relationship' states that current employment relationships are increasingly complex and there is no acceptable definition to define 'employment relationships'. Thus, this paper aims to investigate whether employment relations exist in the informal sector. By using Goss’ framework, this can be understood by two related dimensions. First, the extent to which employers are dependent on his or her employees, and vice versa, and second, the extent to which employees have the capacity, individually or collectively, to challenge the power of their employer. Based on these two dimensions, four distinct categories have been identified that reveal the complexity and diversity of the nature of employment relationships in the informal sector: fraternalism, paternalism, benevolent autocracy, and passive acquiescence. In-depth interviews with four employers and four workers in the informal sector in Lawas, Malaysia were conducted. The findings indicate that the nature of employment relations in the informal sector is benevolent autocracy as employers are less dependent on their employees, resulting in limited labor capacity to challenge the employer's power. A characteristic of the informal sector (such as a family-based business and not legally registered) is the lack of protection for workers, which is the main reason for shaping employment relations in this sector. It is recommended, therefore, to have policy reforms to protect the rights of workers in the informal sector.

The novel coronavirus disease 2019 (COVID-19) in the U.S. is part of the worldwide pandemic of this extremely infectious disease. As of November 2020, the U.S. has experienced 10,200,000 cases and 238,000 COVID-19 fatalities. The pandemic is still ongoing, with around 50,000 new cases and 800 deaths each day. A recent U.S. based report shows that the economic loss due to COVID-19 will be more than $22 trillion. Due to the lockdown and the urgency of a safe re-opening, the impact on different industries varies from state to state. A robust and granular level of analysis is needed to understand the impact of COVID-19 on various industries. This study collected data (before and after COVID-19) from the U.S. Bureau of Labor Statistics (USBLS) to perform a quantitative analysis. Using current employment statistics (CES) data from the USBLS, an observational before-after analysis was conducted by using the difference-in-difference method. The results show the highly-impacted industries, and the temporal patterns of the impact are also evaluated.

Purpose The purpose of this paper to explore socio-demographic factors related to the quality of life (QoL) among older adults in the rural area of Thailand. Design/methodology/approach This cross-sectional study examined socio-demographic factor that may predict the QoL among 470 older adults who lived in a rural area of Northern Thailand. The study questionnaire consisted of four parts, including socio-demographic data, perceptions of the health status, family relationship and QoL (WHOQOL-OLD). Spearman’s ρ or Pearson’s product moment correlation coefficients were determine the factors associated with the QoL. Stepwise multiple regressions were carried out to describe predictors of the QoL. Findings Majority of the participants (71 percent) were between 60 and 79 years old. Three-quarters of participants had primary school educational level. Most (74 percent) were married and no longer work (72 percent). Most (87 percent) had a moderate level of the QoL in all six domains. Six predictors of QoL include age, gender, education, current employment, health status perception and family relationship. These factors could significantly predict the QoL of the older adults by 30 percent. Originality/value Public health officers should collaborate with community partners and relevant stakeholders to increase the QoL of older adults in the rural area through activities which promote health status perception and family relationship.

Like the HIV epidemic under Ronald Reagan and COVID-19 pandemic under Donald Trump, the epidemic in I Deaths of Despair i is the result of deliberate policy actions or rather inactions Case and Deaton provide a thorough accounting of the current employment, health, and social conditions of the white working class and how said factors contribute to the mortality crisis Anne Case and Angus Deaton present a compelling and harrowing description of one of the United States' most severe public health crises in recent history [Extracted from the article] Copyright of Journal of Economic History is the property of Cambridge University Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )

Background Patients (pts) with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), have reduced overall survival (OS) compared with the general population. Previous reports have shown MPN incidence rates of 0.9-1.1, 0.7-1.0, and 0.3 per 100,000 person-years for PV, ET, and primary MF (PMF), respectively (Srour et al. Br J Haematol. 2016;174[3]:382; Deadmond et al. J Cancer Res Clin Oncol. 2015;141[12]:2131), with evidence of an increase in MPN incidence over time (Mesa et al. Blood. 2012;120[21]:2834). The median OS for pts with PV, ET, and PMF has been previously reported in the literature as 13.5, 19.8, and 5.2-5.9 years, respectively (Tefferi et al. Blood. 2014;124[16]:2507; Cervantes et al. Blood. 2009;113[13]:2895; Cervantes et al. J Clin Oncol. 2012;30[24]:2981). Contemporary analyses of MPN incidence and pt survival are needed, as the most recent available real-world analyses were conducted on time periods up to 2012. The objective of this analysis was to describe trends in incidence and OS among pts with MPNs in the United States using data through 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. Study Design and Methods Adult pts with PV, ET, or PMF were identified from the SEER 18 registry (2002-2016) using the primary site of bone marrow (C421) and International Classification of Diseases for Oncology (ICD-O) histology codes (ICD-O-3: 9950 [PV], 9962 [ET], and 9961 [PMF]). Pts were excluded if they were aged Results Data for 34,031 pts (mean age, 65 y; female, 50.5%) were included in this analysis, including 15,141 pts diagnosed with PV, 14,676 with ET, and 4214 with PMF. Over the entire study period, incidence rates (95% CI) for PV, ET, and PMF were 1.57 (1.55-1.60), 1.55 (1.52-1.57), and 0.44 (0.43-0.45) per 100,000 person-years, respectively. The annual incidence rates of PV and PMF were higher for male vs female pts (1.94 vs 1.23 and 0.59 vs 0.33, respectively); however, the ET incidence rate was higher for female pts (1.73 vs 1.34; Table 1). ET and PMF incidence increased across the 3 time periods, whereas PV incidence remained relatively stable. Mortality rates at 1, 2, and 5 years for each MPN subtype are presented by time period in Table 2. Over the 3 time periods, mortality rates decreased for PV and PMF, but not for ET. Improved OS was observed in pts with PMF over time (median [95% CI]: 2002-2006, 3.3 [2.4-3.6] y; 2007-2011, 3.6 [3.3-4.3] y; 2012-2016, 3.8 [3.5-4.2] y). The median (95% CI) OS for the entire time period investigated was 12.0 (11.7-12.4) years for pts with PV, 12.0 (11.7-12.3) years for those with ET, and 3.6 (3.4-3.8) years for pts with PMF. Conclusions In this nationally representative real-world study, incidence of ET and PMF appeared to increase over time from 2002-2016. Median OS of patients with PV, ET, and PMF was shorter than previous reports. A trend of improved survival over time was observed in pts with PV and PMF, which was not observed in pts with ET. Further investigation into the varying OS rates between MPN subtypes is needed, as these data may suggest that ET is lacking improvements in supportive care strategies or therapies that are currently available in PV and MF. Disclosures Verstovsek: Sierra Oncology: Consultancy, Research Funding; Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Gilead: Research Funding; ItalPharma: Research Funding; Blueprint Medicines Corp: Research Funding; Novartis: Consultancy, Research Funding; Genentech: Research Funding; CTI Biopharma Corp: Research Funding; AstraZeneca: Research Funding; Protagonist Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; PharmaEssentia: Research Funding. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Pandya:STATinMED Research: Current Employment; Incyte Corporation: Other: STATinMED Research is a paid consultant of Incyte Corporation. Dieyi:STATinMED Research: Current Employment; Incyte Corporation: Other: STATinMED Research is a paid consultant of Incyte Corporation. Chen:Incyte Corporation: Other: STATinMED Research is a paid consultant of Incyte Corporation; STATinMED Research: Current Employment. Parasuraman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company.

The level of development of human resources in health care is determined by a number of factors, among which an important place belongs to turnover of medical staff. The turnover, or the process of unscheduled dismissal of staff, negatively affects functioning of the organization in any field, including health care. Although the analysis of staff turnover is widely applied in various fields of activity, relatively few studies are related to problems of assessing causes of this phenomenon in health care. The purpose of the study was to assess the characteristics and causes of turnover of medical staff in state medical organizations of the Irkutsk Oblast. The detailed information about the respondents obtained in the study made it possible to get a concept of intensity and characteristics of turnover of physicians and medical nurses, and to study causes of dismissal of respondents from their previous employment as well as causes that influenced current employment and to assess content and effectiveness of measures of professional adaptation and social support of hired specialists.

