Publications by authors named "Tait D Shanafelt"

363 Publications

How Feedback Is Given Matters: A Cross-Sectional Survey of Patient Satisfaction Feedback Delivery and Physician Well-being.

Mayo Clin Proc 2021 Aug 31. Epub 2021 Aug 31.

Stanford Medicine WellMD Center, Stanford School of Medicine, Stanford, CA.

Objective: To evaluate how variation in the way patient satisfaction feedback is delivered relates to physician well-being and perceptions of its impact on patient care, job satisfaction, and clinical decision making.

Participants And Methods: A cross-sectional electronic survey was sent to faculty physicians from a large academic medical center in March 29, 2019. Physicians reported their exposure to feedback (timing, performance relative to peers, or channel) and related perceptions. The Professional Fulfillment Index captured burnout and professional fulfillment. Associations between feedback characteristics and well-being or perceived impact were tested using analysis of variance or logistic regression adjusted for covariates.

Results: Of 1016 survey respondents, 569 (56.0%) reported receiving patient satisfaction feedback. Among those receiving feedback, 303 (53.2%) did not believe that this feedback improved patient care. Compared with physicians who never received feedback, those who received any type of feedback had higher professional fulfillment scores (mean, 6.6±2.1 vs 6.3±2.0; P=.03) but also reported an unfavorable impact on clinical decision making (odds ratio [OR], 2.9; 95% CI, 1.8 to 4.7; P<.001). Physicians who received feedback that included one-on-one discussions (as opposed to feedback without this channel) held more positive perceptions of the feedback's impact on patient care (OR, 2.0; 95% CI, 1.3 to 3.0; P=.003), whereas perceptions were less positive in physicians whose feedback included comparisons to named colleagues (OR, 0.5; 95% CI, 0.3 to 0.8; P=.003).

Conclusion: Providing patient satisfaction feedback to physicians was associated with mixed results, and physician perceptions of the impact of feedback depended on the characteristics of feedback delivery. Our findings suggest that feedback is viewed most constructively by physicians when delivered through one-on-one discussions and without comparison to peers.
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http://dx.doi.org/10.1016/j.mayocp.2021.03.039DOI Listing
August 2021

Measurable Residual Disease Does Not Preclude Prolonged Progression-free Survival in CLL Treated with Ibrutinib.

Blood 2021 Aug 18. Epub 2021 Aug 18.

Mayo Clinic, Rochester, Minnesota, United States.

E1912 was a randomized phase 3 trial comparing indefinite ibrutinib plus six cycles of rituximab (IR) to six cycles of fludarabine, cyclophosphamide and rituximab (FCR) in untreated younger patients with CLL. We describe measurable residual disease (MRD) levels in E1912 over time and correlate them with clinical outcome. Undetectable MRD rates (< 1 CLL cell per 104 leukocytes) were 29.1%, 30.3%, 23.4% and 8.6% at 3, 12, 24 and 36 months for FCR, and significantly lower at 7.9%, 4.2% and 3.7% at 12, 24 and 36 months for IR, respectively. Undetectable MRD at 3, 12, 24 and 36 months was associated with longer progression-free survival (PFS) for the FCR arm with hazard ratios (MRD detectable / MRD undetectable) of 4.29 (95% CI 1.89 - 9.71), 3.91 (95% CI 1.39 - 11.03), 14.12 (95% CI 1.78 - 111.73), and not estimable (no events among those with undetectable MRD), respectively. For the IR arm, patients with detectable MRD did not have significantly worse PFS compared to those in whom MRD was undetectable; however, PFS was longer for those with MRD levels of less than 10-1 compared to those with MRD levels above this threshold. Our observations provide additional support for the use of MRD as a surrogate endpoint for PFS in patients receiving FCR. For patients on indefinite ibrutinib-based therapy, PFS did not differ significantly by undetectable MRD status, while those with MRD less than 10-1 tend to have longer PFS, although continuation of ibrutinib is very likely required to maintain treatment efficacy.
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http://dx.doi.org/10.1182/blood.2020010146DOI Listing
August 2021

Colleagues Meeting to Promote and Sustain Satisfaction (COMPASS) Groups for Physician Well-Being: A Randomized Clinical Trial.

Mayo Clin Proc 2021 Aug 5. Epub 2021 Aug 5.

Division of Hematology, Department of Medicine, Stanford University, Palo Alto, CA.

Objective: To evaluate physician small groups to promote physician well-being in a scenario with provided discussion topics but without trained facilitators, and for which protected time was not provided but meal expenses were compensated.

Participants And Methods: We conducted a randomized controlled trial of 125 practicing physicians in the Department of Medicine, Mayo Clinic, Rochester, Minnesota, between October 2013 and October 2014 with subsequent assessment of organizational program implementation. Twelve biweekly self-facilitated discussion groups involving reflection, shared experience, and small-group learning took place over 6 months. Main outcome measures included meaning in work, burnout, symptoms of depression, quality of life, social support, and job satisfaction assessed using validated metrics.

Results: At 6 months after completion of the intervention (12 months from baseline), the rate of overall burnout had decreased by 12.7% (31/62 to 19/51) in the intervention arm versus a 1.9% increase (25/61 to 24/56) in the control arm (P<.001). The rate of depressive symptoms had decreased by 12.8% (29/62 to 17/50) in the intervention arm versus a 1.1% increase (20/61 to 19/56) in the control arm (P<.001). The proportion of physicians endorsing at least moderate self-reported likelihood of leaving their current practice in the subsequent 2 years had decreased by 1.9% (17/62 to 13/51) in the intervention arm and increased by 6.1% (14/61 to 16/55) in the control arm (P<.001). No statistically significant differences were seen in mean changes in burnout scale scores, meaning, or social support, although numeric differences generally favored the intervention.

Conclusion: Self-facilitated physician small-group meetings improved burnout, depressive symptoms, and job satisfaction. This intervention represents a low-cost strategy to promote important dimensions of physician well-being.

Trial Registration: clinicaltrials.gov Identifier: NCT04466423.
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http://dx.doi.org/10.1016/j.mayocp.2021.02.028DOI Listing
August 2021

Polygenic risk score and risk of monoclonal B-cell lymphocytosis in caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans.

Leukemia 2021 Jul 20. Epub 2021 Jul 20.

Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.

Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated with CLL risk among individuals of European-ancestry(EA). Here, we evaluate these variants, the PRS, and environmental factors for MBL risk. We also evaluate these variants and the CLL-PRS among African-American (AA) and EA-CLL cases and controls. Our study included 560 EA MBLs, 869 CLLs (696 EA/173 AA), and 2866 controls (2631 EA/235 AA). We used logistic regression, adjusting for age and sex, to estimate odds ratios (OR) and 95% confidence intervals within each race. We found significant associations with MBL risk among 21 of 41 variants and with the CLL-PRS (OR = 1.86, P = 1.9 × 10, c-statistic = 0.72). Little evidence of any association between MBL risk and environmental factors was observed. We observed significant associations of the CLL-PRS with EA-CLL risk (OR = 2.53, P = 4.0 × 10, c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10, c-statistic = 0.62). Inherited genetic factors and not environmental are associated with MBL risk. In particular, the CLL-PRS is a strong predictor for both risk of MBL and EA-CLL, but less so for AA-CLL supporting the need for further work in this population.
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http://dx.doi.org/10.1038/s41375-021-01344-9DOI Listing
July 2021

Novel Nonproprietary Measures of Ambulatory Electronic Health Record Use Associated with Physician Work Exhaustion.

Appl Clin Inform 2021 05 14;12(3):637-646. Epub 2021 Jul 14.

Division of General Internal Medicine, Department of Medicine, Stanford University, Stanford, California, United States.

Background: Accumulating evidence indicates an association between physician electronic health record (EHR) use after work hours and occupational distress including burnout. These studies are based on either physician perception of time spent in EHR through surveys which may be prone to bias or by utilizing vendor-defined EHR use measures which often rely on proprietary algorithms that may not take into account variation in physician's schedules which may underestimate time spent on the EHR outside of scheduled clinic time. The Stanford team developed and refined a nonproprietary EHR use algorithm to track the number of hours a physician spends logged into the EHR and calculates the Clinician Logged-in Outside Clinic (CLOC) time, the number of hours spent by a physician on the EHR outside of allocated time for patient care.

Objective: The objective of our study was to measure the association between CLOC metrics and validated measures of physician burnout and professional fulfillment.

Methods: Physicians from adult outpatient Internal Medicine, Neurology, Dermatology, Hematology, Oncology, Rheumatology, and Endocrinology departments who logged more than 8 hours of scheduled clinic time per week and answered the annual wellness survey administered in Spring 2019 were included in the analysis.

Results: We observed a statistically significant positive correlation between CLOC ratio (defined as the ratio of CLOC time to allocated time for patient care) and work exhaustion (Pearson's  = 0.14;  = 0.04), but not interpersonal disengagement, burnout, or professional fulfillment.

Conclusion: The CLOC metrics are potential objective EHR activity-based markers associated with physician work exhaustion. Our results suggest that the impact of time spent on EHR, while associated with exhaustion, does not appear to be a dominant factor driving the high rates of occupational burnout in physicians.
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http://dx.doi.org/10.1055/s-0041-1731678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279819PMC
May 2021

Frustration With Technology and its Relation to Emotional Exhaustion Among Health Care Workers: Cross-sectional Observational Study.

J Med Internet Res 2021 Jul 6;23(7):e26817. Epub 2021 Jul 6.

Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, United States.

Background: New technology adoption is common in health care, but it may elicit frustration if end users are not sufficiently considered in their design or trained in their use. These frustrations may contribute to burnout.

Objective: This study aimed to evaluate and quantify health care workers' frustration with technology and its relationship with emotional exhaustion, after controlling for measures of work-life integration that may indicate excessive job demands.

Methods: This was a cross-sectional, observational study of health care workers across 31 Michigan hospitals. We used the Safety, Communication, Operational Reliability, and Engagement (SCORE) survey to measure work-life integration and emotional exhaustion among the survey respondents. We used mixed-effects hierarchical linear regression to evaluate the relationship among frustration with technology, other components of work-life integration, and emotional exhaustion, with adjustment for unit and health care worker characteristics.

Results: Of 15,505 respondents, 5065 (32.7%) reported that they experienced frustration with technology on at least 3-5 days per week. Frustration with technology was associated with higher scores for the composite Emotional Exhaustion scale (r=0.35, P<.001) and each individual item on the Emotional Exhaustion scale (r=0.29-0.36, P<.001 for all). Each 10-point increase in the frustration with technology score was associated with a 1.2-point increase (95% CI 1.1-1.4) in emotional exhaustion (both measured on 100-point scales), after adjustment for other work-life integration items and unit and health care worker characteristics.

Conclusions: This study found that frustration with technology and several other markers of work-life integration are independently associated with emotional exhaustion among health care workers. Frustration with technology is common but not ubiquitous among health care workers, and it is one of several work-life integration factors associated with emotional exhaustion. Minimizing frustration with health care technology may be an effective approach in reducing burnout among health care workers.
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http://dx.doi.org/10.2196/26817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292941PMC
July 2021

Occupational and Personal Consequences of the COVID-19 Pandemic on US Oncologist Burnout and Well-Being: A Study From the ASCO Clinician Well-Being Task Force.

JCO Oncol Pract 2021 07 21;17(7):e427-e438. Epub 2021 Jun 21.

Northern California (NCAL), Kaiser Permanente, Oakland, CA.

Introduction: The COVID-19 pandemic is an unprecedented global crisis profoundly affecting oncology care delivery.

Purpose: This study will describe the occupational and personal consequences of the COVID-19 pandemic on oncologist well-being and patient care.

Materials And Methods: Four virtual focus groups were conducted with US ASCO member oncologists (September-November 2020). Inquiry and subsequent discussions centered on self-reported accounts of professional and personal COVID-19 experiences affecting well-being, and oncologist recommendations for well-being interventions that the cancer organization and professional societies (ASCO) might implement were explored. Qualitative interviews were analyzed using Framework Analysis.

Results: Twenty-five oncologists were interviewed: median age 44 years (range: 35-69 years), 52% female, 52% racial or ethnic minority, 76% medical oncologists, 64% married, and an average of 51.5 patients seen per week (range: 20-120). Five thematic consequences emerged: (1) impact of pre-COVID-19 burnout, (2) occupational or professional limitations and adaptations, (3) personal implications, (4) concern for the future of cancer care and the workforce, and (5) recommendations for physician well-being interventions. Underlying oncologist burnout exacerbated stressors associated with disruptions in care, education, research, financial practice health, and telemedicine. Many feared delays in cancer screening, diagnosis, and treatment. Oncologists noted personal and familial stressors related to COVID-19 exposure fears and loss of social support. Many participants strongly considered working part-time or taking early retirement. Yet, opportunities arose to facilitate personal growth and rise above pandemic adversity, fostering greater resilience. Recommendations for organizational well-being interventions included psychologic or peer support resources, flexible time-off, and ASCO and state oncology societies involvement to develop care guidelines, well-being resources, and mental health advocacy.

