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ABSTRACT: Monoclonal B-cell lymphocytosis (MBL) progresses to chronic lymphocytic leukemia (CLL) requiring therapy at 1% to 5% per year. Improved prediction of progression would greatly benefit individuals with MBL. Patients with CLL separate into 3 distinct epigenetic subtypes (epitypes) with high prognostic significance, and recently the intermediate epitype has been shown to be enriched for high-risk immunoglobulin lambda variable (IGLV) 3-21 rearrangements, impacting outcomes for these patients. Here, we employed this combined strategy to generate the epigenetic and light chain immunoglobulin (ELCLV3-21) signature to classify 219 individuals with MBL. The ELCLV3-21 high-risk signature distinguished MBL individuals with a high probability of progression (39.9% and 71.1% at 5 and 10 years, respectively). ELCLV3-21 improved the accuracy of predicting time to therapy for individuals with MBL compared with other established prognostic indicators, including the CLL international prognostic index (c-statistic, 0.767 vs 0.668, respectively). Comparing ELCLV3-21 risk groups in MBL vs a cohort of 226 patients with CLL revealed ELCLV3-21 high-risk individuals with MBL had significantly shorter time to therapy (P = .003) and reduced overall survival (P = .03) compared with ELCLV3-21 low-risk individuals with CLL. These results highlight the power of the ELCLV3-21 approach to identify individuals with a higher likelihood of adverse clinical outcome and may provide a more accurate approach to classify individuals with small B-cell clones.
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Linfócitos B , Leucemia Linfocítica Crônica de Células B , Linfocitose , Humanos , Linfocitose/genética , Linfocitose/diagnóstico , Linfocitose/imunologia , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/diagnóstico , Feminino , Masculino , Linfócitos B/imunologia , Linfócitos B/patologia , Idoso , Pessoa de Meia-Idade , Prognóstico , Epigênese Genética , Idoso de 80 Anos ou mais , AdultoRESUMO
The psychological safety of health care workers is an important but often overlooked aspect of the rising rates of burnout and workforce shortages. In addition, mental health conditions are prevalent among health care workers, but the associated stigma is a significant barrier to accessing adequate care. More efforts are therefore needed to foster health care work environments that are safe and supportive of self-care. The purpose of this brief document is to promote a culture of psychological safety in health care organizations. We review ways in which organizations can create a psychologically safe workplace, the benefits of a psychologically safe workplace, and strategies to promote mental health and reduce suicide risk.
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American Heart Association , Pessoal de Saúde , Saúde Mental , Humanos , Pessoal de Saúde/psicologia , Estados Unidos , Esgotamento Profissional/psicologia , Esgotamento Profissional/prevenção & controle , Esgotamento Profissional/epidemiologia , Local de Trabalho/psicologia , Saúde Ocupacional , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/psicologia , Segurança PsicológicaRESUMO
Pooled analysis of six mature phase 3 trials (RESONATE2, ILLUMINATE, ALLIANCE041202, ELEVATE-TN, CLL14, and GLOW) evaluating Bruton's tyrosine kinase inhibitors (BTKis) and venetoclax-based treatments suggests that these agents have reduced but not completely eliminated the overall survival (OS) gap between elderly chronic lymphocytic leukemia (CLL) patients and the age and sex-matched general population (AGMGP).
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Humanos , Idoso , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adenina/uso terapêutico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Sulfonamidas/uso terapêutico , Sulfonamidas/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologiaRESUMO
GOAL: The objective of this study was to evaluate satisfaction with work-life integration (WLI), social isolation, and the impact of work on personal relationships (IWPR) among senior healthcare operational leaders. METHODS: Between June 7 and June 30, 2021, we performed a national survey of CEOs and other senior healthcare operational leaders in the United States to evaluate their personal work experience. Satisfaction with WLI, social isolation, and IWPR were assessed using standardized instruments. Burnout and professional fulfillment were also assessed using standardized scales. PRINCIPAL FINDINGS: The mean IWPR score on the 0-10 scale was 4.39 (standard deviation was 2.36; higher scores were unfavorable). On multivariable analysis to identify demographic and professional factors associated with the IWPR score, each additional hour worked per week decreased the likelihood of a favorable IWPR score. The IWPR, feeling isolated, and satisfaction with WLI were independently associated with burnout after adjusting for other personal and professional factors. On multivariable analysis, healthcare administrators were more likely than U.S. workers in other fields to indicate work had adversely impacted personal relationships in response to the item "In the past year, my job has contributed to me feeling more isolated and detached from the people who are most important to me." PRACTICAL APPLICATIONS: Experiencing an adverse IWPR is common among U.S. healthcare administrators, who are more likely than the general U.S. working population to indicate their job contributes to isolation and detachment from the people most important to them. Problems with WLI, isolation, and an adverse IWPR are associated with increased burnout and lower professional fulfillment. Intentional efforts by both organizations and administrative leaders are necessary to address the work characteristics and professional norms that erode WLI and result in work adversely impacting personal relationships.
