Tait Shanafelt

All Publications

Responsibilities and Job Characteristics of Health Care Chief Wellness Officers in the United States. Mayo Clinic proceedings Shanafelt, T., Farley, H., Wang, H., Ripp, J., CHARM CWO Network 2020; 95 (11): 2563–66
View details for DOI 10.1016/j.mayocp.2020.09.004

View details for PubMedID 33153644
In Reply to Egener. Academic medicine : journal of the Association of American Medical Colleges Ripp, J., Shanafelt, T. 2020; 95 (11): 1627–28
View details for DOI 10.1097/ACM.0000000000003668

View details for PubMedID 33109963
A national study of personal accomplishment, burnout, and satisfaction with work-life integration among advance practice nurses relative to other workers. Journal of the American Association of Nurse Practitioners Dyrbye, L. N., West, C. P., Kelsey, E. A., Gossard, A. A., Satele, D., Shanafelt, T. 2020
Abstract

BACKGROUND: There is a high prevalence of burnout among health care professionals, but little remains known about burnout and satisfaction with work-life integration (WLI) among advance practice nurses (APNs).PURPOSE: To evaluate burnout and satisfaction with WLI among APNs compared with other US workers.METHODS: A national sample of APNs and a probability-based sample of US workers completed a survey that measured burnout and satisfaction with WLI.RESULTS: Of the 976 (47%) APNs who completed the survey 64% had high personal accomplishment, 36.6% had symptoms of overall burnout, and 60.6% were satisfied with their WLI. In multivariable analysis, work hours (for each additional hour odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02-1.04, p < .001) and working in an outpatient setting (overall p = .03; referent hospital: outpatient, OR 1.80, 95% CI 1.17-2.18; other/unknown, OR 1.41, 95% CI 0.90-2.22, p = .13) were independently associated with having higher odds of burnout. Work hours were also independently associated with lower odds of satisfaction with WLI (for each additional hour OR 0.94, 95% CI 0.94-0.95, p < .001). Advance practice nurses were not more likely to have burnout or have greater struggles with WLI than other workers.IMPLICATIONS FOR PRACTICE: Findings from this study suggest APNs have high levels of personal accomplishment and a favorable occupational health profile. Advance practice nurses do not appear at higher risk of burnout or dissatisfaction with WLI than other US workers.

View details for DOI 10.1097/JXX.0000000000000517

View details for PubMedID 33105317
Relationship Between Burnout and Professional Behaviors and Beliefs Among US Nurses. Journal of occupational and environmental medicine Dyrbye, L., West, C. P., Hunderfund, A. L., Johnson, P., Cipriano, P., Peterson, C., Beatty, D., Major-Elechi, B., Shanafelt, T. 2020
Abstract

OBJECTIVE: To evaluate the relationship between burnout and professional behaviors and beliefs among US nurses.METHODS: We used data from 2256 nurses who completed a survey that included the Maslach Burnout Inventory and items exploring their professional conduct (documented something they had not done so they could 'close out' an encounter in the EHR or part of the assessment not completed, requested continuing education credit for an activity not attended) and beliefs about reporting impaired colleagues.RESULTS: On multivariable analysis, burnout was independently associated with higher odds of reporting 1 or more unprofessional behaviors in the last year and not believing nurses have a duty to report impairment among colleagues due to substance use or mental health problems.CONCLUSIONS: Occupational burnout is associated with self-reported unprofessional behaviors and less favorable beliefs about reporting impaired colleagues among nurses.

View details for DOI 10.1097/JOM.0000000000002014

View details for PubMedID 32868601
Hospice Employees' Perceptions of Their Work Environment: A Focus Group Perspective. International journal of environmental research and public health Lehto, R. H., Heeter, C., Forman, J., Shanafelt, T., Kamal, A., Miller, P., Paletta, M. 2020; 17 (17)
Abstract

Burnout in healthcare professionals can lead to adverse effects on physical and mental health, lower quality of care, and workforce shortages as employees leave the profession. Hospice professionals are thought to be at particularly high risk for burnout. The purpose of the study was to evaluate workplace perceptions of interdisciplinary hospice care workers who provide care to patients at end of life. Six focus groups and one semi-structured interview were conducted with mixed group of social workers, managers, nurses, hospice aides, chaplains, support staff, and a physician (n = 19). Findings from the groups depicted both rewards and challenges of hospice caregiving. Benefits included intrinsic satisfaction from the work, receiving positive patient and family feedback, and teamwork. Challenges reflected issues with workload, technology issues, administrative demands, travel-related problems, communication and interruptions, difficulties with taking time off from work and maintaining work-life integration, and coping with witnessing grief/loss. Hospice workers glean satisfaction from making meaningful differences in the lives of patients with terminal illness and their family members. It is an expected part of the job that certain patients and situations are particularly distressing; team support and targeted grief support is available for those times. Participants indicated that workload and administrative demands rather than dealing with death and dying were the biggest contributors to burnout. Participants reported episodic symptoms of burnout followed by deliberate steps to alleviate these symptoms. Notably, for all except one of the participants, burnout was cyclical. Symptoms would begin, they would take steps to deal with it (e.g., taking a mental health day), and they recovered. At an organizational level, a multipronged approach that includes both personal and occupational strategies is needed to support professional caregivers and help mitigate the stressors associated with hospice work.

View details for DOI 10.3390/ijerph17176147

View details for PubMedID 32847036
Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma amongst chronic lymphocytic leukemia patients. Journal of the American Academy of Dermatology Kleinstern, G., Rishi, A., Achenbach, S. J., Rabe, K. G., Kay, N. E., Shanafelt, T. D., Ding, W., Leis, J. F., Norman, A. D., Call, T. G., Cerhan, J. R., Parikh, S. A., Baum, C. L., Slager, S. L. 2020
Abstract

BACKGROUND: The incidence of cutaneous squamous cell carcinoma (SCC) in chronic lymphocytic leukemia (CLL) patients is significantly higher compared to age- and sex- matched controls.OBJECTIVE: To evaluate the association of factors associated with SCC risk.METHODS: Clinical CLL and SCC data were obtained from Mayo Clinic CLL resource and self-reported questionnaires among newly diagnosed CLL patients. We computed the CLL International Prognostic Index (CLL-IPI), from CLL prognostic factors, and a polygenetic risk score (PRS) from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).RESULTS: Among 1269 CLL patients, the median follow-up was 7 years, and 124 patients subsequently developed SCC. Significant associations with SCC risk were history of skin cancer (HR=4.80,CI:3.37-6.83), CLL-IPI (HR=1.42,CI:1.13-1.80), and PRS (HR=2.58,CI:1.50-4.43). In a multivariable model, these factors were independent predictors (c-statistic=0.69,CI:0.62-0.76). T-cell immunosuppressive treatments was also associated with SCC risk (HR=2.29,CI:1.47-3.55, adjusted for age, sex, and prior SCC).LIMITATIONS: Sample size decreases when combining all risk factors in a single model.CONCLUSION: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high-PRS. Future studies should develop prediction models that include these factors to improved screening guidelines.

View details for DOI 10.1016/j.jaad.2020.06.1024

View details for PubMedID 32682027
RESILIENCE AND BURNOUT AMONG PHYSICIANS AND THE GENERAL US WORKING POPULATION West, C. P., Dyrbye, L., Sinsky, C., Trockel, M., Tutty, M., Nedelec, L., Carlasare, L. E., Shanafelt, T. SPRINGER. 2020: S257
View details for Web of Science ID 000567143600578
Resilience and Burnout Among Physicians and the General US Working Population. JAMA network open West, C. P., Dyrbye, L. N., Sinsky, C., Trockel, M., Tutty, M., Nedelec, L., Carlasare, L. E., Shanafelt, T. D. 2020; 3 (7): e209385
Abstract

Importance: The prevalence of physician burnout is well documented, and resilience training has been proposed as an option to support physician well-being. However, the resilience of physicians compared with that of the US working population is not established, and the association between resilience and physician burnout is not well understood.Objectives: To evaluate resilience among physicians and US workers, and to determine the association between resilience and burnout among US physicians.Design, Setting, and Participants: A cross-sectional national survey study of 5445 US physicians and a probability-based sample of 5198 individuals in the US working population was conducted between October 12, 2017, and March 15, 2018.Main Outcomes and Measures: Resilience was measured using the 2-item Connor-Davidson Resilience Scale (total scores range from 0-8; higher scores indicate greater resilience); burnout was measured using the full Maslach Burnout Inventory with overall burnout indicated by a score of at least 27 on the 0 to 54 emotional exhaustion subscale and/or at least 10 on the depersonalization subscale (higher scores indicate greater burnout).Results: Of 30 456 physicians who received an invitation to participate, 5445 (17.9%) completed surveys (2995 men [62.1%]; median [IQR] age of 53 [42-62] years). In multivariable analysis, mean (SD) resilience scores were higher among physicians than the general employed population (6.49 [1.30] vs 6.25 [1.37]; adjusted mean difference, 0.25 points; 95% CI, 0.19-0.32; P<.001). Among physicians, resilience was associated with burnout. Physicians without overall burnout had higher mean (SD) resilience scores than physicians with burnout (6.82 [1.15] vs 6.13 [1.36]; adjusted mean difference, 0.68 points, 95% CI, 0.61-0.76; P<.001). Each 1-point increase in resilience score was associated with 36% lower odds of overall burnout (odds ratio, 0.64; 95% CI, 0.60-0.67; P<.001). However, 392 of 1350 physicians (29%) with the highest possible resilience score had burnout.Conclusions and Relevance: The findings of this national survey study suggest that physicians exhibited higher levels of resilience than the general working population in the US. Resilience was inversely associated with burnout symptoms, but burnout rates were substantial even among the most resilient physicians. Additional solutions, including efforts to address system issues in the clinical care environment, are needed to reduce burnout and promote physician well-being.

View details for DOI 10.1001/jamanetworkopen.2020.9385

View details for PubMedID 32614425
Describing the emotional exhaustion, depersonalization, and low personal accomplishment symptoms associated with Maslach Burnout Inventory subscale scores in US physicians: an item response theory analysis. Journal of patient-reported outcomes Brady, K. J., Ni, P., Sheldrick, R. C., Trockel, M. T., Shanafelt, T. D., Rowe, S. G., Schneider, J. I., Kazis, L. E. 2020; 4 (1): 42
Abstract

PURPOSE: Current US health policy discussions regarding physician burnout have largely been informed by studies employing the Maslach Burnout Inventory (MBI); yet, there is little in the literature focused on interpreting MBI scores. We described the burnout symptoms and precision associated with MBI scores in US physicians.METHODS: Using item response theory (IRT) analyses of secondary, cross-sectional survey data, we created response profiles describing the probability of burnout symptoms associated with US physicians' MBI emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA) subscale scores. Response profiles were mapped to raw subscale scores and used to predict symptom endorsements at mean scores and commonly used cut-points.RESULTS: The average US physician was likely to endorse feeling he/she is emotionally drained, used up, frustrated, and working too hard and all PA indicators once weekly or more but was unlikely to endorse feeling any DP symptoms once weekly or more. At the commonly used EE and DP cut-points of 27 and 10, respectively, a physician was unlikely to endorse feeling burned out or any DP symptoms once weekly or more. Each subscale assessed the majority of sample score ranges with ≥ 0.70 reliability.CONCLUSIONS: We produced a crosswalk mapping raw MBI subscale scores to scaled scores and response profiles calibrated in a US physician sample. Our results can be used to better understand the meaning and precision of MBI scores in US physicians; compare individual/group MBI scores against a reference population of US physicians; and inform the selection of subscale cut-points for defining categorical physician burnout outcomes.

View details for DOI 10.1186/s41687-020-00204-x

View details for PubMedID 32488344
Association of Perceived Electronic Health Record Usability With Patient Interactions and Work-Life Integration Among US Physicians. JAMA network open Melnick, E. R., Sinsky, C. A., Dyrbye, L. N., Trockel, M., West, C. P., Nedelec, L., Shanafelt, T. 2020; 3 (6): e207374
View details for DOI 10.1001/jamanetworkopen.2020.7374

View details for PubMedID 32568397
Advancing Physician Well-Being: A Population Health Framework. Mayo Clinic proceedings Trockel, M., Corcoran, D., Minor, L. B., Shanafelt, T. D. 2020
View details for DOI 10.1016/j.mayocp.2020.02.014

View details for PubMedID 32499127
Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib: risk prediction, management, and clinical outcomes. Annals of hematology Archibald, W. J., Rabe, K. G., Kabat, B. F., Herrmann, J., Ding, W., Kay, N. E., Kenderian, S. S., Muchtar, E., Leis, J. F., Wang, Y., Chanan-Khan, A. A., Schwager, S. M., Koehler, A. B., Fonder, A. L., Slager, S. L., Shanafelt, T. D., Call, T. G., Parikh, S. A. 2020
Abstract

BACKGROUND: Ibrutinib therapy is associated with an increased risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL). Risk assessment tools and outcomes of AF in these patients are not well described.METHODS: We performed a retrospective review of patients with CLL treated with ibrutinib at Mayo Clinic between October 2012 and November 2018.RESULTS: Two hundred ninety-eight patients were identified with a median time on ibrutinib of 19 months (range 0.23-69.7 months). Fifty-one patients developed treatment-emergent AF; the risk of treatment-emergent AF at 6 months, 1 year, and 2 years was 9%, 12%, and 16%, respectively. The following were associated with an increased risk of treatment-emergent AF on multivariable analyses: past history of AF (hazard ratio [HR] 3.5, p = 0.0072) and heart failure (HR 3.4, p = 0.0028). Most patients are able to continue ibrutinib therapy (dose reduced in 43%). Development of treatment-emergent AF was associated with shorter event-free survival (EFS; HR 2.0, p = 0.02) and shorter overall survival (OS; HR 3.2, p = 0.001), after adjusting for age, prior treatment status, TP53 disruption, heart failure, valvular disease, and past history of AF.CONCLUSIONS: Patient comorbidities, rather than CLL-related factors, predict risk of treatment-emergent AF in patients treated with ibrutinib. Although the vast majority of patients with treatment-emergent AF are able to continue ibrutinib (with dose reduction in 43%), treatment-emergent AF appears to be associated with worse outcomes, independent of other adverse prognostic factors.

View details for DOI 10.1007/s00277-020-04094-3

View details for PubMedID 32488603
Cause of death in patients with newly diagnosed chronic lymphocytic leukemia (CLL) stratified by the CLL-International Prognostic Index (CLL-IPI). Wang, Y., Achenbach, S. J., Rabe, K. G., Shanafelt, T. D., Call, T., Ding, W., Kenderian, S., Muchtar, E., Leis, J., Koehler, A., Schwager, S. M., Cerhan, J., Slager, S. L., Kay, N. E., Parikh, S. AMER SOC CLINICAL ONCOLOGY. 2020
View details for Web of Science ID 000560368303246
Burnout and satisfaction with work-life integration among PAs relative to other workers. JAAPA : official journal of the American Academy of Physician Assistants Dyrbye, L. N., West, C. P., Halasy, M., OʼLaughlin, D. J., Satele, D., Shanafelt, T. 2020; 33 (5): 35–44
Abstract

OBJECTIVE: To evaluate burnout and satisfaction with work-life integration among physician assistants (PAs) compared with other US workers.METHODS: We surveyed PAs and a probability-based sample of US workers. The survey included the Maslach Burnout Inventory and an item on satisfaction with work-life integration.RESULTS: Overall, 41.4% of PAs had burnout symptoms and 65.3% were satisfied with their work-life integration. In multivariable analysis, working in emergency medicine and dissatisfaction with control of workload and work-life integration were independently associated with having higher odds of burnout. PAs were more likely to have burnout than other workers but did not have greater struggles with work-life integration.CONCLUSION: Findings from this study suggest burnout and dissatisfaction with work-life integration are common. PAs appear at higher risk for burnout than workers in other fields.

View details for DOI 10.1097/01.JAA.0000660156.17502.e6

View details for PubMedID 32345947
The Health Care Chief Wellness Officer: What the Role Is and Is Not. Academic medicine : journal of the Association of American Medical Colleges Ripp, J., Shanafelt, T. 2020
Abstract

Occupational distress among clinicians and its impact on quality of care is a major threat to the health care delivery system. To address threats to clinician well-being, many institutions have introduced a new senior leadership position-the health care chief wellness officer (CWO). This role is distinct from CWOs or other wellness leadership positions that have historically existed outside of medicine. The health care CWO role was established to reduce widespread occupational distress in clinicians by improving the work environment rather than by promoting health behaviors to reduce health insurance costs. A complex array of system-level drivers has contributed to clinician distress. Developing and overseeing the execution of a strategy to address these challenges and working in partnership with other operational leaders to improve well-being require a correctly placed senior leader with the appropriate authority and resources, such as a CWO.Health care CWOs must focus primarily on improving their organizations' work environment and culture, not on developing individual-level interventions, such as personal resilience, mindfulness, and self-care offerings. The goal of this work is to address what is wrong with the practice environment, not to make individuals better able to tolerate a broken system. Metrics to evaluate organizational progress as well as the efficacy of the health care CWO and his or her team are discussed in this Perspective. Occupational distress in clinicians is widespread and has implications for quality of care. Vanguard organizations have begun to put into place the leaders, infrastructure, and improvement teams necessary to address this issue. The health care CWO plays a critical role in the effectiveness of these efforts.

View details for DOI 10.1097/ACM.0000000000003433

View details for PubMedID 32324635
Fortifying Our Teams to Best Serve Our Patients: A Report of the 2019 Summer Intersociety Meeting. Journal of the American College of Radiology : JACR Kruskal, J., Meltzer, C. C., Shanafelt, T., Gupta, S., Rawson, J., Deitte, L., Gibbs, I., Raybon, C., West, D., Canon, C. 2020
Abstract

Continuing the thematic focus on fostering wellness and professional fulfillment in our workplace, the 2019 Radiology Intersociety Committee Conference focused on understanding and leading multigenerational workforces and developing high-functioning teams. To lead a multigenerational workforce and to understand and embrace traditional versus emerging cultures in our workplace, effective leaders should foster diversity of their teams. Sustaining such teams requires an understanding of different styles and preferences for bidirectional communication and clarity of information sharing and learning; active efforts may be needed to focus on practical approaches to succession planning, breaking down traditional hierarchies, clarifying role delineation, and managing authority gradients. An effective team requires attention to the well-being of team members and professional behavior in and out of the workplace. Conference participants unanimously endorsed multi-organizational support statements and activities assuring professional behavior of their members, along with the desire to explore codes of conduct and ethics.

View details for DOI 10.1016/j.jacr.2020.03.007

View details for PubMedID 32289282
Original Research: An Investigation of Career Choice Regret Among American Nurses. The American journal of nursing Dyrbye, L., West, C., Johnson, P., Cipriano, P., Peterson, C., Beatty, D., Major-Elechi, B., Shanafelt, T. 2020; 120 (4): 24–33
Abstract

PURPOSE: To explore whether burnout is an independent predictor of career choice regret among nurses.METHODS: In November 2017 we invited a random sample of 89,995 members of the American Nurses Association to participate in an anonymous online survey. The survey collected demographic and professional information and included the Maslach Burnout Inventory-Human Services Survey for Medical Personnel (known as the MBI-HSS [MP]), as well as several items exploring career choice regret. Of the 86,858 nurses who received the e-mail invitation, 8,638 (9.9%) responded. Multivariable logistic regression analysis was conducted for the final sample of 6,933 nurses who provided complete responses to the MBI-HSS (MP) and the career choice regret survey items.RESULTS: Fifteen percent of the 6,933 participating nurses had career choice regret. On multivariable analysis, experiencing burnout, working unplanned or mandatory overtime, being male, and having a higher academic degree related to nursing were independent predictors of career choice regret. Burnout was the strongest such predictor.CONCLUSION: Career choice regret among U.S. nurses is relatively common. Of the independent predictors this study identified, burnout had the strongest relationship with career choice regret. Organizational strategies aimed at reducing burnout and supporting nurses' ongoing professional development should be pursued.

View details for DOI 10.1097/01.NAJ.0000660020.17156.ae

View details for PubMedID 32218044
Association of Occupational Distress and Sleep-Related Impairment in Physicians With Unsolicited Patient Complaints. Mayo Clinic proceedings Welle, D., Trockel, M. T., Hamidi, M. S., Hickson, G. B., Menon, N. K., Shanafelt, T. D., Cooper, W. O. 2020; 95 (4): 719–26
Abstract

OBJECTIVE: To study the relationship between occupational distress and sleep-related impairment in physicians and unsolicited patient complaints.PARTICIPANTS AND METHODS: We used deidentified data from an academic medical center's physician survey administered in April and May of 2013 to perform a retrospective cohort study. Third-party stewards of the identifiable information regarding unsolicited patient complaints from January 1, 2013, through December 31, 2016, matched these data with corresponding physicians' occupational distress data. Unsolicited patient complaints were used to calculate the Patient Advocacy Reporting System (PARS) score, a validated predictor of malpractice litigation risk and clinical outcomes. Physicians were grouped into 1 of 3 PARS risk categories based on previously defined thresholds: low risk (score of 0), intermediate risk (score of 1-12), or high risk (score ≥13).RESULTS: Each 1-point increase in burnout and sleep-related impairment, on a 5-point scale, was associated with a 69% (odds ratio [OR], 1.69; 95% CI, 1.12-2.54) and 49% (OR, 1.49; 95% CI, 1.08-2.05) increased odds of being in the next higher PARS risk category, respectively, averaged across all 4 years. Professional fulfillment was a protective factor, associated with fewer unsolicited patient complaints. Each 1-point decrease in professional fulfillment was associated with a 68% (OR, 1.68; 95% CI, 1.16-2.44) increased odds of being in the next higher PARS risk category. The effect of depression on PARS risk category was not significant (OR, 1.33; 95% CI, 0.84-2.10).CONCLUSION: Findings from this research suggest that occupational distress and sleep-related impairment in physicians are associated with unsolicited patient complaints.