Conclusion: Our study suggests that the COVID-19 pandemic has adversely affected oncologist burnout, fulfillment, practice health, cancer care, and workforce. It illuminates where professional organizations could play a significant role in oncologist well-being.
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http://dx.doi.org/10.1200/OP.21.00147DOI Listing
July 2021

Examining the measurement equivalence of the Maslach Burnout Inventory across age, gender, and specialty groups in US physicians.

J Patient Rep Outcomes 2021 Jun 5;5(1):43. Epub 2021 Jun 5.

Department of Health Law, Policy & Management, Boston University School of Public Health, Boston, MA, 02118, USA.

Background: Disparities in US physician burnout rates across age, gender, and specialty groups as measured by the Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI) are well documented. We evaluated whether disparities in US physician burnout are explained by differences in the MBI's functioning across physician age, gender, and specialty groups.

Methods: We assessed the measurement equivalence of the MBI across age, gender, and specialty groups in multi-group item response theory- (IRT-) based differential item functioning (DIF) analyses using secondary, cross-sectional survey data from US physicians (n = 6577). We detected DIF using two IRT-based methods and assessed its impact by estimating the overall average difference in groups' subscale scores attributable to DIF. We assessed DIF's practical significance by comparing differences in individuals' subscale scores and burnout prevalence estimates from models unadjusted and adjusted for DIF.

Results: We detected statistically significant age-, gender-, and specialty- DIF in all but one MBI item. However, in all cases, average differences in expected subscale-level scores due to DIF were < 0.10 SD on each subscale. Differences in physicians' individual-level subscale scores and burnout symptom prevalence estimates across DIF- adjusted and unadjusted IRT models were also small (in all cases, mean absolute differences in individual subscale scores were < 0.04 z-score units; prevalence estimates differed by < 0.70%).

Conclusions: Age-, gender-, and specialty-related disparities in US physician burnout are not explained by differences in the MBI's functioning across these demographic groups. Our findings support the use of the MBI as a valid tool to assess age-, gender-, and specialty-related disparities in US physician burnout.
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http://dx.doi.org/10.1186/s41687-021-00312-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179856PMC
June 2021

Creating a Blueprint of Well-Being in Oncology: An Approach for Addressing Burnout From ASCO's Clinician Well-Being Taskforce.

Am Soc Clin Oncol Educ Book 2021 Jun;41:e339-e353

Kaiser Permanente, Northern California (NCAL), Oakland, CA.

Optimizing the well-being of the oncology clinician has never been more important. Well-being is a critical priority for the cancer organization because burnout adversely impacts the quality of care, patient satisfaction, the workforce, and overall practice success. To date, 45% of U.S. ASCO member medical oncologists report experiencing burnout symptoms of emotional exhaustion and depersonalization. As the COVID-19 pandemic remains widespread with periods of outbreaks, recovery, and response with substantial personal and professional consequences for the clinician, it is imperative that the oncologist, team, and organization gain direct access to resources addressing burnout. In response, the Clinician Well-Being Task Force was created to improve the quality, safety, and value of cancer care by enhancing oncology clinician well-being and practice sustainability. Well-being is an integrative concept that characterizes quality of life and encompasses an individual's work- and personal health-related environmental, organizational, and psychosocial factors. These resources can be useful for the cancer organization to develop a well-being blueprint: a detailed start plan with recognized strategies and interventions targeting all oncology stakeholders to support a culture of community in oncology.
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http://dx.doi.org/10.1200/EDBK_320873DOI Listing
June 2021

Personal and Professional Factors Associated With Work-Life Integration Among US Physicians.

JAMA Netw Open 2021 May 3;4(5):e2111575. Epub 2021 May 3.

Duke Center for Healthcare Safety and Quality, Duke University Health System, Durham, North Carolina.

Importance: Poor work-life integration (WLI) occurs when career and personal responsibilities come in conflict and may contribute to the ongoing high rates of physician burnout. The characteristics associated with WLI are poorly understood.

Objective: To identify personal and professional factors associated with WLI in physicians and identify factors that modify the association between gender and WLI.

Design, Setting, And Participants: This cross-sectional study was based on electronic and paper surveys administered October 2017 to March 2018 at private, academic, military, and veteran's practices across the US. It used a population-based sample of US physicians across all medical specialties. Data analysis was performed from November 2019 to July 2020.

Main Outcomes And Measures: WLI was assessed using an 8-item scale (0-100 point scale, with higher scores indicating favorable WLI), alongside personal and professional factors. Multivariable linear regressions evaluated independent associations with WLI as well as factors that modify the association between gender and WLI.

Results: Of 5197 physicians completing surveys, 4370 provided complete responses. Of the physicians who provided complete responses, 2719 were men, 3491 were White/Caucasian (80.8%), 3560 were married (82.4%), and the mean (SD) age was 52.3 (12.0) years. The mean (SD) WLI score was 55 (23). Women reported lower (worse) mean (SD) WLI scores than men overall (52 [22] vs 57 [23]; mean difference, -5 [-0.2 SDs]; P < .001). In multivariable regression, lower WLI was independently associated with being a woman (linear regression coefficient, -6; SE, 0.7; P < .001) as well as being aged 35 years or older (eg, aged 35 to 44 years: linear regression coefficient, -7; SE, 1.4; P < .001), single (linear regression coefficient, -3 vs married; SE, 1.1; P = .003), working more hours (eg, 50 to 59 hours per week vs less than 40 hours per week: linear regression coefficient, -9; SE, 1.0; P < .001) and call nights (linear regression coefficient, -1 for each call night per week; SE, 0.2; P < .001), and being in emergency medicine (linear regression coefficient, -18; SE, 1.6, P < .001), urology (linear regression coefficient, -11; SE, 4.0; P = .009), general surgery (linear regression coefficient, -4; SE, 2.0; P = .04), anesthesiology (linear regression coefficient, -4; SE, 1.7; P = .03), or family medicine (linear regression coefficient, -3; SE, 1.4; P = .04) (reference category, internal medicine subspecialties). In interaction modeling, physician age, youngest child's age, and hours worked per week modified the associations between gender and WLI, such that the largest gender disparities were observed in physicians who were aged 45 to 54 years (estimated WLI score for women, 49; 95% CI, 47-51; estimated WLI score for men, 57, 95% CI, 55-59; P < .001), had youngest child aged 23 years or older (estimated WLI score for women, 51; 95% CI, 48-54; estimated WLI score for men, 60; 95% CI, 58-62; P < .001), and were working less than 40 hours per week (estimated WLI score for women, 61; 95% CI, 59-63; estimated WLI score for men; 70; 95% CI, 68-72; P < .001).

