Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL.

BACKGROUND: Ibrutinib has been approved by the Food and Drug Administration for the treatment of patients with untreated chronic lymphocytic leukemia (CLL) since 2016 but has not been compared with chemoimmunotherapy. We conducted a phase 3 trial to evaluate the efficacy of ibrutinib, either alone or in combination with rituximab, relative to chemoimmunotherapy. METHODS: Patients 65 years of age or older who had untreated CLL were randomly assigned to receive bendamustine plus rituximab, ibrutinib, or ibrutinib plus rituximab. The primary end point was progression-free survival. The Alliance Data and Safety Monitoring Board made the decision to release the data after the protocol-specified efficacy threshold had been met. RESULTS: A total of 183 patients were assigned to receive bendamustine plus rituximab, 182 to receive ibrutinib, and 182 to receive ibrutinib plus rituximab. Median progression-free survival was reached only with bendamustine plus rituximab. The estimated percentage of patients with progression-free survival at 2 years was 74% with bendamustine plus rituximab and was higher with ibrutinib alone (87%; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.26 to 0.58; P<0.001) and with ibrutinib plus rituximab (88%; hazard ratio, 0.38; 95% CI, 0.25 to 0.59; P<0.001). There was no significant difference between the ibrutinib-plus-rituximab group and the ibrutinib group with regard to progression-free survival (hazard ratio, 1.00; 95% CI, 0.62 to 1.62; P=0.49). With a median follow-up of 38 months, there was no significant difference among the three treatment groups with regard to overall survival. The rate of grade 3, 4, or 5 hematologic adverse events was higher with bendamustine plus rituximab (61%) than with ibrutinib or ibrutinib plus rituximab (41% and 39%, respectively), whereas the rate of grade 3, 4, or 5 nonhematologic adverse events was lower with bendamustine plus rituximab (63%) than with the ibrutinib-containing regimens (74% with each regimen). CONCLUSIONS: Among older patients with untreated CLL, treatment with ibrutinib was superior to treatment with bendamustine plus rituximab with regard to progression-free survival. There was no significant difference between ibrutinib and ibrutinib plus rituximab with regard to progression-free survival. (Funded by the National Cancer Institute and Pharmacyclics; ClinicalTrials.gov number, NCT01886872 .).

Comparison of bleach, acetic acid, and other topical anti-infective treatments in pediatric atopic dermatitis: A retrospective cohort study on antibiotic exposure.

BACKGROUND/OBJECTIVES: Skin infection is common in atopic dermatitis (AD), often necessitating treatment with systemic antibiotics. Topical adjunctive therapies such as dilute bleach baths are increasingly recommended, and topical dilute acetic acid (AA) has not been widely studied. The objective of this study was to evaluate whether various topical anti-infective bathing recommendations were associated with decreased systemic antibiotic exposure in pediatric AD, as well as evaluate topical anti-infective recommendations over time within our institution. METHODS: Clinical data were extracted from charts of pediatric patients from 1/1/2000 to 12/31/2005 and 1/1/2009 to 12/31/2014 who visited outpatient dermatology clinics at Mayo Clinic, Rochester, a tertiary referral center. Recommendations for topical anti-infectives (dilute AA, dilute bleach, other, or none) at any time after patient had clinically proven or suspected AD superinfection were recorded as exposures to topical anti-infective. Primary outcome was the number of systemic antibiotic courses in a 1-year period. RESULTS: Of 1111 patients with AD, 753 met inclusion criteria (303 in 2000-2005; 450 in 2009-2014). Of these, 351 (46.6%) had culture-proven or clinically suspected superinfection. Topical anti-infective recommendations increased between the time periods (23.3% to 79.2%; P < 0.001) and number of courses of systemic antibiotics decreased (1.9 per year vs 1.5 per year, P = 0.010). Number of systemic antibiotic courses did not differ between those who received bathing recommendations and those who did not, nor between different anti-infective groups (P = 0.398). CONCLUSIONS: Practice behaviors have changed, and topical anti-infectives are now commonly recommended. Neither dilute AA nor bleach baths were associated with fewer subsequent exposures to systemic antibiotics in the treatment of pediatric AD.

Characterization of Nonphysician Health Care Workers' Burnout and Subsequent Changes in Work Effort.