View details for DOI 10.1016/j.mayocp.2019.09.025

View details for PubMedID 32247345
The impact of dose modification and temporary interruption of ibrutinib on outcomes of chronic lymphocytic leukemia patients in routine clinical practice. Cancer medicine Parikh, S. A., Achenbach, S. J., Call, T. G., Rabe, K. G., Ding, W., Leis, J. F., Kenderian, S. S., Chanan-Khan, A. A., Koehler, A. B., Schwager, S. M., Muchtar, E., Fonder, A. L., McCullough, K. B., Nedved, A. N., Smith, M. D., Slager, S. L., Kay, N. E., Finnes, H. D., Shanafelt, T. D. 2020
Abstract

To study the impact of dose modification and temporary interruption of ibrutinib in routine clinical practice, we conducted a retrospective study of consecutive CLL patients treated with ibrutinib outside the context of a clinical trial at Mayo Clinic, (Rochester, MN) from 11/2013 to 12/2017. Of 209 patients, 131 (74%) had unmutated IGHV, 38 (20%) had TP53 disruption, and 47 (22%) were previously untreated. A total of 87/209 (42%) patients started reduced dose ibrutinib (<420mg daily; n=43, physician preference; n=33, concomitant medications; and n=11, other). During 281 person-years of treatment, 91/209 patients had temporary dose interruption (54%, nonhematologic toxicity; 29%, surgical procedures; 10%, hematologic toxicity; and 7%, other). After a median follow-up of 24months, the estimated median event-free survival (EFS) was 36months, and median overall survival (OS) was not reached. On multivariable analyses, temporary ibrutinib interruption (hazard ratio [HR]: 2.37, P=.006) and TP53 disruption at ibrutinib initiation (HR: 1.81, P=.048) were associated with shorter EFS, whereas only TP53 disruption (HR: 2.38, P=.015) was associated with shorter OS. Initial ibrutinib dose and dose modification during therapy did not appear to impact EFS or OS. These findings illustrate the challenges associated with continuous oral therapy with ibrutinib in patients with CLL.

View details for DOI 10.1002/cam4.2998

View details for PubMedID 32187452
Risk of serious infection among individuals with and without low count monoclonal B-cell lymphocytosis (MBL). Leukemia Shanafelt, T. D., Kay, N. E., Parikh, S. A., Achenbach, S. J., Lesnick, C. E., Hanson, C. A., Kleinstern, G., Olson, J. E., Norman, A. D., Rabe, K. G., Schwager, S. M., Call, T. G., Slager, S. L. 2020
View details for DOI 10.1038/s41375-020-0799-8

View details for PubMedID 32203143
The etiology of pleural effusions requiring thoracentesis in patients with chronic lymphocytic leukemia (CLL) Koehler, A., Ayed, A., Albitar, H., Call, T., Rabe, K., Ding, W., Kenderian, S., Leis, J., Muchtar, E., Hayman, S., Fonder, A., Schwager, S., Slager, S., Pinto, C., Kay, N., Shanafelt, T., Iyer, V., Parikh, S. TAYLOR & FRANCIS LTD. 2020: 229–31
View details for Web of Science ID 000534385400161
Targeted therapy in relapsed/refractory CLL: a systematic review and network meta-analysis Molica, S., Giannareli, D., Shanafelt, T. TAYLOR & FRANCIS LTD. 2020: 189–91
View details for Web of Science ID 000534385400134
Metrics for assessing physician activity using electronic health record log data. Journal of the American Medical Informatics Association : JAMIA Sinsky, C. A., Rule, A., Cohen, G., Arndt, B. G., Shanafelt, T. D., Sharp, C. D., Baxter, S. L., Tai-Seale, M., Yan, S., Chen, Y., Adler-Milstein, J., Hribar, M. 2020
Abstract

Electronic health record (EHR) log data have shown promise in measuring physician time spent on clinical activities, contributing to deeper understanding and further optimization of the clinical environment. In this article, we propose 7 core measures of EHR use that reflect multiple dimensions of practice efficiency: total EHR time, work outside of work, time on documentation, time on prescriptions, inbox time, teamwork for orders, and an aspirational measure for the amount of undivided attention patients receive from their physicians during an encounter, undivided attention. We also illustrate sample use cases for these measures for multiple stakeholders. Finally, standardization of EHR log data measure specifications, as outlined here, will foster cross-study synthesis and comparative research.

View details for DOI 10.1093/jamia/ocz223

View details for PubMedID 32027360
Address Physician Burnout By Restoring Control of Health Care to Physicians-Reply. JAMA internal medicine Dyrbye, L. N., Shanafelt, T. D., West, C. P. 2020; 180 (2): 334–35
View details for DOI 10.1001/jamainternmed.2019.6004

View details for PubMedID 32011636
Developing institutional infrastructure for physician wellness: qualitative Insights from VA physicians. BMC health services research Schwartz, R., Shanafelt, T. D., Gimmler, C., Osterberg, L. 2020; 20 (1): 7
Abstract

The prevalence and detrimental effect of physician burnout requires new strategies for supporting physicians. In this project, we describe the development, and assessment, of a "Balint-like" physician support group that provided social cohesion and delivered novel didactic curricula for building resilience.The project began with a nine-month facilitated peer-support group for physicians that met every other week. Based on input from the first group, tailored content was developed to address physician wellness needs. These curricula were delivered to participants in the second nine-month Balint-like group. We then conducted semi-structured interviews with 7 hospitalists and 2 outpatient primary care physicians who participated in the Balint-like groups to explore the intervention's value and to identify remaining unmet physician wellness needs. Using an inductive thematic analysis approach, we identified a set of institutional-, community- and individual-level factors affecting physician wellness and corresponding intervention opportunities.Physicians spoke of systems-level factors that contributed to distress, and proposed infrastructure, both physical and procedural, that they felt could better support physician wellness. They highlighted the emotional challenges of daily work, and the need for a forum by which to process these interactions in order to maintain their own wellness. Participants reported that participation in Balint-like groups provided this forum and served to help the physicians normalize struggles, reduce isolation and provide new strategies for navigating challenging interactions.Institutional infrastructure, in the form of regular, psychologically-safe forums for processing with peers and learning relational strategies for preserving wellness, may mitigate physician distress. This project provides a model for how to develop and deliver a low-cost physician wellness program that can be tailored to the needs of individual clinical units.

View details for DOI 10.1186/s12913-019-4783-9

View details for PubMedID 31900137
Development of a conceptual model for understanding the learning environment and surgical resident well-being. American journal of surgery Zhang, L. M., Cheung, E. O., Eng, J. S., Ma, M., Etkin, C. D., Agarwal, G., Shanafelt, T. D., Riall, T. S., Nasca, T., Bilimoria, K. Y., Hu, Y. Y., Johnson, J. K. 2020
Abstract

Surgeon burnout is linked to poor outcomes for physicians and patients. Several conceptual models exist that describe drivers of physician wellness generally. No such model exists for surgical residents specifically.A conceptual model for surgical resident well-being was adapted from published models with input gained iteratively from an interdisciplinary team. A survey was developed to measure residents' perceptions of their program. A confirmatory factor analysis (CFA) tested the fit of our proposed model construct.The conceptual model outlines eight domains that contribute to surgical resident well-being: Efficiency and Resources, Faculty Relationships and Engagement, Meaning in Work, Resident Camaraderie, Program Culture and Values, Work-Life Integration, Workload and Job Demands, and Mistreatment. CFA demonstrated acceptable fit of the proposed 8-domain model.Eight distinct domains of the learning environment influence surgical resident well-being. This conceptual model forms the basis for the SECOND Trial, a study designed to optimize the surgical training environment and promote well-being.

View details for DOI 10.1016/j.amjsurg.2020.10.026

View details for PubMedID 33121657
Promoting Oncologist Well-Being to Foster Delivery of Ethical, High-Quality Cancer Care: Priorities for 2020 and Beyond. JCO oncology practice Shanafelt, T. D., Kamal, A. H., Hlubocky, F. J. 2020; 16 (4): 188–90
View details for DOI 10.1200/OP.20.00069

View details for PubMedID 32275849
Socioeconomic Factors Associated With Burnout Among Oncology Trainees. JCO oncology practice Ahmed, A. A., Ramey, S. J., Dean, M. K., Takita, C., Schwartz, D., Wilson, L. D., Vapiwala, N., Thomas, C. R., Shanafelt, T. D., Deville, C., Jagsi, R., Holliday, E. 2020; 16 (4): e415–e424
Abstract

Burnout in the medical workforce leads to early retirement, absenteeism, career changes, financial losses for medical institutions, and adverse outcomes for patients. Recent literature has explored burnout in different specialties of medicine. This article examines burnout among medical oncology trainees and identifies factors associated with burnout and professional dissatisfaction, including socioeconomic factors.US medical oncology programs were sent a survey that included the Maslach Burnout Index-Human Services Survey as well as demographic, socioeconomic, and program-specific questions tailored to medical oncology fellowship. Primary binary end points included burnout, satisfaction with being a physician, and satisfaction with being a medical oncologist. Binomial logistic models determined associations between various characteristics and end points.Overall, 261 US fellows completed the survey. Seventy percent of international medical graduates reported no educational debt, whereas only 36% of US graduates reported no educational debt. Eighty-two percent of survey respondents reported their mother had at least a bachelor's degree, and 87% of respondents reported their father had at least a bachelor's degree. At least 27% of respondents had symptoms of burnout. Factors inversely associated with burnout on multivariable analysis included having a mother who graduated college (odds ratio [OR], 0.27), reporting an adequate perceived balance between work and personal life (OR, 0.22), feeling that faculty care about educational success (OR, 0.16), and being in the final year of training (OR, 0.45). Having debt ≥ $150,000 (OR, 2.14) was directly associated with burnout.Symptoms of burnout are common among medical oncology fellows and are associated with educational debt and socioeconomic factors.

View details for DOI 10.1200/JOP.19.00703

View details for PubMedID 32275851
Tumor mutational load predicts time to first treatment in chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis beyond the CLL international prognostic index. American journal of hematology Kleinstern, G., O'Brien, D. R., Li, X., Tian, S., Kabat, B. F., Rabe, K. G., Norman, A. D., Yan, H., Vachon, C. M., Boddicker, N. J., Call, T. G., Parikh, S. A., Bruins, L., de Campos, C. B., Leis, J. F., Shanafelt, T. D., Ding, W., Cerhan, J. R., Kay, N. E., Slager, S. L., Braggio, E. 2020
Abstract

Next-generation sequencing identified ~60 genes recurrently mutated in chronic lymphocytic leukemia (CLL). We examined the additive prognostic value of the total number of recurrently mutated CLL genes [i.e., tumor mutational load (TML)] or the individually mutated genes beyond the CLL international prognostic index (CLL-IPI) in newly diagnosed CLL and high-count monoclonal B-cell lymphocytosis (HC MBL). We sequenced 59 genes among 557 individuals (112 HC MBL/445 CLL) in a multi-stage design, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time-to-first treatment (TTT), adjusted for CLL-IPI and sex. TML was associated with shorter TTT in the discovery and validation cohorts, with a combined estimate of continuous HR=1.27 (CI:1.17-1.39, P=2.6x10-8 ; c-statistic=0.76). When stratified by CLL-IPI, the association of TML with TTT was stronger and validated within low/intermediate risk (combined HR=1.54, CI:1.37-1.72, P=7.0x10-14 ). Overall, 80% of low/intermediate CLL-IPI cases with 2+ mutated genes progressed to require therapy within 5 years, compared to 24% among those without mutations. TML was also associated with shorter TTT in the HC MBL cohort (HR=1.53, CI:1.12-2.07, P=0.007; c-statistic=0.71). TML is a strong prognostic factor for TTT independent of CLL-IPI, especially among low/intermediate CLL-IPI risk and a better predictor than any single gene. Mutational screening at early stages may improve risk stratification and better predict TTT. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ajh.25831

View details for PubMedID 32279347
A Call to Action: Ethics Committee Roundtable Recommendations for Addressing Burnout and Moral Distress in Oncology. JCO oncology practice Hlubocky, F. J., Taylor, L. P., Marron, J. M., Spence, R. A., McGinnis, M. M., Brown, R. F., McFarland, D. C., Tetzlaff, E. D., Gallagher, C. M., Rosenberg, A. R., Popp, B., Dragnev, K., Bosserman, L. D., Dudzinski, D. M., Smith, S., Chatwal, M., Patel, M. I., Markham, M. J., Levit, K., Bruera, E., Epstein, R. M., Brown, M., Back, A. L., Shanafelt, T. D., Kamal, A. H. 2020: JOP1900806
Abstract

Oncologist well-being is critical to initiating and maintaining the physician-patient relationship, yet many oncologists suffer from symptoms of burnout. Burnout has been linked to poor physical and mental health, as well as increased medical errors, patient dissatisfaction, and workforce attrition. In this Call to Action article, we discuss causes of and interventions for burnout and moral distress in oncology, highlight existing interventions, and provide recommendations for addressing burnout and improving well-being at the individual and organizational levels to deliver ethical, quality cancer care.

View details for DOI 10.1200/JOP.19.00806

View details for PubMedID 32223701
Pandemic-Driven Posttraumatic Growth for Organizations and Individuals. JAMA Olson, K., Shanafelt, T., Southwick, S. 2020
View details for DOI 10.1001/jama.2020.20275

View details for PubMedID 33034630
Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1/PD-1 immunotherapy. Blood Ioannou, N., Hagner, P. R., Stokes, M., Gandhi, A. K., Apollonio, B., Fanous, M., Papazoglou, D., Sutton, L. A., Rosenquist, R., Amini, R. M., Chiu, H., Lopez-Girona, A., Janardhanan, P., Awan, F. T., Jones, J. A., Kay, N. E., Shanafelt, T. D., Tallman, M. S., Stamatopoulos, K., Patten, P. E., Vardi, A., Ramsay, A. G. 2020
Abstract

Cancer treatment has been transformed by checkpoint blockade therapies, with the highest anti-tumor activity of anti-programmed death 1 (PD-1) antibody therapy seen in Hodgkin lymphoma (HL). Disappointingly, response rates have been low in the non-Hodgkin lymphomas (NHLs), with no activity seen in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) with PD-1 blockade. Thus, identifying more powerful combination therapy is required for these patients. Here, we pre-clinically demonstrate enhanced anti-CLL activity following combinational therapy with anti-PD-1 or anti-PD-1 ligand (PD-L1) and avadomide, a cereblon E3 ligase modulator (CELMoD). Avadomide induced type I and II interferon (IFN) signaling in patient T cells, triggering a feedforward cascade of reinvigorated T cell responses. Immune modeling assays demonstrated that avadomide stimulated T cell activation, chemokine expression, motility and lytic synapses with CLL cells, as well as IFN-inducible feedback inhibition through upregulation of PD-L1. Patient-derived xenograft tumors treated with avadomide were converted to CD8+ T cell-inflamed tumor microenvironments (TMEs) that responded to anti-PD-L1/PD-1-based combination therapy. Notably, clinical analyses showed increased PD-L1 expression on T cells, as well as intratumoral expression of chemokine signaling genes in B cell malignancy patients receiving avadomide-based therapy. These data illustrate the importance of overcoming a low inflammatory T cell state to successfully sensitize CLL to checkpoint blockade-based combination therapy.

View details for DOI 10.1182/blood.2020006073

View details for PubMedID 33024998
Developing institutional infrastructure for physician wellness: qualitative Insights from VA physicians BMC Health Services Research Schwartz, R., Shanafelt, T. D., Gimmler, C., Osterberg, L. 2020; 20 (7)
View details for DOI 10.1186/s12913-019-4783-9
Disparities in Burnout and Satisfaction With Work-Life Integration in U.S. Physicians By Gender and Practice Setting. Academic medicine : journal of the Association of American Medical Colleges Marshall, A. L., Dyrbye, L. N., Shanafelt, T. D., Sinsky, C. A., Satele, D., Trockel, M., Tutty, M., West, C. P. 2020
Abstract

To explore the interaction between practice setting (academic practice [AP], private practice [PP]) and gender in relation to physician burnout and satisfaction with work-life integration (WLI).In 2017, the authors administered a cross-sectional survey of U.S. physicians and characterized rates of burnout and satisfaction with WLI using previously validated and/or standardized tools. They conducted multivariable logistic regression to determine the interaction between the included variables.Of the 3,603 participants in the final analysis, female physicians reported a higher prevalence of burnout than male physicians in both AP (50.7% vs 38.2%, P < .0001) and PP (48.1% vs 40.7%, P = .001). However, the multivariable analysis found no statistically significant gender-based differences in burnout (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.76 - 1.17, P = .60). Women and men in AP were less likely to report burnout than men in PP (OR 0.70, 95% CI 0.52 - 0.94, P = .01 and OR 0.69, 95% CI 0.53 - 0.90, P < .01, respectively); women in PP did not report different burnout rates from men in PP (OR 0.89, 95% CI 0.68 - 1.16, P = .38). Women in both AP and PP were less likely to be satisfied with WLI than men in PP (OR 0.62, 95% CI 0.47 - 0.83, P < .01 and OR 0.75, 95% CI 0.58 - 0.97, P = .03, respectively); men in AP did not report different satisfaction with WLI than men in PP (OR 1.05, 95% CI 0.82 - 1.33, P = .71).Gender differences in rates of burnout are related to practice setting and other differences in physicians' personal and professional lives. These results highlight the complex relationships among gender, practice setting, and other personal and professional factors in their influence on burnout and satisfaction with WLI.

View details for DOI 10.1097/ACM.0000000000003521

View details for PubMedID 32459677
Association of Burnout, Professional Fulfillment, and Self-care Practices of Physician Leaders With Their Independently Rated Leadership Effectiveness. JAMA network open Shanafelt, T. D., Makowski, M. S., Wang, H., Bohman, B., Leonard, M., Harrington, R. A., Minor, L., Trockel, M. 2020; 3 (6): e207961
Abstract

Although leadership behavior of physician supervisors is associated with the occupational well-being of the physicians they supervise, the factors associated with leadership behaviors are poorly understood.To evaluate the associations between burnout, professional fulfillment, and self-care practices of physician leaders and their independently assessed leadership behavior scores.This survey study of physicians and physician leaders at Stanford University School of Medicine (n = 1924) was conducted from April 1 to May 13, 2019. The survey included assessments of professional fulfillment, self-valuation, sleep-related impairment, and burnout. Physicians also rated the leadership behaviors of their immediate physician supervisors using a standardized assessment. Leaders' personal well-being metrics were paired with their leadership behavior scores as rated by the physicians they supervised. All assessment scores were converted to a standardized scale (range, 0-10). Data were analyzed from October 20, 2019, to March 10, 2020.Association between leaders' own well-being scores and their independently assessed leadership behavior.Of 1924 physicians invited to participate, 1285 (66.8%) returned surveys, including 67 of 117 physician leaders (57.3%). Among these respondents, 651 (50.7%) were women and 729 (56.7%) were 40 years or older. Among the 67 leaders, 57 (85.1%) had their leadership behaviors evaluated by at least 5 physicians (median, 11 [interquartile range, 9-15]) they supervised. Overall, 9.8% of the variation in leaders' aggregate leadership behavior scores was associated with their own degree of burnout. In models adjusted for age and sex, each 1-point increase in burnout score of the leaders was associated with a 0.19-point decrement in leadership behavior score (β = -0.19; 95% CI, -0.35 to -0.03; P = .02), whereas each 1-point increase in their professional fulfillment and self-valuation scores was associated with a 0.13-point (β = 0.13; 95% CI, 0.01-0.26; P = .03) and 0.15-point (β = 0.15; 95% CI, 0.02-0.29; P = .03) increase in leadership behavior score, respectively. Each 1-point increase in leaders' sleep-related impairment was associated with a 0.15-point increment in sleep-related impairment among those they supervised (β = 0.15; 95% CI, 0.02-0.29; P = .03). The associations between leaders' well-being scores in other dimensions and the corresponding well-being measures of those they supervised were not significant.In this survey study, burnout, professional fulfillment, and self-care practices of physician leaders were associated with their independently assessed leadership effectiveness. Training, skill building, and support to improve leader well-being should be considered a dimension of leadership development rather than simply a dimension of self-care.

View details for DOI 10.1001/jamanetworkopen.2020.7961

View details for PubMedID 32543700
Understanding and Addressing Sources of Anxiety Among Health Care Professionals During the COVID-19 Pandemic. JAMA Shanafelt, T., Ripp, J., Trockel, M. 2020
View details for DOI 10.1001/jama.2020.5893

View details for PubMedID 32259193
Burnout, Depression, Career Satisfaction, and Work-Life Integration by Physician Race/Ethnicity. JAMA network open Garcia, L. C., Shanafelt, T. D., West, C. P., Sinsky, C. A., Trockel, M. T., Nedelec, L., Maldonado, Y. A., Tutty, M., Dyrbye, L. N., Fassiotto, M. 2020; 3 (8): e2012762
Abstract

Previous research suggests that the prevalence of occupational burnout varies by demographic characteristics, such as sex and age, but the association between physician race/ethnicity and occupational burnout is less well understood.To investigate possible differences in occupational burnout, depressive symptoms, career satisfaction, and work-life integration by race/ethnicity in a sample of US physicians.In this cross-sectional study, data for this secondary analysis of 4424 physicians were originally collected from a cross-sectional survey of US physicians between October 12, 2017, and March 15, 2018. The dates of analysis were March 8, 2019, to May 21, 2020. Multivariable logistic regression, including statistical adjustment for physician demographic and clinical practice characteristics, was performed to examine the association between physician race/ethnicity and occupational burnout, depressive symptoms, career satisfaction, and work-life integration.Physician demographic and clinical practice characteristics included race/ethnicity, sex, age, clinical specialty, hours worked per week, primary practice setting, and relationship status.Physicians with a high score on the emotional exhaustion or depersonalization subscale of the Maslach Burnout Inventory were classified as having burnout. Depressive symptoms were measured using the Primary Care Evaluation of Mental Disorders instrument. Physicians who marked "strongly agree" or "agree" in response to the survey items "I would choose to become a physician again" and "My work schedule leaves me enough time for my personal/family life" were considered to be satisfied with their career and work-life integration, respectively.Data were available for 4424 physicians (mean [SD] age, 52.46 [12.03] years; 61.5% [2722 of 4424] male). Most physicians (78.7% [3480 of 4424]) were non-Hispanic White. Non-Hispanic Asian, Hispanic/Latinx, and non-Hispanic Black physicians comprised 12.3% (542 of 4424), 6.3% (278 of 4424), and 2.8% (124 of 4424) of the sample, respectively. Burnout was observed in 44.7% (1540 of 3447) of non-Hispanic White physicians, 41.7% (225 of 540) of non-Hispanic Asian physicians, 38.5% (47 of 122) of non-Hispanic Black physicians, and 37.4% (104 of 278) of Hispanic/Latinx physicians. The adjusted odds of burnout were lower in non-Hispanic Asian physicians (odds ratio [OR], 0.77; 95% CI, 0.61-0.96), Hispanic/Latinx physicians (OR, 0.63; 95% CI, 0.47-0.86), and non-Hispanic Black physicians (OR, 0.49; 95% CI, 0.30-0.79) compared with non-Hispanic White physicians. Non-Hispanic Black physicians were more likely to report satisfaction with work-life integration compared with non-Hispanic White physicians (OR, 1.69; 95% CI, 1.05-2.73). No differences in depressive symptoms or career satisfaction were observed by race/ethnicity.Physicians in minority racial/ethnic groups were less likely to report burnout compared with non-Hispanic White physicians. Future research is necessary to confirm these results, investigate factors contributing to increased rates of burnout among non-Hispanic White physicians, and assess factors underlying the observed patterns in measures of physician wellness by race/ethnicity.