Conclusions And Relevance: This study found that lower WLI was reported by physicians who are women, single, aged 35 years or older, and who work more hours and call nights. These findings suggest that systemic change is needed to improve WLI among physicians.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.11575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160595PMC
May 2021

Burnout Phenotypes Among U.S. General Surgery Residents.

J Surg Educ 2021 Apr 29. Epub 2021 Apr 29.

Surgical Outcomes and Quality Improvement Center (SOQIC), Department of Surgery and Center for Health Services and Outcomes Research, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Division of Pediatric Surgery, Ann & Robert H. Lurie Children's Hospital, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address:

Objective: Although well-established metrics exist to measure workplace burnout, researchers disagree about how to categorize individuals based on assessed symptoms. Using a person-centered approach, this study identifies classes of burnout symptomatology in a large sample of general surgery residents in the United States.

Design, Setting, Participants: A survey was administered following the 2018 American Board of Surgery In-Training Examination (ABSITE) to study wellness among U.S. general surgery residents. Latent class models identified distinct classes of residents based on their responses to the emotional exhaustion and depersonalization questions of the modified abbreviated Maslach Burnout Inventory (aMBI). Classes were assigned representative names, and the characteristics of their members and residency programs were compared.

Results: The survey was completed by 7415 surgery residents from 263 residency programs nationwide (99.3% response rate). Five burnout classes were found: Burned Out (unfavorable score on all six items, 9.8% of total), Fully Engaged (favorable score on all six items, 23.1%), Fatigued (favorable on all items except frequent fatigue, 32.2%), Overextended (frequent fatigue and burnout from work, 16.7%), and Disengaged (weekly symptoms of fatigue and callousness, 18.1%). Within the more symptomatic classes (Burned Out, Overextended, and Disengaged), men manifested more depersonalization symptoms, whereas women reported more emotional exhaustion symptoms. Burned Out residents were characterized by reports of mistreatment (abuse, sexual harassment, and gender-, racial-, or pregnancy and/or childcare-based discrimination), duty hour violations, dissatisfaction with duty hour regulations or time for rest, and low ABSITE scores.

Conclusions: Burnout is multifaceted, with complex and variable presentations. Latent class modeling categorizes general surgery residents based on their burnout symptomatology. Organizations should tailor their efforts to address the unique manifestations of each class as well as shared drivers.
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http://dx.doi.org/10.1016/j.jsurg.2021.03.019DOI Listing
April 2021

Understanding memorably negative provider care delivery experiences: Why patient experiences matter for providers.

Healthc (Amst) 2021 Sep 22;9(3):100544. Epub 2021 Apr 22.

Stanford University School of Medicine, USA.

Background: Negative experiences contribute to provider dissatisfaction and burnout. Prior research suggests that negative experiences have greater impact on individuals than positive experiences.

Methods: Interviews were conducted with surgical and oncology care providers (107 MDs, 253 non-MDs) working in 10 geographically diverse, academic and community hospitals across the U.S. Using a thematic network approach, we identified core themes describing drivers of memorably negative experiences. We applied logistic regression with adjustments for multiple comparisons to evaluate the relationship between demographic characteristics and types of experiences.

Results: We identified 13 themes from 360 experiences and from these, developed a framework describing how work culture, environment, individual factors, and patient experiences lead to memorably, negative provider experiences. Providers most frequently described negative work environment experiences (158/360) and poor communication experiences with patients and other care professionals (151/360). Across themes, one third of respondents attributed memorably negative experiences to patient experiences (119/360). Midwest providers described patient centeredness more than other providers (OR = 3.9, p < 0.001). Providers from the Northeast, MDs compared to non-MDs, and providers with 15+ years of work experience identified negative insurance-related experiences more frequently (OR = 0.2, P = 0.007; OR = 2.9, P = 0.002 OR = 4.2, P < 0.001).

Conclusions: We offer a framework for understanding negative experiences among providers. Our study suggests that across a broad set of causes, improving patient experiences could substantially improve the negative, memorable experiences of providers.

Implications: Addressing negative patient experiences may have the double benefit of improving patient care and reducing provider burnout.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1016/j.hjdsi.2021.100544DOI Listing
September 2021

The CLL International Prognostic Index predicts outcomes in monoclonal B-cell lymphocytosis and Rai 0 CLL.

Blood 2021 07;138(2):149-159

Division of Hematology, Stanford University School of Medicine, Palo Alto, CA.

The utility of the chronic lymphocytic leukemia-international prognostic index (CLL-IPI) in predicting outcomes of individuals with Rai 0 stage CLL and monoclonal B-cell lymphocytosis (MBL) is unclear. We identified 969 individuals (415 MBL and 554 Rai 0 CLL; median age, 64 years; 65% men) seen at Mayo Clinic between 1 January 2001 and 1 October 2018, and ascertained time to first therapy (TTFT) and overall survival (OS). After a median follow up of 7 years, the risk of disease progression needing therapy was 2.9%/y for MBL (median, not reached) and 5%/y for Rai 0 CLL (median, 10.4 years). Among patients with low, intermediate, and high/very high-risk CLL-IPI risk groups, the estimated 5-year risk of TTFT was 13.5%, 30%, and 58%, respectively, P< .0001 (c-statistic = 0.69); and the estimated 5-year OS was 96.3%, 91.5%, and 76%, respectively, P< .0001 (c-statistic = 0.65). In a multivariable analysis of absolute B-cell count with individual factors of the CLL-IPI, the absolute B-cell count was associated with shorter TTFT (hazard ratio [HR] for each 10 × 109/L increase: 1.31; P< .0001) and shorter OS (HR: 1.1; P = .02). The OS of the entire cohort was similar to that of the age- and sex-matched general population of Minnesota (P = .17), although Rai 0 CLL patients with high and very high-risk CLL-IPI score had significantly shorter OS (P= .01 and P= .0001, respectively). The results of this study demonstrate the ability of CLL-IPI to predict time from diagnosis to first treatment (an end point not affected by therapy) in a large cohort of patients whose only manifestation of disease is a circulating clonal lymphocyte population.
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http://dx.doi.org/10.1182/blood.2020009813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288657PMC
July 2021

Establishing Crosswalks Between Common Measures of Burnout in US Physicians.

