Tait Shanafelt

All Publications

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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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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