View details for DOI 10.1001/jamanetworkopen.2020.12762

View details for PubMedID 32766802
Personal-Professional Boundaries and Ethical Issues in Palliative Care AMERICAN JOURNAL OF BIOETHICS Swetz, K. M., Frazier, S. L., Richardson, J. W., Shanafelt, T. D. 2019; 19 (12): 60–62
View details for DOI 10.1080/15265161.2019.1675800

View details for Web of Science ID 000497266300019
Relationship Between Burnout, Professional Behaviors, and Cost-Conscious Attitudes Among US Physicians. Journal of general internal medicine Dyrbye, L. N., West, C. P., Hunderfund, A. L., Sinsky, C. A., Trockel, M., Tutty, M., Carlasare, L., Satele, D., Shanafelt, T. 2019
Abstract

BACKGROUND: Despite the importance of professionalism, little is known about how burnout relates to professionalism among practicing physicians.OBJECTIVE: To evaluate the relationship between burnout and professional behaviors and cost-conscious attitudes.DESIGN AND PARTICIPANTS: Cross-sectional study in a national sample of physicians of whom a fourth received a sub-survey with items exploring professional behaviors and cost-conscious attitudes. Responders who were not in practice or in select specialties were excluded.MEASURES: Maslach Burnout Inventory and items on professional behaviors and cost-conscious attitudes.KEY RESULTS: Among those who received the sub-survey 1008/1224 (82.3%) responded, and 801 were eligible for inclusion. Up to one third of participants reported engaging in unprofessional behaviors related to administrative aspects of patient care in the last year, such as documenting something they did not do to close an encounter in the medical record (243/759, 32.0%). Fewer physicians reported other dishonest behavior (e.g., claiming unearned continuing medical education credit; 40/815, 4.9%). Most physicians endorsed cost-conscious attitudes with over 75% (618/821) agreeing physicians have a responsibility to try to control health-care costs and 62.9% (512/814) agreeing that cost to society is important in their care decisions regarding use of an intervention. On multivariable analysis adjusting for personal and professional characteristics, burnout was independently associated with reporting 1 or more unprofessional behaviors (OR 2.01, 95%CI 1.47-2.73, p < 0.0001) and having less favorable cost-conscious attitudes (difference on 6-24 scale - 0.90, 95%CI - 1.44 to - 0.35, p = 0.001).CONCLUSIONS: Professional burnout is associated with self-reported unprofessional behaviors and less favorable cost-conscious attitudes among physicians.

View details for DOI 10.1007/s11606-019-05376-x

View details for PubMedID 31734790
Comparison of venetoclax plus rituximab with B-cell receptor inhibitors in patients with relapsed/refractory chronic lymphocytic leukemia: a systematic review and network Meta-analysis. Leukemia & lymphoma Molica, S., Giannarelli, D., Shanafelt, T. D. 2019: 1–4
View details for DOI 10.1080/10428194.2019.1691193

View details for PubMedID 31724894
Letter to the Editor regarding "Prevalence and Predictors of Burnout Among Hospice and Palliative Care Professionals from 2016 Apr;51(4):690-6. Journal of pain and symptom management Kamal, A., Bull, J. H., Wolf, S. P., Swetz, K. M., Shanafelt, T. D., Ast, K., Kavalieratos, D., Sinclair, C. T. 2019
View details for DOI 10.1016/j.jpainsymman.2019.11.001

View details for PubMedID 31734409
Ibrutinib and Rituximab Provides Superior Clinical Outcome Compared to FCR in Younger Patients with Chronic Lymphocytic Leukemia (CLL): Extended Follow-up from the E1912 Trial. Blood Shanafelt, T. D., Wang, V., Kay, N. E., Hanson, C. A., O'Brien, S. M., Barrientos, J. C., Jelinek, D. F., Braggio, E., Leis, J. F., Zhang, C. C., Coutre, S., Barr, P. M., Cashen, A. F., Mato, A. R., Singh, A., Mullane, M. P., Little, R. F., Erba, H. P., Stone, R. M., Litzow, M., Tallman, M. S. 2019; 134 (Supplement_1): 33
Abstract

DISCLOSURES: Shanafelt: Pharmacyclics: Research Funding; Patent: Patents & Royalties: US14/292,075 on green tea extract epigallocatechin gallate in combination with chemotherapy for chronic lymphocytic leukemia; Polyphenon E International: Research Funding; Merck: Research Funding; Abbvie: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Glaxo-SmithKline: Research Funding; Hospira: Research Funding; Cephalon: Research Funding. Kay:MorphoSys: Other: Data Safety Monitoring Board; Infinity Pharmaceuticals: Other: DSMB; Celgene: Other: Data Safety Monitoring Board; Agios: Other: DSMB. O'Brien:Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Astellas: Consultancy; Aptose Biosciences, Inc: Consultancy; Amgen: Consultancy; Alexion: Consultancy; Acerta: Research Funding; Eisai: Consultancy; Gilead: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Verastem: Consultancy; Celgene: Consultancy; Sunesis: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; Regeneron: Research Funding; Kite: Research Funding. Barrientos:AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy; Genentech: Consultancy; Bayer: Consultancy; Gilead: Consultancy; Janssen: Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Sandoz: Consultancy; Oncternal Therapeutics: Research Funding. Coutre:Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Research Funding; Gilead: Research Funding; BeiGene: Other: Travel, Accommodations, Expenses & Data Safety Monitoring Committee; Genentech: Consultancy. Barr:Pharmacyclics LLC, an AbbVie company: Consultancy, Research Funding; Gilead: Consultancy; Verastem: Consultancy; Genentech: Consultancy; Seattle Genetics: Consultancy; Merck: Consultancy; Celgene: Consultancy; Janssen: Consultancy; AbbVie: Consultancy; Astra Zeneca: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding. Cashen:Celgene: Other: Speaker's Bureau; Seattle Genetics: Other: Speaker's Bureau; Novartis: Other: Speaker's Bureau. Mato:AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Celgene: Consultancy; Johnson & Johnson: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB member , Research Funding; LOXO: Consultancy, Research Funding; DTRM Biopharma: Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Gilead: Research Funding; Acerta: Consultancy; Janssen: Consultancy. Erba:Amgen: Consultancy; MacroGenics: Consultancy, Other: Lecture fees, Research Funding; MacroGenics: Consultancy, Other: Lecture fees, Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; ImmunoGen: Consultancy, Research Funding; Astellas Pharma: Consultancy; Astellas Pharma: Consultancy; Amgen: Consultancy; GlycoMimetics: Consultancy, Other: Chair, data and safety monitoring board, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Celgene: Consultancy, Other: chair, AML Registry Scientific Steering Committee, Speakers Bureau; ImmunoGen: Consultancy, Research Funding; AbbVie: Consultancy, Other: Chair, IRC for phase III studies, Research Funding; GlycoMimetics: Consultancy, Other: Chair, data and safety monitoring board, Research Funding; Covance: Other: Fees for serving as chair on an independent review board for AbbVie Phase III studies; Covance: Other: Fees for serving as chair on an independent review board for AbbVie Phase III studies; AbbVie: Consultancy, Other: Chair, IRC for phase III studies, Research Funding; Celgene: Consultancy, Other: chair, AML Registry Scientific Steering Committee, Speakers Bureau; Pfizer: Consultancy; Pfizer: Consultancy; Seattle Genetics: Consultancy; Seattle Genetics: Consultancy; Daiichi Sankyo: Consultancy, Research Funding. Stone:Arog Pharmaceuticals: Consultancy, Honoraria, Research Funding; Otsuka-Astex Pharmaceuticals: Consultancy; Fujifilm: Consultancy; AstraZeneca: Consultancy; Celator Pharmaceuticals: Consultancy; Abbvie: Consultancy, Research Funding; Ono Pharmaceutical-Theradex Oncology: Consultancy; Cornerstone Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Takeda: Other: Fees for serving on a data and safety monitoring board ; Orsenix: Consultancy; MacroGenics: Consultancy; Jazz Pharmaceuticals: Consultancy; Agios: Consultancy, Research Funding; Stemline Therapeutics: Consultancy; Pfizer: Consultancy; Celgene: Consultancy, Other: Fees for serving on a steering committee, and fees for serving on a data and safety monitoring board; Novartis: Consultancy, Research Funding; Actinium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Astellas Pharma: Membership on an entity's Board of Directors or advisory committees; Argenx: Other: Fees for serving on a data and safety monitoring board ; Roche: Consultancy. Tallman:Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncolyze: Consultancy, Membership on an entity's Board of Directors or advisory committees.

View details for DOI 10.1182/blood-2019-126824

View details for PubMedID 31723996
The Association Between Perceived Electronic Health Record Usability and Professional Burnout Among US Physicians. Mayo Clinic proceedings Melnick, E. R., Dyrbye, L. N., Sinsky, C. A., Trockel, M., West, C. P., Nedelec, L., Tutty, M. A., Shanafelt, T. 2019
Abstract

OBJECTIVE: To describe and benchmark physician-perceived electronic health record (EHR) usability as defined by a standardized metric of technology usability and evaluate the association with professional burnout among physicians.PARTICIPANTS AND METHODS: This cross-sectional survey of US physicians from all specialty disciplines was conducted between October 12, 2017, and March 15, 2018, using the American Medical Association Physician Masterfile. Among the 30,456 invited physicians, 5197 (17.1%) completed surveys. A random 25% (n=1250) of respondents in the primary survey received a subsurvey evaluating EHR usability, and 870 (69.6%) completed it. EHR usability was assessed using the System Usability Scale (SUS; range 0-100). SUS scores were normalized to percentile rankings across more than 1300 previous studies from other industries. Burnout was measured using the Maslach Burnout Inventory.RESULTS: Mean ± SD SUS score was 45.9±21.9. A score of 45.9 is in the bottom 9% of scores across previous studies and categorized in the "not acceptable" range or with a grade of F. On multivariate analysis adjusting for age, sex, medical specialty, practice setting, hours worked, and number of nights on call weekly, physician-rated EHR usability was independently associated with the odds of burnout with each 1 point more favorable SUS score associated with a 3% lower odds of burnout (odds ratio, 0.97; 95% CI, 0.97-0.98; P<.001).CONCLUSION: The usability of current EHR systems received a grade of F by physician users when evaluated using a standardized metric of technology usability. A strong dose-response relationship between EHR usability and the odds of burnout was observed.

View details for DOI 10.1016/j.mayocp.2019.09.024

View details for PubMedID 31735343
Author response: Age and sex differences in burnout, career satisfaction, and well-being in US neurologists. Neurology LaFaver, K., Miyasaki, J. M., Keran, C. M., Rheaume, C., Gulya, L., Levin, K. H., Jones, E. C., Schwarz, H. B., Molano, J. R., Hessler, A., Singhal, D., Shanafelt, T. D., Sloan, J. A., Novotny, P. J., Cascino, T. L., Busis, N. A. 2019; 93 (19): 863
View details for DOI 10.1212/WNL.0000000000008451

View details for PubMedID 31685708
Developing a Portfolio to Support Physicians' Efforts to Promote Well-being: One Piece of the Puzzle. Mayo Clinic proceedings Menon, N. K., Trockel, M. T., Hamidi, M. S., Shanafelt, T. D. 2019; 94 (11): 2171–77
View details for DOI 10.1016/j.mayocp.2019.09.010

View details for PubMedID 31685149
Estimating the Attributable Cost of Physician Burnout in the United States. Annals of internal medicine Dyrbye, L. N., Awad, K. M., Fiscus, L. C., Sinsky, C. A., Shanafelt, T. D. 2019; 171 (8): 600–601
View details for DOI 10.7326/L19-0522

View details for PubMedID 31610567
Self-valuation: Attending to the Most Important Instrument in the Practice of Medicine. Mayo Clinic proceedings Trockel, M. T., Hamidi, M. S., Menon, N. K., Rowe, S. G., Dudley, J. C., Stewart, M. T., Geisler, C. Z., Bohman, B. D., Shanafelt, T. D. 2019
Abstract

OBJECTIVE: To measure self-valuation, involving constructive prioritization of personal well-being and a growth mindset perspective that seeks to learn and improve as the primary response to errors, in physicians and evaluate its relationship with burnout and sleep-related impairment.METHODS: We analyzed cross-sectional survey data collected between July 1, 2016, and October 31, 2017, from 5 academic medical centers in the United States. All faculty and medical-staff physicians at participating organizations were invited to participate. The self-valuation scale included 4 items measured on a 5-point (0-4) Likert scale (summative score range, 0-16). The self-valuation scale was developed and pilot tested in a sample of 250 physicians before inclusion in the multisite wellness survey, which also included validated measures of burnout and sleep-related impairment.RESULTS: Of the 6189 physicians invited to participate, 3899 responded (response rate, 63.0%). Each 1-point score increase in self-valuation was associated with-1.10 point lower burnout score (95% CI,-1.16 to-1.05; standardized beta=-0.53; P<.001) and 0.81 point lower sleep-related impairment score (95% CI,-0.85 to-0.76; standardized beta=-0.47; P<.001), adjusting for sex and medical specialty. Women had lower self-valuation (Cohen d=0.30) and higher burnout (Cohen d=0.22) than men. Lower self-valuation scores in women accounted for most of the sex difference in burnout.CONCLUSION: Low self-valuation among physicians is associated with burnout and sleep-related impairment. Further research is warranted to develop and test interventions that increase self-valuation as a mechanism to improve physician well-being.

View details for DOI 10.1016/j.mayocp.2019.04.040

View details for PubMedID 31543254
Characteristics of Academic Physicians Associated With Patient Satisfaction AMERICAN JOURNAL OF MEDICAL QUALITY Heidenreich, P., Shieh, L., Fassiotto, M., Kahn, J., Weinacker, A., Smith, R., Trockel, M., Shanafelt, T., Palaniappan, L. 2019: 1062860619876344
View details for DOI 10.1177/1062860619876344

View details for Web of Science ID 000488727200001

View details for PubMedID 31529975
Associations Between Dietary Patterns and Sleep-Related Impairment in a Cohort of Community Physicians: A Cross-sectional Study AMERICAN JOURNAL OF LIFESTYLE MEDICINE Hamidi, M. S., Shanafelt, T. D., Hausel, A., Bohman, B. D., Roberts, R., Trockel, M. T. 2019
View details for DOI 10.1177/1559827619871923

View details for Web of Science ID 000487182900002
Physician Work-Life Integration: Challenges and Strategies for Improvement CLINICAL OBSTETRICS AND GYNECOLOGY Karakash, S., Solone, M., Chavez, J., Shanafelt, T. 2019; 62 (3): 455–65
View details for DOI 10.1097/GRF.0000000000000442

View details for Web of Science ID 000479115300006
Changes in Burnout and Satisfaction With Work-Life Integration in Physicians and the General US Working Population Between 2011 and 2017 MAYO CLINIC PROCEEDINGS Shanafelt, T. D., West, C. P., Sinsky, C., Trockel, M., Tutty, M., Satele, D., Carlasare, L. E., Dyrbye, L. N. 2019; 94 (9): 1681–94
View details for DOI 10.1016/j.mayocp.2018.10.023

View details for Web of Science ID 000483753900010
Association of elevated serumfree light chains with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Blood cancer journal Clay-Gilmour, A. I., Rishi, A. R., Goldin, L. R., Greenberg-Worisek, A. J., Achenbach, S. J., Rabe, K. G., Maurer, M. J., Kay, N. E., Shanafelt, T. D., Call, T. G., Brice Weinberg, J., Camp, N. J., Cerhan, J. R., Leis, J., Norman, A., Murray, D. L., Vincent Rajkumar, S., Caporaso, N. E., Landgren, O., McMaster, M. L., Slager, S. L., Vachon, C. M. 2019; 9 (8): 59
Abstract

Chronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n=154), (2) sporadic CLL (n=302), (3) familial MBL (n=87), (4) unaffected first-degree relatives from CLL/MBL families (n=263), and (5) reference population (n=15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p's<0.05). However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p's>0.05). Unaffected relatives and MBL cases from CLL/MBL families, ages >60 years, showed elevated monoclonal sFLC, compared to the reference population (p's<0.05). This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls. Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.

View details for DOI 10.1038/s41408-019-0220-x

View details for PubMedID 31383849
Effect of a Professional Coaching Intervention on the Well-being and Distress of Physicians: A Pilot Randomized Clinical Trial. JAMA internal medicine Dyrbye, L. N., Shanafelt, T. D., Gill, P. R., Satele, D. V., West, C. P. 2019
Abstract

Importance: Burnout symptoms among physicians are common and have potentially serious ramifications for physicians and their patients. Randomized studies testing interventions to address burnout have been uncommon.Objective: To explore the effect of individualized coaching on the well-being of physicians.Design, Setting, and Participants: A pilot randomized clinical trial involving 88 practicing physicians in the departments of medicine, family medicine, and pediatrics who volunteered for coaching was conducted between October 9, 2017, and March 27, 2018, at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin. Statistical analysis was conducted from August 24, 2018, to March 25, 2019.Interventions: A total of 6 coaching sessions facilitated by a professional coach.Main Outcomes and Measures: Burnout, quality of life, resilience, job satisfaction, engagement, and meaning at work using established metrics. Analysis was performed on an intent-to-treat basis.Results: Among the 88 physicians in the study (48 women and 40 men), after 6 months of professional coaching, emotional exhaustion decreased by a mean (SD) of 5.2 (8.7) points in the intervention group compared with an increase of 1.5 (7.7) points in the control group by the end of the study (P<.001). Absolute rates of high emotional exhaustion at 5 months decreased by 19.5% in the intervention group and increased by 9.8% in the control group (-29.3% [95% CI, -34.0% to -24.6%]) (P<.001). Absolute rates of overall burnout at 5 months also decreased by 17.1% in the intervention group and increased by 4.9% in the control group (-22.0% [95% CI, -25.2% to -18.7%]) (P<.001). Quality of life improved by a mean (SD) of 1.2 (2.5) points in the intervention group compared with 0.1 (1.7) points in the control group (1.1 points [95% CI, 0.04-2.1 points]) (P=.005), and resilience scores improved by a mean (SD) of 1.3 (5.2) points in the intervention group compared with 0.6 (4.0) points in the control group (0.7 points [95% CI, 0.0-3.0 points]) (P=.04). No statistically significant differences in depersonalization, job satisfaction, engagement, or meaning in work were observed.Conclusions and Relevance: Professional coaching may be an effective way to reduce emotional exhaustion and overall burnout as well as improve quality of life and resilience for some physicians.Trial Registration: ClinicalTrials.gov identifier: NCT03207581.

View details for DOI 10.1001/jamainternmed.2019.2425

View details for PubMedID 31380892
KRAS, NRAS, and BRAF mutations are highly enriched in trisomy 12 chronic lymphocytic leukemia and are associated with shorter treatment-free survival LEUKEMIA Vendramini, E., Bomben, R., Pozzo, F., Benedetti, D., Bittolo, T., Rossi, F., Dal Bo, M., Rabe, K. G., Pozzato, G., Zaja, F., Chiarenza, A., Di Raimondo, F., Braggio, E., Parikh, S. A., Kay, N. E., Shanafelt, T. D., Del Poeta, G., Gattei, V., Zucchetto, A. 2019; 33 (8): 2111–15
View details for DOI 10.1038/s41375-019-0444-6

View details for Web of Science ID 000479118400025
Assessing Burnout and Professional Fulfillment in Breast Surgery: Results From a National Survey of the American Society of Breast Surgeons. Annals of surgical oncology Zhang, J. Q., Riba, L., Magrini, L., Fleishman, A., Ukandu, P., Alapati, A., Shanafelt, T., James, T. A. 2019
Abstract

BACKGROUND: Physician burnout is a well-recognized problem in health care that has a negative impact on professional well-being and quality of patient care. Rates of burnout in breast surgery are not well-defined. This study sought to understand the degree of burnout among breast surgeons and to identify factors that influence professional fulfillment.METHODS: All U.S. members of the American Society of Breast Surgeons with a valid email address were surveyed in October 2017. The results were anonymous, and the participants were blinded to the study hypothesis. The survey included 30 questions (16-item Professional Fulfillment Index [PFI] and 14-item demographics/practice patterns). Multivariable linear regressions were performed to assess overall burnout and high professional fulfillment.RESULTS: Of the 2568 surveys delivered, 708 surveys were initiated, and 660 were completed. Among breast surgeons, 270 (41.3%) expressed burnout, whereas 281 (42.5%) reported high professional fulfillment. In the multivariable analysis, years in practice was inversely associated with burnout and positively correlated with professional fulfillment. Working more than 60h per week was positively associated with burnout, and having more than 50% of practice dedicated to breast surgery correlated positively with fulfillment.CONCLUSION: Approximately 4 of 10 breast surgeons have symptoms of burnout, whereas 4 of 10 surgeons report high professional fulfillment. Specific clinical practice conditions largely influence rates of burnout and professional fulfillment. The contributing factors identified in the study analysis may be useful in identifying breast surgeons at higher risk for burnout. The study findings also help to inform the design of interventions focused on the clinical practice environment to promote professional fulfillment and sustainability.

View details for DOI 10.1245/s10434-019-07532-3

View details for PubMedID 31342357
Healing the Professional Culture of Medicine. Mayo Clinic proceedings Shanafelt, T. D., Schein, E., Minor, L. B., Trockel, M., Schein, P., Kirch, D. 2019
Abstract

The past decade has been a time of great change for US physicians. Many physicians feel that the care delivery system has become a barrier to providing high-quality care rather than facilitating it. Although physician distress and some of the contributing factors are now widely recognized, much of the distress physicians are experiencing is related to insidious issues affecting the cultures of our profession, our health care organizations, and the health care delivery system. Culture refers to the shared and fundamental beliefs of a group that are so widely accepted that they are implicit and often no longer recognized. When challenges with culture arise, they almost always relate to a problem with a subcomponent of the culture even as the larger culture does many things well. In this perspective, we consider the role of culture in many of the problems facing our health care delivery system and contributing to the high prevalence of professional burnout plaguing US physicians. A framework, drawn from the field of organizational science, to address these issues and heal our professional culture is considered.