J Gen Intern Med 2021 Mar 31. Epub 2021 Mar 31.

Stanford Medicine WellMD Center, Stanford University, Stanford, CA, USA.

Background: Physician burnout is often assessed by healthcare organizations. Yet, scores from different burnout measures cannot currently be directly compared, limiting the interpretation of results across organizations or studies.

Objective: To link common measures of burnout to a single metric in psychometric analyses such that group-level scores from different assessments can be compared.

Design: Cross-sectional survey.

Setting: US practices.

Participants: A total of 1355 physicians sampled from the American Medical Association Physician Masterfile.

Main Measures: We linked the Stanford Professional Fulfillment Index (PFI) and Mini-Z Single-Item Burnout (MZSIB) scale to the Maslach Burnout Inventory (MBI) in item response theory (IRT) fixed-calibration and equipercentile analyses and created crosswalks mapping PFI and MZSIB scores to corresponding MBI scores. We evaluated the accuracy of the results by comparing physicians' actual MBI scores to those predicted by linking and described the closest cut-point equivalencies across scales linked to the same MBI subscale using the resulting crosswalks.

Key Results: IRT linking produced the most accurate results and was used to create crosswalks mapping (1) PFI Work Exhaustion (PFI-WE) and MZSIB scores to MBI Emotional Exhaustion (MBI-EE) scores and (2) PFI Interpersonal Disengagement (PFI-ID) scores to MBI Depersonalization (MBI-DP) scores. The commonly used MBI-EE raw score cut-point of ≥27 corresponded most closely with respective PFI-WE and MZSIB raw score cut-points of ≥7 and ≥3. The commonly used MBI-DP raw score cut-point of ≥10 corresponded most closely with a PFI-ID raw score cut-point of ≥9.

Conclusions: Our findings allow healthcare organizations using the PFI or MZSIB to compare group-level scores to historical, regional, or national MBI scores (and vice-versa).
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http://dx.doi.org/10.1007/s11606-021-06661-4DOI Listing
March 2021

Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.

Int J Epidemiol 2021 Aug;50(4):1325-1334

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.

Methods: We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus.

Conclusion: These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.
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http://dx.doi.org/10.1093/ije/dyab042DOI Listing
August 2021

Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

Blood Cancer Discov 2021 Jan 3;2(1):54-69. Epub 2020 Dec 3.

Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany.

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition. Patient methylomes showed remarkable stability with natural disease and post-therapy progression. Single CLL cells were consistently aberrantly methylated, indicating a homogeneous transition to the altered epigenetic state, and a distinct expression profile together with MBL cells compared to normal B cells. Our longitudinal analysis reveals the cancer methylome to emerge early, which may provide a platform for subsequent genetically-driven growth dynamics and together with its persistent presence suggests a central role in the normal-to-cancer transition.
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http://dx.doi.org/10.1158/2643-3230.BCD-19-0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888194PMC
January 2021

Assessment of the Association of Leadership Behaviors of Supervising Physicians With Personal-Organizational Values Alignment Among Staff Physicians.

JAMA Netw Open 2021 02 1;4(2):e2035622. Epub 2021 Feb 1.

Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.

Importance: Although misalignment of values between physicians and their organization is associated with increased risk of burnout, actionable organizational factors that contribute to perceived values alignment are poorly understood.

Objective: To evaluate the association between the leadership behaviors of immediate supervisors and physicians' perception of personal-organizational values alignment.

Design, Setting, And Participants: This survey study of faculty physicians and physician leaders at Stanford University School of Medicine was conducted from April 1 to May 13, 2019. The survey included assessments of perceived personal-organizational values alignment, professional fulfillment, and burnout. Physicians also evaluated the leadership behaviors of their immediate supervisor (eg, division chief) using a standardized assessment. Data analysis was performed from May to December 2020.

Main Outcomes And Measures: Association between mean leadership behavior score (range, 0-10) of each supervisor and the mean personal-organizational values alignment scores (range, 0-12) for the physicians in their work unit.

Results: Of 1924 physicians eligible to participate, 1285 (67%) returned surveys. Among these, 651 (51%) were women and 729 (57%) were aged 40 years or older. Among the 117 physician leaders evaluated, 66 (56%) had their leadership behavior independently evaluated by at least 5 physicians and were included in analyses. The mean (SD) personal-organizational values alignment score on the 0 to 12 scale was 6.19 (3.21). As the proportion of work effort devoted to clinical care increased, values alignment scores decreased. Personal-organizational values alignment scores demonstrated an inverse correlation with burnout (r = -0.39; P < .001) and a positive correlation with professional fulfillment (r = 0.52; P < .001). The aggregate leader behavior score of the 66 leaders evaluated correlated with the mean values alignment score for physicians in their work unit (r = 0.53; P < .001). Aggregate leader behavior score was associated with 21.6% of the variation in personal-organizational values alignment scores between work units. After adjusting for age, gender, academic rank, work hours, physician-leader gender concordance, and time devoted to clinical care, each 1-point increase in leadership score of immediate supervisor was associated with a 0.56-point (95% CI, 0.46-0.66; P < .001) increase in personal-organizational values alignment score.

Conclusions And Relevance: This survey study's results suggest that physicians experience their organization through the prism of their work unit leader. Organizational efforts to improve values alignment should attend to the development of first-line physician leaders.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.35622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873777PMC
February 2021

Natural history of monoclonal B-cell lymphocytosis among relatives in CLL families.

Blood 2021 04;137(15):2046-2056

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Chronic lymphocytic lymphoma (CLL) has one of the highest familial risks among cancers. Monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, has a higher prevalence (13%-18%) in families with 2 or more members with CLL compared with the general population (5%-12%). Although, the rate of progression to CLL for high-count MBLs (clonal B-cell count ≥500/µL) is ∼1% to 5%/y, no low-count MBLs have been reported to progress to date. We report the incidence and natural history of MBL in relatives from CLL families. In 310 CLL families, we screened 1045 relatives for MBL using highly sensitive flow cytometry and prospectively followed 449 of them. MBL incidence was directly age- and sex-adjusted to the 2010 US population. CLL cumulative incidence was estimated using Kaplan-Meier survival curves. At baseline, the prevalence of MBL was 22% (235/1045 relatives). After a median follow-up of 8.1 years among 449 relatives, 12 individuals progressed to CLL with a 5-year cumulative incidence of 1.8%. When considering just the 139 relatives with low-count MBL, the 5-year cumulative incidence increased to 5.7%. Finally, 264 had no MBL at baseline, of whom 60 individuals subsequently developed MBL (2 high-count and 58 low-count MBLs) with an age- and sex-adjusted incidence of 3.5% after a median of 6 years of follow-up. In a screening cohort of relatives from CLL families, we reported progression from normal-count to low-count MBL to high-count MBL to CLL, demonstrating that low-count MBL precedes progression to CLL. We estimated a 1.1% annual rate of progression from low-count MBL, which is in excess of that in the general population.
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http://dx.doi.org/10.1182/blood.2020006322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057266PMC
April 2021

The humoral immune response to high-dose influenza vaccine in persons with monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL).