Background : Ibrutinib (ibr) is a once-daily Bruton's tyrosine kinase (BTK) inhibitor approved in the US for patients (pts) with mantle cell lymphoma (MCL) who have received ≥1 prior therapy. Venetoclax (ven) is a BCL-2 inhibitor approved for pts with CLL or previously untreated AML. Ibr + ven have shown synergistic antitumor activity in preclinical models and complementary clinical activity in early phase studies (Zhao Br J Haematol 2015; Tam NEJM 2018; Jain NEJM 2019). The ongoing phase 3 SYMPATICO study (PCYC-1143-CA, NCT03112174) evaluates the safety and efficacy of ibr + ven in pts with relapsed/refractory (R/R) MCL. A safety run-in (SRI) was conducted to inform whether a 1-month (mo) ibr lead-in would be implemented for the randomized portion of the study; initial data from the SRI evaluating tumor lysis syndrome (TLS) events and dose-limiting toxicities (DLTs) concluded that the study would proceed with concurrent ibr + ven, with no ibr lead-in (Wang ICML 2019). Updated safety and efficacy from the SRI are presented. Methods : The phase 3 SYMPATICO study is comprised of an open-label SRI and a double-blind randomized period. Key eligibility criteria were pathologically confirmed MCL with measurable disease, 1-5 prior therapies, and no prior treatment with BTK or BCL inhibitors. In the SRI, pts received oral, once-daily 560 mg ibr + ven in a 5-week ramp-up to 400 mg ven. Ibr + ven are dosed concurrently for 2 years; thereafter, ven is discontinued in all pts and ibr is continued until progressive disease (PD) or unacceptable toxicity. The primary endpoint of the SRI was occurrence of TLS events and DLTs. Secondary endpoints included complete response (CR) and partial response (PR) per the 2014 Lugano criteria, progression-free survival (PFS), and duration of response (DOR). Rates of undetectable minimal residual disease (MRD) were assessed in bone marrow and peripheral blood. Efficacy and safety were analyzed by TLS risk (low or high). TP53 mutational status was determined by next-generation sequencing. Results: Twenty-one pts were enrolled in the SRI, with a median time on study of 22 (range, 2-31) mo. The median age was 68 (range, 53-84) years, and the median number of prior therapies was 2 (range, 1-4); 6 pts were considered at low risk for TLS and 15 pts were considered at high risk for TLS. All pts had at least 1 lesion >2 cm at baseline; 11/21 (52%) had baseline detectable MRD in peripheral blood or bone marrow. Of the 11 pts with available TP53 mutation data, 4 (36%) had mutated TP53. Median time on treatment was 18 (range, Conclusions : Ibr + ven is an all-oral, once-daily, chemotherapy-free regimen being studied for treatment of pts with R/R MCL. With a median of 22 mo on study, no new safety signals were observed; TLS events and DLTs were rare. Ibr + ven had sustained efficacy, with an ORR of 81%, CR rate of 62%, and the median PFS not reached. All MRD-assessable pts achieved undetectable MRD. The ongoing randomized portion of the SYMPATICO study is evaluating the efficacy and safety of ibr + ven compared with ibr + placebo in pts with R/R MCL; additionally, a single-arm, open-label cohort in previously untreated pts, including pts with TP53 mutations, is ongoing. Disclosures Tam: AbbVie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; BeiGene: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria. Ramchandren:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Janssen: Research Funding. Chen:Autolus Therapeutics: Current Employment. Karlin:Sanofi: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Celgene: Other: Personal fees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees. Chong:Hutchison Medipharma: Research Funding; Bayer: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Servier: Research Funding; Isofol: Research Funding; Merck Serono: Research Funding; Bristol-Myers Squibb: Research Funding. Jurczak:AstraZeneca, Epizyme: Consultancy; BeiGene: Consultancy, Research Funding; Sandoz Novartis: Consultancy; Janssen: Consultancy, Research Funding; Acerta: Consultancy; Loxo: Consultancy; TG Therapeutics, Acerta, Bayer, MeiPharma: Research Funding; Merck: Research Funding; Pharmacyclics LLC, an AbbVie Company,: Research Funding; Roche: Research Funding; Takeda: Research Funding. Bishton:AbbVie: Research Funding; Gilead: Other: Travel/accomodations/expenses, Research Funding; Roche: Other: Travel/accommodations/expenses, Research Funding; Takeda: Other: Travel/accommodations/expenses, Research Funding; Janssen: Consultancy. Collins:Novartis: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria; Celleron: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; Amgen: Research Funding; Celgene: Research Funding; MSD: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; BeiGene: Consultancy. Szafer-Glusman:Pharmacyclics LLC, an AbbVie Company: Current Employment. Lee:AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Eckert:Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Neuenburg:Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Wang:Targeted Oncology: Honoraria; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding; Nobel Insights: Consultancy; Guidepoint Global: Consultancy; Dava Oncology: Honoraria; Acerta Pharma: Research Funding; Verastem: Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Molecular Templates: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; OncLive: Honoraria; Lu Daopei Medical Group: Honoraria; Beijing Medical Award Foundation: Honoraria; MoreHealth: Consultancy; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Juno: Consultancy, Research Funding; VelosBio: Research Funding; BioInvent: Research Funding. OffLabel Disclosure: Ibrutinib in combination with venetoclax is not approved in any indication

Background: Aggressive hematological malignancies in relapsed/refractory setting bear a dire prognosis with low cure rates and short survival. Matching these patients to therapies is challenged by complexity due to spatial and temporal tumor evolution and incomplete understanding of genotype to phenotype correlations. Direct functional testing could address these impediments. The EXALT trial is an interventional, one-arm study designed to assess the clinical value of next generation functional drug screening (ngFDS). An interim analysis on 17 patients suggested a clinical benefit (Snijder et al., Lancet Hematol. 2017). Methods: We applied image-based ngFDS to quantify differential ex-vivo sensitivity of primary patient tumor cells to respective non-tumor cells towards 136 small molecule drugs, including EMA approved for any indication or experimental. We screened bone marrow, peripheral blood or lymph node material from 143 patients who suffered from late stage aggressive hematological malignancies (acute leukemias, aggressive B- and T-cell lymphomas) , discussed the results in a multidisciplinary tumor board and recommended treatments to physicians (A). The primary endpoint of this study was the percentage of patients reaching a PFS-ratio (PFS(ngFDS treatment)/PFS(previous treatment)) of ≥1.3 with an H0 hypothesis < 15% patients. The secondary endpoint was overall response rate (ORR) defined as proportion of patients reaching complete remission (CR) or partial remission (PR). Additionally, we performed a post hoc analysis to evaluate the matching of ngFDS to drugs used in actual treatment (matching score of received treatment). Results: 56 (39%) patients were evaluable and treated according to ngFDS based recommendations. With 30 of 56 (54%) ngFDS guided patients experiencing a PFS ratio of ≥1.3, the primary study endpoint was reached. 11 patients (37%) had ongoing response at censoring date (B). The median follow-up was 718 days. The median number of days from sampling to treatment was 21 (range 4-77). The ngFDS treatment regimens consisted of a median of 2 drugs (range: 1-6). ORR was 55% for all evaluable ngFDS treated patients, 60% for the lymphoid subgroup and 41% for the myeloid subgroup. Patients on ngFDS guided treatment with performance status ECOG ≤ 1 had a median PFS of 207 days compared to a median PFS of 29 days for patients with higher ECOG (p < 0.001, C). 24 of 39 (62%) patients with ECOG ≤ 1 had a PFS ratio of ≥1.3 (D). In disease specific subgroup analysis median PFS of T-cell lymphoma patients was 235 days versus 60 days for B-cell lymphoma patients (p = 0.018, E). Age (≤60 vs. >60), sex, lineage (myeloid vs. lymphoid), number of previous treatment lines (≤2 vs. >2), and clinical presentation (leukemia vs. lymphoma) did not have an impact on PFS of ngFDS guided treatment. Post hoc analysis including additional 17 non-ngFDS treated patients demonstrated that only patients receiving treatment with a positive ngFDS matching score demonstrated clinical benefit (HR: 0.53, p=0.005; vs. HR: 1.4, p=0.4). ngFDS matched treatments resulted in higher PFS for patients with tumor samples that had a cancer cell fraction of 10-50% in comparison to patients with samples of lower or higher cancer cell percentage (HR:0.35, p=0.01). Conclusion: ngFDS could be integrated in the routine clinical work flow. ngFDS guided treatments led to high rates of PFS prolongation compared to previous treatments of individual patients. ngFDS guided treatment is feasible and effective in patients with late stage aggressive hematological malignancies. These results prompted a prospective randomized trial comparing treatment guidance based on ngFDS or comprehensive genomic profiling or physician's choice (EXALT-2 trial, NCT04470947). Figure Disclosures Vladimer: Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Jaeger:Karyopharm: Honoraria; Amgen: Honoraria; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; True North: Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria; CDR Life AG: Consultancy, Research Funding; F. Hoffmann-La Roche: Honoraria, Research Funding; Infinity: Honoraria; Takeda: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria. Krall:Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Valent:Allcyte GmbH: Research Funding; Cellgene: Honoraria, Research Funding; Pfizer: Honoraria. Wolf:Celgene: Honoraria, Research Funding. Zielinski:MSD: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Imugene: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Merrimack: Consultancy, Honoraria, Speakers Bureau; Merck KGaA: Consultancy, Honoraria, Speakers Bureau; Fibrogen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Tesaro: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Speakers Bureau; Athenex: Consultancy, Honoraria, Speakers Bureau. Superti-Furga:Allcyte GmbH: Current equity holder in private company, Other: Founder. Snijder:Allcyte GmbH: Current equity holder in private company, Other: Founder. Staber:Roche: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Celgene/ BMS: Consultancy, Honoraria; msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria.