View details for DOI 10.1016/j.mayocp.2019.03.026

View details for PubMedID 31303431
Developmental subtypes assessed by DNA methylation-iPLEX forecast the natural history of chronic lymphocytic leukemia. Blood Giacopelli, B., Zhao, Q., Ruppert, A. S., Agyeman, A., Weigel, C., Wu, Y., Gerber, M. M., Rabe, K. G., Larson, M. C., Lu, J., Blachly, J. S., Rogers, K. A., Wierda, W. G., Brown, J. R., Rai, K. R., Keating, M., Rassenti, L. Z., Kipps, T. J., Zenz, T., Shanafelt, T. D., Kay, N. E., Abruzzo, L. V., Coombes, K. R., Woyach, J. A., Byrd, J. C., Oakes, C. C. 2019
Abstract

Alterations in global DNA methylation patterns are a major hallmark of cancer and represent attractive biomarkers for personalized risk stratification. Chronic lymphocytic leukemia (CLL) risk stratification studies typically focus on time to first treatment (TTFT), time to progression (TTP) after treatment, and overall survival (OS). Whereas TTFT risk stratification remains similar over time, TTP and OS have changed dramatically with the introduction of targeted therapies such as the Bruton's tyrosine kinase inhibitor, ibrutinib. We have shown genome-wide DNA methylation patterns in CLL are highly associated with phenotypic differentiation and patient outcomes. Here we developed a novel assay, termed methylation-iPLEX (Me-iPLEX), for high-throughput quantification of targeted panels of single CpGs from multiple independent loci. Me-iPLEX was used to classify CLL samples into one of three known epigenetic subtypes (epitypes). We examined the impact of epitype in 1,286 CLL patients from four independent cohorts representing a comprehensive view of CLL disease course and therapies. We found epitype significantly predicted TTFT and OS among newly diagnosed CLL patients. Additionally, epitype predicted TTP and OS with two common CLL therapies, chemoimmunotherapy (CIT) and Ibrutinib. Epitype upheld significance after stratifying by biologically-related biomarkers, IGHV-mutational status and ZAP70 expression, as well as other common prognostic markers. Furthermore, among several biological traits enriched between epitypes, we found highly-biased immunogenetic features, including IGLV3-21 usage in the poorly-characterized intermediate-programmed (IP)-CLL epitype. In summary, Me-iPLEX is an elegant method to assess epigenetic signatures, including robust classification of CLL epitypes that independently stratify patient risk at diagnosis and time of treatment.

View details for DOI 10.1182/blood.2019000490

View details for PubMedID 31292113
Burnout and Satisfaction with Work-Life Integration Among Nurses. Journal of occupational and environmental medicine Dyrbye, L. N., West, C. P., Johnson, P. O., Cipriano, P. F., Beatty, D. E., Peterson, C., Major-Elechi, B., Shanafelt, T. 2019
Abstract

OBJECTIVES: To evaluate characteristics associated with burnout and satisfaction with work-life integration (WLI) among nurses and compare their experience to other American workers.METHODS: We used data from 8638 nurses and 5198 workers to evaluate factors associated with burnout and satisfaction with WLI, and compare nurses to workers in other fields.RESULTS: In the multivariable analysis, demographics, work hours, and highest academic degree obtained related to nursing were independent predictors of burnout. Factors independently associated with satisfaction with WLI included work hours. In pooled multivariable analyses including nurses and other workers, nurses were not more likely to have symptoms of burnout but were more likely to have lower satisfaction with WLI.CONCLUSIONS: Work hours and professional development related to the risk of burnout among nurses. Nurses are at similar risk for burnout relative to other US workers but experience greater struggles with WLI.

View details for DOI 10.1097/JOM.0000000000001637

View details for PubMedID 31348422
The magnitude of improvement in progression-free survival with targeted therapy in relapsed/refractory chronic lymphocytic leukemia based on prognostic risk category: a systematic review and meta-analysis LEUKEMIA & LYMPHOMA Molica, S., Giannarelli, D., Mirabelli, R., Levato, L., Shanafelt, T. D. 2019; 60 (7): 1644–49
View details for DOI 10.1080/10428194.2018.1543882

View details for Web of Science ID 000478841300007
A Road Map to Foster Wellness and Engagement in Our Workplace-A Report of the 2018 Summer Intersociety Meeting JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY Kruskal, J. B., Shanafelt, T., Eby, P., Meltzer, C. C., Rawson, J., Essex, L. N., Canon, C., West, D., Bender, C. 2019; 16 (6): 869–77
View details for DOI 10.1016/j.jacr.2018.10.025

View details for Web of Science ID 000470799800019
Vascular Surgeon Burnout - A Report From the Society for Vascular Surgery Wellness Task Force Coleman, D. M., Meltzer, A. J., Wohlauer, M., Drudi, L. M., Hallbeck, M., Shanafelt, T., Money, S., Sheahan, M. MOSBY-ELSEVIER. 2019: E97
View details for DOI 10.1016/j.jvs.2019.04.103

View details for Web of Science ID 000469220300101
Estimating the Attributable Cost of Physician Burnout in the United States. Annals of internal medicine Han, S., Shanafelt, T. D., Sinsky, C. A., Awad, K. M., Dyrbye, L. N., Fiscus, L. C., Trockel, M., Goh, J. 2019
Abstract

Background: Although physician burnout is associated with negative clinical and organizational outcomes, its economic costs are poorly understood. As a result, leaders in health care cannot properly assess the financial benefits of initiatives to remediate physician burnout.Objective: To estimate burnout-associated costs related to physician turnover and physicians reducing their clinical hours at national (U.S.) and organizational levels.Design: Cost-consequence analysis using a mathematical model.Setting: United States.Participants: Simulated population of U.S. physicians.Measurements: Model inputs were estimated by using the results of contemporary published research findings and industry reports.Results: On a national scale, the conservative base-case model estimates that approximately $4.6 billion in costs related to physician turnover and reduced clinical hours is attributable to burnout each year in the United States. This estimate ranged from $2.6 billion to $6.3 billion in multivariate probabilistic sensitivity analyses. At an organizational level, the annual economic cost associated with burnout related to turnover and reduced clinical hours is approximately $7600 per employed physician each year.Limitations: Possibility of nonresponse bias and incomplete control of confounders in source data. Some parameters were unavailable from data and had to be extrapolated.Conclusion: Together with previous evidence that burnout can effectively be reduced with moderate levels of investment, these findings suggest substantial economic value for policy and organizational expenditures for burnout reduction programs for physicians.

View details for DOI 10.7326/M18-1422

View details for PubMedID 31132791
Atrial fibrillation (AF) in patients with CLL treated with ibrutinib: Assessing prediction models and clinical outcomes. Archibald, W., Rabe, K. G., Kabat, B., Call, T., Ding, W., Kay, N. E., Kenderian, S., Muchtar, E., Leis, J., Schwager, S. M., Koehler, A., Fonder, A. L., Slager, S. L., Shanafelt, T. D., Parikh, S. AMER SOC CLINICAL ONCOLOGY. 2019
View details for Web of Science ID 000487345806284
Rapid disease progression following discontinuation of ibrutinib in patients with chronic lymphocytic leukemia treated in routine clinical practice LEUKEMIA & LYMPHOMA Hampel, P. J., Ding, W., Call, T. G., Rabe, K. G., Kenderian, S. S., Witzig, T. E., Muchtar, E., Leis, J. F., Chanan-Khan, A. A., Koehler, A. B., Fonder, A. L., Schwager, S. M., Slager, S. L., Shanafelt, T. D., Kay, N. E., Parikh, S. A. 2019
View details for DOI 10.1080/10428194.2019.1602268

View details for Web of Science ID 000469572200001
Physician Work-Life Integration: Challenges and Strategies for Improvement. Clinical obstetrics and gynecology Karakash, S., Solone, M., Chavez, J., Shanafelt, T. 2019
Abstract

Increasing evidence shows physician well-being is linked to patient outcomes, patient and physician satisfaction, and workforce retention. Physician well-being is a broad construct that includes various dimensions of distress (stress, anxiety, fatigue, burnout) and professional fulfillment (meaning in work, engagement). Work-life integration (WLI) is one important component of physician well-being. We will review the current state of WLI among physicians as well as some strategies to improve this aspect of physician well-being. We address this topic through the lens of obstetrics and gynecology, including a discussion of specialty-specific characteristics that present unique challenges and opportunities to improve WLI.

View details for PubMedID 30950862
Clarifications Needed on Study of Association Between Physician Burnout and Patient Safety JAMA INTERNAL MEDICINE Dyrbye, L. N., Shanafelt, T. D., West, C. P. 2019; 179 (4): 593
View details for DOI 10.1001/jamainternmed.2019.0149

View details for Web of Science ID 000465155100040
Perceived risk for cancer progression and psychological status in chronic lymphocytic leukemia patients: CALGB 70603 (Alliance). Leukemia & lymphoma Deshields, T. L., Dueck, A. C., Rogers, K., Brown, J. R., Shanafelt, T., Mintzer, D., Byrd, J. C. 2019: 1–4
View details for DOI 10.1080/10428194.2019.1594218

View details for PubMedID 30916608
KRAS, NRAS, and BRAF mutations are highly enriched in trisomy 12 chronic lymphocytic leukemia and are associated with shorter treatment-free survival. Leukemia Vendramini, E., Bomben, R., Pozzo, F., Benedetti, D., Bittolo, T., Rossi, F. M., Dal Bo, M., Rabe, K. G., Pozzato, G., Zaja, F., Chiarenza, A., Di Raimondo, F., Braggio, E., Parikh, S. A., Kay, N. E., Shanafelt, T. D., Del Poeta, G., Gattei, V., Zucchetto, A. 2019
View details for PubMedID 30872781
Clarifications Needed on Study of Association Between Physician Burnout and Patient Safety. JAMA internal medicine Dyrbye, L. N., Shanafelt, T. D., West, C. P. 2019
View details for PubMedID 30830173
Organizational factors affecting physician well-being. Current treatment options in pediatrics Tawfik, D. S., Profit, J., Webber, S., Shanafelt, T. D. 2019; 5 (1): 11–25
Abstract

Purpose of review: Symptoms of burnout affect approximately half of pediatricians and pediatric subspecialists at any given time, with similarly concerning prevalence of other aspects of physician distress, including fatigue, depressive symptoms, and suicidal ideation. Physician well-being affects quality of care, patient satisfaction, and physician turnover. Organizational factors influence well-being, stressing the need for organizations to address this epidemic.Recent findings: Organizational characteristics, policies, and culture influence physician well-being, and specific strategies may support an environment where physicians thrive. We highlight four organizational opportunities to improve physician well-being: developing leaders, cultivating community and organizational culture, improving practice efficiency, and optimizing administrative policies. Leaders play a key role in aligning organizational and individual values, promoting professional fulfillment, and fostering a culture of collegiality and social support among physicians. Reducing documentation burden and improving practice efficiency may help balance job demands and resources. Finally, reforming administrative policies may reduce work-home conflict, support physician's efforts to attend to their own well-being, and normalize use of supportive resources.Summary: Physician well-being is critical to organizational success, sustainment of an adequate workforce, and optimal patient outcomes. Because burnout is primarily influenced by organizational factors, organizational interventions are key to promoting well-being. Developing supportive leadership, fostering a culture of wellness, optimizing practice efficiency, and improving administrative policies are worthy of organizational action and further research.

View details for DOI 10.1007/s40746-019-00147-6

View details for PubMedID 31632895
Burnout Among Physicians Compared With Individuals With a Professional or Doctoral Degree in a Field Outside of Medicine. Mayo Clinic proceedings Shanafelt, T. D., Sinsky, C., Dyrbye, L. N., Trockel, M., West, C. P. 2019; 94 (3): 549–51
View details for PubMedID 30832797
Efficacy of the Well-Being Index to identify distress and stratify well-being in Nurse Practitioners and Physician Assistants. Journal of the American Association of Nurse Practitioners Dyrbye, L. N., Johnson, P. O., Johnson, L. M., Halasy, M. P., Gossard, A. A., Satele, D., Shanafelt, T. 2019
Abstract

BACKGROUND AND PURPOSE: To evaluate the ability of the Well-Being Index (WBI) to stratify distress and well-being (high quality of life [QOL]) in nurse practitioners and physician assistants (NPs and PAs) and identify those whose degree of distress place them at an increased risk for medical error or turnover.METHODS: A national sample of NPs and PAs completed a survey that included the WBI and instruments to measure QOL, fatigue, burnout, recent suicidal ideation, medical error, and intent to leave the current job.CONCLUSIONS: Overall, 1,576 of 4,106 (38.4%) NPs and PAs completed the survey. Those NPs and PAs with low mental QOL, extreme fatigue, recent suicidal ideation, or burnout had less favorable WBI scores (all p < .0001). Using a prevalence of low overall QOL among APPs of 14.4% as the pretest probability, the WBI score can reduce the posttest probability of low QOL to 2% or increase it to 64.7%. As the WBI score worsened, the posttest probability of high overall QOL decreased from 73% to 8.2%. Also, WBI score stratified the NPs and PAs likelihood of reporting recent medical errors and intent to leave his or her current job.IMPLICATIONS FOR PRACTICE: The WBI is a useful screening tool to stratify distress and well-being in APPs across a variety of domains and identify those NPs and PAs whose degree of distress may increase the risk of medical error or turnover.

View details for DOI 10.1097/JXX.0000000000000179

View details for PubMedID 30829967
Changes in Burnout and Satisfaction With Work-Life Integration in Physicians and the General US Working Population Between 2011 and 2017. Mayo Clinic proceedings Shanafelt, T. D., West, C. P., Sinsky, C., Trockel, M., Tutty, M., Satele, D. V., Carlasare, L. E., Dyrbye, L. N. 2019
Abstract

OBJECTIVE: To evaluate the prevalence of burnout and satisfaction with work-life integration among physicians and other US workers in 2017 compared with 2011 and2014.PARTICIPANTS AND METHODS: Between October 12, 2017, and March 15, 2018, we surveyed US physicians and a probability-based sample of the US working population using methods similar to our 2011 and 2014 studies. A secondary survey with intensive follow-up was conducted in a sample of nonresponders to evaluate response bias. Burnout and work-life integration were measured using standard tools.RESULTS: Of 30,456 physicians who received an invitation to participate, 5197 (17.1%) completed surveys. Among the 476 physicians in the secondary survey of nonresponders, 248 (52.1%) responded. A comparison of responders in the 2 surveys revealed no significant differences in burnout scores (P=.66), suggesting that participants were representative of US physicians. When assessed using the Maslach Burnout Inventory, 43.9% (2147 of 4893) of the physicians who completed the MBI reported at least one symptom of burnout in 2017 compared with 54.4% (3680 of 6767) in 2014 (P<.001) and 45.5% (3310 of 7227) in 2011 (P=.04). Satisfaction with work-life integration was more favorable in 2017 (42.7% [2056 of 4809]) than in 2014 (40.9% [2718 of 6651]; P<.001) but less favorable than in 2011 (48.5% [3512 of 7244]; P<.001). On multivariate analysis adjusting for age, sex, relationship status, and hours worked per week, physicians were at increased risk for burnout (odds ratio, 1.39; 95% CI, 1.26-1.54; P<.001) and were less likely to be satisfied with work-life integration (odds ratio, 0.77; 95% CI, 0.70-0.85; P<.001) than other working US adults.CONCLUSION: Burnout and satisfaction with work-life integration among US physicians improved between 2014 and 2017, with burnout currently near 2011 levels. Physicians remain at increased risk for burnout relative to workers in other fields.

View details for PubMedID 30803733
Evidence Relating Health Care Provider Burnout and Quality of Care: A Systematic Review and Meta-analysis. Annals of internal medicine Tawfik, D. S., Scheid, A., Profit, J., Shanafelt, T., Trockel, M., Adair, K. C., Sexton, J. B., Ioannidis, J. P. 2019
Abstract

Whether health care provider burnout contributes to lower quality of patient care is unclear.To estimate the overall relationship between burnout and quality of care and to evaluate whether published studies provide exaggerated estimates of this relationship.MEDLINE, PsycINFO, Health and Psychosocial Instruments (EBSCO), Mental Measurements Yearbook (EBSCO), EMBASE (Elsevier), and Web of Science (Clarivate Analytics), with no language restrictions, from inception through 28 May 2019.Peer-reviewed publications, in any language, quantifying health care provider burnout in relation to quality of patient care.2 reviewers independently selected studies, extracted measures of association of burnout and quality of care, and assessed potential bias by using the Ioannidis (excess significance) and Egger (small-study effect) tests.A total of 11 703 citations were identified, from which 123 publications with 142 study populations encompassing 241 553 health care providers were selected. Quality-of-care outcomes were grouped into 5 categories: best practices (n = 14), communication (n = 5), medical errors (n = 32), patient outcomes (n = 17), and quality and safety (n = 74). Relations between burnout and quality of care were highly heterogeneous (I2 = 93.4% to 98.8%). Of 114 unique burnout-quality combinations, 58 indicated burnout related to poor-quality care, 6 indicated burnout related to high-quality care, and 50 showed no significant effect. Excess significance was apparent (73% of studies observed vs. 62% predicted to have statistically significant results; P = 0.011). This indicator of potential bias was most prominent for the least-rigorous quality measures of best practices and quality and safety.Studies were primarily observational; neither causality nor directionality could be determined.Burnout in health care professionals frequently is associated with poor-quality care in the published literature. The true effect size may be smaller than reported. Future studies should prespecify outcomes to reduce the risk for exaggerated effect size estimates.Stanford Maternal and Child Health Research Institute.

View details for DOI 10.7326/M19-1152

View details for PubMedID 31590181
Rapid disease progression following discontinuation of ibrutinib in patients with chronic lymphocytic leukemia treated in routine clinical practice. Leukemia & lymphoma Hampel, P. J., Ding, W., Call, T. G., Rabe, K. G., Kenderian, S. S., Witzig, T. E., Muchtar, E., Leis, J. F., Chanan-Khan, A. A., Koehler, A. B., Fonder, A. L., Schwager, S. M., Slager, S. L., Shanafelt, T. D., Kay, N. E., Parikh, S. A. 2019: 1–8
Abstract

We identified all patients with chronic lymphocytic leukemia at Mayo Clinic treated with ibrutinib outside the context of a clinical trial; timing and reasons for discontinuation were ascertained, as were symptoms, exam and radiographic findings, and laboratory changes following discontinuation. Of 202 patients who received ibrutinib, 52 discontinued therapy (estimated 1- and 2-year risk of discontinuation 18% and 28%, respectively). The most common reasons for discontinuation were toxicity (56%) and progression of disease (32%, including Richter's transformation in 15%). Rapid progression of disease within 4 weeks after discontinuation was observed in 9/36 (25%) patients with adequate records for review, mostly in those stopping ibrutinib for disease progression (n = 8) rather than toxicity (n = 1). This was evident by sudden worsening of disease-related symptoms (n = 9), exam/radiographic changes (n = 7), and laboratory changes (n = 8). An estimated one in every three patients discontinued ibrutinib by 2 years, with 25% developing rapid disease progression afterwards.

View details for PubMedID 31014142
Role of long non-coding RNAs in disease progression of early stage unmutated chronic lymphocytic leukemia. Oncotarget Tschumper, R. C., Shanafelt, T. D., Kay, N. E., Jelinek, D. F. 2019; 10 (1): 60–75
Abstract

Predicting disease progression in chronic lymphocytic leukemia (CLL) remains challenging particularly in patients with Rai Stage 0/I disease that have an unmutated immunoglobulin heavy chain variable region (UM IGHV). Even though patients with UM IGHV have a poor prognosis and generally require earlier treatment, not all UM IGHV patients experience more rapid disease progression with some remaining treatment free for many years. This observation suggests biologic characteristics other than known prognostic factors influence disease progression. Alterations in long non-coding RNA (lncRNA) expression levels have been implicated in diagnosis and prognosis of various cancers, however, their role in disease progression of early Rai stage UM CLL is unknown. Here we use microarray analysis to compare lncRNA and mRNA profiles of Rai 0/I UM IGHV patients who progressed in <2 years relative to patients who had not progressed for >5 years. Over 1,300 lncRNAs and 940 mRNAs were differentially expressed (fold change ≥ 2.0; p-value ≤ 0.05). Of interest, the differentially expressed lncRNAs T204050, NR_002947, and uc.436+, have known associated genes that have been linked to CLL. Thus, our study reveals differentially expressed lncRNAs in progressive early stage CLL requiring therapy versus indolent early Rai stage UM CLL. These lncRNAs have the potential to impact relevant biological processes and pathways that influence clinical outcome in CLL.

View details for PubMedID 30713603
Prognostic risk score for patients with relapsed or refractory chronic lymphocytic leukaemia treated with targeted therapies or chemoimmunotherapy: a retrospective, pooled cohort study with external validations. The Lancet. Haematology Soumerai, J. D., Ni, A., Darif, M., Londhe, A., Xing, G., Mun, Y., Kay, N. E., Shanafelt, T. D., Rabe, K. G., Byrd, J. C., Chanan-Khan, A. A., Furman, R. R., Hillmen, P., Jones, J., Seymour, J. F., Sharman, J. P., Ferrante, L., Mobasher, M., Stark, T., Reddy, V., Dreiling, L. K., Bhargava, P., Howes, A., James, D. F., Zelenetz, A. D. 2019
Abstract

Clinically validated prognostic models for overall survival do not exist for patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) who are on targeted therapies. We aimed to create a prognostic model to identify high-risk individuals who do not achieve a good outcome with available targeted therapies.In this retrospective, pooled cohort study, 2475 patients with CLL treated between June 22, 2012, and Sept 23, 2015, in six randomised trials of ibrutinib, idelalisib, and venetoclax, or at the Mayo Clinic CLL Database (MCCD) were included. Eligible patients had CLL, were previously treated, were aged 18 years or older, had ECOG performance status 0-1, and required further treatment as per the international workshop on CLL 2008 criteria. There was heterogeneity in other eligibility criteria. We evaluated 28 candidate factors known to affect the overall survival of these patients and applied univariate and multivariate analyses to derive the risk score in a training dataset (n=727) of patients treated with ibrutinib or chemoimmunotherapy. We validated the score in an internal-validation dataset (n=242) of patients treated with ibrutinib or chemoimmunotherapy and three external-validation datasets (ibrutinib or chemoimmunotherapy dataset, n=897; venetoclax or chemoimmunotherapy dataset, n=389; and the MCCD [including patients treated with heterogeneous therapies], n=220), applying C-statistics as a measure of discrimination.The derived model consisted of four factors (one point each; serum β2-microglobulin ≥5 mg/dL, lactate dehydrogenase >upper limit of normal, haemoglobin <110 g/L for women or <120 g/L for men, and time from initiation of last therapy <24 months), separating patients into low (score 0-1), intermediate (score 2-3), and high risk (score 4) groups. The risk score was prognostic for overall survival in the training dataset (CS=0·74, 95% CI 0·60-0·85, log-rank p<0·0001), and in the internal-validation (CS=0·79, 0·56-0·97, log-rank p=0·0003), and all three external-validation cohorts (idelalisib or chemoimmunotherapy: CS=0·71, 0·59-0·81, log-rank p<0·0001; venetoclax or chemoimmunotherapy: CS =0·76, 0·66-0·85, log-rank p=0·014; MCCD cohort: CS=0·61, 0·56-0·66), log-rank p<0·0001). The risk score is available on Calculate by QxMD.We present the first validated risk score to predict overall survival in patients with relapsed or refractory CLL treated with targeted therapy. The model is applicable to patients treated with all currently approved targeted therapies (ibrutinib, idelalisib, and venetoclax) and chemoimmunotherapy. This tool allows the identification of a well defined cohort of previously treated patients with CLL who are at high risk of death, and could be used in future prospective trials to test therapeutic options for these patients with an unmet clinical need.Lymphoma Research Foundation, Lymphoma Research Fund (Andrew D Zelenetz), and National Institutes of Health/National Cancer Institute.