Importance: Burnout is a pervasive, unrelenting problem among health care workers (HCWs), with detrimental impact to patients. Data on the impact of burnout on workforce staffing are limited and could help build a financial case for action to address system-level contributors to burnout. Objective: To explore the association of burnout and professional satisfaction with changes in work effort over 24 months in a large cohort of nonphysician HCWs. Design, Setting, and Participants: This longitudinal cohort study was conducted in Rochester, Minnesota; Scottsdale and Phoenix, Arizona; Jacksonville, Florida; and community-based hospitals and health care facilities in the Midwest among nonphysician HCWs who responded to 2 surveys from 2015 to 2017. Analysis was completed November 25, 2020. Exposures: Burnout, as measured by 2 items from the Maslach Burnout Inventory, and professional satisfaction. Main Outcomes and Measures: The main outcome was work effort, as measured in full-time equivalent (FTE) units, recorded in payroll records. Results: Data from 26 280 responders (7293 individuals aged 45-54 years [27.8%]; 20 263 [77.1%] women) were analyzed. A total of 8115 individuals (30.9%) had worked for the organization more than 15 years, and 6595 individuals (25.1%) were nurses. After controlling for sex, age, duration of employment, job category, baseline FTE, and baseline burnout, overall burnout (odds ratio [OR], 1.53; 95% CI, 1.38-1.70; P < .001), high emotional exhaustion at baseline (OR, 1.54; 95% CI, 1.39-1.71; P < .001), and high depersonalization at baseline (OR, 1.40; 95% CI, 1.21-1.62; P < .001) were associated with an HCW reducing their FTE over the following 24 months. Conversely, satisfaction with the organization at baseline was associated with lower likelihood of reduced FTE (OR, 0.73; 95% CI, 0.65-0.83; P < .001). Findings were similar when emotional exhaustion (OR per 1-point increase, 1.12; 95% CI, 1.10-1.16; P < .001), depersonalization (OR per 1-point increase, 1.10; 95% CI, 1.06-1.14; P < .001) and satisfaction with the organization (OR per 1-point increase, 0.83; 95% CI, 0.79-0.88; P < .001) were modeled as continuous measures. Nurses represented the largest group (1026 of 1997 nurses [51.4%]) reducing their FTE over the 24 months. Conclusions and Relevance: This cohort study found that burnout and professional satisfaction of HCWs were associated with subsequent changes in work effort over the following 24 months. These findings highlight the importance of addressing factors contributing to high stress among all HCWs as a workforce retention and cost reduction strategy.

Physicians' Ratings of their Supervisor's Leadership Behaviors and Their Subsequent Burnout and Satisfaction: A Longitudinal Study.

OBJECTIVE: To evaluate the relationships between immediate supervisors' leadership qualities and the subsequent levels and changes in burnout and satisfaction of supervised physicians 2 years later. PARTICIPANTS AND METHODS: In 2015 and 2017 physicians were asked to complete surveys that included the 9-item Mayo Clinic Leadership Score (range, 9 to 45) assessing their supervisor, an item about satisfaction with the organization, and two items from the Maslach Burnout Inventory. Individual participants' responses to the surveys were linked. RESULTS: Among the 3698 physicians invited to complete both the 2015 and 2017 survey, 1795 (48.5%) responded. The mean composite baseline leadership score was 38.1 (SD, 8.4). Lower mean baseline leadership scores were reported by physicians who had burnout (mean [SD], 36.0 [9.7] vs 39.1 [7.3]; P<.001) 2 years later in comparison to those who did not have burnout 2 years later. In multivariable analysis, higher baseline leadership score of supervisors was independently associated with lower odds of physicians having burnout 2 years later (for each 1-point increase, odds ratio, 0.98; 95% CI, 0.96 to 0.99; P=.002) after adjusting for burnout at baseline, age, gender, length of service, and specialty. Baseline composite leadership score of supervisors was also independently associated with physicians' satisfaction with the organization 2 years later (odds ratio, 1.05; 95% CI, 1.03 to 1.07; P<.0001). CONCLUSION: Physicians' ratings of their immediate supervisors' leadership qualities were associated with their subsequent levels and changes in burnout and satisfaction 2 years later. Additional studies are needed to determine the effect of sharing such scores with immediate supervisors and providing additional leadership training to those with low scores, and if doing so ultimately reduces burnout and improves satisfaction of the supervised physicians.

Original Research: An Investigation of Career Choice Regret Among American Nurses.

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

Relationship Between Organizational Leadership and Health Care Employee Burnout and Satisfaction.

