Tait Shanafelt

All Publications

• 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 DOI 10.18632/oncotarget.26538

  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

• 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 DOI 10.1080/10428194.2018.1543882

  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 DOI 10.1111/bjh.15690

  View details for PubMedID 30506764

• 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 DOI 10.1111/ejh.13149

  View details for Web of Science ID 000446560100017

  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 DOI 10.1097/JHM-D-18-00209

  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 DOI 10.1111/bjh.15545

  View details for Web of Science ID 000450015400010

  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 DOI 10.1016/j.mayocp.2018.08.014

  View details for PubMedID 30392548

• 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 DOI 10.1007/s00277-018-3350-5

  View details for Web of Science ID 000441512900030

  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 DOI 10.1097/ACM.0000000000002437

  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 DOI 10.1002/ajh.25206

  View details for Web of Science ID 000446055700001

  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 DOI 10.1097/ACM.0000000000002415

  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 DOI 10.1038/s41375-018-0100-6

  View details for Web of Science ID 000441284000030

  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 DOI 10.1016/j.mayocp.2018.05.014

  View details for PubMedID 30001832

• 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 DOI 10.1182/blood-2017-11-814608

  View details for Web of Science ID 000434789800005

  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 DOI 10.3324/haematol.2017.183194

  View details for Web of Science ID 000435033400003

  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 DOI 10.1016/S0140-6736(18)30422-7

  View details for Web of Science ID 000429926000028

  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 DOI 10.1001/jamainternmed.2018.0163

  View details for Web of Science ID 000428884500029

  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 DOI 10.1182/blood-2017-09-806034

  View details for Web of Science ID 000423449900013

  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 DOI 10.1080/17474086.2018.1442716

  View details for Web of Science ID 000428675400012

  View details for PubMedID 29460654

• Reimagining Clinical Documentation With Artificial Intelligence. Mayo Clinic proceedings Lin, S. Y., Shanafelt, T. D., Asch, S. M. 2018

  View details for DOI 10.1016/j.mayocp.2018.02.016

  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 DOI 10.1001/jamainternmed.2017.4340

  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 DOI 10.7326/M16-2956

  View details for Web of Science ID 000401240200019

  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 DOI 10.1007/s40596-017-0849-3

  View details for PubMedID 29196982

• 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 Web of Science ID 000371729200001

  View details for PubMedID 26956414

  View details for PubMedCentralID PMC4786871

• 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