View details for DOI 10.1016/S2352-3026(19)30085-7

View details for PubMedID 31109827
Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. The New England journal of medicine Shanafelt, T. D., Wang, X. V., Kay, N. E., Hanson, C. A., O'Brien, S., Barrientos, J., Jelinek, D. F., Braggio, E., Leis, J. F., Zhang, C. C., Coutre, S. E., Barr, P. M., Cashen, A. F., Mato, A. R., Singh, A. K., Mullane, M. P., Little, R. F., Erba, H., Stone, R. M., Litzow, M., Tallman, M. 2019; 381 (5): 432–43
Abstract

Data regarding the efficacy of treatment with ibrutinib-rituximab, as compared with standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) have been limited.In a phase 3 trial, we randomly assigned (in a 2:1 ratio) patients 70 years of age or younger with previously untreated CLL to receive either ibrutinib and rituximab for six cycles (after a single cycle of ibrutinib alone), followed by ibrutinib until disease progression, or six cycles of chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. The primary end point was progression-free survival, and overall survival was a secondary end point. We report the results of a planned interim analysis.A total of 529 patients underwent randomization (354 patients to the ibrutinib-rituximab group, and 175 to the chemoimmunotherapy group). At a median follow-up of 33.6 months, the results of the analysis of progression-free survival favored ibrutinib-rituximab over chemoimmunotherapy (89.4% vs. 72.9% at 3 years; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.22 to 0.56; P<0.001), and the results met the protocol-defined efficacy threshold for the interim analysis. The results of the analysis of overall survival also favored ibrutinib-rituximab over chemoimmunotherapy (98.8% vs. 91.5% at 3 years; hazard ratio for death, 0.17; 95% CI, 0.05 to 0.54; P<0.001). In a subgroup analysis involving patients without immunoglobulin heavy-chain variable region (IGHV) mutation, ibrutinib-rituximab resulted in better progression-free survival than chemoimmunotherapy (90.7% vs. 62.5% at 3 years; hazard ratio for progression or death, 0.26; 95% CI, 0.14 to 0.50). The 3-year progression-free survival among patients with IGHV mutation was 87.7% in the ibrutinib-rituximab group and 88.0% in the chemoimmunotherapy group (hazard ratio for progression or death, 0.44; 95% CI, 0.14 to 1.36). The incidence of adverse events of grade 3 or higher (regardless of attribution) was similar in the two groups (in 282 of 352 patients [80.1%] who received ibrutinib-rituximab and in 126 of 158 [79.7%] who received chemoimmunotherapy), whereas infectious complications of grade 3 or higher were less common with ibrutinib-rituximab than with chemoimmunotherapy (in 37 patients [10.5%] vs. 32 [20.3%], P<0.001).The ibrutinib-rituximab regimen resulted in progression-free survival and overall survival that were superior to those with a standard chemoimmunotherapy regimen among patients 70 years of age or younger with previously untreated CLL. (Funded by the National Cancer Institute and Pharmacyclics; E1912 ClinicalTrials.gov number, NCT02048813.).

View details for DOI 10.1056/NEJMoa1817073

View details for PubMedID 31365801
A cross-sectional study exploring the relationship between burnout, absenteeism, and job performance among American nurses. BMC nursing Dyrbye, L. N., Shanafelt, T. D., Johnson, P. O., Johnson, L. A., Satele, D., West, C. P. 2019; 18: 57
Abstract

Background: Studies suggest a high prevalence of burnout among nurses. The aim of this study was to evaluate the relationship between burnout among nurses and absenteeism and work performance.Methods: A national sample of U.S. nurses was sent an anonymous, cross-sectional survey in 2016. The survey included items about demographics, fatigue, and validated instruments to measure burnout, absenteeism, and poor work performance in the last month.Results: Of the 3098 nurses who received the survey, 812 (26.2%) responded. The mean age was 52.3years (SD 12.5), nearly all were women (94.5%) and most were married (61.9%) and had a child (75.2%). Participating nurses had a mean of 25.7 (SD 13.9) years of experience working as nurse and most held a baccalaureate (38.2%) or masters of science (37.1%) degree in nursing. A quarter worked in the inpatient setting (25.5%) and the average hours worked per week was 41.3 (SD 14.1). Overall, 35.3% had symptoms of burnout, 30.7% had symptoms of depression, 8.3% had been absent 1 or more days in the last month due to personal health, and 43.8% had poor work performance in the last month. Nurses who had burnout were more likely to have been absent 1 or more days in the last month (OR 1.85, 95% CI 1.25-2.72) and have poor work performance (referent: high performer; medium performer, OR 2.68,95% CI 1.82-3.99; poor performer, OR 5.01, 95% CI 3.09-8.14). After adjusting for age, sex, relationship and parental status, highest academic degree, practice setting, burnout, depression, and satisfaction with work-life integration, nurses who were more fatigued (for each point worsening, OR 1.22, 95% CI 1.10-1.37) were more likely to have had absenteeism while those who worked more hours (for each additional hour OR 0.98, 95% CI 0.96-1.00) were less likely to have had absenteeism. Factors independently associated with poor work performance included burnout (OR 2.15, 95% CI 1.43-3.24) and fatigue (for each point of worsening, OR 1.22, 95% CI 1.12-1.33).Conclusions: These findings suggest burnout is prevalent among nurses and likely impacts work performance.

View details for DOI 10.1186/s12912-019-0382-7

View details for PubMedID 31768129
IGH translocations in chronic lymphocytic leukemia (CLL): clinicopathologic features and clinical outcomes. American journal of hematology Fang, H., Reichard, K. K., Rabe, K. G., Hanson, C. A., Call, T. G., Ding, W., Kenderian, S. S., Muchtar, E., Schwager, S. M., Leis, J. F., Chanan-Khan, A. A., Slager, S. L., Braggio, E., Smoley, S. A., Kay, N. E., Shanafelt, T. D., Van Dyke, D. L., Parikh, S. A. 2018
Abstract

The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH-BCL2 and IGH-BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between 3/1/2002 and 9/30/2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT) and overall survival (OS) of patients with IGH-BCL2 and IGH-BCL3 translocation were compared to patients without these abnormalities (non-IGH group). Of 1684 patients who met the inclusion criteria, 38 (2.2%) had IGH-BCL2, and 16 (0.9%) had IGH-BCL3 translocation at diagnosis. Patients with IGH-BCL3 translocation were more likely to have high and very-high CLL-International Prognostic Index, compared to patients with IGH-BCL2 translocation and the non-IGH group. The 5-year probability of requiring therapy was significantly higher for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (84% vs. 33% vs. 29%, respectively, p<0.0001). The 5-year OS was significantly shorter for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (45% vs. 89% vs. 86%, respectively, p<0.0001). On multivariable analyses, IGH-BCL3 translocation was associated with a shorter TTT (hazard ratio (HR)=2.7; p=0.005) and shorter OS (HR=5.5; p<0.0001); IGH-BCL2 translocation did not impact TTT and OS. In conclusion, approximately 3% of all newly diagnosed CLL patients have either an IGH-BCL2 or IGH-BCL3 translocation. Patients with IGH-BCL3 translocations have a distinct prognostic profile and outcome. These results support the inclusion of an IGH probe during the routine evaluation of FISH abnormalities in newly diagnosed CLL. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ajh.25385

View details for PubMedID 30575108
Chronic lymphocytic leukemia cells from ibrutinib treated patients are sensitive to Axl receptor tyrosine kinase inhibitor therapy. Oncotarget Sinha, S., Boysen, J. C., Chaffee, K. G., Kabat, B. F., Slager, S. L., Parikh, S. A., Secreto, C. R., Call, T., Shanafelt, T. D., Leis, J. F., Warner, S. L., Bearss, D. J., Ghosh, A. K., Kay, N. E. 2018; 9 (98): 37173–84
Abstract

Earlier we have shown the expression of a constitutively active receptor tyrosine kinase Axl in CLL B-cells from previously untreated CLL patients, and that Axl inhibitor TP-0903 induces robust leukemic B-cell death. To explore whether Axl is an effective target in relapsed/refractory CLL patients, we analyzed CLL B-cells obtained from CLL patients on ibrutinib therapy. Ibrutinib-exposed CLL B-cells were treated with increasing doses (0.01- 0.50muM) of a new formulation of high-affinity Axl inhibitor, TP-0903 (tartrate salt), for 24 hours and LD50 doses were determined. Sensitivity of CLL B-cells was compared with known prognostic factors and effect of TP-0903 was also evaluated on Axl signaling pathway in CLL B-cells from this cohort. We detected sustained overexpression of Axl in CLL B-cells from CLL patients on ibrutinib treatment, suggests targeting Axl could be a promising strategy to overcome drug resistance and killing of CLL B-cells in these patients. We found that CLL B-cells from sixty-nine percent of relapsed CLL patients actively on ibrutinib therapy were found to be highly sensitive to TP-0903 with induction of apoptosis at nanomolar doses (≤0.50 muM). TP-0903 treatment effectively inhibited Axl phosphorylation and reduced expression levels of anti-apoptotic proteins (Mcl-1, XIAP) in ibrutinib exposed CLL B-cells. In total, our in vitro preclinical studies showing that TP-0903 is very effective at inducing apoptosis in CLL B-cells obtained from ibrutinib-exposed patients supports further testing of this drug in relapsed/refractory CLL.

View details for DOI 10.18632/oncotarget.26444

View details for PubMedID 30647852
A Road Map to Foster Wellness and Engagement in Our Workplace-A Report of the 2018 Summer Intersociety Meeting. Journal of the American College of Radiology : JACR Kruskal, J. B., Shanafelt, T., Eby, P., Meltzer, C. C., Rawson, J., Essex, L. N., Canon, C., West, D., Bender, C. 2018
Abstract

The 2018 radiology Intersociety Committee reviewed the current state of stress and burnout in our workplaces and identified approaches for fostering engagement, wellness, and job satisfaction. In addition to emphasizing the importance of personal wellness (the fourth aim of health care), the major focus of the meeting was to identify strategies and themes to mitigate the frequency, manifestations, and impact of stress. Strategies include reducing the stigma of burnout, minimizing isolation through community building and fostering connectivity, utilizing data and benchmarking to guide effectiveness of improvement efforts, resourcing and training "wellness" committees, acknowledging value contributions of team members, and improving efficiency in the workplace. Four themes were identified toprioritize organizational efforts: (1) collecting, analyzing, and benchmarking data; (2) developing effective leadership; (3) building high-functioning teams; and (4) amplifying our voice to increase our influence.

View details for PubMedID 30559039
The magnitude of improvement in progression-free survival with targeted therapy in relapsed/refractory chronic lymphocytic leukemia based on prognostic risk category: a systematic review and meta-analysis. Leukemia & lymphoma Molica, S., Giannarelli, D., Mirabelli, R., Levato, L., Shanafelt, T. D. 2018: 1–6
Abstract

Chronic lymphocytic leukemia (CLL) guidelines highlight the relevance of cytogenetic and molecular testing to identify patients with high-risk genetic features. However, at the moment, only 17p del/TP53 mutation are universally recognized parameters influencing choice of therapy. We conducted a systematic review and meta-analysis assessing the magnitude of improvement in progression-free survival (PFS) with B-cell receptor (BCR) (i.e. ibrutinib and idelalisib) or BCL2 (i.e. venetoclax) pathway inhibitors based on the presence or absence of 17p deletion/TP53 mutations, 11q deletion and IGHV mutational status in relapsed/refractory (R/R) CLL patients. Meta-analysis of seven randomized trials comprising 2409 patients with R/R CLL revealed that improvement over traditional treatments observed with BCR or BCL2 pathway inhibitors is common to all patients, including those patients with unfavorable and favorable prognostic parameters. These findings provide quantitative evidence to support the choice of therapy in R/R CLL not solely on the basis of 17p del/TP53 mutations.

View details for PubMedID 30516079
Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis. British journal of haematology Brown, J. R., Moslehi, J., Ewer, M. S., O'Brien, S. M., Ghia, P., Cymbalista, F., Shanafelt, T. D., Fraser, G., Rule, S., Coutre, S. E., Dilhuydy, M., Cramer, P., Jaeger, U., Dreyling, M., Byrd, J. C., Treon, S., Liu, E. Y., Chang, S., Bista, A., Vempati, R., Boornazian, L., Valentino, R., Reddy, V., Mahler, M., Yang, H., Graef, T., Burger, J. A. 2018
Abstract

Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B-cell malignancies. In ibrutinib clinical studies, low-grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N=1768), including 4 randomised controlled trials (RCTs). Rates of any-grade bleeding were similar for single-agent ibrutinib and ibrutinib combinations (39% and 40%). Low-grade bleeding was more common in ibrutinib-treated than comparator-treated patients (35% and 15%), and early low-grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13months vs. 6months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person-months). MH led to treatment discontinuation in 1% of all ibrutinib-treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure-adjusted relative risk for MH in both the total ibrutinib-treated population (1.9; 95% confidence interval, 1.2-3.0) and RCT comparator-treated patients (2.4; 95% confidence interval, 1.0-5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B-cell malignancies.

View details for PubMedID 30506764
Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Chronic Lymphocytic Leukemia (CLL) Driver Genes: Risk of CLL and Monoclonal B-Cell Lymphocytosis (MBL) Boddicker, N. J., O'Brien, D. R., Braggio, E., Achenbach, S. J., Chaffee, K. G., Norman, A. D., Vachon, C. M., Kabat, B., Call, T. G., Parikh, S. A., Leis, J. F., Ding, W., Muchtar, E., Cerhan, J. R., Shanafelt, T. D., Kay, N. E., Caporaso, N. E., Slager, S. L. AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-117044

View details for Web of Science ID 000454842800270
Telomere Length Is Associated with Epigenetic Programming in CLL and Is a Superior Predictor of Clinical Outcome with the Ability to Bifurcate Patients with the Same CLL-IPI Score Norris, K., Oakes, C. C., Giacopelli, B., Shanafelt, T. D., Kay, N. E., Chaffee, K. G., Fegan, C., Baird, D. M., Pepper, C. AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-114488

View details for Web of Science ID 000454837605188
Risk Model for Overall Survival for Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Validated for Patients on Ibrutinib, Idelalisib, Venetoclax, or Chemoimmuniotheraphy Soumerai, J. D., Ni, A., Darif, M., Londhe, A., Xing, G., Mun, Y., Kay, N. E., Shanafelt, T. D., Chaffee, K. G., Furman, R. R., Hillmen, P., Sharman, J., Seymour, J. F., Chanan-Khan, A. A., Byrd, J. C., Jones, J. A., Ferrante, L. A., Dreiling, L. K., Mobasher, M., Stark, T., Reddy, V., Howes, A. J., James, D., Bhargava, P., Zelenetz, A. D. AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-112989

View details for Web of Science ID 000454842804063
Association between the Risk of Low/High-Count Monoclonal B-Cell Lymphocytosis (MBL) and the Chronic Lymphocytic Leukemia (CLL) Polygenic Risk Score (PRS) Kleinstern, G., Achenbach, S. J., Robinson, D. P., Norman, A. D., Chaffee, K. G., Lesnick, C. E., Parikh, S. A., Call, T. G., Olson, J. E., Cerhan, J. R., Kay, N. E., Hanson, C. A., Shanafelt, T. D., Slager, S. L. AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-116414

View details for Web of Science ID 000454842806381
The Magnitude of Improvement in Progression-Free Survival with Targeted Therapy in Relapsed/Refractory Chronic Lymphocytic Leukemia Based on Genetic Risk: A Systematic Review and Meta-Analysis Molica, S., Giannarelli, D., Mirabelli, R., Levato, L., Shanafelt, T. D. AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-112580

View details for Web of Science ID 000454842806406
Predictive value of the CLL-IPI in CLL patients receiving chemo-immunotherapy as first-line treatment EUROPEAN JOURNAL OF HAEMATOLOGY Gentile, M., Shanafelt, T. D., Mauro, F., Reda, G., Rossi, D., Laurenti, L., Del Principe, M., Cutrona, G., Angeletti, I., Coscia, M., Herishanu, Y., Chiarenza, A., Molica, S., Ciolli, S., Goldschmidt, N., Angrilli, F., Giordano, A., Rago, A., Bairey, O., Tripepi, G., Chaffee, K. G., Sameer, P. A., Vigna, E., Zirlik, K., Shvidel, L., Innocenti, I., Recchia, A., Di Raimondo, F., Del Poeta, G., Cortelezzi, A., Neri, A., Ferrarini, M., Gaidano, G., Kay, N. E., Polliack, A., Foa, R., Morabito, F. 2018; 101 (5): 703–6
View details for PubMedID 30039576
Autoimmune cytopenias in patients with chronic lymphocytic leukaemia treated with ibrutinib in routine clinical practice at an academic medical centre BRITISH JOURNAL OF HAEMATOLOGY Hampel, P. J., Larson, M. C., Kabat, B., Call, T. G., Ding, W., Kenderian, S. S., Bowen, D., Boysen, J., Schwager, S. M., Leis, J. F., Chanan-Khan, A. A., Muchtar, E., Hanson, C. A., Slager, S. L., Kay, N. E., Chaffee, K. G., Shanafelt, T. D., Parikh, S. A. 2018; 183 (3): 421–27
Abstract

The effects of ibrutinib on the natural history of autoimmune cytopenias (AIC) among chronic lymphocytic leukaemia (CLL) patients treated in routine clinical practice require further investigation. Using the Mayo Clinical CLL Database, 193 CLL patients treated with ibrutinib between November 2013 and January 2017 outside the context of a clinical trial were identified; complete review of their medical records was performed for details of past history of AIC and treatment-emergent AIC. We identified 29/193 (15%) patients with history of AIC prior to ibrutinib start. Of 12 patients requiring AIC therapy at ibrutinib start, 8 (67%) were able to discontinue or de-escalate AIC treatment, and no patient had worsening of their AIC after initiating ibrutinib. Eleven (6%) patients developed treatment-emergent AIC after a median of 59 (range, 6-319) days following the initiation of ibrutinib, 7 of whom (64%) were able to continue ibrutinib. Overall and event-free survival from time of ibrutinib start were not significantly different between patients with history of AIC and those with no history of AIC. Treatment-emergent AIC were seen exclusively in patients with unmutated IGHV and were associated with a shorter EFS. These results suggest a low rate of treatment-emergent AIC and improvement in patients with existing AIC.

View details for PubMedID 30117139

View details for PubMedCentralID PMC6234062
In Reply-Burnout Is Not Associated With Increased Medical Errors. Mayo Clinic proceedings Tawfik, D. S., Profit, J., Morgenthaler, T. I., Satele, D. V., Sinsky, C., Dyrbye, L., Tutty, M., West, C. P., Shanafelt, T. D. 2018; 93 (11): 1683–84
View details for PubMedID 30392548
In Reply-Burnout Is Not Associated With Increased Medical Errors MAYO CLINIC PROCEEDINGS Tawfik, D. S., Profit, J., Morgenthaler, T. I., Satele, D. V., Sinsky, C., Dyrbye, L., Tutty, M., West, C. P., Shanafelt, T. D. 2018; 93 (11): 1683–84
View details for DOI 10.1016/j.mayocp.2018.08.014

View details for Web of Science ID 000448967300021
Physician and Nurse Well-Being: Seven Things Hospital Boards Should Know. Journal of healthcare management / American College of Healthcare Executives Shanafelt, T., Swensen, S. J., Woody, J., Levin, J., Lillie, J. 2018; 63 (6): 363–69
View details for PubMedID 30418362
Age and sex differences in burnout, career satisfaction, and well-being in US neurologists. Neurology LaFaver, K., Miyasaki, J. M., Keran, C. M., Rheaume, C., Gulya, L., Levin, K. H., Jones, E. C., Schwarz, H. B., Molano, J. R., Hessler, A., Singhal, D., Shanafelt, T. D., Sloan, J. A., Novotny, P. J., Cascino, T. L., Busis, N. A. 2018
Abstract

OBJECTIVE: To examine age and sex differences in burnout, career satisfaction, and well-being in US neurologists.METHODS: Quantitative and qualitative analyses of men's (n = 1,091) and women's (n = 580) responses to a 2016 survey of US neurologists.RESULTS: Emotional exhaustion in neurologists initially increased with age, then started to decrease as neurologists got older. Depersonalization decreased as neurologists got older. Fatigue and overall quality of life in neurologists initially worsened with age, then started to improve as neurologists got older. More women (64.6%) than men (57.8%) met burnout criteria on univariate analysis. Women respondents were younger and more likely to work in academic and employed positions. Sex was not an independent predictive factor of burnout, fatigue, or overall quality of life after controlling for age. In both men and women, greater autonomy, meaning in work, reasonable amount of clerical tasks, and having effective support staff were associated with lower burnout risk. More hours worked, more nights on call, higher outpatient volume, and higher percent of time in clinical practice were associated with higher burnout risk. For women, greater number of weekends doing hospital rounds was associated with higher burnout risk. Women neurologists made proportionately more negative comments than men regarding workload, work-life balance, leadership and deterioration of professionalism, and demands of productivity eroding the academic mission.CONCLUSIONS: We identified differences in burnout, career satisfaction, and well-being in neurologists by age and sex. This may aid in developing strategies to prevent and mitigate burnout and promote professional fulfillment for different demographic subgroups of neurologists.