OBJECTIVE: To explore the relationship between immediate supervisor leadership behaviors and burnout and professional satisfaction of health care employees. PARTICIPANTS AND METHODS: From October 2 to 20, 2017, we surveyed nonphysician health care employees. The survey included 2 items from the Maslach Burnout Inventory and items on their immediate supervisor leadership behaviors. Logistic regression was performed to evaluate the relationship between the leadership score and the prevalence of burnout and satisfaction after adjusting for age, sex, duration of employment, and job category. Sensitivity analysis was performed using mixed models with a random intercept for work unit to assess the impact of the correlation within work units on burnout and satisfaction with the organization. RESULTS: Of the 57,414 employees surveyed, 39,896 (69.5%) responded and answered the leadership questions. Supervisor scores in each dimension and composite leadership scores correlated with burnout and satisfaction of employees (P<.001 for all). In logistic regression, each 1-point increase in leadership score was associated with a 7% decrease in odds of burnout and an 11% increase in odds of satisfaction (P<.001 for both) of employees. The mean composite leadership score rating of each immediate supervisor correlated with rate of burnout (r=-0.247; P<.001) and the satisfaction with the organization (r=0.416; P<.001) at the work unit level. CONCLUSION: Leadership qualities of immediate supervisors relate to burnout and satisfaction of nonphysician health care employees working in a large organization. Further studies are needed to determine whether strategies to monitor and improve supervisor leadership scores result in reduction in burnout and improved satisfaction among health care employees.

Relationship Between Burnout and Professional Behaviors and Beliefs Among US Nurses.

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

Neurological safety of oxaliplatin in patients with uncommon variants in Charcot-Marie-tooth disease genes.

Oxaliplatin therapy can be complicated by chemotherapy-induced peripheral neuropathy (CIPN). Other neurotoxic chemotherapies have been linked to single nucleotide variants (SNV) in Charcot-Marie-Tooth disease (CMT) genes. Whether oxaliplatin carries increased risks of CIPN due to SNV in CMT-associated genes is unknown. 353 patients receiving oxaliplatin in NCCTG N08CB were serially evaluated for CIPN using a validated patient-reported outcome (PRO) instrument, the CIPN20 questionnaire (sensory scale). 49 canonical CMT-associated genes were analyzed for rare and common SNV by nextgen sequencing. The 157 patients with the highest and lowest susceptibility to CIPN (cases and controls) harbored 270 non-synonymous SNV in CMT-associated genes (coding regions). 143 of these were rare, occurring only once ("singletons"). CIPN cases had 0.84 singletons per patient compared with 0.98 in controls. An imbalance in favor of cases was noted only in few genes including PRX, which was previously highlighted as a candidate CIPN gene in patients receiving paclitaxel. However, the imbalance was only modest (5 singleton SNV in cases and 2 in controls). Therefore, while singleton SNV were common, they did overall not portend an increased risk of CIPN. Furthermore, testing CMT-associated genes using recurrent non-synonymous SNV did not reveal any significant association with CIPN. Genetic analysis of patients from N08CB provides clinical guidance that oxaliplatin chemotherapy decisions should not be altered by the majority of SNV that may be encountered in CMT-associated genes when common genetic tests are performed, such as exome or genome sequencing. Oxaliplatin's CIPN risk appears unrelated to CMT-associated genes.

Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: Report of CALGB 361006 (Alliance).

OBJECTIVE: To demonstrate feasibility of performing geriatric assessment (GA) in the National Clinical Trials Network (NCTN) and to explore the utility of GA to characterize treatment tolerance. MATERIALS AND METHODS: We conducted a multisite companion study (CALGB 361006) to CALGB 11001, a phase 2 trial of adults ≥60 years old with newly diagnosed FLT3- mutated AML, testing the efficacy of adding sorafenib to intensive chemotherapy. On 361006, a GA was administered prior to induction and prior to post-remission therapy. The GA is divided into items requiring administration by a health care professional (HCP) and patient self-administered questionnaires. Feasibility outcomes were recruitment rate, time to GA completion, difficulty with GA administration, percent of patients requiring assistance, and satisfaction. Change in GA measures pre- and post-induction were compared using Wilcoxon signed rank test and McNemar's tests. RESULTS: The recruitment rate was 80% (N = 43, median age 68 years). Median completion time of the GA was 30 min; (10 and 21 min for HCP and patients, respectively). HCP reported no difficulty completing assessments (100%). Most patients completed questionnaires without assistance (77%), and were satisfied with the length (89%). Self-reported physical function, mental health, social activity and nutritional parameters worsened after induction. CONCLUSION: GA is feasible to administer in the setting of intensive induction for older adults with AML in the NCTN and provides evidence of the impact of induction therapy on physical and emotional health.