Introduction : Glofitamab (RG6026) is a novel T-cell-engaging, bispecific, full-length antibody with a 2:1 molecular configuration that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Preclinically, glofitamab had superior potency compared with other tested bispecifics with 1:1 formats (Bacac, et al. Clin Cancer Res 2018). NP30179 (NCT03075696) is an ongoing multicenter, Phase I/Ib, dose-escalation and dose-expansion trial evaluating the safety, tolerability, pharmacokinetics, biomarker responses, and efficacy of glofitamab in patients (pts) with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL). Clinical data from NP30179 demonstrated that fixed dosing of glofitamab (0.6-25mg) induced high and durable complete responses with a manageable safety profile in pts with heavily pre-treated R/R NHL (Dickinson, et al. EHA 2020). Obinutuzumab pretreatment (Gpt) was shown to be effective in mitigating the risk of cytokine release syndrome (CRS), allowing for rapid escalation of glofitamab to clinically active doses (Dickinson, et al. EHA 2020). Step-up dosing of glofitamab was used in addition to Gpt to further reduce the risk of CRS. For the first time, we present clinical data of glofitamab step-up dosing with Gpt in pts with R/R NHL. Methods: Pts received 1000mg obinutuzumab 7 days prior to first glofitamab administration. Glofitamab was given intravenously with step-up dosing on Cycle (C) 1 Day (D) 1 and 8 and then at the target dose from C2D1, every 3 weeks for up to 12 cycles (2.5/10/16mg or 2.5/10/30mg). Response rates reported are based on the Lugano criteria (Cheson, et al. J Clin Oncol 2014). Results: As of April 17, 2020, 38 pts received step-up doses of glofitamab; 17 pts received 2.5/10/16mg, and 21 pts received 2.5/10/30mg. Twenty-eight pts (73.7%) had aggressive NHL (aNHL) histologies and ten pts had indolent NHL (iNHL; Table). The median age was 68 years (range 52-85) and median number of prior lines of therapy was 3 (range 1-12). Twenty-seven (71.1%) pts were refractory to their last therapy, and 28 (73.7%) pts were refractory to prior CD20 therapy. After a median follow-up of 2.8 months, across all efficacy-evaluable pts (n=32) the overall response rate (ORR) and complete metabolic response (CMR) rate was 62.5% and 40.6%, respectively. For pts with aNHL (n=24), the ORR was 50.0% with CMR rates of 29.2%. As of the data cut-off date, 17 pts with aNHL (70.8%) had reached the first response assessment only (C3) and remain on treatment; four pts (16.7%) had reached the second response assessment (C6). For pts with iNHL (n=8), the ORR was 100.0% with 75.0% of pts achieving CMR. Across the safety-evaluable population (n=38), the most common AEs were CRS (57.9%), pyrexia (31.6%), neutropenia, thrombocytopenia and hypophosphatemia (28.9% each). No AEs led to treatment discontinuation. Of 22 patients who experienced CRS events, the CRS events only occurred in C1 and C2; 15 had CRS after the 2.5mg dose, 12 after the 10mg dose, and 5 during C2 (16 or 30mg dose; Figure). Eight pts (21.1%) and 13 pts (34.2%) experienced Grade (Gr) 1 and 2 CRS, respectively; none experienced Gr 3 CRS. One pt (2.6%) experienced Gr 4 CRS after the 30mg dose. No CRS events occurred after C2. Tocilizumab was used to manage CRS in six (15.8%) pts: n=2 for 2.5/10/16mg and n=4 for 2.5/10/30mg cohorts. CRS events were manageable and resolved for 21 pts (95.4%) at data cut-off. No Gr ≥3 neurologic adverse events were reported. Consistent with prior biomarker data from fixed-dose regimens (Bröske, et al. EHA 2020), glofitamab administered with step-up dosing induced a transient T-cell redistribution. Conclusions: Step-up dosing of glofitamab allowed escalation up to 30mg to maximize efficacy, while minimizing the risk of increased CRS. High ORR and CMR rates were observed in pts with NHL who had failed several lines of treatment. Toxicity was manageable with the main safety signal being low-grade CRS observed in early cycles. Updated results will be presented at the congress which will include data from at least 50 pts receiving glofitamab step-up dosing with Gpt. Disclosures Hutchings: Genmab, F. Hoffmann-La Roche, Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene, Genmab, Janssen, Novartis, F. Hoffmann-La Roche, Takeda: Research Funding. Carlo-Stella:Servier, Novartis, Genenta Science srl, ADC Therapeutics, F. Hoffmann-La Roche, Karyopharm, Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics and Rhizen Pharmaceuticals: Research Funding; Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen Oncology, AstraZeneca: Honoraria; Boehringer Ingelheim and Sanofi: Consultancy. Bachy:Roche, Gilead: Consultancy; Amgen: Research Funding; Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi: Honoraria; Beigene: Membership on an entity's Board of Directors or advisory committees. Morschhauser:F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Servier: Consultancy; Genentech, Inc.: Consultancy. Crump:Kite/Gilead: Consultancy; Roche: Consultancy; Servier: Consultancy. Iacoboni:Novartis, Gilead, Celgene, Roche: Honoraria. Sureda Balari:BMS: Speakers Bureau; Roche: Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy; Gilead/Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria. Martinez-Lopez:Novartis: Consultancy; Janssen: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Janssen-cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Lundberg:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Dixon:Roche Products Limited: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Perez Callejo:F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Relf:Roche Products Ltd: Current Employment. Carlile:AstraZeneca: Current equity holder in publicly-traded company, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Piccione:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Humphrey:F. Hoffmann-La Roche: Current Employment, Current equity holder in private company, Current equity holder in publicly-traded company. Dickinson:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy. OffLabel Disclosure: Glofitamab (RG6026; CD20-TCB) is a full-length, fully humanized immunoglobulin G1 (IgG1) bispecific antibody with a 2:1 molecular format that facilitates bivalent binding to CD20 on B-cells, and monovalent binding to CD3 on T-cells. Glofitamab redirects T cells to engage and eliminate malignant B cells. Glofitamab is an investigational agent.