View details for DOI 10.1212/WNL.0000000000006497

View details for PubMedID 30305448
A simple score based on geriatric assessment predicts survival in elderly newly diagnosed chronic lymphocytic leukemia patients. Leukemia & lymphoma Molica, S., Giannarelli, D., Levato, L., Mirabelli, R., Levato, D., Lentini, M., Piro, E. 2018: 1–3
View details for DOI 10.1080/10428194.2018.1508674

View details for PubMedID 30277125
Chronic lymphocytic leukemia international prognostic index (CLL-IPI) in patients receiving chemoimmuno or targeted therapy: a systematic review and meta-analysis ANNALS OF HEMATOLOGY Molica, S., Giannarelli, D., Mirabelli, R., Levato, L., Shanafelt, T. D. 2018; 97 (10): 2005–8
View details for PubMedID 29740683
Emotional Intelligence as a Possible Safeguard to Surgeon Wellness Lee, E. W., Hasty, B. N., Lau, J. N., Merrell, S., Hawn, M. T., Shanafelt, T., Salles, A., Lin, D. T. ELSEVIER SCIENCE INC. 2018: S145
View details for DOI 10.1016/j.jamcollsurg.2018.07.307

View details for Web of Science ID 000447760600278
Surgeon Emotional Intelligence Is Strongly Correlated with Patient Satisfaction Lee, E. W., Hasty, B. N., Lau, J. N., Merrell, S., Hawn, M. T., Shanafelt, T., Salles, A., Lin, D. T. ELSEVIER SCIENCE INC. 2018: S164–S165
View details for DOI 10.1016/j.jamcollsurg.2018.07.350

View details for Web of Science ID 000447760600321
Association of Clinical Specialty With Symptoms of Burnout and Career Choice Regret Among US Resident Physicians JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Dyrbye, L. N., Burke, S. E., Hardeman, R. R., Herrin, J., Wittlin, N. M., Yeazel, M., Dovidio, J. F., Cunningham, B., White, R. O., Phelan, S. M., Satele, D. V., Shanafelt, T. D., van Ryn, M. 2018; 320 (11): 1114–30
View details for DOI 10.1001/jama.2018.12615

View details for Web of Science ID 000444878600013
A Prognostic Index to Identify the Risk of Developing Depression Symptoms Among U.S. Medical Students Derived From A National, Four-Year Longitudinal Study. Academic medicine : journal of the Association of American Medical Colleges Dyrbye, L. N., Wittlin, N. M., Hardeman, R. R., Yeazel, M., Herrin, J., Dovidio, J. F., Burke, S. E., Cunningham, B., Phelan, S. M., Shanafelt, T. D., van Ryn, M. 2018
Abstract

PURPOSE: To determine baseline individual and school-related factors associated with increased risk of developing depression symptoms by year four (Y4) of medical school, and to develop a prognostic index that stratifies risk of developing depression symptoms (Depression-PI) among medical students.METHOD: The authors analyzed data from 3,743 students (79% of 4,732) attending 49 U.S. medical schools who completed baseline (2010) and Y4 (2014) surveys. Surveys included validated scales measuring depression, stress, coping, and social support. The authors collected demographics and school characteristics and conducted multivariate analysis to identify baseline factors independently associated with Y4 depression symptoms. They used these factors to create a prognostic index for developing depression. They randomly divided the data into discovery (n = 2,455) and replication (n = 1,288) datasets and calculated c-statistics (c).RESULTS: The authors identified eight independent prognostic factors for experiencing depression symptoms during training within the discovery dataset: age, race, ethnicity, tuition, plus baseline depression symptoms, stress, coping behaviors, and social support. The Depression-PI stratified four risk groups. Compared to the low risk group, those in the intermediate, high, and very high risk group had an odds ratio of developing depression of, respectively, 1.75, 3.98, and 9.19 (c = 0.71). The replication dataset confirmed the risk groups.CONCLUSIONS: Demographics, tuition, depression symptoms, stress, coping behaviors, and social support at baseline are independently associated with the risk of developing depression during training among U.S. medical students. By stratifying students into four risk groups, the Depression-PI may allow for a tiered primary prevention approach.

View details for PubMedID 30188367
Immunoglobulin heavy chain variable region gene and prediction of time to first treatment in patients with chronic lymphocytic leukemia: Mutational load or mutational status? Analysis of 1003 cases AMERICAN JOURNAL OF HEMATOLOGY Morabito, F., Shanafelt, T. D., Gentile, M., Reda, G., Mauro, F., Rossi, D., Di Renzo, N., Molica, S., Angrilli, F., Chiarenza, A., Cutrona, G., Chaffee, K. G., Parikh, S. A., Tripepi, G., D'Arrigo, G., Vigna, E., Recchia, A., Cortelezzi, A., Gaidano, G., Di Raimondo, F., Fais, F., Foa, R., Neri, A., Ferrarini, M. 2018; 93 (9): E216–E219
View details for PubMedID 29984867
Efficacy of the Well-Being Index to Identify Distress and Well-Being in U.S. Nurses. Nursing research Dyrbye, L. N., Johnson, P. O., Johnson, L. M., Satele, D., Shanafelt, T. 2018
Abstract

BACKGROUND: Studies suggest there is a high prevalence of burnout and depression among U.S. nurses.OBJECTIVES: To gauge the capability of the Well-Being Index (WBI) to stratify nurse distress (e.g., low quality of life [QOL], extreme fatigue, burnout, recent suicidal ideation) and well-being (high quality of life), and detect those whose level of distress may negatively affect retention or work performance METHODS: In 2016, we conducted a cross-sectional survey of 3,147 U.S. nurses. The survey included the WBI and standard instruments to assess overall QOL, fatigue, burnout, recent suicidal ideation, patient-care errors, and intent to leave current job. We used Fisher exact test and Wilcoxon/2-sample t-test procedures with a 5% type I error rate and a two-sided alternative.RESULTS: Of the 812 (26%) nurses who completed the survey, 637 were eligible for the present analysis. Nurses with low mental QOL, extreme fatigue, recent suicidal ideation, or burnout had a higher total score (all P < .001) resulting in less favorable WBI scores. With a 17% pretest probability of low overall QOL, the WBI score can decrease the posttest probability of low QOL to 2% or increase it to 72%. The likelihood of high overall QOL decreased in a stepwise fashion from 3.38 to 0.04 as the WBI score increased. WBI score also stratified nurses' likelihood of reporting a recent patient-care error and/or intent to leave current job.The WBI is a useful screening tool to stratify both distress and well-being across a variety of domains in nurses and identify those nurses whose severity of distress may negatively affect patient care and retention.

View details for DOI 10.1097/NNR.0000000000000313

View details for PubMedID 30138124
Building a Program on Well-Being: Key Design Considerations to Meet the Unique Needs of Each Organization. Academic medicine : journal of the Association of American Medical Colleges Shanafelt, T., Trockel, M., Ripp, J., Murphy, M. L., Sandborg, C., Bohman, B. 2018
Abstract

The current health care practice environment has resulted in a crescendo of burnout among physicians, nurses, and advanced practice providers. Burnout among health care professionals is primarily caused by organizational factors rather than problems with personal resilience. Four major drivers motivate health care leaders to build well-being programs: the moral-ethical case (caring for their people), the business case (cost of turnover and lower quality), the tragic case (a physician suicide), and the regulatory case (accreditation requirements). Ultimately, health care provider burnout harms patients. The authors discuss the purpose; scope; structure and resources; metrics of success; and a framework for action for organizational well-being programs. The purpose such a program is to oversee organizational efforts to reduce the occupational risk for burnout, cultivate professional well-being among health care professionals and, in turn, optimize the function of health care systems. The program should measure, benchmark, and longitudinally assess these domains. The successful program will develop deep expertise regarding the drivers of professional fulfillment among health care professionals; an approach to evaluate system flaws and relevant dimensions of organizational culture; and knowledge and experience with specific tactics to foster improvement. Different professional disciplines have both shared challenges and unique needs. Effective programs acknowledge and address these differences rather than ignore them. Ultimately, a professional workforce with low burnout and high professional fulfillment is vital to providing the best care to patients. Vanguard institutions have embraced this understanding and are pursuing health care provider well-being as a core organizational strategy.

View details for PubMedID 30134268
Validation of a biological score to predict response in chronic lymphocytic leukemia patients treated front-line with bendamustine and rituximab LEUKEMIA Gentile, M., Shanafelt, T. D., Reda, G., Mauro, F., Zirlik, K., Ciolli, S., Laurenti, L., Del Principe, M., Rossi, D., Di Renzo, N., Molica, S., Angrilli, F., Coscia, M., Chiarenza, A., Giordano, A., Cutrona, G., Chaffee, K. G., Parikh, S. A., Uccello, G., Innocenti, I., Tripepi, G., D'Arrigo, G., Vigna, E., Recchia, A., Herishanu, Y., Shvidel, L., Tadmor, T., Cortelezzi, A., Del Poeta, G., Gaidano, G., Di Raimondo, F., Neri, A., Ferrarini, M., Foa, R., Polliack, A., Morabito, F. 2018; 32 (8): 1869–73
View details for PubMedID 29588545
Physician Burnout, Well-being, and Work Unit Safety Grades in Relationship to Reported Medical Errors. Mayo Clinic proceedings Tawfik, D. S., Profit, J., Morgenthaler, T. I., Satele, D. V., Sinsky, C. A., Dyrbye, L. N., Tutty, M. A., West, C. P., Shanafelt, T. D. 2018
Abstract

OBJECTIVE: To evaluate physician burnout, well-being, and work unit safety grades in relationship to perceived major medical errors.PARTICIPANTS AND METHODS: From August 28, 2014, to October 6, 2014, we conducted a population-based survey of US physicians in active practice regarding burnout, fatigue, suicidal ideation, work unit safety grade, and recent medical errors. Multivariate logistic regression and mixed-effects hierarchical models evaluated the associations among burnout, well-being measures, work unit safety grades, and medical errors.RESULTS: Of 6695 responding physicians in active practice, 6586 provided information on the areas of interest: 3574 (54.3%) reported symptoms of burnout, 2163 (32.8%) reported excessive fatigue, and 427 (6.5%) reported recent suicidal ideation, with 255 of 6563 (3.9%) reporting a poor or failing patient safety grade in their primary work area and 691 of 6586 (10.5%) reporting a major medical error in the prior 3 months. Physicians reporting errors were more likely to have symptoms of burnout (77.6% vs 51.5%; P<.001), fatigue (46.6% vs 31.2%; P<.001), and recent suicidal ideation (12.7% vs 5.8%; P<.001). In multivariate modeling, perceived errors were independently more likely to be reported by physicians with burnout (odds ratio [OR], 2.22; 95% CI, 1.79-2.76) or fatigue (OR, 1.38; 95% CI, 1.15-1.65) and those with incrementally worse work unit safety grades (OR, 1.70; 95% CI, 1.36-2.12; OR, 1.92; 95% CI, 1.48-2.49; OR, 3.12; 95% CI, 2.13-4.58; and OR, 4.37; 95% CI, 2.06-9.28 for grades of B, C, D, and F, respectively), adjusted for demographic and clinical characteristics.CONCLUSION: In this large national study, physician burnout, fatigue, and work unit safety grades were independently associated with major medical errors. Interventions to reduce rates of medical errors must address both physician well-being and work unit safety.

View details for PubMedID 30001832
The prevalence of non-chronic lymphocytic leukemia (CLL) phenotype monoclonal B-cell lymphocytosis (MBL) in a population-based cohort of US adults Parikh, S. A., Achenbach, S. J., Chaffee, K. G., Kay, N. E., Lesnick, C. E., Cerhan, J. R., Hanson, C. A., Shanafelt, T. D., Slager, S. L. AMER ASSOC CANCER RESEARCH. 2018
View details for DOI 10.1158/1538-7445.AM2018-3256

View details for Web of Science ID 000468819501078
Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis BLOOD Kleinstern, G., Camp, N. J., Goldin, L. R., Vachon, C. M., Vajdic, C. M., de Sanjose, S., Weinberg, J., Benavente, Y., Casabonne, D., Liebow, M., Nieters, A., Hjalgrim, H., Melbye, M., Glimelius, B., Adami, H., Boffetta, P., Brennan, P., Maynadie, M., McKay, J., Cocco, P., Shanafelt, T. D., Call, T. G., Norman, A. D., Hanson, C., Robinson, D., Chaffee, K. G., Brooks-Wilson, A. R., Monnereau, A., Clavel, J., Glenn, M., Curtin, K., Conde, L., Bracci, P. M., Morton, L. M., Cozen, W., Severson, R. K., Chanock, S. J., Spinelli, J. J., Johnston, J. B., Rothman, N., Skibola, C. F., Leis, J. F., Kay, N. E., Smedby, K. E., Berndt, S. I., Cerhan, J. R., Caporaso, N., Slager, S. L. 2018; 131 (23): 2541–51
Abstract

Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.

View details for PubMedID 29674426

View details for PubMedCentralID PMC5992865
Outcomes of a large cohort of individuals with clinically ascertained high-count monoclonal B-cell lymphocytosis HAEMATOLOGICA Parikh, S. A., Chaffee, K. G., Larson, M. C., Hampel, P. J., Call, T. G., Ding, W., Kenderian, S. S., Leis, J. F., Chanan-Khan, A. A., Conte, M. J., Bowen, D., Schwager, S. M., Slager, S. L., Hanson, C. A., Kay, N. E., Shanafelt, T. D. 2018; 103 (6): E237–E240
View details for PubMedID 29419435
Chronic lymphocytic leukaemia LANCET Hallek, M., Shanafelt, T. D., Eichhorst, B. 2018; 391 (10129): 1524–37
Abstract

Important advances in understanding the pathogenesis of chronic lymphocytic leukaemia in the past two decades have led to the development of new prognostic tools and novel targeted therapies that have improved clinical outcome. Chronic lymphocytic leukaemia is the most common type of leukaemia in developed countries, and the median age at diagnosis is 72 years. The criteria for initiating treatment rely on the Rai and Binet staging systems and on the presence of disease-related symptoms. For many patients with chronic lymphocytic leukaemia, treatment with chemotherapy and anti-CD20 monoclonal antibodies is the standard of care. The impressive efficacy of kinase inhibitors ibrutinib and idelalisib and the BCL-2 antagonist venetoclax have changed the standard of care in specific subsets of patients. In this Seminar, we review the recent progress in the management of chronic lymphocytic leukaemia and highlight new questions surrounding the optimal disease management.

View details for PubMedID 29477250
Physician Burnout-Overdiagnosis and Unproven Interventions Reply JAMA INTERNAL MEDICINE Shanafelt, T., Goh, J., Sinsky, C. 2018; 178 (4): 577–78
View details for PubMedID 29610889
Addressing Uncertainty in Burnout Assessment ACADEMIC MEDICINE Palamara, K., Linzer, M., Shanafelt, T. D. 2018; 93 (4): 518
View details for Web of Science ID 000428540700007
Chronic lymphocytic leukemia international prognostic index: a systematic review and meta-analysis BLOOD Molica, S., Giannarelli, D., Mirabelli, R., Levato, L., Kay, N. E., Shanafelt, T. D. 2018; 131 (3): 365–68
View details for PubMedID 29084773
Association of Clinical Specialty With Symptoms of Burnout and Career Choice Regret Among US Resident Physicians. JAMA Dyrbye, L. N., Burke, S. E., Hardeman, R. R., Herrin, J., Wittlin, N. M., Yeazel, M., Dovidio, J. F., Cunningham, B., White, R. O., Phelan, S. M., Satele, D. V., Shanafelt, T. D., van Ryn, M. 2018; 320 (11): 1114–30
Abstract

Burnout among physicians is common and has been associated with medical errors and lapses in professionalism. It is unknown whether rates for symptoms of burnout among resident physicians vary by clinical specialty and if individual factors measured during medical school relate to the risk of burnout and career choice regret during residency.To explore factors associated with symptoms of burnout and career choice regret during residency.Prospective cohort study of 4732 US resident physicians. First-year medical students were enrolled between October 2010 and January 2011 and completed the baseline questionnaire. Participants were invited to respond to 2 questionnaires; one during year 4 of medical school (January-March 2014) and the other during the second year of residency (spring of 2016). The last follow-up was on July 31, 2016.Clinical specialty, demographic characteristics, educational debt, US Medical Licensing Examination Step 1 score, and reported levels of anxiety, empathy, and social support during medical school.Prevalence during second year of residency of reported symptoms of burnout measured by 2 single-item measures (adapted from the Maslach Burnout Inventory) and an additional item that evaluated career choice regret (defined as whether, if able to revisit career choice, the resident would choose to become a physician again).Among 4696 resident physicians, 3588 (76.4%) completed the questionnaire during the second year of residency (median age, 29 [interquartile range, 28.0-31.0] years in 2016; 1822 [50.9%] were women). Symptoms of burnout were reported by 1615 of 3574 resident physicians (45.2%; 95% CI, 43.6% to 46.8%). Career choice regret was reported by 502 of 3571 resident physicians (14.1%; 95% CI, 12.9% to 15.2%). In a multivariable analysis, training in urology, neurology, emergency medicine, and general surgery were associated with higher relative risks (RRs) of reported symptoms of burnout (range of RRs, 1.24 to 1.48) relative to training in internal medicine. Characteristics associated with higher risk of reported symptoms of burnout included female sex (RR, 1.17 [95% CI, 1.07 to 1.28]; risk difference [RD], 7.2% [95% CI, 3.1% to 11.3%]) and higher reported levels of anxiety during medical school (RR, 1.08 per 1-point increase [95% CI, 1.06 to 1.11]; RD, 1.8% per 1-point increase [95% CI, 1.6% to 2.0%]). A higher reported level of empathy during medical school was associated with a lower risk of reported symptoms of burnout during residency (RR, 0.99 per 1-point increase [95% CI, 0.99 to 0.99]; RD, -0.5% per 1-point increase [95% CI, -0.6% to -0.3%]). Reported symptoms of burnout (RR, 3.20 [95% CI, 2.58 to 3.82]; RD, 15.0% [95% CI, 12.8% to 17.3%]) and clinical specialty (range of RRs, 1.66 to 2.60) were both significantly associated with career choice regret.Among US resident physicians, symptoms of burnout and career choice regret were prevalent, but varied substantially by clinical specialty. Further research is needed to better understand these differences and to address these issues.

View details for PubMedID 30422299
Work-life balance behaviours cluster in work settings and relate to burnout and safety culture: a cross-sectional survey analysis. BMJ quality & safety Schwartz, S. P., Adair, K. C., Bae, J., Rehder, K. J., Shanafelt, T. D., Profit, J., Sexton, J. B. 2018
Abstract

Healthcare is approaching a tipping point as burnout and dissatisfaction with work-life integration (WLI) in healthcare workers continue to increase. A scale evaluating common behaviours as actionable examples of WLI was introduced to measure work-life balance.(1) Explore differences in WLI behaviours by role, specialty and other respondent demographics in a large healthcare system. (2) Evaluate the psychometric properties of the work-life climate scale, and the extent to which it acts like a climate, or group-level norm when used at the work setting level. (3) Explore associations between work-life climate and other healthcare climates including teamwork, safety and burnout.Cross-sectional survey study completed in 2016 of US healthcare workers within a large academic healthcare system.10 627 of 13 040 eligible healthcare workers across 440 work settings within seven entities of a large healthcare system (81% response rate) completed the routine safety culture survey. The overall work-life climate scale internal consistency was α=0.830. WLI varied significantly among healthcare worker role, length of time in specialty and work setting. Random effects analyses of variance for the work-life climate scale revealed significant between-work setting and within-work setting variance and intraclass correlations reflected clustering at the work setting level. T-tests of top versus bottom WLI quartile work settings revealed that positive work-life climate was associated with better teamwork and safety climates, as well as lower personal burnout and burnout climate (p<0.001).Problems with WLI are common in healthcare workers and differ significantly based on position and time in specialty. Although typically thought of as an individual difference variable, WLI appears to operate as a climate, and is consistently associated with better safety culture norms.

View details for PubMedID 30309912
Reimagining Clinical Documentation With Artificial Intelligence. Mayo Clinic proceedings Lin, S. Y., Shanafelt, T. D., Asch, S. M. 2018
View details for PubMedID 29631808
Cumulative experience and long term follow-up of pentostatin-based chemoimmunotherapy trials for patients with chronic lymphocytic leukemia EXPERT REVIEW OF HEMATOLOGY Kay, N. E., LaPlant, B. R., Pettinger, A. M., Call, T. G., Leis, J. F., Ding, W., Parikh, S. A., Conte, M. J., Bowen, D. A., Shanafelt, T. D. 2018; 11 (4): 337–49
Abstract

7 regimens of pentostatin based chemoimmunotherapy (CIT) for progressive previously untreated CLL primarily with long term follow-up to update both efficacy and toxicity.Prognostic markers including assessment of IGVH and FISH status were done on all. Response rates and 95% binomial confidence intervals were calculated for each regimen and in the combined cohort. Overall survival and treatment-free survival were evaluated using Kaplan-Meier methods.The initial CIT trial was pentostatin (2 mgs/m2), cyclophosphamide (600 mg/m2) and rituximab (PCR) but subsequent P based CIT trials with modifications in subsequent trials. The cohort (n = 288) included 52% with unmutated IGVH status and del17p (4.5%) and del11q (14.9%). Toxicity profiles were primarily hematologic and no patient has developed MDS or AML after a median follow-up of 6.4 years. The overall response rate across all trials was found to be over 90% with a 41% complete response rate. We validated that the CLL IPI model segregates progressive CLL patients into 4 risk groups associated with OS and TFS.The high overall and complete response levels in favorable genetic risk CLL along with favorable toxicity profiles provide rationale for consideration of a PC based strategy for previously untreated progressive CLL.

View details for PubMedID 29460654
An Organization Model to Assist Individual Physicians, Scientists, and Senior Health Care Administrators With Personal and Professional Needs MAYO CLINIC PROCEEDINGS Shanafelt, T. D., Lightner, D. J., Conley, C. R., Petrou, S. P., Richardson, J. W., Schroeder, P. J., Brown, W. A. 2017; 92 (11): 1688–96
Abstract

Working as a physician, scientist, or senior health care administrator is a demanding career. Studies have demonstrated that burnout and other forms of distress are common among individuals in these professions, with potentially substantive personal and professional consequences. In addition to system-level interventions to promote well-being globally, health care organizations must provide robust support systems to assist individuals in distress. Here, we describe the 15-year experience of the Mayo Clinic Office of Staff Services (OSS) providing peer support to physicians, scientists, and senior administrators at one center. Resources for financial planning (retirement, tax services, college savings for children) and peer support to assist those experiencing distress are intentionally combined in the OSS to normalize the use of the Office and reduce the stigma associated with accessing peer support. The Office is heavily used, with approximately 75% of physicians, scientists, and senior administrators accessing the financial counseling and 5% to 7% accessing the peer support resources annually. Several critical structural characteristics of the OSS are specifically designed to minimize potential stigma and reduce barriers to seeking help. These aspects are described here with the hope that they may be informative to other medical practices considering how to create low-barrier access to help individuals deal with personal and professional challenges. We also detail the results of a recent pilot study designed to extend the activity of the OSS beyond the reactive provision of peer support to those seeking help by including regular, proactive check-ups for staff covering a range of topics intended to promote personal and professional well-being.