Public feedback on a proposed statewide virtual translational research community.

INTRODUCTION: Researchers have explored using the internet and social media to recruit participants to specific research projects. Less systematic work has been done to inform the engagement of large populations in virtual communities to advance clinical and translational science. We report on our first step to use social media to engage Minnesota residents by studying the willingness of participants to engage in a virtual (Facebook) community about the concepts of health and health-related research. METHODS: Data were collected at the 2018 Minnesota State Fair using a cross-sectional, 46-item survey with assessment including sociodemographics and willingness to engage in a Facebook group for health-related research. Quantitative analysis included univariate, bivariate, and multivariate analyses. Content analysis was used to generate themes from open-ended survey responses. RESULTS: Five hundred people completed the survey; after data cleaning, 418 participant responses informed this report. A majority were younger than age 50 (73%), female (66%), and married/partnered (54%). Overall, 46% of participants agreed/strongly agreed they are willing to join the Facebook group. Multivariate logistic regression identified social media use over the past 6 months as the sole variable independently associated with willingness to join the Facebook group (once a day vs. never or rarely OR = 1.82 (0.86, 3.88), several hours a day vs. never or rarely OR = 2.17 (1.17, 4.02, overall p-value 0.048). CONCLUSION: Facebook holds potential for reaching a broader community, democratizing access to and engagement with clinical and translational research. Social media infrastructure and content could be disseminated to other institutions with Clinical and Translational Science Awards.

Burnout and Satisfaction With Work-Life Integration Among Nurses.

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

Combining Survival and Toxicity Effect Sizes from Clinical Trials: NCCTG 89-20-52 (Alliance).

BACKGROUND: How can a clinician and patient incorporate survival and toxicity information into a single expression of comparative treatment benefit? Sloan et al. recently extended the ½ standard deviation concept for judging the clinical importance of findings from clinical trials to survival and tumor response endpoints. A new method using this approach to combine survival and toxicity effect sizes from clinical trials into a quality-adjusted effect size is presented. METHODS: The quality-adjusted survival effect size (QASES) is calculated as survival effect size (ESS) minus the calibrated toxicity effect sizes (EST) (QASES=ESS-EST). This combined effect size can be weighted to adjust for the relative emphasis placed by the patient on survival and toxicity effects. RESULTS: As an example, consider clinical trial NCCTG 89-20-52 which randomized patients to once-daily thoracic radiotherapy (ODTRT) versus twice-daily treatment of thoracic radiotherapy (TDRT) for the treatment of lung cancer. The ODTRT vs. TDRT arms had median survival time of 22 vs. 20 months (p=0.49) and toxicity rate of 39% vs. 54%, (p<0.05). The QASES of 0.18 standard deviations translates to a quality-adjusted survival difference of 5.7 months advantage for the ODRT arm over the TDRT treatment arm (22(16.3) months), p<0.05). Similar results are presented for the four possible case combinations of significant/non-significant survival and toxicity benefits using completed clinical trials. CONCLUSIONS: We used a novel approach to re-analyze clinical trial data to produce a single estimate for each treatment that combines survival and toxicity data. The QASES approach is an intuitive and mathematically simple yet robust approach.

Using Garden Cafés to engage community stakeholders in health research.

Science Cafés, informal venues to promote bidirectional dialog, inquiry and learning about science between community members, scientists, healthcare and service providers, hold promise as an innovative tool for healthcare researchers and community members to improve health outcomes, especially among populations with health disparities. However, the process of optimizing science cafés is under-studied. We describe the pilot evaluation of a series of Science Cafés, called Garden Cafés (n = 9), conducted from September 2015 through April 2016 in Olmsted County, MN and Duval County, FL to connect Mayo Clinic researchers and local service providers with the community. Selection of discussion topics was guided by a county health needs assessment, which identified community priorities. Before leaving the events, community participants completed a brief anonymous survey assessing sociodemographics and their knowledge of research benefits, readiness to participate as a partner in health research, and health and science literacy confidence. Of the 112 attendees who responded, 51% were female and 51% were Black. Respondents reported that participating in the event significantly improved (all at p<0.001) their understanding on all three measures. Preliminary findings suggest that Garden Cafés are an effective forum to increase community understanding and disposition to collaborate in health research, especially in members from diverse backgrounds.