Introduction: The activity of immune checkpoint blockade including anti-cytotoxic T-lymphocyte associated protein-4 and anti-programmed cell death protein-1 monoclonal antibodies in hematologic malignancies is limited outside of classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Tumor mutational burden (TMB), programmed death ligand-1 (PD-L1) expression, and microsatellite instability-high (MSI-H) are well-established biomarkers predicting response to checkpoint blockade in solid malignancies. In addition, tumors with high TMB, defined as ≥10 mutations/megabase (mut/Mb), and/or MSI-H are Food and Drug Administration (FDA) approved tissue agnostic biomarkers for treatment with pembrolizumab. The frequencies of high TMB, MSI-H, and expression pattern of PD-L1 across specific hematologic malignancies are undefined. Methods: Patients with hematologic malignancies who had next generation sequencing (NGS) performed by Foundation One Heme were identified. TMB and MSI were measured by NGS. TMB was classified as high if ≥10 mut/Mb and low if Results: A total of 390 patients with hematologic malignancies with NGS were identified. Forty eight of the 390 samples (12%) had a high TMB (Table 1). Twenty five of 45 (56%) patients with DLBCL had a high TMB (Table 2). The TMB was low in all myeloid malignancies tested. None of the 302 samples tested were MSI-H. PD-L1 IHC was performed on 86 samples. Eleven (13%) had high expression, 26 (30%) had low expression, and 49 (57%) had no expression of PD-L1 on the tumor cells (Table 1). The majority of samples with PD-L1 expression were mature lymphomas (81%). TMB and PD-L1 score had a significant linear relationship (R = 0.22,p= 0.04, 95% CI 0.01 - 0.41) (Figure 1). Conclusion: This study provides detailed characteristics of TMB, MSI status, and PD-L1 expression for hematologic malignancies. Notably, a subset of lymphomas had high TMB and/or PD-L1 expression. Biomarker driven studies of checkpoint blockade in hematologic malignancies with high TMB and/or PD-L1 expression are warranted. Disclosures Sokol: Foundation Medicine:Current Employment;Roche:Current equity holder in publicly-traded company.Kurzrock:Medimmune:Research Funding;Foundation Medicine:Research Funding;Konica Minolta:Research Funding;IDbyDNA:Current equity holder in private company;Pfizer:Consultancy, Research Funding;Sequenom:Research Funding;Bicara Therapeutics, Inc.:Consultancy;Incyte:Research Funding;Takeda:Research Funding;TopAlliance:Research Funding;Boehringer Ingelheim:Research Funding;CureMatch Inc:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees;Grifols:Research Funding;Guardant:Research Funding;X Biotech:Consultancy;Neomed:Consultancy;Actuate Therapeutics:Consultancy;Roche:Consultancy;Merck Serono:Research Funding;Genentech:Research Funding;Debiopharm:Research Funding;CureMetrix:Membership on an entity's Board of Directors or advisory committees;OmniSeq:Research Funding;TD2/Volastra:Consultancy;Turning Point Therapeutics:Consultancy.Goodman:EUSA Pharma:Consultancy;Seattle Genetics:Consultancy.

