Physician Distress and Burnout: The Neurobiological Perspective

Physician burnout and other forms of occupational distress are a significant problem in modern medicine, especially during the coronavirus disease pandemic, yet few doctors are familiar with the neurobiology that contributes to these problems. Burnout has been linked to changes that reduce a physician’s sense of control over their own practice, undermine connections with patients and colleagues, interfere with work-life integration, and result in uncontrolled stress. Brain research has revealed that uncontrollable stress, but not controllable stress, impairs the functioning of the prefrontal cortex, a recently evolved brain region that provides top-down regulation over thought, action, and emotion. The prefrontal cortex governs many cognitive operations essential to physicians, including abstract reasoning, higher-order decision making, insight, and the ability to persevere through challenges. However, the prefrontal cortex is remarkably reliant on arousal state and is impaired under conditions of fatigue and/or uncontrollable stress when there are inadequate or excessive levels of the arousal modulators (eg, norepinephrine, dopamine, acetylcholine). With chronic stress exposure, prefrontal gray matter connections are lost, but they can be restored by stress relief. Reduced prefrontal cortex self-regulation may explain several challenges associated with burnout in physicians, including reduced motivation, unprofessional behavior, and suboptimal communication with patients. Understanding this neurobiology may help physicians have a more informed perspective to help relieve or prevent symptoms of burnout and may help administrative leaders to optimize the work environment to create more effective organizations. Efforts to restore a sense of control to physicians may be particularly helpful.     

Current approach to diagnosis and management of chronic lymphocytic leukemia

The care of patients with chronic lymphocytic leukemia (CLL) has changed dramatically during the past decade. This review summarizes the work-up of lymphocytosis and the current diagnostic criteria and management of CLL. Although clinical staging (Rai and Binet) remains the foundation for determining prognosis, 50% of patients with early-stage disease at diagnosis will experience an aggressive course of disease with early progression and premature death due to CLL. New laboratory techniques (CD38, fluorescence in situ hybridization [FISH]) can identify some patients with early-stage CLL at high risk of rapid disease progression. The array of treatment options has expanded in recent years and now includes monoclonal antibodies used alone or in combination with purine nucleoside analogues and alkylating agents, which have culminated in dramatically improved response rates. Supportive care guidelines now include vaccination strategies, surveillance for secondary malignancies, and aggressive management of infectious complications. An early hematology consultation is recommended for all patients at diagnosis to identify and counsel high-risk patients with early-stage disease who may benefit from more frequent follow-up or early treatment as part of a clinical trial.     

A Group Randomized Intervention Trial Increases Participation in the School Breakfast Program in 16 Rural High Schools in Minnesota

BackgroundBreakfast consumption is associated with better diet quality and healthier weights, yet many adolescents miss breakfast. Nationally, 17.1% of students participate in the School Breakfast Program (SBP). Only 10% of high school students participate.ObjectiveOur aim was to evaluate an environmental intervention to increase SBP participation in high schools.DesignA group randomized trial was carried out from 2012 to 2015.Participants/settingNinth- and 10th-grade students enrolled in 16 rural schools in Minnesota (median 387 students) were randomized to intervention or control condition.InterventionA school-based intervention that included two key components was implemented over a 12-month period. One component focused on increasing SBP participation by increasing student access to school breakfast through changes in school breakfast service practices (eg, serving breakfast from a grab-n-go cart in the atrium; expanding breakfast service times). The other component focused on promoting school breakfast through student-directed marketing campaigns.Main outcome measureChange in school-level participation in the SBP was assessed between baseline (among ninth and tenth graders) and follow-up (among tenth and eleventh graders). School meal and attendance records were used to assess change in school-level participation rates in the SBP.Statistical analysesThe Wilcoxon test was used for analysis of difference in change in mean SBP participation rate by experimental group.ResultsThe median change in SBP participation rate between baseline and follow-up was 3% (interquartile range=13.5%) among the eight schools in the intervention group and 0.5% (interquartile range=0.7%) among the eight schools in the control group. This difference in change between groups was statistically significant (Wilcoxon test, P=0.03). The intervention effect increased throughout the intervention period, with change in mean SBP participation rate by the end of the school year reaching 10.3% (95% CI 3.0 to 17.6). However, among the intervention schools, the change in mean SBP participation rates was highly variable (range=–0.8% to 24.8%).ConclusionsInterventions designed to improve access to the SBP by reducing environmental and social barriers have potential to increase participation among high school students.     

Tumor mutational load predicts time to first treatment in chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis beyond the CLL international prognostic index

Next-generation sequencing identified about 60 genes recurrently mutated in chronic lymphocytic leukemia (CLL). We examined the additive prognostic value of the total number of recurrently mutated CLL genes (i.e., tumor mutational load [TML]) or the individually mutated genes beyond the CLL international prognostic index (CLL-IPI) in newly diagnosed CLL and high-count monoclonal B-cell lymphocytosis (HC MBL). We sequenced 59 genes among 557 individuals (112 HC MBL/445 CLL) in a multi-stage design, to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time-to-first treatment (TTT), adjusted for CLL-IPI and sex. TML was associated with shorter TTT in the discovery and validation cohorts, with a combined estimate of continuous HR = 1.27 (CI:1.17-1.39, P = 2.6 × 10⁻⁸; c-statistic = 0.76). When stratified by CLL-IPI, the association of TML with TTT was stronger and validated within low/intermediate risk (combined HR = 1.54, CI:1.37-1.72, P = 7.0 × 10⁻¹⁴). Overall, 80% of low/intermediate CLL-IPI cases with two or more mutated genes progressed to require therapy within 5 years, compared to 24% among those without mutations. TML was also associated with shorter TTT in the HC MBL cohort (HR = 1.53, CI:1.12-2.07, P = .007; c-statistic = 0.71). TML is a strong prognostic factor for TTT independent of CLL-IPI, especially among low/intermediate CLL-IPI risk, and a better predictor than any single gene. Mutational screening at early stages may improve risk stratification and better predict TTT.     

In vitro characterization of the human recombinant soluble granulocyte- macrophage colony-stimulating factor receptor

We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic domains that are presumably removed from the intact receptor cDNA by a mechanism of alternative splicing. The resulting soluble 55- to 60-kD glycosylated receptor species binds GM-CSF with a dissociation constant (kd) of 3.8 nmol/L. The soluble GM-CSF receptor successfully competes for GM-CSF binding not only with the transmembrane-anchored GM-CSF receptor alpha subunit but also with the native oligomeric high-affinity receptor complex. In addition, in human bone marrow colony-forming assays, the soluble GM-CSF receptor species can antagonize the activity of GM-CSF. Our data suggest that the soluble GM-CSF receptor may be capable of acting in vivo as a modulator of the biologic activity of GM-CSF.     

Changes in Burnout and Satisfaction With Work-Life Integration in Physicians and the General US Working Population Between 2011 and 2017

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