Vaccine 2021 02 16;39(7):1122-1130. Epub 2021 Jan 16.

Division of General Internal Medicine and Vaccine Research Group, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.

Background: Limited data are available regarding the immunogenicity of high-dose influenza vaccine among persons with chronic lymphocytic leukemia (CLL) and monoclonal B cell lymphocytosis (MBL).

Methods: A prospective pilot study of humoral immune responses to 2013-2014 and 2014-2015 high-dose trivalent influenza vaccine (HD IIV; Fluzone® High-Dose; Sanofi Pasteur) was conducted among individuals with MBL and previously untreated CLL. Serum hemagglutination inhibition (HAI) antibody titers were measured at baseline and Day 28 after vaccination; seroprotection and seroconversion rates were determined. Memory B cell responses were assessed by B-cell enzyme-linked immune absorbent spotassays.

Results: Thirty subjects (17 CLL and 13 MBL) were included. Median age was 69.5 years. Day 28 seroprotection rates for the cohort were 19/30 (63.3%) for A/H1N1; 21/23 (91.3%) for A/H3N2; and 13/30 (43.3%) for influenza B. Those with MBL achieved higher day 28 HAI geometric mean titers (54.1 [4.9, 600.1] vs. 12.1 [1.3, 110.1]; p = 0.01) and higher Day 28 seroprotection rates (76.9% vs. 17.6%; p = 0.002) against the influenza B-vaccine strain virus than those with CLL.

Conclusions: Immunogenicity of the HD IIV3 in patients with CLL and MBL is lower than reported in healthy adults. Immunogenicity to influenza B was greater in those with MBL than CLL.
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http://dx.doi.org/10.1016/j.vaccine.2021.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189080PMC
February 2021

Assessment of Electronic Health Record Use Between US and Non-US Health Systems.

JAMA Intern Med 2021 Feb;181(2):251-259

Department of Medicine, Stanford University, Stanford, California.

Importance: Understanding how the electronic health record (EHR) system changes clinician work, productivity, and well-being is critical. Little is known regarding global variation in patterns of use.

Objective: To provide insights into which EHR activities clinicians spend their time doing, the EHR tools they use, the system messages they receive, and the amount of time they spend using the EHR after hours.

Design, Setting, And Participants: This cross-sectional study analyzed the deidentified metadata of ambulatory care health systems in the US, Canada, Northern Europe, Western Europe, the Middle East, and Oceania from January 1, 2019, to August 31, 2019. All of these organizations used the EHR software from Epic Systems and represented most of Epic Systems's ambulatory customer base. The sample included all clinicians with scheduled patient appointments, such as physicians and advanced practice practitioners.

Exposures: Clinician EHR use was tracked by deidentified and aggregated metadata across a variety of clinical activities.

Main Outcomes And Measures: Descriptive statistics for clinician EHR use included time spent on clinical activities, note documentation (as measured by the percentage of characters in the note generated by automated or manual data entry source), messages received, and time spent after hours.

Results: A total of 371 health systems were included in the sample, of which 348 (93.8%) were located in the US and 23 (6.2%) were located in other countries. US clinicians spent more time per day actively using the EHR compared with non-US clinicians (mean time, 90.2 minutes vs 59.1 minutes; P < .001). In addition, US clinicians vs non-US clinicians spent significantly more time performing 4 clinical activities: notes (40.7 minutes vs 30.7 minutes; P < .001), orders (19.5 minutes vs 8.75 minutes; P < .001), in-basket messages (12.5 minutes vs 4.80 minutes; P < .001), and clinical review (17.6 minutes vs 14.8 minutes; P = .01). Clinicians in the US composed more automated note text than their non-US counterparts (77.5% vs 60.8% of note text; P < .001) and received statistically significantly more messages per day (33.8 vs 12.8; P < .001). Furthermore, US clinicians used the EHR for a longer time after hours, logging in 26.5 minutes per day vs 19.5 minutes per day for non-US clinicians (P = .01). The median US clinician spent as much time actively using the EHR per day (90.1 minutes) as a non-US clinician in the 99th percentile of active EHR use time per day (90.7 minutes) in the sample. These results persisted after controlling for organizational characteristics, including structure, type, size, and daily patient volume.

Conclusions And Relevance: This study found that US clinicians compared with their non-US counterparts spent substantially more time actively using the EHR for a wide range of clinical activities or tasks. This finding suggests that US clinicians have a greater EHR burden that may be associated with nontechnical factors, which policy makers and health system leaders should consider when addressing clinician wellness.
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http://dx.doi.org/10.1001/jamainternmed.2020.7071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737152PMC
February 2021

Assessment of Electronic Health Record Use Between US and Non-US Health Systems.

JAMA Intern Med 2021 Feb;181(2):251-259

Department of Medicine, Stanford University, Stanford, California.

Importance: Understanding how the electronic health record (EHR) system changes clinician work, productivity, and well-being is critical. Little is known regarding global variation in patterns of use.

Objective: To provide insights into which EHR activities clinicians spend their time doing, the EHR tools they use, the system messages they receive, and the amount of time they spend using the EHR after hours.

Design, Setting, And Participants: This cross-sectional study analyzed the deidentified metadata of ambulatory care health systems in the US, Canada, Northern Europe, Western Europe, the Middle East, and Oceania from January 1, 2019, to August 31, 2019. All of these organizations used the EHR software from Epic Systems and represented most of Epic Systems's ambulatory customer base. The sample included all clinicians with scheduled patient appointments, such as physicians and advanced practice practitioners.

Exposures: Clinician EHR use was tracked by deidentified and aggregated metadata across a variety of clinical activities.

Main Outcomes And Measures: Descriptive statistics for clinician EHR use included time spent on clinical activities, note documentation (as measured by the percentage of characters in the note generated by automated or manual data entry source), messages received, and time spent after hours.