Background: Hereditary pyruvate kinase (PK) deficiency results in lifelong hemolytic anemia and several significant comorbidities, the epidemiology of which are not well characterized. Among these is reduced bone mineral density (BMD), which can result in premature osteopenia, osteoporosis, and fractures. To better characterize the bone density abnormalities in patients with PK deficiency, this study evaluated pooled pre-treatment baseline data from 3 clinical trials involving patients with PK deficiency investigating mitapivat, an allosteric activator of PK: DRIVE-PK (NCT02476916), ACTIVATE (NCT03548220), and ACTIVATE-T (NCT03559699). This is the first large PK deficiency cohort in which dual-energy x-ray absorptiometry (DXA) scores were systematically and consistently assessed. Methods: DRIVE-PK is a completed phase 2, global, randomized, open-label study. ACTIVATE is an ongoing phase 3, global, randomized, double-blind, placebo-controlled study. ACTIVATE-T is an ongoing phase 3, global, open-label, single-arm study. In all 3 studies, patients ≥ 18 years of age with a confirmed diagnosis of PK deficiency were eligible to participate. Patients were eligible to participate in DRIVE-PK and in ACTIVATE if they were not regularly transfused (DRIVE-PK: ≤ 3 units of red blood cells in the prior 12 months; no transfusions in the prior 4 months; ACTIVATE: ≤ 4 transfusion episodes in the previous year; no transfusions in the prior 3 months) and in ACTIVATE-T if they were regularly transfused (≥ 6 transfusion episodes in the previous year). BMD was measured using DXA scans at baseline; scans were obtained locally for all 3 studies. Scans were interpreted locally for DRIVE-PK and centrally for ACTIVATE and ACTIVATE-T. Osteopenia and osteoporosis were identified on DXA scanning according to standard definitions, and the prevalence of each was compared to the prevalence ascertained via medical history. Results: Full demographics and characteristics of patients at baseline are shown in the Table. Of 159 patients evaluated (DRIVE-PK, n = 52; ACTIVATE, n = 80; ACTIVATE-T, n = 27), the median age was 34 years (range, 18-78) and the majority were female (n = 88; 55.3%). Of 155 patients who had baseline T-scores for total femur, spine, and femoral neck, 38 (24.5%) had a T-score of ≥ -1.0 at all locations, indicating normal BMD; 91 (58.7%) had a T-score of < -1.0 to > -2.5 at 1 or more locations, indicating osteopenia; and 26 (16.8%) had a T-score of ≤ -2.5 at 1 or more locations, indicating osteoporosis. The proportion of patients in each T-score range for each of the 3 locations is shown in the Figure. In contrast to the DXA scan findings, only 28 (17.6%) patients had a known medical history of osteopenia and 23 (14.5%) had a known medical history of osteoporosis. Taking together DXA scan results and medical history for all 159 patients, 85 patients (53.5%) had osteopenia and 33 patients (20.8%) had osteoporosis. The median age for patients with either osteopenia or osteoporosis (n = 118) was 36 years (range, 18-78). Of these, 20 patients (16.9%) were regularly transfused and 98 patients (83.1%) were not regularly transfused. Conclusions: In this large cohort, universal DXA scanning revealed that over three-quarters of adults with PK deficiency had osteopenia or osteoporosis, irrespective of transfusion requirements. Given the young median age of the cohort (34 years), these findings have considerable significance and implications for the screening and care of patients with PK deficiency throughout their adult lives. Early monitoring of these patients with DXA scans in order to ensure a prompt diagnosis of bone density abnormalities and indicated treatment may be warranted. Disclosures Al-Samkari: Argenx: Consultancy; Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding; Rigel: Consultancy; Amgen: Research Funding. Grace:Novartis: Research Funding; Agios: Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding. Glenthoej:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bluebird: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexicon: Research Funding; Novo Nordisk: Honoraria. Barcellini:Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: invited speaker , Research Funding; Novartis: Honoraria, Other: invited speaker , Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Galactéros:Addmedica: Membership on an entity's Board of Directors or advisory committees. Kuo:Bluebird Bio: Consultancy; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Apellis: Consultancy; Celgene: Consultancy; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding. Layton:Cerus: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Morado:Sanofi Genzyme: Honoraria, Other: Grants. Viprakasit:BMS, Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Agios Pharmaceuticals, Ionis Pharmaceuticals, La Jolla Pharmaceuticals, Protagonist Therapeutics, Vifor Pharma: Consultancy, Research Funding. Dong:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Tai:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Hawkins:Agios Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company; Bristol-Myers Squibb: Current equity holder in publicly-traded company; Infinity Pharmaceuticals: Current equity holder in publicly-traded company; Jazz Pharmaceuticals: Current equity holder in publicly-traded company. Gheuens:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Bowden:Agios Pharmaceuticals: Current Employment, Current equity holder in private company. Porter:Silence Therapeutics: Honoraria; La Jolla Pharmaceuticals: Honoraria; Vifor Pharmaceuticals: Honoraria; Protagonist Therapeutics: Honoraria; Agios Pharmaceuticals: Consultancy, Honoraria; bluebird bio, Inc.: Consultancy, Honoraria; BMS: Consultancy, Honoraria. van Beers:Novartis: Research Funding; Pfizer: Research Funding; RR mechatronics: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction Betibeglogene autotemcel (beti-cel; LentiGlobin for β-thalassemia) gene therapy is being evaluated for the treatment of transfusion-dependent β-thalassemia (TDT). Initial positive results of beti-cel in the phase 3 studies, HGB-207 (NCT02906202; non-β0/β0 genotypes) and HGB-212 (NCT03207009; β0/β0, β0/β+ IVS-I-110 and β+ IVS-I-110/β+ IVS-I-110 genotypes), showed 10/12 adult patients achieved transfusion independence. The studies expanded enrollment to include adolescents and children. We present interim results from pediatric patients Methods After mobilization and apheresis, autologous CD34+ cells were transduced ex vivo with BB305 lentiviral vector, containing a modified human β-globin gene to produce beti-cel drug product (DP). Patients underwent busulfan myeloablation and infusion with beti-cel and were then followed longitudinally. Transfusion independence (TI; weighted average hemoglobin [Hb] ≥9 g/dL without transfusions for ≥12 mo) was the primary endpoint in HGB-207 and a secondary endpoint in HGB-212. Transfusion reduction (≥60% reduction in transfusion volume between Month 12 to 24 versus baseline) is the primary endpoint in HGB-212. Hb levels, TI characteristics, and quality of life were secondary endpoints. Assessments of ineffective erythropoiesis were exploratory. Data presented as median (min-max). Results Twenty-four pediatric patients were treated including 13 patients 3 mo follow-up achieved platelet engraftment and had platelets ≥100 x109/L by Month 12; one 17-yr old patient did not have platelets ≥100 x109/L until Month 15. In HGB-207, 6/7 (86%) patients 3 mo follow-up have stopped transfusions for ≥6 mo. TI was achieved in 3/4 (75%) evaluable patients In HGB-212, 3/5 (60%) patients 3mo follow-up have stopped transfusions for ≥6 mo. TI was achieved in 1/2 evaluable patients Post-infusion non-hematologic grade ≥3 adverse events (AEs) in ≥3 patients aged Summary Interim results in HGB-207 and HGB-212 show that after treatment with beti-cel, pediatric patients Disclosures Thompson: CRISPR/Vertex: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Baxalta: Research Funding; BMS: Consultancy, Research Funding; Biomarin: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding. Kwiatkowski:Novartis: Research Funding; Agios: Consultancy; Sangamo: Research Funding; bluebird bio,Inc.: Consultancy, Research Funding; Apopharma: Research Funding; Imara: Consultancy; BMS: Consultancy; Terumo Co: Research Funding; Celgene: Consultancy. Porter:Vifor Pharmaceuticals: Honoraria; bluebird bio, Inc.: Consultancy, Honoraria; Agios Pharmaceuticals: Consultancy, Honoraria; La Jolla Pharmaceuticals: Honoraria; Silence Therapeutics: Honoraria; Protagonist Therapeutics: Honoraria; BMS: Consultancy, Honoraria. Kulozik:Novartis: Consultancy, Honoraria; bluebird bio, Inc.: Consultancy, Honoraria. Thrasher:Rocket Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Generation bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Equity ownership; Orchard Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Equity ownership; 4Bio Capital: Consultancy, Membership on an entity's Board of Directors or advisory committees. Thuret:Novartis pharma: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; bluebird bio, Inc.: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials; Apopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Investigator in clinical trials. Lal:Insight Magnetics: Research Funding; Celgene, BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Terumo Corporation: Research Funding; Agios Pharmaceuticals: Consultancy; Chiesi USA: Consultancy; La Jolla Pharmaceutical Company: Research Funding; bluebird bio, Inc.: Research Funding; Protagonist Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Guo:bluebird bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Liu:bluebird bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Colvin:bluebird bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Walters:Veevo Biomedicine: Consultancy; AllCells, Inc: Consultancy; Editas: Consultancy. Locatelli:Jazz Pharmaceeutical: Speakers Bureau; Medac: Speakers Bureau; Miltenyi: Speakers Bureau; Bellicum Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) are >70 years old and have poor clinical outcomes attributable to treatment-related factors or to disease biology. Genotyping data in elderly DLBCL patients is limited because of lack of representation in clinical trials. R-mini-CHOP is better tolerated than R-CHOP in elderly DLBCL but with reduced efficacy. The addition of ibrutinib to R-CHOP has been shown to be effective in younger pts aged < 60 years but is associated with poor tolerability and outcomes in older patients. The ALLG Ibrutinib with R-mini-CHOP (IRiC) study, a prospective multicentre single-arm phase II study in elderly (≥ 75 years) DLBCL patients provided an opportunity to genotype this uncommon cohort. We therefore aimed to map the genetic landscape of mutations in elderly DLBCL and compare them to a non-trial younger cohort. Methods: Mutations in genes commonly associated with DLBCL were assessed in 55 IRIC study patients with a median age of 81 years (75-91 years) and a gender ratio of 1.0 (27 M/28 F). A cohort of 51 non-trial patients withde novoDLBCL treated with anthracycline-based regimens was also genotyped. The median age of the control group was 65 years (29-91 years) with a gender ratio of 1.2:1 (28 M/23 F). The cell of origin (COO) measured using gene expression profiling on 39/55 trial patients (non-GC=13, GC= 22, unclassified= 4), and Hans algorithm on 45/51 non-trial patients (non-GC=14, GC=31) was comparable (p=0.571). Outcome data was available at a median follow-up of 18 and 40 months for the trial and non-trial cohorts respectively. We extracted genomic DNA from and performed next generation sequencing on diagnostic formalin-fixed paraffin-embedded or fresh frozen tissue samples using a customized capture library (SureSelectXT Target Enrichment System, Aqilent Technologies) covering genes involved in lymphomagenesis. The purified libraries were sequenced on the Illumina NextSeq500 platform at AGRF (Australian Genome Research Facility, Australia). Mutations in the following genes were compared across the two cohorts: ARID1A, BCL2, BTG1, BTG2, CARD11, CCND3, DTX1, EP300, ETS1, EZH2, FOXO1, GNA13, HIST1H1C, IKBKB, IRF8, KDM2B, KLHL6, MYC, MYD88, NOTCH1, NOTCH2, PIK3CD, PIM1, PRDM1, PTEN, PTPN21, SGK1, SPEN, STAT3, TET2, TNFAIP3, TNFRSF11A, TNFRSF14, TP53 and TRAF5. Statistical analysis for nominal data was done using the chi-square test and for ordinal data using the Kruskal-Wallis test (p < 0.05= significant). Kaplan-Meier curves were calculated for patients with and without each mutation and the curves compared using a log-rank approach. Results: Patients were divided into 2 groups, IRiC trial cohort aged >75 years (n=55) + non-trial elderly patients >75 years (n=9) =elderly cohort(n=64) and non-trialnon-elderly cohortof patients < 75 years (n=42). As expected, elderly patients were more likely to have high-risk disease with higher IPI of ≥ 3 (n=42, n=17, p=0.009). There was no significant difference in gender or COO. The frequency of mutations in the elderly (n=64) was compared to the non-elderly cohort (n=42). NOTCH2 was the most common mutation irrespective of age (34 [53%]; 16 [38%], p=0.129). Notably, we found that mutations in MYC (8 [12.5%]; 0, p= 0.021), PTEN (17 [26.5%]; 4 [9%], p=0.045) and TET2 (28 [43.7%]); 7 [16.6%], p=0.004) were more frequent in the elderly. As expected, MYD88 and CD79B mutations were more frequently associated with non-GC subtype (p=0.001). No other associations with COO were identified. No clear prognostic individual genes or gene clusters could be identified in the trial or the elderly cohort. Ibrutinib-responsive (MYD88 [L265P n=7] and CD79B [n=11]) and ibrutinib-resistant mutations (CARD11 [n=6] or PIM1 [n=12]) did not show clear associations with response rate, overall survival or progression-free survival. Conclusions: Our study found that the mutational profile of elderly DLBCL patients aged ≥ 75 years is enriched for targetable mutations in MYC, PTEN and TET2 compared to those < 75 years. PTEN and TET2 are tumour suppressors and MYC is an oncogene with an important regulatory role in cell growth and proliferation. We hypothesize that hypo-methylating agents targeting TET2, BET inhibitors in MYC mutated tumours and PI3K inhibitors to target PTEN deficient lymphoma may help improve clinical outcomes in elderly DLBCL. No clear prognostic markers were identified in this small cohort. Disclosures Trotman: Celgene:Research Funding;BeiGene:Research Funding;Takeda:Research Funding;PCYC:Research Funding;F. Hoffmann-La Roche:Research Funding.Verner:Janssen Cilag Pty Ltd.:Research Funding.Gandhi:Celgene:Research Funding;Bristol-Myers Squibb:Research Funding;Mater Research:Current Employment;Janssen-Cilag:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Roche:Other: Travel, accommodation, expenses ;Genentech:Honoraria;Gilead Sciences:Honoraria;Amgen:Honoraria;Merck Sharp & Dohme:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.Gandhi:Integrated Sciences:Current Employment.Talaulikar:Takeda:Research Funding;Amgen:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction: Hemophilia A (HA) is a congenital bleeding disorder caused by a deficiency in clotting factor VIII (FVIII). There are currently limited data on the impact of HA on daily life. Here we examine the impact of HA on the daily life of adult persons with HA (PwHA) without current FVIII inhibitors according to disease severity. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey II (CHESS II) is a retrospective, burden-of-illness study in adults with mild, moderate, and severe HA or hemophilia B (defined by endogenous FVIII/IX [IU/dL] relative to normal; mild, 5- Results: Of 258 PwHA completing questionnaires, 15.9% (n=41), 27.9% (n=72), and 56.2% (n=145) had mild, moderate, and severe HA, respectively. Of those with severe HA, 60.0% were currently receiving FVIII prophylaxis (standard of care for severe HA); in comparison, 4.9% and 6.9% of those with mild and moderate HA were receiving prophylaxis (Table 1). Treatment adaptation in anticipation of physical or social activity was reported by 19.5%, 23.6%, and 38.6% of those with mild, moderate, and severe HA, respectively. Over a third of participants with mild (36.6%) and moderate (44.4%) HA, and 64.8% of those with severe HA (58.6% with severe HA receiving on-demand treatment and 69.0% receiving prophylaxis) agreed or strongly agreed that HA had reduced their physical activity (Figure 1). Overall, 38.9% of those with moderate HA and 58.6% of those with severe HA (63.8% with severe HA receiving on-demand treatment and 55.2% receiving prophylaxis) agreed or strongly agreed that their HA had reduced their social activity; this was less pronounced in mild HA (9.8%). Additionally, 31.7%, 36.1%, and 64.1% of those with mild, moderate, and severe HA (62.1% with severe HA receiving on-demand treatment and 65.5% receiving prophylaxis) agreed or strongly agreed that their HA had caused them to miss opportunities. Correspondingly, frustration due to HA was felt by 19.5%, 34.7% and 57.9% (56.9% with severe HA receiving on-demand treatment and 58.6% receiving prophylaxis) of people, respectively. When asked whether they believed their daily life was compromised due to their hemophilia, 24.4%, 37.5%, and 63.4% of those with mild, moderate, and severe HA, respectively, agreed. Pain, as reported by the physician, was noted in 36.6% of people with mild HA (100% was reported as 'mild'); in people with moderate HA, pain was reported as 'mild', 'moderate', and 'severe' in 44.4%, 20.8%, and 1.4% of PwHA, respectively. In people with severe HA, pain was reported as 'mild', 'moderate', and 'severe' in 39.7%, 27.6%, and 8.6% for those receiving on-demand treatment, and 37.9%, 32.2%, and 8.0% for those receiving prophylaxis, respectively. Conclusions: In all disease severity groups, there was a notable group of PwHA that felt that they have had to reduce their physical and social activity, have had fewer opportunities and are frustrated due to their disease. While the impact on daily life is most pronounced in people with severe HA (including those receiving on-demand treatment and those receiving prophylaxis), it is also apparent in mild and moderate HA, indicating that there may be an unmet medical need in these groups. Disclosures Noone: Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; Research Investigator PROBE: Research Funding; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees. Nissen:F. Hoffmann-La Roche Ltd: Current Employment; Actelion: Consultancy; Novartis: Research Funding; GSK: Research Funding. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Burke:University of Chester: Current Employment; HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar:HCD Economics: Current Employment. Dhillon:F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. ; HCD Economics: Current Employment. Aizenas:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara:HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Khair:Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Haemnet: Membership on an entity's Board of Directors or advisory committees.