View details for DOI 10.1016/j.mayocp.2017.08.020

View details for Web of Science ID 000414202000014

View details for PubMedID 29101937
The Business Case for Investing in Physician Well-being. JAMA internal medicine Shanafelt, T., Goh, J., Sinsky, C. 2017
Abstract

Importance: Widespread burnout among physicians has been recognized for more than 2 decades. Extensive evidence indicates that physician burnout has important personal and professional consequences.Observations: A lack of awareness regarding the economic costs of physician burnout and uncertainty regarding what organizations can do to address the problem have been barriers to many organizations taking action. Although there is a strong moral and ethical case for organizations to address physician burnout, financial principles (eg, return on investment) can also be applied to determine the economic cost of burnout and guide appropriate investment to address the problem. The business case to address physician burnout is multifaceted and includes costs associated with turnover, lost revenue associated with decreased productivity, as well as financial risk and threats to the organization's long-term viability due to the relationship between burnout and lower quality of care, decreased patient satisfaction, and problems with patient safety. Nearly all US health care organizations have used similar evidence to justify their investments in safety and quality. Herein, we provide conservative formulas based on readily available organizational characteristics to determine the financial return on organizational investments to reduce physician burnout. A model outlining the steps of the typical organization's journey to address this issue is presented. Critical ingredients to making progress include prioritization by leadership, physician involvement, organizational science/learning, metrics, structured interventions, open communication, and promoting culture change at the work unit, leader, and organization level.Conclusions and Relevance: Understanding the business case to reduce burnout and promote engagement as well as overcoming the misperception that nothing meaningful can be done are key steps for organizations to begin to take action. Evidence suggests that improvement is possible, investment is justified, and return on investment measurable. Addressing this issue is not only the organization's ethical responsibility, it is also the fiscally responsible one.

View details for PubMedID 28973070
Development of a Research Agenda to Identify Evidence-Based Strategies to Improve Physician Wellness and Reduce Burnout ANNALS OF INTERNAL MEDICINE Dyrbye, L. N., Trockel, M., Frank, E., Olson, K., Linzer, M., Lemaire, J., Swensen, S., Shanafelt, T., Sinsky, C. A. 2017; 166 (10): 743-+
View details for PubMedID 28418518
A Brief Instrument to Assess Both Burnout and Professional Fulfillment in Physicians: Reliability and Validity, Including Correlation with Self-Reported Medical Errors, in a Sample of Resident and Practicing Physicians. Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry Trockel, M., Bohman, B., Lesure, E., Hamidi, M. S., Welle, D., Roberts, L., Shanafelt, T. 2017
Abstract

The objective of this study was to evaluate the performance of the Professional Fulfillment Index (PFI), a 16-item instrument to assess physicians' professional fulfillment and burnout, designed for sensitivity to change attributable to interventions or other factors affecting physician well-being.A sample of 250 physicians completed the PFI, a measure of self-reported medical errors, and previously validated measures including the Maslach Burnout Inventory (MBI), a one-item burnout measure, the World Health Organization's abbreviated quality of life assessment (WHOQOL-BREF), and PROMIS short-form depression, anxiety, and sleep-related impairment scales. Between 2 and 3 weeks later, 227 (91%) repeated the PFI and the sleep-related impairment scale.Principal components analysis justified PFI subscales for professional fulfillment, work exhaustion, and interpersonal disengagement. Test-retest reliability estimates were 0.82 for professional fulfillment (α = 0.91), 0.80 for work exhaustion (α = 0.86), 0.71 for interpersonal disengagement (α = 0.92), and 0.80 for overall burnout (α = 0.92). PFI burnout measures correlated highly (r ≥ 0.50) with their closest related MBI equivalents. Cohen's d effect size differences in self-reported medical errors for high versus low burnout classified using the PFI and the MBI were 0.55 and 0.44, respectively. PFI scales correlated in expected directions with sleep-related impairment, depression, anxiety, and WHOQOL-BREF scores. PFI scales demonstrated sufficient sensitivity to detect expected effects of a two-point (range 8-40) change in sleep-related impairment.PFI scales have good performance characteristics including sensitivity to change and offer a novel contribution by assessing professional fulfillment in addition to burnout.

View details for PubMedID 29196982
Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica Brown, J. R., Moslehi, J., O'Brien, S., Ghia, P., Hillmen, P., Cymbalista, F., Shanafelt, T. D., Fraser, G., Rule, S., Kipps, T. J., Coutre, S., Dilhuydy, M. S., Cramer, P., Tedeschi, A., Jaeger, U., Dreyling, M., Byrd, J. C., Howes, A., Todd, M., Vermeulen, J., James, D. F., Clow, F., Styles, L., Valentino, R., Wildgust, M., Mahler, M., Burger, J. A. 2017; 102 (10): 1796–1805
Abstract

The first-in-class Bruton's tyrosine kinase inhibitor ibrutinib has proven clinical benefit in B-cell malignancies; however, atrial fibrillation (AF) has been reported in 6-16% of ibrutinib patients. We pooled data from 1505 chronic lymphocytic leukemia and mantle cell lymphoma patients enrolled in four large, randomized, controlled studies to characterize AF with ibrutinib and its management. AF incidence was 6.5% [95% Confidence Interval (CI): 4.8, 8.5] for ibrutinib at 16.6-months versus 1.6% (95%CI: 0.8, 2.8) for comparator and 10.4% (95%CI: 8.4, 12.9) at the 36-month follow up; estimated cumulative incidence: 13.8% (95%CI: 11.2, 16.8). Ibrutinib treatment, prior history of AF and age 65 years or over were independent risk factors for AF. Multiple AF events were more common with ibrutinib (44.9%; comparator, 16.7%) among patients with AF. Most (85.7%) patients with AF did not discontinue ibrutinib, and more than half received common anticoagulant/antiplatelet medications on study. Low-grade bleeds were more frequent with ibrutinib, but serious bleeds were uncommon (ibrutinib, 2.9%; comparator, 2.0%). Although the AF rate among older non-trial patients with comorbidities is likely underestimated by this dataset, these results suggest that AF among clinical trial patients is generally manageable without ibrutinib discontinuation (clinicaltrials.gov identifier: 01578707, 01722487, 01611090, 01646021).

View details for PubMedID 28751558
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia NATURE COMMUNICATIONS Berndt, S. I., Camp, N. J., Skibola, C. F., Vijai, J., Wang, Z., Gu, J., Nieters, A., Kelly, R. S., Smedby, K. E., Monnereau, A., Cozen, W., Cox, A., Wang, S. S., Lan, Q., Teras, L. R., Machado, M., Yeager, M., Brooks-Wilson, A. R., Hartge, P., Purdue, M. P., Birmann, B. M., Vajdic, C. M., Cocco, P., Zhang, Y., Giles, G. G., Zeleniuch-Jacquotte, A., Lawrence, C., Montalvan, R., Burdett, L., Hutchinson, A., Ye, Y., Call, T. G., Shanafelt, T. D., Novak, A. J., Kay, N. E., Liebow, M., Cunningham, J. M., Allmer, C., Hjalgrim, H., Adami, H., Melbye, M., Glimelius, B., Chang, E. T., Glenn, M., Curtin, K., Cannon-Albright, L. A., Diver, W. R., Link, B. K., Weiner, G. J., Conde, L., Bracci, P. M., Riby, J., Arnett, D. K., Zhi, D., Leach, J. M., Holly, E. A., Jackson, R. D., Tinker, L. F., Benavente, Y., Sala, N., Casabonne, D., Becker, N., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., McKay, J., Staines, A., Chaffee, K. G., Achenbach, S. J., Vachon, C. M., Goldin, L. R., Strom, S. S., Leis, J. F., Weinberg, J. B., Caporaso, N. E., Norman, A. D., De Roos, A. J., Morton, L. M., Severson, R. K., Riboli, E., Vineis, P., Kaaks, R., Masala, G., Weiderpass, E., Chirlaque, M., Vermeulen, R. C., Travis, R. C., Southey, M. C., Milne, R. L., Albanese, D., Virtamo, J., Weinstein, S., Clavel, J., Zheng, T., Holford, T. R., Villano, D. J., Maria, A., Spinelli, J. J., Gascoyne, R. D., Connors, J. M., Bertrand, K. A., Giovannucci, E., Kraft, P., Kricker, A., Turner, J., Ennas, M. G., Ferri, G. M., Miligi, L., Liang, L., Ma, B., Huang, J., Crouch, S., Park, J., Chatterjee, N., North, K. E., Snowden, J. A., Wright, J., Fraumeni, J. F., Offit, K., Wu, X., de Sanjose, S., Cerhan, J. R., Chanock, S. J., Rothman, N., Slager, S. L. 2016; 7
Abstract

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

View details for DOI 10.1038/ncomms10933

View details for PubMedID 26956414
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Sampson, J. N., Wheeler, W. A., Yeager, M., Panagiotou, O., Wang, Z., Berndt, S. I., Lan, Q., Abnet, C. C., Amundadottir, L. T., Figueroa, J. D., Landi, M. T., Mirabello, L., Savage, S. A., Taylor, P. R., De Vivo, I., McGlynn, K. A., Purdue, M. P., Rajaraman, P., Adami, H., Ahlbom, A., Albanes, D., Amary, M. F., An, S., Andersson, U., Andriole, G., Andrulis, I. L., Angelucci, E., Ansell, S. M., Arici, C., Armstrong, B. K., Arslan, A. A., Austin, M. A., Baris, D., Barkauskas, D. A., Bassig, B. A., Becker, N., Benavente, Y., Benhamou, S., Berg, C., Van Den Berg, D., Bernstein, L., Bertrand, K. A., Birmann, B. M., Black, A., Boeing, H., Boffetta, P., Boutron-Ruault, M., Bracci, P. M., Brinton, L., Brooks-Wilson, A. R., Bueno-de-Mesquita, H. B., Burdett, L., Buring, J., Butler, M. A., Cai, Q., Cancel-Tassin, G., Canzian, F., Carrato, A., Carreon, T., Carta, A., Chan, J. K., Chang, E. T., Chang, G., Chang, I., Chang, J., Chang-Claude, J., Chen, C., Chen, C., Chen, C., Chen, C., Chen, C., Chen, H., Chen, K., Chen, K., Chen, K., Chen, Y., Chen, Y., Chen, Y., Chen, Y., Chien, L., Chirlaque, M., Choi, J. E., Choi, Y. Y., Chow, W., Chung, C. C., Clavel, J., Clavel-Chapelon, F., Cocco, P., Colt, J. S., Comperat, E., Conde, L., Connors, J. M., Conti, D., Cortessis, V. K., Cotterchio, M., Cozen, W., Crouch, S., Crous-Bou, M., Cussenot, O., Davis, F. G., Ding, T., Diver, W. R., Dorronsoro, M., Dossus, L., Duell, E. J., Ennas, M. G., Erickson, R. L., Feychting, M., Flanagan, A. M., Foretova, L., Fraumeni, J. F., Freedman, N. D., Freeman, L. E., Fuchs, C., Gago-Dominguez, M., Gallinger, S., Gao, Y., Gapstur, S. M., Garcia-Closas, M., Garcia-Closas, R., Gascoyne, R. D., Gastier-Foster, J., Gaudet, M. M., Gaziano, J. M., Giffen, C., Giles, G. G., Giovannucci, E., Glimelius, B., Goggins, M., Gokgoz, N., Goldstein, A. M., Gorlick, R., Gross, M., Grubb, R., Gu, J., Guan, P., Gunter, M., Guo, H., Habermann, T. M., Haiman, C. A., Halai, D., Hallmans, G., Hassan, M., Hattinger, C., He, Q., He, X., Helzlsouer, K., Henderson, B., Henriksson, R., Hjalgrim, H., Hoffman-Bolton, J., Hohensee, C., Holford, T. R., Holly, E. A., Hong, Y., Hoover, R. N., Horn-Ross, P. L., Hosain, G. M., Hosgood, H. D., Hsiao, C., Hu, N., Hu, W., Hu, Z., Huang, M., Huerta, J., Hung, J., Hutchinson, A., Inskip, P. D., Jackson, R. D., Jacobs, E. J., Jenab, M., Jeon, H., Ji, B., Jin, G., Jin, L., Johansen, C., Johnson, A., Jung, Y. J., Kaaks, R., Kamineni, A., Kane, E., Kang, C. H., Karagas, M. R., Kelly, R. S., Khaw, K., Kim, C., Kim, H. N., Kim, J. H., Kim, J. S., Kim, Y. H., Kim, Y. T., Kim, Y., Kitahara, C. M., Klein, A. P., Klein, R. J., Kogevinas, M., Kohno, T., Kolonel, L. N., Kooperberg, C., Kricker, A., Krogh, V., Kunitoh, H., Kurtz, R. C., Kweon, S., LaCroix, A., Lawrence, C., Lecanda, F., Lee, V. H., Li, D., Li, H., Li, J., Li, Y., Li, Y., Liao, L. M., Liebow, M., Lightfoot, T., Lim, W., Lin, C., Lin, D., Lindstrom, S., Linet, M. S., Link, B. K., Liu, C., Liu, J., Liu, L., Ljungberg, B., Lloreta, J., di Lollo, S., Lu, D., Lund, E., Malats, N., Mannisto, S., Le Marchand, L., Marina, N., Masala, G., Mastrangelo, G., Matsuo, K., Maynadie, M., McKay, J., McKean-Cowdin, R., Melbye, M., Melin, B. S., Michaud, D. S., Mitsudomi, T., Monnereau, A., Montalvan, R., Moore, L. E., Mortensen, L. M., Nieters, A., North, K. E., Novak, A. J., Oberg, A. L., Offit, K., Oh, I., Olson, S. H., Palli, D., Pao, W., Park, I. K., Park, J. Y., Park, K. H., Patino-Garcia, A., Pavanello, S., Peeters, P. H., Perng, R., Peters, U., Petersen, G. M., Picci, P., Pike, M. C., Porru, S., Prescott, J., Prokunina-Olsson, L., Qian, B., Qiao, Y., Rais, M., Riboli, E., Riby, J., Risch, H. A., Rizzato, C., Rodabough, R., Roman, E., Roupret, M., Ruder, A. M., de Sanjose, S., Scelo, G., Schned, A., Schumacher, F., Schwartz, K., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H. D., Setiawan, V. W., Severi, G., Severson, R. K., Shanafelt, T. D., Shen, H., Shen, W., Shin, M., Shiraishi, K., Shu, X., Siddiq, A., Sierrasesumaga, L., Sihoe, A. D., Skibola, C. F., Smith, A., Smith, M. T., Southey, M. C., Spinelli, J. J., Staines, A., Stampfer, M., Stern, M. C., Stevens, V. L., Stolzenberg-Solomon, R. S., Su, J., Su, W., Sund, M., Sung, J. S., Sung, S. W., Tan, W., Tang, W., Tardon, A., Thomas, D., Thompson, C. A., Tinker, L. F., Tirabosco, R., Tjonneland, A., Travis, R. C., Trichopoulos, D., Tsai, F., Tsai, Y., Tucker, M., Turner, J., Vajdic, C. M., Vermeulen, R. C., Villano, D. J., Vineis, P., Virtamo, J., Visvanathan, K., Wactawski-Wende, J., Wang, C., Wang, C., Wang, J., Wang, J., Wei, F., Weiderpass, E., Weiner, G. J., Weinstein, S., Wentzensen, N., White, E., Witzig, T. E., Wolpin, B. M., Wong, M. P., Wu, C., Wu, G., Wu, J., Wu, T., Wu, W., Wu, X., Wu, Y., Wunder, J. S., Xiang, Y., Xu, J., Xu, P., Yang, P., Yang, T., Ye, Y., Yin, Z., Yokota, J., Yoon, H., Yu, C., Yu, H., Yu, K., Yuan, J., Zelenetz, A., Zeleniuch-Jacquotte, A., Zhang, X., Zhang, Y., Zhao, X., Zhao, Z., Zheng, H., Zheng, T., Zheng, W., Zhou, B., Zhu, M., Zucca, M., Boca, S. M., Cerhan, J. R., Ferri, G. M., Hartge, P., Hsiung, C. A., Magnani, C., Miligi, L., Morton, L. M., Smedby, K. E., Teras, L. R., Vijai, J., Wang, S. S., Brennan, P., Caporaso, N. E., Hunter, D. J., Kraft, P., Rothman, N., Silverman, D. T., Slager, S. L., Chanock, S. J., Chatterjee, N. 2015; 107 (12)
Abstract

Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

View details for DOI 10.1093/jnci/djv279

View details for Web of Science ID 000366970900015

View details for PubMedID 26464424

View details for PubMedCentralID PMC4806328
The Impact of Stigma and Personal Experiences on the Help-Seeking Behaviors of Medical Students With Burnout ACADEMIC MEDICINE Dyrbye, L. N., Eacker, A., Durning, S. J., Brazeau, C., Moutier, C., Massie, F. S., Satele, D., Sloan, J. A., Shanafelt, T. D. 2015; 90 (7): 961-969
Abstract

Because of the high prevalence of burnout among medical students and its association with professional and personal consequences, the authors evaluated the help-seeking behaviors of medical students with burnout and compared their stigma perceptions with those of the general U.S. population and age-matched individuals.The authors surveyed students at six medical schools in 2012. They measured burnout, symptoms of depression, and quality of life using validated instruments and explored help-seeking behaviors, perceived stigma, personal experiences, and attitudes toward seeking mental health treatment.Of 2,449 invited students, 873 (35.6%) responded. A third of respondents with burnout (154/454; 33.9%) sought help for an emotional/mental health problem in the last 12 months. Respondents with burnout were more likely than those without burnout to agree or strongly agree with 8 of 10 perceived stigma items. Respondents with burnout who sought help in the last 12 months were twice as likely to report having observed supervisors negatively judge students who sought care (odds ratio [OR] 2.06 [95% confidence interval (CI) 1.25-3.39], P < .01). They also were more likely to have observed peers reveal a student's emotional/mental health problem to others (OR 1.63 [95% CI 1.08-2.47], P = .02). A smaller percentage of respondents would definitely seek professional help for a serious emotional problem (235/872; 26.9%) than of the general population (44.3%) and age-matched individuals (38.8%).Only a third of medical students with burnout seek help. Perceived stigma, negative personal experiences, and the hidden curriculum may contribute.

View details for DOI 10.1097/ACM.0000000000000655

View details for Web of Science ID 000357094100011

View details for PubMedID 25650824
Distress Among Matriculating Medical Students Relative to the General Population ACADEMIC MEDICINE Brazeau, C. M., Shanafelt, T., Durning, S. J., Massie, F. S., Eacker, A., Moutier, C., Satele, D. V., Sloan, J. A., Dyrbye, L. N. 2014; 89 (11): 1520-1525
Abstract

Many medical students experience distress during medical school. If matriculating medical students (MMSs) begin training with similar or better mental health than age-similar controls, this would support existing concerns about the negative impact of training on student well-being. The authors compared mental health indicators of MMSs versus those of a probability-based sample of the general U.S. population.In 2012 all MMSs at six U.S. medical schools were invited to participate in a survey during orientation. The research team surveyed a probability-based sample of U.S. individuals using the same questions in 2011. Individuals from the population sample who completed a four-year college degree and matched within the appropriate age strata (< 30, 31-35, 36-40, > 40) were compared with MMSs. Surveys included demographics and validated instruments to measure burnout; depression symptoms; and mental, emotional, physical, and overall of quality of life (QOL).Demographic characteristics of the 582/938 (62%) responding MMSs were similar to U.S. MMSs. Relative to 546 age-similar college graduates, MMSs had lower rates of burnout (27.3% versus 37.3%, P < .001) and depression symptoms (26.2% versus 42.4%, P < .0001) and higher scores across the four QOL domains assessed relative to controls (all P < .0001). These findings persisted on multivariate analysis after adjusting for age, sex, relationship status, and race/ethnicity.These findings, along with high rates of distress reported in medical students and residents, support concerns that the training process and environment contribute to the deterioration of mental health in developing physicians.

View details for DOI 10.1097/ACM.0000000000000482

View details for Web of Science ID 000343897500028

View details for PubMedID 25250752
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia NATURE GENETICS Berndt, S. I., Skibola, C. F., Joseph, V., Camp, N. J., Nieters, A., Wang, Z., Cozen, W., Monnereau, A., Wang, S. S., Kelly, R. S., Lan, Q., Teras, L. R., Chatterjee, N., Chung, C. C., Yeager, M., Brooks-Wilson, A. R., Hartge, P., Purdue, M. P., Birmann, B. M., Armstrong, B. K., Cocco, P., Zhang, Y., Severi, G., Zeleniuch-Jacquotte, A., Lawrence, C., Burdette, L., Yuenger, J., Hutchinson, A., Jacobs, K. B., Call, T. G., Shanafelt, T. D., Novak, A. J., Kay, N. E., Liebow, M., Wang, A. H., Smedby, K. E., Adami, H., Melbye, M., Glimelius, B., Chang, E. T., Glenn, M., Curtin, K., Cannon-Albright, L. A., Jones, B., Diver, W. R., Link, B. K., Weiner, G. J., Conde, L., Bracci, P. M., Riby, J., Holly, E. A., Smith, M. T., Jackson, R. D., Tinker, L. F., Benavente, Y., Becker, N., Boffetta, P., Brennan, P., Foretova, L., Maynadie, M., McKay, J., Staines, A., Rabe, K. G., Achenbach, S. J., Vachon, C. M., Goldin, L. R., Strom, S. S., Lanasa, M. C., Spector, L. G., Leis, J. F., Cunningham, J. M., Weinberg, J. B., Morrison, V. A., Caporaso, N. E., Norman, A. D., Linet, M. S., De Roos, A. J., Morton, L. M., Severson, R. K., Riboli, E., Vineis, P., Kaaks, R., Trichopoulos, D., Masala, G., Weiderpass, E., Chirlaque, M., Vermeulen, R. C., Travis, R. C., Giles, G. G., Albanes, D., Virtamo, J., Weinstein, S., Clavel, J., Zheng, T., Holford, T. R., Offit, K., Zelenetz, A., Klein, R. J., Spinelli, J. J., Bertrand, K. A., Laden, F., Giovannucci, E., Kraft, P., Kricker, A., Turner, J., Vajdic, C. M., Ennas, M. G., Ferri, G. M., Miligi, L., Liang, L., Sampson, J., Crouch, S., Park, J., North, K. E., Cox, A., Snowden, J. A., Wright, J., Carracedo, A., Lopez-Otin, C., Bea, S., Salaverria, I., Martin-Garcia, D., Campo, E., Fraumeni, J. F., de Sanjose, S., Hjalgrim, H., Cerhan, J. R., Chanock, S. J., Rothman, N., Slager, S. L. 2013; 45 (8): 868-U202
View details for DOI 10.1038/ng.2652

View details for Web of Science ID 000322374900008

View details for PubMedID 23770605
A Multi-institutional Study Exploring the Impact of Positive Mental Health on Medical Students' Professionalism in an Era of High Burnout ACADEMIC MEDICINE Dyrbye, L. N., Harper, W., Moutier, C., Durning, S. J., Power, D. V., Massie, F. S., Eacker, A., Thomas, M. R., Satele, D., Sloan, J. A., Shanafelt, T. D. 2012; 87 (8): 1024-1031
Abstract

Although burnout is associated with erosion of professionalism and serious personal consequences, whether positive mental health can enhance professionalism and how it shapes personal experience remain poorly understood. The study simultaneously explores the relationship between positive mental health and burnout with professionalism and personal experience.The authors surveyed 4,400 medical students at seven U.S. medical schools in 2009 to assess mental health (categorized as languishing, moderate, and flourishing) and burnout. Additional items explored professional behaviors, beliefs, suicidal ideation, and serious thoughts of dropping out.A total of 2,682/4,400 (61%) responded. Prevalence of suicidal ideation (55/114 [48.2%], 281/1,128 [24.9%], and 127/1,409 [9.1%]) and serious thoughts of dropping out (15/114 [13.2%], 30/1,128 [2.7%], and 14/1,409 [1.0%]) decreased as mental health improved from languishing, moderate, and flourishing, respectively (all P < .0001); this relationship between personal experience and mental health persisted independent of burnout (all P < .001). As mental health improved, the prevalence of unprofessional behaviors (i.e., cheating and dishonest behaviors) also declined, whereas students' altruistic beliefs regarding physicians' responsibility toward society improved. For example, 33/113 (29.2%), 426/1,120 (38.0%), and 718/1,391 (51.6%) of students with languishing, moderate, and flourishing mental health endorsed all five altruistic professional beliefs (P < .0001). The relationship between professional beliefs and mental health persisted among students with burnout, whereas fewer relationships were found among students without burnout.Findings suggest that positive mental health attenuates some adverse consequences of burnout. Medical student wellness programs should aspire to prevent burnout and promote mental health.