Results: A total of 371 health systems were included in the sample, of which 348 (93.8%) were located in the US and 23 (6.2%) were located in other countries. US clinicians spent more time per day actively using the EHR compared with non-US clinicians (mean time, 90.2 minutes vs 59.1 minutes; P < .001). In addition, US clinicians vs non-US clinicians spent significantly more time performing 4 clinical activities: notes (40.7 minutes vs 30.7 minutes; P < .001), orders (19.5 minutes vs 8.75 minutes; P < .001), in-basket messages (12.5 minutes vs 4.80 minutes; P < .001), and clinical review (17.6 minutes vs 14.8 minutes; P = .01). Clinicians in the US composed more automated note text than their non-US counterparts (77.5% vs 60.8% of note text; P < .001) and received statistically significantly more messages per day (33.8 vs 12.8; P < .001). Furthermore, US clinicians used the EHR for a longer time after hours, logging in 26.5 minutes per day vs 19.5 minutes per day for non-US clinicians (P = .01). The median US clinician spent as much time actively using the EHR per day (90.1 minutes) as a non-US clinician in the 99th percentile of active EHR use time per day (90.7 minutes) in the sample. These results persisted after controlling for organizational characteristics, including structure, type, size, and daily patient volume.

Conclusions And Relevance: This study found that US clinicians compared with their non-US counterparts spent substantially more time actively using the EHR for a wide range of clinical activities or tasks. This finding suggests that US clinicians have a greater EHR burden that may be associated with nontechnical factors, which policy makers and health system leaders should consider when addressing clinician wellness.
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http://dx.doi.org/10.1001/jamainternmed.2020.7071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737152PMC
February 2021

Assessment of Physician Sleep and Wellness, Burnout, and Clinically Significant Medical Errors.

JAMA Netw Open 2020 12 1;3(12):e2028111. Epub 2020 Dec 1.

Stanford University School of Medicine, Palo Alto, California.

Importance: Sleep-related impairment in physicians is an occupational hazard associated with long and sometimes unpredictable work hours and may contribute to burnout and self-reported clinically significant medical error.

Objective: To assess the associations between sleep-related impairment and occupational wellness indicators in physicians practicing at academic-affiliated medical centers and the association of sleep-related impairment with self-reported clinically significant medical errors, before and after adjusting for burnout.

Design, Setting, And Participants: This cross-sectional study used physician wellness survey data collected from 11 academic-affiliated medical centers between November 2016 and October 2018. Analysis was completed in January 2020. A total of 19 384 attending physicians and 7257 house staff physicians at participating institutions were invited to complete a wellness survey. The sample of responders was used for this study.

Exposures: Sleep-related impairment.

Main Outcomes And Measures: Association between sleep-related impairment and occupational wellness indicators (ie, work exhaustion, interpersonal disengagement, overall burnout, and professional fulfillment) was hypothesized before data collection. Assessment of the associations of sleep-related impairment and burnout with self-reported clinically significant medical errors (ie, error within the last year resulting in patient harm) was planned after data collection.

Results: Of all physicians invited to participate in the survey, 7700 of 19 384 attending physicians (40%) and 3695 of 7257 house staff physicians (51%) completed sleep-related impairment items, including 5279 women (46%), 5187 men (46%), and 929 (8%) who self-identified as other gender or elected not to answer. Because of institutional variation in survey domain inclusion, self-reported medical error responses from 7538 physicians were available for analyses. Spearman correlations of sleep-related impairment with interpersonal disengagement (r = 0.51; P < .001), work exhaustion (r = 0.58; P < .001), and overall burnout (r = 0.59; P < .001) were large. Sleep-related impairment correlation with professional fulfillment (r = -0.40; P < .001) was moderate. In a multivariate model adjusted for gender, training status, medical specialty, and burnout level, compared with low sleep-related impairment levels, moderate, high, and very high levels were associated with increased odds of self-reported clinically significant medical error, by 53% (odds ratio, 1.53; 95% CI, 1.12-2.09), 96% (odds ratio, 1.96; 95% CI, 1.46-2.63), and 97% (odds ratio, 1.97; 95% CI, 1.45-2.69), respectively.

Conclusions And Relevance: In this study, sleep-related impairment was associated with increased burnout, decreased professional fulfillment, and increased self-reported clinically significant medical error. Interventions to mitigate sleep-related impairment in physicians are warranted.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.28111DOI Listing
December 2020

Physician Task Load and the Risk of Burnout Among US Physicians in a National Survey.

Jt Comm J Qual Patient Saf 2021 02 4;47(2):76-85. Epub 2020 Oct 4.

Background: Cognitive task load can affect providers' ability to perform their job well and may contribute to burnout.

Methods: The researchers evaluated whether task load, measured by the National Aeronautics and Space Administration (NASA) Task Load Index (TLX), correlated with burnout scores in a large national study of US physicians between October 2017 and March 2018 with a 17.1% response rate. Burnout was measured using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, and a high score on either score was considered a manifestation of professional burnout. The NASA-TLX was chosen to evaluate physician task load (PTL) due to its robust validation and use across many industries, including health care, over the past 30 years. The domains included in the PTL were mental, physical, and temporal demands, and perception of effort.

Results: Mean score in task load dimension varied by specialty. In aggregate, high emotional exhaustion, depersonalization, and one symptom of burnout was seen in 38.8%, 27.4%, and 44.0% of participants, respectively. The mean PTL score was 260.9/400 (standard deviation = 71.4). The specialties with the highest PTL score were emergency medicine, urology, anesthesiology, general surgery subspecialties, radiology, and internal medicine subspecialties. A dose response relationship between PTL and burnout was observed. For every 40-point (10%) decrease in PTL there was 33% lower odds of experiencing burnout (odds ratio = 0.67, 95% confidence interval = 0.65-0.70, p < 0.0001).

Conclusion: The relationship between PTL and burnout may suggest areas of particular focus to improve the practice environment and reduce physician burnout.
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http://dx.doi.org/10.1016/j.jcjq.2020.09.011DOI Listing
February 2021

Development of a conceptual model for understanding the learning environment and surgical resident well-being.

Am J Surg 2021 02 21;221(2):323-330. Epub 2020 Oct 21.

Surgical Outcomes and Quality Improvement Center (SOQIC), Department of Surgery, Feinberg School of Medicine, Northwestern University, 633 N. St. Clair Street, 20th Floor, Chicago, IL, 60611, USA. Electronic address:

Background: Surgeon burnout is linked to poor outcomes for physicians and patients. Several conceptual models exist that describe drivers of physician wellness generally. No such model exists for surgical residents specifically.