Young adults are increasingly taking on caregiving roles in the United States, and cancer caregivers often experience a greater burden than other caregivers. An unexpected caregiving role may disrupt caregiver employment, leading to lost earning potential and workforce re-entry challenges. We examined caregiving employment among young adult caregivers (i.e., family or friends) using the 2015 Behavioral Risk Factor Surveillance System (BRFSS), which included caregiving, employment, and sociodemographic variables. Respondents’ ages varied between 18 and 39, and they were categorized as non-caregivers (n = 16,009), other caregivers (n = 3512), and cancer caregivers (n = 325). Current employment was compared using Poisson regressions to estimate adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95% CI), including gender-stratified models. We estimated employment by cancer caregiving intensity (low, moderate, high). Cancer caregivers at all other income levels were more likely to be employed than those earning below USD 20,000 (aIRR ranged: 1.88–2.10, all p< 0.015). Female cancer caregivers who were 25–29 (aIRR = 0.71, 95% CI = 0.51–1.00) and single (aIRR = 0.70, 95% CI = 0.52–0.95) were less likely to be employed than their counterparts. College-educated males were 19% less likely to be employed than high school-educated caregivers (95% CI = 0.68–0.98). Evaluating caregiver employment goals and personal financial situations may help identify those at risk for employment detriments, especially among females, those with lower educational attainment, and those earning below USD 20,000 annually.

Resumo Este artigo tem por objetivo analisar a transição do estado de emprego para o desemprego no mercado de trabalho brasileiro visando compreender que efeito a qualidade do posto de trabalho atual possui sobre a probabilidade de o trabalhador perder sua ocupação no período futuro. A intenção é entender o quanto as características pessoais, socioeconômicas, capital humano e as características de ocupação podem influenciar na probabilidade de os trabalhadores transitarem para o desemprego. São usados dados da Pesquisa Mensal do Emprego dos anos de 2002 a 2016. Os resultados apontam que trabalhadores alocados em categorias mais altas têm menor probabilidade de perder seu posto de trabalho. Ademais, é observado que a escolha da categoria da ocupação tende a ser mais importante para as mulheres, ou seja, os efeitos de uma escolha inadequada hoje afetam negativamente a probabilidade de emprego futura. Abstract The objective of this paper is to analyze the transition from employment to unemployment in the Brazilian labor market. Specifically, the study aims to understand what effect the quality a citizen’s current employment has on the probability of them losing their job in the future. The intention is to understand how personal and socioeconomic characteristics, human capital and occupation characteristics can influence the probability of workers becoming unemployed. Data from the Monthly Employment Survey (PME) for the years 2002 to 2016 are used. The results show that workers in higher categories of employment are less likely to lose their jobs. Moreover, it is observed that the choice of occupational category tends to be more important for women than for men, that is, the effects of inadequate choices negatively affect the probability of future employment.

Background: Orthopaedic surgery is ever changing and depends on diverse technical and intellectual skill sets. The purpose of the current study was to evaluate the percentage of academic orthopaedic surgeons with additional graduate degrees in the United States. Methods: Data including advanced degree(s) (eg, PhD, MS, MBA, MPH, JD, and DVM), academic rank, leadership position, subspecialty, years since training completion, and sex were collected from websites for all academic orthopaedic surgery departments in the United States. Univariate analyses were performed to evaluate for differences in demographic data based on the advanced degree status. Data from the National Resident Matching Program (NRMP) were used to characterize graduate degree-holding US senior medical students who ranked orthopaedic surgery first relative to peers without additional advanced degrees and to applicants who ranked other specialties first. Results: Of 4,519 faculty at 175 academic orthopaedic surgery departments in the United States, 7.1% held a graduate degree in addition to a medical doctorate. There was no difference in the percentage of faculty who held departmental leadership positions (P = 0.62) or who were full professors (P = 0.66) based on holding an additional graduate degree. Of 678 US senior applicants who ranked orthopaedic surgery first and successfully matched into the specialty in 2018, 12.5% held an additional graduate degree and 1.3% were MD-PhDs. Orthopaedic surgery had the second lowest percentage of matched medical students with additional advanced degrees, which was significantly lower than the top 10 specialties (range 16.1% to 21.6%; P < 0.05). Orthopaedic surgery recruited 1.6% of all MD-PhD applicants in 2018. Discussion: Few academic orthopaedic surgery faculty and admitted orthopaedic residency candidates have additional graduate school training. The low percentage of orthopaedic faculty and trainees with additional advanced degrees relative to other specialties may represent a missed opportunity to recruit individuals with diverse skills to advance the field of orthopaedic surgery.