View details for DOI 10.1097/ACM.0b013e31825cfa35

View details for Web of Science ID 000306843000013

View details for PubMedID 22722352
Distress and empathy do not drive changes in specialty preference among US medical students MEDICAL TEACHER Dyrbye, L. N., Eacker, A. M., Harper, W., Power, D. V., Massie, F. S., Satele, D., Thomas, M. R., Sloan, J. A., Shanafelt, T. D. 2012; 34 (2): E116-E122
Abstract

Although medical student specialty choices shape the future of the healthcare workforce, factors influencing changes in specialty preference during training remain poorly understood.To explore if medical student distress and empathy predicts changes in students' specialty preference.A total of 858/1321 medical students attending five medical schools responded to surveys in 2006 and 2007. The survey included questions about specialty choice, burnout, depression, quality of life, and empathy.A total of 26% (205/799) changed their specialty preference over 1 year. Depersonalization--an aspect of burnout--was the only distress variable associated with change in specialty preference (OR, odds ratio 0.962 for each 1-point increase in score, p = 0.03). Empathy at baseline and changes in empathy over the course of 1 year did not predict change in specialty preference (all p > 0.05). On multi-variable analysis, being a third year (OR 1.92), being male (OR 1.48), and depersonalization score (OR 0.962 for each point increase) independently predicted a change in specialty preference. Distress and empathy did not independently predict students' losing interest in primary care whereas being a fourth-year student (OR 1.83) and being female (OR 1.83) did.Among those who did have a major change in their specialty preference, distress and empathy did not play a major role.

View details for DOI 10.3109/0142159X.2012.644830

View details for Web of Science ID 000299701500004

View details for PubMedID 22289009
Relationship of Pass/Fail Grading and Curriculum Structure With Well-Being Among Preclinical Medical Students: A Multi-Institutional Study ACADEMIC MEDICINE Reed, D. A., Shanafelt, T. D., Satele, D. W., Power, D. V., Eacker, A., Harper, W., Moutier, C., Durning, S., Massie, F. S., Thomas, M. R., Sloan, J. A., Dyrbye, L. N. 2011; 86 (11): 1367-1373
Abstract

Psychological distress is common among medical students. Curriculum structure and grading scales are modifiable learning environment factors that may influence student well-being. The authors sought to examine relationships among curriculum structures, grading scales, and student well-being.The authors surveyed 2,056 first- and second-year medical students at seven U.S. medical schools in 2007. They used the Perceived Stress Scale, Maslach Burnout Inventory, and Medical Outcomes Study Short Form (SF-8) to measure stress, burnout, and quality of life, respectively. They measured curriculum structure using hours spent in didactic, clinical, and testing experiences. Grading scales were categorized as two categories (pass/fail) versus three or more categories (e.g., honors/pass/fail).Of the 2,056 students, 1,192 (58%) responded. In multivariate analyses, students in schools using grading scales with three or more categories had higher levels of stress (beta 2.65; 95% CI 1.54-3.76, P<.0001), emotional exhaustion (beta 5.35; 95% CI 3.34-7.37, P<.0001), and depersonalization (beta 1.36; 95% CI 0.53-2.19, P=.001) and were more likely to have burnout (OR 2.17; 95% CI 1.41-3.35, P=.0005) and to have seriously considered dropping out of school (OR 2.24; 95% CI 1.54-3.27, P<.0001) compared with students in schools using pass/fail grading. There were no relationships between time spent in didactic and clinical experiences and well-being.How students are evaluated has a greater impact than other aspects of curriculum structure on their well-being. Curricular reform intended to enhance student well-being should incorporate pass/fail grading.

View details for DOI 10.1097/ACM.0b013e3182305d81

View details for Web of Science ID 000296624900044

View details for PubMedID 21952063
Patterns of distress in US medical students MEDICAL TEACHER Dyrbye, L. N., Harper, W., Durning, S. J., Moutier, C., Thomas, M. R., Massie, F. S., Eacker, A., Power, D. V., Szydlo, D. W., Sloan, J. A., Shanafelt, T. D. 2011; 33 (10): 834-839
Abstract

How multiple forms of psychological distress coexist in individual medical students has not been formally studied.To explore the prevalence of various forms of distress in medical students and their relationship to recent suicidal ideation or serious thoughts of dropping out of school.All medical students at seven US schools were surveyed with standardized instruments to evaluate burnout, depression, stress, mental quality of life (QOL), physical QOL, and fatigue. Additional items explored recent suicidal ideation and serious thoughts of dropping out of medical school.Nearly all (1846/2246, 82%) of medical students had at least one form of distress with 1066 (58%) having ≥3 forms of distress. A dose-response relationship was found between the number of manifestations of distress and recent suicidal ideation or serious thoughts of dropping out. For example, students with 2, 4, or 6 forms of distress were 5, 15, and 24 fold, respectively, more likely to have suicidal ideation than students with no forms of distress assessed. All forms of distress were independently associated with suicidal ideation or serious thoughts of dropping out on multivariable analysis.Most medical students experience ≥1 manifestation of distress with many experiencing multiple forms of distress simultaneously. The more forms of distress experienced the greater the risk for suicidal ideation and thoughts of dropping out of medical school.

View details for DOI 10.3109/0142159X.2010.531158

View details for Web of Science ID 000295218300016

View details for PubMedID 21942482
The problems program directors inherit: medical student distress at the time of graduation MEDICAL TEACHER Dyrbye, L. N., Moutier, C., Durning, S. J., Massie, F. S., Power, D. V., Eacker, A., Harper, W., Thomas, M. R., Satele, D., Sloan, J. A., Shanafelt, T. D. 2011; 33 (9): 756-758
Abstract

Distress is prevalent among residents and often attributed to rigors of training.To explore the prevalence of burnout and depression and measured mental quality of life (QOL) among graduating medical students shortly before they began residency.Pooled analysis of data from 1428 fourth year medical students who responded to 1 of 3 multi-institutional studies. Students completed the Maslach Burnout Inventory, PRIME MD, and SF-8 to measure burnout, depression, and low mental QOL (defined as mean mental SF-8 scores ½ a standard deviation below the population norm) and answered demographic items.Shortly before beginning residency, 49% of responding medical students had burnout, 38% endorsed depressive symptoms, and 34% had low mental QOL. While no differences in the prevalence of distress was observed by residency specialty area, there were subtle differences in the manifestation of burnout by specialty. Medical students entering surgical fields had lower mean emotional scores, students entering primary care fields had lower mean depersonalization scores, and students entering non-primary care/non-surgical fields reported the lowest mean personal accomplishment scores (all p ≤ 0.03).Our results indicate a high prevalence of distress among graduating medical students across all specialty disciplines before they even begin residency training.

View details for DOI 10.3109/0142159X.2011.577468

View details for Web of Science ID 000294065800019

View details for PubMedID 21854153
Factors associated with resilience to and recovery from burnout: a prospective, multi-institutional study of US medical students MEDICAL EDUCATION Dyrbye, L. N., Power, D. V., Massie, F. S., Eacker, A., Harper, W., Thomas, M. R., Szydlo, D. W., Sloan, J. A., Shanafelt, T. D. 2010; 44 (10): 1016-1026
Abstract

Burnout is prevalent among medical students and is a predictor of subsequent serious consideration of dropping out of medical school and suicide ideation. Understanding of the factors that protect against burnout is needed to guide student wellness programmes.A total of 1321 medical students attending five institutions were studied longitudinally (2006-2007). The surveys included standardised instruments to evaluate burnout, quality of life, fatigue and stress. Additional items explored social support, learning climate, life events, employment status and demographics. Students who did not have burnout at either time-point (resilient students) were compared with those who indicated burnout at one or both time-points (vulnerable students) using a Wilcoxon-Mann-Whitney test or Fisher's exact test. Similarly, the differences between those who recovered and those who were chronically burned out were also compared in students with burnout at the first time-point. Logistic regression modelling was employed to evaluate associations between the independent variables and resiliency to and recovery from burnout.Overall, 792 (60.0%) students completed the burnout inventory at both time-points. No differences in demographic characteristics were observed between resilient (290/792 [36.6%]) and vulnerable (502/792 [63.4%]) students. Resilient students were less likely to experience depression, had a higher quality of life, were less likely to be employed, had experienced fewer stressful life events, reported higher levels of social support, perceived their learning climate more positively and experienced less stress and fatigue (all p < 0.05) than vulnerable students. On multivariable analysis, perceiving student education as a priority for faculty staff, experiencing less stress, not being employed and being a minority were factors independently associated with recovery from burnout.Modifiable individual factors and learning climate characteristics including employment status, stress level and perceptions of the prioritising of student education by faculty members relate to medical students' vulnerability to burnout.

View details for DOI 10.1111/j.1365-2923.2010.03754.x

View details for Web of Science ID 000282541000011

View details for PubMedID 20880371
Relationship Between Burnout and Professional Conduct and Attitudes Among US Medical Students JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Dyrbye, L. N., Massie, F. S., Eacker, A., Harper, W., Power, D., Durning, S. J., Thomas, M. R., Moutier, C., Satele, D., Sloan, J., Shanafelt, T. D. 2010; 304 (11): 1173-1180
Abstract

The relationship between professionalism and distress among medical students is unknown.To determine the relationship between measures of professionalism and burnout among US medical students.Cross-sectional survey of all medical students attending 7 US medical schools (overall response rate, 2682/4400 [61%]) in the spring of 2009. The survey included the Maslach Burnout Inventory (MBI), the PRIME-MD depression screening instrument, and the SF-8 quality of life (QOL) assessment tool, as well as items exploring students' personal engagement in unprofessional conduct, understanding of appropriate relationships with industry, and attitudes regarding physicians' responsibility to society.Frequency of self-reported cheating/dishonest behaviors, understanding of appropriate relationships with industry as defined by American Medical Association policy, attitudes about physicians' responsibility to society, and the relationship of these dimensions of professionalism to burnout, symptoms of depression, and QOL.Of the students who responded to all the MBI items, 1354 of 2566 (52.8%) had burnout. Cheating/dishonest academic behaviors were rare (endorsed by <10%) in comparison to unprofessional conduct related to patient care (endorsed by up to 43%). Only 14% (362/2531) of students had opinions on relationships with industry consistent with guidelines for 6 scenarios. Students with burnout were more likely to report engaging in 1 or more unprofessional behaviors than those without burnout (35.0% vs 21.9%; odds ratio [OR], 1.89; 95% confidence interval [CI], 1.59-2.24). Students with burnout were also less likely to report holding altruistic views regarding physicians' responsibility to society. For example, students with burnout were less likely to want to provide care for the medically underserved than those without burnout (79.3% vs 85.0%; OR, 0.68; 95% CI, 0.55-0.83). After multivariable analysis adjusting for personal and professional characteristics, burnout was the only aspect of distress independently associated with reporting 1 or more unprofessional behaviors (OR, 1.76; 95% CI, 1.45-2.13) or holding at least 1 less altruistic view regarding physicians' responsibility to society (OR, 1.65; 95% CI, 1.35-2.01).Burnout was associated with self-reported unprofessional conduct and less altruistic professional values among medical students at 7 US schools.

View details for Web of Science ID 000281770600009

View details for PubMedID 20841530
Burnout and Serious Thoughts of Dropping Out of Medical School: A Multi-Institutional Study ACADEMIC MEDICINE Dyrbye, L. N., Thomas, M. R., Power, D. V., Durning, S., Moutier, C., Massie, F. S., Harper, W., Eacker, A., Szydlo, D. W., Sloan, J. A., Shanafelt, T. D. 2010; 85 (1): 94-102
Abstract

Little is known about students who seriously consider dropping out of medical school. The authors assessed the severity of thoughts of dropping out and explored the relationship of such thoughts with burnout and other indicators of distress.The authors surveyed medical students attending five medical schools in 2006 and 2007 (prospective cohort) and included two additional medical schools in 2007 (cross-sectional cohort). The survey included questions about thoughts of dropping out, life events in the previous 12 months, and validated instruments evaluating burnout, depression symptoms, and quality of life (QOL).Data were provided by 858 (65%) students in the prospective cohort and 2,248 (52%) in the cross-sectional cohort. Of 2,222 respondents, 243 (11%) indicated having serious thoughts of dropping out within the last year. Burnout (P < .0001), QOL (P < .003 each domain), and depressive symptoms (P < .0001) at baseline predicted serious thoughts of dropping out during the following year. Each one-point increase in emotional exhaustion and depersonalization score and one-point decrease in personal accomplishment score at baseline was associated with a 7% increase in the odds of serious thoughts of dropping out during the following year. On subsequent confirmatory multivariable analysis, low scores for personal accomplishment, lower mental and physical QOL, and having children were independent predictors of students having serious thoughts of dropping out during the following year.Approximately 11% of students have serious thoughts of dropping out of medical school each year. Burnout seems to be associated with increased likelihood of serious thoughts of dropping out.

View details for DOI 10.1097/ACM.0b013e3181c46aad

View details for Web of Science ID 000276131300024

View details for PubMedID 20042833
Aberrant regulation of pVHL levels by microRNA promotes the HIF/VEGF axis in CLL B cells BLOOD Ghosh, A. K., Shanafelt, T. D., Cimmino, A., Taccioli, C., Volinia, S., Liu, C., Calin, G. A., Croce, C. M., Chan, D. A., Giaccia, A. J., Secreto, C., Wellik, L. E., Lee, Y. K., Mukhopadhyay, D., Kay, N. E. 2009; 113 (22): 5568-5574
Abstract

The molecular mechanism of autocrine regulation of vascular endothelial growth factor (VEGF) in chronic lymphocytic leukemia (CLL) B cells is unknown. Here, we report that CLL B cells express constitutive levels of HIF-1alpha under normoxia. We have examined the status of the von Hippel-Lindau gene product (pVHL) that is responsible for HIF-1alpha degradation and found it to be at a notably low level in CLL B cells compared with normal B cells. We demonstrate that the microRNA, miR-92-1, overexpressed in CLL B cells, can target the VHL transcript to repress its expression. We found that the stabilized HIF-1alpha can form an active complex with the transcriptional coactivator p300 and phosphorylated-STAT3 at the VEGF promoter and recruit RNA polymerase II. This is initial evidence that pVHL, without any genetic alteration, can be regulated by microRNA and explains the aberrant autocrine VEGF secretion in CLL.

View details for DOI 10.1182/blood-2008-10-185686

View details for Web of Science ID 000266634700026

View details for PubMedID 19336759

View details for PubMedCentralID PMC2689054
The learning environment and medical student burnout: a multicentre study MEDICAL EDUCATION Dyrbye, L. N., Thomas, M. R., Harper, W., Massie, F. S., Power, D. V., Eacker, A., Szydlo, D. W., Novotny, P. J., Sloan, J. A., Shanafelt, T. D. 2009; 43 (3): 274-282
Abstract

Little is known about specific personal and professional factors influencing student distress. The authors conducted a comprehensive assessment of how learning environment, clinical rotation factors, workload, demographics and personal life events relate to student burnout.All medical students (n = 3080) at five medical schools were surveyed in the spring of 2006 using a validated instrument to assess burnout. Students were also asked about the aforementioned factors.A total of 1701 medical students (response rate 55%) completed the survey. Learning climate factors were associated with student burnout on univariate analysis (odds ratio [OR] 1.36-2.07; all P < or = 0.02). Being on a hospital ward rotation or a rotation requiring overnight call was also associated with burnout (ORs 1.69 and 1.48, respectively; both P < or = 0.02). Other workload characteristics (e.g. number of admissions) had no relation to student burnout. Students who experienced a positive personal life event had a lower frequency of burnout (OR 0.70; P < or = 0.02), whereas those who experienced negative personal life events did not have a higher frequency of burnout than students who did not experience a negative personal life event. On multivariate analysis personal characteristics, learning environment and personal life events were all independently related to student burnout.Although a complex array of personal and professional factors influence student well-being, student satisfaction with specific characteristics of the learning environment appears to be a critical factor. Studies determining how to create a learning environment that cultivates student well-being are needed.

View details for DOI 10.1111/j.1365-2923.2008.03282.x

View details for Web of Science ID 000263466200013

View details for PubMedID 19250355
Burnout and suicidal ideation among US medical students ANNALS OF INTERNAL MEDICINE Dyrbye, L. N., Thomas, M. R., Massie, F. S., Power, D. V., Eacker, A., Harper, W., Durning, S., Moutier, C., Szydlo, D. W., Novotny, P. J., Sloan, J. A., Shanafelt, T. D. 2008; 149 (5): 334-W70
Abstract

Little is known about the prevalence of suicidal ideation among U.S. medical students or how it relates to burnout.To assess the frequency of suicidal ideation among medical students and explore its relationship with burnout.Cross-sectional 2007 and longitudinal 2006 to 2007 cohort study.7 medical schools in the United States.4287 medical students at 7 medical schools, with students at 5 institutions studied longitudinally.Prevalence of suicidal ideation in the past year and its relationship to burnout, demographic characteristics, and quality of life.Burnout was reported by 49.6% (95% CI, 47.5% to 51.8%) of students, and 11.2% (CI, 9.9% to 12.6%) reported suicidal ideation within the past year. In a sensitivity analysis that assumed all nonresponders did not have suicidal ideation, the prevalence of suicidal ideation in the past 12 months would be 5.8%. In the longitudinal cohort, burnout (P < 0.001 for all domains), quality of life (P < 0.002 for each domain), and depressive symptoms (P < 0.001) at baseline predicted suicidal ideation over the following year. In multivariable analysis, burnout and low mental quality of life at baseline were independent predictors of suicidal ideation over the following year. Of the 370 students who met criteria for burnout in 2006, 99 (26.8%) recovered. Recovery from burnout was associated with markedly less suicidal ideation, which suggests that recovery from burnout decreased suicide risk.Although response rates (52% for the cross-sectional study and 65% for the longitudinal cohort study) are typical of physician surveys, nonresponse by some students reduces the precision of the estimated frequency of suicidal ideation and burnout.Approximately 50% of students experience burnout and 10% experience suicidal ideation during medical school. Burnout seems to be associated with increased likelihood of subsequent suicidal ideation, whereas recovery from burnout is associated with less suicidal ideation.

View details for Web of Science ID 000259229300006

View details for PubMedID 18765703
Race, ethnicity, and medical student well-being in the United States ARCHIVES OF INTERNAL MEDICINE Dyrbye, L. N., Thomas, M. R., Eacker, A., Harper, W., Massie, S., Power, D. V., Huschka, M., Novotny, P. J., Sloan, J. A., Shanafelt, T. D. 2007; 167 (19): 2103-2109
Abstract

Little is known about the training experience of minority medical students. We explore differences in the prevalence of burnout, depressive symptoms, and quality of life (QOL) among minority and nonminority medical students as well as the role race/ethnicity plays in students' experiences.Medical students (N = 3080) at 5 medical schools were surveyed in 2006 using validated instruments to assess burnout, depression, and QOL. Students were also asked about the impact of race/ethnicity on their training experience.The response rate was 55%. Nearly half of students reported burnout (47%) and depressive symptoms (49%). Mental QOL scores were lower among students than among the age-matched general population (43.1 vs 47.2; P < .001). Prevalence of depressive symptoms was similar regardless of minority status, but more nonminority students had burnout (39% vs 33%; P < .03). Minority students were more likely to report that their race/ethnicity had adversely affected their medical school experience (11% vs 2%; P < .001) and cited racial discrimination, racial prejudice, feelings of isolation, and different cultural expectations as causes. Minority students reporting such experiences were more likely to have burnout, depressive symptoms, and low mental QOL scores than were minority students without such experiences (all P < .05).Symptoms of distress are prevalent among medical students. While minorities appear to be at lower risk for burnout than nonminority students, race does contribute to the distress minority students do experience. Additional studies are needed to define the causes of these perceptions and to improve the learning climate for all students.

View details for Web of Science ID 000250326900014

View details for PubMedID 17954805
Medical education research and IRB review: An analysis and comparison of the IRB review process at six institutions ACADEMIC MEDICINE Dyrbye, L. N., Thomas, M. R., Mechaber, A. J., Eacker, A., Harper, W., Massie, F. S., Power, D. V., Shanafelt, T. D. 2007; 82 (7): 654-660
Abstract

To compare how different institutional review boards (IRBs) process and evaluate the same multiinstitutional educational research proposal of medical students' quality of life.Prospective collection in 2005 of key variables regarding the IRB submission and review process of the same educational research proposal involving medical students, which was submitted to six IRBs, each associated with a different medical school.Four IRBs determined the protocol was appropriate for expedited review, and the remaining two required full review. Substantial variation existed in the time to review the protocol by an IRB administrator/IRB member (range 1-101 days) and by the IRB committee (range 6-115 days). One IRB committee approved the study as written. The remaining five IRB committees had a median of 13 requests for additional information/changes to the protocol. Sixty-eight percent of requests (36 of 53) pertained to the informed consent letter; one third (12 of 36) of these requests were unique modifications requested by one IRB but not the others. Although five IRB committees approved the survey after a median of 47 days (range 6-73), one committee had not responded six months after submission (164 days), preventing that school from participating.The findings suggest variability in the timeliness and consistency of IRB review of medical education research across institutions that may hinder multi-institutional research and slow evidence-based medical education reform. The findings demonstrate the difficulties of having medical education research reviewed by IRBs, which are typically designed to review clinical trials, and suggest that the review process for medical education research needs reform.

View details for Web of Science ID 000247810100005

View details for PubMedID 17595560

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