Methods: A conceptual model for surgical resident well-being was adapted from published models with input gained iteratively from an interdisciplinary team. A survey was developed to measure residents' perceptions of their program. A confirmatory factor analysis (CFA) tested the fit of our proposed model construct.

Results: The conceptual model outlines eight domains that contribute to surgical resident well-being: Efficiency and Resources, Faculty Relationships and Engagement, Meaning in Work, Resident Camaraderie, Program Culture and Values, Work-Life Integration, Workload and Job Demands, and Mistreatment. CFA demonstrated acceptable fit of the proposed 8-domain model.

Conclusion: Eight distinct domains of the learning environment influence surgical resident well-being. This conceptual model forms the basis for the SECOND Trial, a study designed to optimize the surgical training environment and promote well-being.
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http://dx.doi.org/10.1016/j.amjsurg.2020.10.026DOI Listing
February 2021

Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1/PD-1 immunotherapy.

Blood 2021 01;137(2):216-231

School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.

Cancer treatment has been transformed by checkpoint blockade therapies, with the highest anti-tumor activity of anti-programmed death 1 (PD-1) antibody therapy seen in Hodgkin lymphoma. Disappointingly, response rates have been low in the non-Hodgkin lymphomas, with no activity seen in relapsed/refractory chronic lymphocytic leukemia (CLL) with PD-1 blockade. Thus, identifying more powerful combination therapy is required for these patients. Here, we preclinically demonstrate enhanced anti-CLL activity following combinational therapy with anti-PD-1 or anti-PD-1 ligand (PD-L1) and avadomide, a cereblon E3 ligase modulator (CELMoD). Avadomide induced type I and II interferon (IFN) signaling in patient T cells, triggering a feedforward cascade of reinvigorated T-cell responses. Immune modeling assays demonstrated that avadomide stimulated T-cell activation, chemokine expression, motility and lytic synapses with CLL cells, as well as IFN-inducible feedback inhibition through upregulation of PD-L1. Patient-derived xenograft tumors treated with avadomide were converted to CD8+ T cell-inflamed tumor microenvironments that responded to anti-PD-L1/PD-1-based combination therapy. Notably, clinical analyses showed increased PD-L1 expression on T cells, as well as intratumoral expression of chemokine signaling genes in B-cell malignancy patients receiving avadomide-based therapy. These data illustrate the importance of overcoming a low inflammatory T-cell state to successfully sensitize CLL to checkpoint blockade-based combination therapy.
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http://dx.doi.org/10.1182/blood.2020006073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820876PMC
January 2021

Burnout, Depression, Career Satisfaction, and Work-Life Integration by Physician Race/Ethnicity.

JAMA Netw Open 2020 08 3;3(8):e2012762. Epub 2020 Aug 3.

Office of Faculty Development and Diversity, Stanford University School of Medicine, Stanford, California.

Importance: Previous research suggests that the prevalence of occupational burnout varies by demographic characteristics, such as sex and age, but the association between physician race/ethnicity and occupational burnout is less well understood.

Objective: To investigate possible differences in occupational burnout, depressive symptoms, career satisfaction, and work-life integration by race/ethnicity in a sample of US physicians.

Design, Setting, And Participants: In this cross-sectional study, data for this secondary analysis of 4424 physicians were originally collected from a cross-sectional survey of US physicians between October 12, 2017, and March 15, 2018. The dates of analysis were March 8, 2019, to May 21, 2020. Multivariable logistic regression, including statistical adjustment for physician demographic and clinical practice characteristics, was performed to examine the association between physician race/ethnicity and occupational burnout, depressive symptoms, career satisfaction, and work-life integration.

Exposures: Physician demographic and clinical practice characteristics included race/ethnicity, sex, age, clinical specialty, hours worked per week, primary practice setting, and relationship status.

Main Outcomes And Measures: Physicians with a high score on the emotional exhaustion or depersonalization subscale of the Maslach Burnout Inventory were classified as having burnout. Depressive symptoms were measured using the Primary Care Evaluation of Mental Disorders instrument. Physicians who marked "strongly agree" or "agree" in response to the survey items "I would choose to become a physician again" and "My work schedule leaves me enough time for my personal/family life" were considered to be satisfied with their career and work-life integration, respectively.

Results: Data were available for 4424 physicians (mean [SD] age, 52.46 [12.03] years; 61.5% [2722 of 4424] male). Most physicians (78.7% [3480 of 4424]) were non-Hispanic White. Non-Hispanic Asian, Hispanic/Latinx, and non-Hispanic Black physicians comprised 12.3% (542 of 4424), 6.3% (278 of 4424), and 2.8% (124 of 4424) of the sample, respectively. Burnout was observed in 44.7% (1540 of 3447) of non-Hispanic White physicians, 41.7% (225 of 540) of non-Hispanic Asian physicians, 38.5% (47 of 122) of non-Hispanic Black physicians, and 37.4% (104 of 278) of Hispanic/Latinx physicians. The adjusted odds of burnout were lower in non-Hispanic Asian physicians (odds ratio [OR], 0.77; 95% CI, 0.61-0.96), Hispanic/Latinx physicians (OR, 0.63; 95% CI, 0.47-0.86), and non-Hispanic Black physicians (OR, 0.49; 95% CI, 0.30-0.79) compared with non-Hispanic White physicians. Non-Hispanic Black physicians were more likely to report satisfaction with work-life integration compared with non-Hispanic White physicians (OR, 1.69; 95% CI, 1.05-2.73). No differences in depressive symptoms or career satisfaction were observed by race/ethnicity.

Conclusions And Relevance: Physicians in minority racial/ethnic groups were less likely to report burnout compared with non-Hispanic White physicians. Future research is necessary to confirm these results, investigate factors contributing to increased rates of burnout among non-Hispanic White physicians, and assess factors underlying the observed patterns in measures of physician wellness by race/ethnicity.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.12762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414389PMC
August 2020

Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia.

J Am Acad Dermatol 2020 Dec 16;83(6):1581-1589. Epub 2020 Jul 16.

Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls.

Objective: To evaluate the association of factors associated with SCC risk.

Methods: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC).

Limitations: The sample size decreases when combining all risk factors in a single model.

Conclusion: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.
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http://dx.doi.org/10.1016/j.jaad.2020.06.1024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669637PMC
December 2020
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