Objective To examine the career outcomes of 20 years of PhD graduates from Canadian health services and policy research (HSPR) doctoral training programs. Methods The deans of the doctoral training programs were invited to participate in this national cohort study. A standardized career-tracking template was developed. Internet searches of publicly accessible sources were used to track graduates' employment. Descriptive analyses summarized PhD program characteristics and current employment. Results Of the 1,208 trainees who graduated during our study period, 884 (73.2% of 1,208, or 90.3% of the 979 with complete data) could be successfully tracked. HSPR PhD graduates are highly employable, but employment trends have changed over time. Today's graduates are more likely to enter careers in a wider variety of sectors and roles and are less likely to be employed in academia than previous graduates. However, over 50% of graduates are currently employed in professorial positions within the academic sector or in research roles or departments within healthcare delivery organizations. Conclusions This article provides an initial descriptive profile of the career outcomes of HSPR PhD graduates in Canada from 10 university-based doctoral training programs. To ensure that PhD graduates are prepared to contribute fully within diverse sectors and roles, doctoral training must evolve to keep pace with employment trends and encompass, in addition to research skills, the professional skills demanded in the public, private, not-for-profit and healthcare delivery sectors.

Newly certified teachers in the province of Ontario, Canada encounter a series of hurdles imposed by Regulation 274 before they qualify for full-time employment in the profession. Provincial Faculties of Education and US border colleges, which were certifying Ontario teachers, graduated an unprecedented number of newly certified teachers. Between the years 2006 - 2015, the annual surplus of newly certified teachers in the province reached 7,800. Faced with the results of heavy over-certification and underemployment of teachers brought on in large part by lax government control and seemingly unrestricted access to teacher education programmes, the provincial government initiated an ill-conceived reaction and introduced legislation, known as Regulation 274, to staunch the flow of newly certified teachers. In addition to Regulation 274, the government launched a plan-of-action that resulted in changing the one-year teacher education program to a two-year program while cutting the number of seats available within Faculties of Education to one-half post 2015 numbers. Regulation 274, characterized at the time by the Premier, as an “over-correction”, required newly certified teachers, beginning in 2015, to be subject to policies and standards that restricted their immediate entry into the rank and file of classroom teachers. While the trend in supply and demand has favoured employment opportunities for Ontario teachers since 2016, Regulation 274 is still in effect. Given the restrictions of 274 and the added expense of another year of specialized education, this study sought to identify the job-seeking behaviours and plans, in the current employment climate of the province of the first cohort of graduates from the two-year program in a northern Ontario university, exiting in 2017. Employment prospects and other social factors were found to influence employment decisions of these new teachers.

The majority of research on sexual minority individuals relies on nonprobability community venue samples. These samples are prone to selection bias; however, empirical syntheses of evidence of these biases are not available. We conducted, therefore, a systematic review of published sexual minority health research to summarize methods used to identify characteristics and health outcomes found to differ in nonprobability samples. We searched five health and social science databases to identify observational studies that included a nonprobability sexual minority community sample and applied an empirical method to infer selection bias. We extracted data regarding sociodemographic characteristics, behaviors, and health outcomes and examined whether the nonprobability sample was found to differ disproportionately (over- or underrepresenting the characteristic) based on appropriate statistical tests (p 50% of studies examined, for nine variables. Nonprobability community venue samples tended to overrepresent sexual minority individuals with the following characteristics: higher income, current employment, lesbian/gay-identified, greater number of sex partners, past-year sexually transmitted infection diagnosis, suicidal ideation, alcohol use, and substance use; nonprobability community venue samples tended to underrepresent married/partnered sexual minority individuals. This review provides a nuanced empirical picture of aggregate differences in sample characteristics presumed to threaten the validity of nonprobability sexual minority community venue studies, and highlights feasible methods that can be applied to future studies to add specificity to researchers' description of selection biases.

This study analyzed factors affecting the acquisition and retention of employment among individuals with intellectual disabilities (ID). These factors were verified according to job type and were classified into general characteristics, family-related factors, psychological factors, and abilities. Data from 398 individuals with ID were analyzed using chi-square tests, independent t-tests, and regression analyses using the second wave of the first year Panel Survey of Employment for the Disabled in Korea. We found significant differences in sex, education level, receipt of basic living security assistance, transportation use, household income level, and family support between employed and unemployed participants. Additionally, the employed (vs. unemployed) ID group had significantly higher scores for all variables related to psychological factors and abilities. Factors affecting employment among individuals with ID included age, education level, receipt of basic living security assistance, family support, and vocational ability. Older age, higher education level, absence of basic living security assistance, greater family support, and higher vocational ability were associated with a higher probability of current employment. Transportation use and parents’ education were associated with a high probability of non-manufacturing-type jobs. Being married, absence of basic living security assistance, greater householder income level, family support, and manufacturing industry work were associated with increased job retention. Consequently, modifying the benefit system and developing family support systems may promote employment acquisition and retention among people with ID. Efforts are also needed to expand the job types available to individuals with ID.

This paper explores the efficacy of current employment services in Australia, jobactive, from the perspectives of young job seekers and their employment officers. As high youth unemployment rates and the efficacy of jobactive employment services are currently areas of priority for the Australian Government, the study offers a timely contribution to the social policy and youth employment literature by exploring the tensions experienced by young job seekers while registered with a jobactive provider, and employment officers when assisting young people to find sustainable employment. The study analyses data from 46 interviews with young job seekers and their employment officers in an outer western Melbourne region. The findings reveal particular concerns about appropriate and adequate service provision for marginalized young job seekers that are similar to those in evaluations of previous marketwise employment service contracts, Job Network and Job Services Australia. Suggestions for tailored employment assistance for young job seekers to gain sustainable employment are offered for future consideration.

Objective As part of a statewide Supplemental Nutrition Assistance Program–Education program evaluation, Fresh Conversations (FC) facilitators (ie, educators) provided input into a new delivery model. Methods The researchers interviewed 25 FC facilitators. Interviews were recorded, transcribed verbatim, and analyzed for common themes. Results Most facilitators were women with at least 1 year of FC experience. Key motivators for serving as an FC facilitator included alignment with current employment responsibilities and gerontology interest. Training was viewed as helpful, thorough, and self-explanatory. Implementation challenges included recruitment, public speaking, and time management. Nearly all stated that FC content was important and that other seniors at other congregate meal sites would be interested in FC. Conclusions and Implications Findings suggest that facilitators were pleased with FC; however, their experiences might be further improved through enhanced training. Further exploration into community food and nutrition program educators’ feedback is needed to ensure these programs meet their needs as well as those of the audience.

ObjectivesLittle is known about what shapes the choice of employment location in a competitive surgical specialty like otolaryngology – head and neck surgery. This study aimed to identify factors important in determining practice location among Canadian otolaryngologistsMethodsAn online survey was distributed nationally to active members of the Canadian Society of Otolaryngology – Head and Neck Surgery. The survey collected data on general demographics, current practice description, training location, factors deemed important in practice location decisions, and job satisfaction.ResultsA total of 122 survey responses were collected, with a similar proportion of participants in academic versus community practice. The majority of respondents (73 per cent) practised in the same province as their residency training. Participants identified job vacancy, colleague interaction, spouse opinion and hospital services as important in the decision of practice location.ConclusionKey determinants of practice location among Canadian otolaryngologists include job vacancies, spouse opinion, and colleague interactions. Overall, Canadian otolaryngologists report high satisfaction with current employment.

Although exposure to indoor tanning has been established as a clear risk factor for skin cancer, sunbeds are still commonly used in Europe. Understanding the determinants of sunbed use in Europe is key to plan educational interventions, behavioural strategies and legislative measures, which should be tailored to subgroups with different risk profiles. Evidences show that the typical sunbed users in Europe are young-adult women, with intermediate skin type, a current employment and a medium/high socio-economic status. Typical users display sun-seeking behaviours and other risky behaviours such as smoking. Indoor tanning seems more common in northern than southern Europe. However, sunbed use remains common in fair-skinned individuals and among adolescents/pre-adolescents. Commonly reported reasons for sunbed use in Europe include aesthetic motives (i.e. looking attractive), the pursue of a prevacation tan, the influence of peers/parents engaging in the same habit, and the treatment of health conditions. The most commonly reported places to get an artificial tan in Europe are tanning studios and beauty salons. However, sunbeds are also available in sport venues, such as swimming pools and gyms, hotels and private houses. All these factors should be taken into account when planning educational, behavioural and legislative interventions to reduce the popularity of artificial tanning in Europe.