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Esgotamento Profissional , Satisfação no Emprego , Humanos , Estados Unidos , Atenção à Saúde , Isolamento Social , Integração Social , Inquéritos e QuestionáriosRESUMO
This Viewpoint summarizes methods used by health care organizations to assess and improve clinician well-being, discusses the potential downsides of public reporting of clinician well-being survey data, and calls for making organizations' adherence to structure and process measures a part of accreditation criteria.
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To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials. Patients treated with TAs demonstrated a higher 5-year RMST (58.1 months; 95% CI: 57.4 to 58.8) compared to those treated with CIT (5-year RMST, 56.9 months; 95% CI: 56.7-58.2). Furthermore, the OS comparison of treatment groups with the AGMGP suggests that TAs may mitigate the impact of CLL on OS during the first five years post-treatment initiation. In summary, the 5-year RMST difference was -0.4 months (95% CI: -0.8 to 0.2; p = 0.10) when comparing CLL patients treated with TAs to the Italian age- and gender-matched general population (AGMGP). A similar trend was observed when CLL patients treated with TAs were compared to the US AGMGP (5-year RMST difference, 0.3 months; 95% CI: -0.1 to 0.9; p = 0.12). In contrast, CLL patients treated with FCR exhibited sustained OS differences when compared to both the Italian cohort (5-year RMST difference: -1.6 months; 95% CI: -2.4 to -0.9; p < 0.0001) and the US AGMGP cohort (5-year RMST difference: -0.9 months; 95% CI: -1.7 to -0.2; p = 0.015). Although these results support TAs as the preferred first-line treatment for younger CLL patients, it is crucial to acknowledge that variations in patient selection criteria and clinical profiles across clinical trials necessitate a cautious interpretation of these findings that should be viewed as directional and hypothesis-generating. A longer follow-up is needed to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP.
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OBJECTIVES: Dentists' well-being is being challenged today by many factors. However, effective screening tools to assess their distress and well-being are yet to be validated. The present study aims to evaluate the ability of the Well-Being Index (WBI) to identify distress and stratify dentists' well-being and their likelihood for adverse professional consequences. METHOD AND MATERIALS: A convenience sample of dentists completed a web-based 9-item WBI survey along with other instruments that measured quality of life (QOL), fatigue, burnout, and questions about suicidal ideation, recent dental error, and intent to leave their current job. RESULTS: A total of 597 dentists completed the survey. The overall mean WBI score was 2.3. The mean WBI score was significantly greater in dentists with low QOL than among dentists without low QOL (4.1 vs 1.6, p < 0.001). Dentists with extreme fatigue, burnout, and suicidal ideation had significantly higher mean WBI score than those without distress (all p < 0.001). WBI score stratified the dentists' likelihood of reporting a recent dental error and intent to leave their current job. CONCLUSION: The WBI may be a useful screening tool to assess well-being among dentists and identify those in distress and at risk for adverse professional consequences.
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OBJECTIVE: To evaluate the ability of routinely collected electronic health record (EHR) use measures to predict clinical work units at increased risk of burnout and potentially most in need of targeted interventions. METHODS: In this observational study of primary care physicians, we compiled clinical workload and EHR efficiency measures, then linked these measures to 2 years of well-being surveys (using the Stanford Professional Fulfillment Index) conducted from April 1, 2019, through October 16, 2020. Physicians were grouped into training and confirmation data sets to develop predictive models for burnout. We used gradient boosting classifier and other prediction modeling algorithms to quantify the predictive performance by the area under the receiver operating characteristics curve (AUC). RESULTS: Of 278 invited physicians from across 60 clinics, 233 (84%) completed 396 surveys. Physicians were 67% women with a median age category of 45 to 49 years. Aggregate burnout score was in the high range (≥3.325/10) on 111 of 396 (28%) surveys. Gradient boosting classifier of EHR use measures to predict burnout achieved an AUC of 0.59 (95% CI, 0.48 to 0.77) and an area under the precision-recall curve of 0.29 (95% CI, 0.20 to 0.66). Other models' confirmation set AUCs ranged from 0.56 (random forest) to 0.66 (penalized linear regression followed by dichotomization). Among the most predictive features were physician age, team member contributions to notes, and orders placed with user-defined preferences. Clinic-level aggregate measures identified the top quartile of clinics with 56% sensitivity and 85% specificity. CONCLUSION: In a sample of primary care physicians, routinely collected EHR use measures demonstrated limited ability to predict individual burnout and moderate ability to identify high-risk clinics.