There exist strong direct and indirect employment contributions in producer services, which have become an important way to solve the employment problems in developed countries. In contrast, the overall employment ratio of producer services is low in China. It is important and necessary to study the influencing factors of producer services employment in order to fully explore the employment growth potential of producer services and promote the solution of current structural employment difficulties in China. This paper analyzes the conditions, under which the development of producer services drive the employment growth from the perspectives of demand and supply. The theoretical model of the influencing factors of producer services employment is constructed and the empirical method is adopted to measure the influencing effects of these factors. It is helpful for policy makers to grasp the key of producer services employment at the implementation level, so as to more actively and effectively defuse the negative impacts of economic recessions on the employment and alleviate the current employment pressures in China.

In this paper, we shed light on the impacts of the COVID-19 pandemic on the labor market, and how they have evolved over most of the year 2020. Relying primarily on microdata from the CPS and state-level data on virus caseloads, mortality, and policy restrictions, we consider a range of employment outcomes—including permanent layoffs, which generate large and lasting costs—and how these outcomes vary across demographic groups, occupations, and industries over time. We also examine how these employment patterns vary across different states, according to the timing and severity of virus caseloads, deaths, and closure measures. We find that the labor market recovery of the summer and early fall stagnated in late fall and early winter. As noted by others, we find low-wage and minority workers are hardest hit initially, but that recoveries have varied, and not always consistently, between Blacks and Hispanics. Statewide business closures and other restrictions on economic activity reduce employment rates concurrently, but do not seem to have lingering effects once relaxed. In contrast, virus deaths—but not caseloads—not only depress current employment, but produce accumulating harm. We conclude with policy options for states to repair their labor markets.

Introduction: Data on lymphoma patients with SARS-CoV-2 infection (COVID-19) are lacking. A large cancer cohort study showed that number of comorbidities, active cancer, and worse performance status were associated with increased 30-day mortality (Kuderer 2020). Variables contributing to risk of poor outcomes of COVID-19 in lymphoma patients have not been reported. We aimed to investigate the effect of COVID-19 on lymphoma patients' clinical outcomes including the effect of lymphoma-specific therapies on COVID-19 recovery. Methods: We conducted a multicenter, retrospective, observational cohort study. Data was obtained from 4,302 patients flagged in the electronic health records system with COVID-19, of which 89 lymphoma patients were identified. Presenting clinical information was abstracted from review of unstructured notes as well as structured data. Demographic and baseline parameters were summarized. The differences in the distributions between CD20 antibody treated or non-treated patients were compared using Mann-Whitney's test for continuous variables and Pearson's chi-squared test for categorical variables. The Kaplan-Meier method was utilized to compare the median time from date of diagnosis to date of last follow up or death. Results: 89 lymphoma patients were evaluable. The median age was 67 (range 29-94) with a male predominance (63%). The most common presenting symptoms were fever (54%), shortness of breath (52%), cough (47%), and gastrointestinal (13%). Hypertension and diabetes were present in 51 of 89 (57%) and 19 of 89 (21%) patients, respectively. Laboratory abnormalities included a median absolute neutrophil count of 4.67x103/mcL (range 0-15.9) and lymphocyte count 0.8x103/mcL (range 0-97.7). Inflammatory markers at diagnosis showed median CRP 9.4 mg/dL (0.7-126, n=62) and ferritin of 966 ng/mL (96-14,511, n=42). 76 of 89 (85%) patients required hospitalization, 11 (12%) required mechanical ventilation, and 31 (Case Fatality Rate=35%) died. The overall survival of lymphoma patients is shown in Figure 1A. The presence of hypertension (HR 3.7, p=.005), diabetes (HR 2.6, p=.02), or advanced age ≥70 (HR 2.2, p=.03) were associated with increased COVID-19 related mortality (Figure 1B-D). Lymphoma subtypes included CLL (n=32), DLBCL or Burkitt's (n=18), indolent non-Hodgkin (n=20), Hodgkin (n=6), T cell lymphoma (n=6), and other (n=7). 76% were stage III-IV (n=68), with 40 patients (44%) on active lymphoma treatment at the time of COVID-19 diagnosis. 41 patients (48%) received rituximab within the last 3 years, with 11 requiring chronic immune gamma globulin replacement. 25 patients were tested for seropositivity to COVID-19 at median of 42 days from COVID-19 diagnosis (IQR 32-50). 5 of 9 (55%) patients who did not receive CD20 antibody therapy showed immunity. In contrast, out of 16 patients who received anti-CD20 treatment and had a COVID-19 IGG antibody test, only 2 (12.5%) became seropositive (p =.03). Patients who tested seronegative in the CD20 antibody group and had a second negative IgG antibody test (n=6) were a median of 50 days (range 12-82 days) from COVID-19 diagnosis. The median time from diagnosis until a negative COVID-19 PCR test in CD20 antibody treated patients was 56 days (IQR 29-67.5) compared to 14 days (IQR 13-54) (p=0.037) in CD20 antibody naïve patients. Conclusion: Survival was poor in lymphoma patients with hypertension, diabetes, or age ≥ 70. The rate of seropositivity in patients treated with CD20 antibody therapy was significantly lower (12.5% vs 55%). Patients exposed to anti-CD20 therapy also required significantly more days to clear viral shedding (median 56 days vs 14 days). While limited by sample size, this study merits further validation and suggests anti-CD20 therapy may place lymphoma patients at higher risk of prolonged or repeated COVID-19 infection. Further investigations to determine infectivity of patients with prolonged SARS-CoV2 shedding are needed. Disclosures Mato: Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Adaptive: Consultancy, Research Funding; Loxo: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding. Leslie:Celgene/BMS: Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Speakers Bureau. Goy:Constellation: Research Funding; Genentech/Roche: Research Funding; Infinity: Research Funding; Karyopharm: Research Funding; Morphosys: Research Funding; AbbVie: Research Funding; MD Anderson: Research Funding; Regional Cancer Care Associates/OMI: Current Employment; Infinity Verastem: Research Funding; Xcenda: Consultancy; Hackensack UMC and University of Nebraska: Research Funding; COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding; Celgene: Honoraria, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; RCCA/OMI: Current Employment; PracticeUpdate Oncology: Consultancy; Bayer: Research Funding; CALBG: Research Funding. Feldman:Kyowa Kirin: Consultancy, Research Funding; Celgene: Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Portola: Research Funding; Takeda: Honoraria, Other: Travel expenses; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Corvus: Research Funding; Rhizen: Research Funding; Pfizer: Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Viracta: Research Funding; Trillium: Research Funding; Bayer: Consultancy, Honoraria; Pharmacyclics: Honoraria, Other, Speakers Bureau; Amgen: Research Funding; Eisai: Research Funding; Cell Medica: Research Funding; Abbvie: Honoraria.

As an intermediary between school and society, employment guidance plays an important role in promoting students' employment. With the rapid development of economy, the social requirements for the professional quality of students in higher vocational colleges are also higher and higher, which means that in higher vocational colleges, the cultivation of students' professional ability can not be ignored. This paper analyzes the role of counselors in the construction of teaching staff in employment guidance courses. Counselors are the main body of the current employment guidance teachers, and their employment guidance courses have their advantages and disadvantages. Counselors are strengthening their study, giving full play to their advantages and making up for their disadvantages. Schools should also set up teaching and research sections of employment guidance courses, and introduce training and incentive mechanisms to promote the construction of employment guidance teachers with counselors as the main body. Building a professional teaching staff of employment guidance course is the key to improve the teaching quality.

In this paper, we shed light on the impacts of the COVID-19 pandemic on the labor market, and how they have evolved over most of the year 2020. Relying primarily on microdata from the CPS and state-level data on virus caseloads, mortality, and policy restrictions, we consider a range of employment outcomes—including permanent layoffs, which generate large and lasting costs—and how these outcomes vary across demographic groups, occupations, and industries over time. We also examine how these employment patterns vary across different states, according to the timing and severity of virus caseloads, deaths, and closure measures. We find that the labor market recovery of the summer and early fall stagnated in late fall and early winter. As noted by others, we find low-wage and minority workers are hardest hit initially, but that recoveries have varied, and not always consistently, between Blacks and Hispanics. Statewide business closures and other restrictions on economic activity reduce employment rates concurrently, but do not seem to have lingering effects once relaxed. In contrast, virus deaths—but not caseloads—not only depress current employment, but produce accumulating harm. We conclude with policy options for states to repair their labor markets.