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Objective: To identify the characteristics that distinguish occupationally well outliers (OWO), a subset of academic psychiatrists and neurologists with consistently high professional fulfillment and low burnout, from their counterparts with lower levels of occupational well-being. Participants and Methods: Participants included faculty physicians practicing psychiatry and neurology in academic medical centers affiliated with the Professional Well-being Academic Consortium. In this prospective, longitudinal study, a mixed qualitative and quantitative approach was used. Quantitative measures were administered to physicians in a longitudinal occupational well-being survey sponsored by the academic organizations where they work. Four organizations participated in the qualitative study. Psychiatrists and neurologists at these organizations who competed survey measures at 2 consecutive time points between 2019 and 2021 were invited to participate in an interview. Results: Of 410 (213 psychiatrists and 197 neurologists) who completed professional fulfillment and burnout measures at 2 time points, 84 (20.5%) met OWO criteria. Occupationally well outliers psychiatrists and neurologists had more favorable scores on hypothesized determinants of well-being (values alignment, perceived gratitude, supportive leadership, peer support, and control of schedule). Ultimately, 31 psychiatrists (25% of 124 invited) and 33 neurologists (18.5% of 178 invited) agreed to participate in an interview. Qualitatively, OWO physicians differed from all others in 3 thematic domains: development of life grounded in priorities, ability to shape day-to-day work context, and professional relationships that provide joy and support. Conclusion: A multilevel approach is necessary to promote optimal occupational well-being, targeting individual-level factors, organizational-level factors, and broader system-level factors.
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Importance: Physician burnout has reached crisis levels. Supportive leadership is one of the strongest drivers of physician well-being, and monitoring supervisor support is key to developing well-being focused leadership skills. Existing measures of leader support were designed within "direct report" supervision structures limiting their applicability to matrixed leadership reporting structures where direct reports are not the predominant norm. Antecedently, no measure of leadership support is validated specifically for implementation in matrixed leadership structures. Objective: Adapt and validate the Mayo Leadership Impact Index (MLII) for settings with matrixed leadership structures. Design: A psychometric validation study utilizing classical test theory and item response theory. Setting: A tripartite hospital system in the southwestern US. Participants: Physician-respondents to a 2023 cross-sectional survey. Main Outcomes and Measures: After pilot testing, the adapted MLII was examined using a unidimensional graded response model and confirmatory factor analyses. Convergent validity was investigated via correlations with professional fulfillment, perceived autonomy support, self-valuation, and peer connectedness/respect. Divergent validity was tested via correlations with burnout. Results: Of the three candidate revisions of the MLII, the 9-item adaptation was selected for its superior validity/reliability indices. Standardized Cronbach's and Ordinal alpha coefficients were 0.958 and 0.973, respectively. CFA loadings exceeded 0.70 (p < 0.001), and coefficients of variation (R2) exceeded 0.60 for all items. GRM slope parameters indicated "high" to "very high" item discrimination. Items 2, 5, and 8 were the most informative. Positive correlations of the adapted MLII with professional fulfillment, perceived autonomy support, and peer connectedness/respect were observed, supporting convergent validity. Negative correlation with overall burnout supports divergent validity. Conclusions and Relevance: The findings provide evidence of the adapted MLII's validity, reliability, and appropriateness for implementation within matrixed leadership settings. Prior to this study, no leadership support measure had been validated for use among the growing number of healthcare systems with matrixed leadership reporting structures.
Question: : What is the validity and reliability of a well-being centered leadership measure adapted for use in healthcare systems with matrixed, multiform reporting structures? Findings: : Classical test theory and item response theory analyses of cross-sectional survey data from 158 physician-respondents supported the adapted measure's construct validity. All reliability coefficients were strong. Leadership ratings positively correlated with professional fulfillment, autonomy support, self-valuation, and peer connectedness/respect, and negatively correlated with burnout. Meaning: : Findings support the adapted measure's validity and reliability. This study is the first to demonstrate a valid empirical measure of well-being centered leadership behaviors in settings with multiform, matrixed leadership structures.
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Importance: Vacation has been shown to be an important restorative activity in the general population; less is known about physicians' vacation behaviors and their association with burnout and professional fulfillment. Objective: To examine the number of vacation days taken per year and the magnitude of physician work while on vacation and their association with physician burnout and professional fulfillment, by individual and organizational characteristics. Design, Setting, and Participants: This cross-sectional survey of US physicians was conducted between November 20, 2020, and March 23, 2021. Data analysis was performed from March to July 2023. Main Outcomes and Measures: Burnout was measured using the Maslach Burnout Index, and professional fulfillment was measured using the Stanford Professional Fulfillment Index. Number of vacation days taken in the last year, time spent working on patient care and other professional tasks per typical vacation day (ie, work on vacation), electronic health record (EHR) inbox coverage while on vacation, barriers to taking vacation, and standard demographics were collected. Results: Among 3024 respondents, 1790 of 3004 (59.6%), took 15 or fewer days of vacation in the last year, with 597 of 3004 (19.9%) taking 5 or fewer days. The majority, 2104 respondents (70.4%), performed patient care-related tasks on vacation, with 988 of 2988 (33.1%) working 30 minutes or more on a typical vacation day. Less than one-half of physicians (1468 of 2991 physicians [49.1%]) reported having full EHR inbox coverage while on vacation. On multivariable analysis adjusting for personal and professional factors, concern about finding someone to cover clinical responsibilities (odds ratio [OR], 0.48 [95% CI, 0.35-0.65] for quite a bit; OR, 0.30 [95% CI, 0.21-0.43] for very much) and financial concerns (OR, 0.49 [95% CI, 0.36-0.66] for quite a bit; OR, 0.38 [95% CI, 0.27-0.54] for very much) were associated with decreased likelihood of taking more than 3 weeks of vacation per year. Taking more than 3 weeks of vacation per year (OR, 0.66 [95% CI, 0.45-0.98] for 16-20 days; OR, 0.59 [95% CI, 0.40-0.86] for >20 days vs none) and having full EHR inbox coverage while on vacation (OR, 0.74; 95% CI, 0.63-0.88) were associated with lower rates of burnout on multivariable analysis, whereas spending 30 minutes or longer per vacation day on patient-related work (OR, 1.58; 95% CI, 1.22-2.04 for 30-60 minutes; OR, 1.97; 95% CI, 1.41-2.77 for 60-90 minutes; OR, 1.92; 95% CI, 1.36-2.73 for >90 minutes) was associated with higher rates of burnout. Conclusions and Relevance: In this cross-sectional study of 3024 physicians, the number of vacation days taken and performing patient-related work while on vacation were associated with physician burnout. System-level efforts to ensure physicians take adequate vacation and have coverage for clinical responsibilities, including EHR inbox, may reduce physician burnout.
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Esgotamento Profissional , Médicos , Humanos , Estudos Transversais , Esgotamento Profissional/epidemiologia , Registros Eletrônicos de Saúde , Grupos PopulacionaisRESUMO
Importance: The emergence and promise of generative artificial intelligence (AI) represent a turning point for health care. Rigorous evaluation of generative AI deployment in clinical practice is needed to inform strategic decision-making. Objective: To evaluate the implementation of a large language model used to draft responses to patient messages in the electronic inbox. Design, Setting, and Participants: A 5-week, prospective, single-group quality improvement study was conducted from July 10 through August 13, 2023, at a single academic medical center (Stanford Health Care). All attending physicians, advanced practice practitioners, clinic nurses, and clinical pharmacists from the Divisions of Primary Care and Gastroenterology and Hepatology were enrolled in the pilot. Intervention: Draft replies to patient portal messages generated by a Health Insurance Portability and Accountability Act-compliant electronic health record-integrated large language model. Main Outcomes and Measures: The primary outcome was AI-generated draft reply utilization as a percentage of total patient message replies. Secondary outcomes included changes in time measures and clinician experience as assessed by survey. Results: A total of 197 clinicians were enrolled in the pilot; 35 clinicians who were prepilot beta users, out of office, or not tied to a specific ambulatory clinic were excluded, leaving 162 clinicians included in the analysis. The survey analysis cohort consisted of 73 participants (45.1%) who completed both the presurvey and postsurvey. In gastroenterology and hepatology, there were 58 physicians and APPs and 10 nurses. In primary care, there were 83 physicians and APPs, 4 nurses, and 8 clinical pharmacists. The mean AI-generated draft response utilization rate across clinicians was 20%. There was no change in reply action time, write time, or read time between the prepilot and pilot periods. There were statistically significant reductions in the 4-item physician task load score derivative (mean [SD], 61.31 [17.23] presurvey vs 47.26 [17.11] postsurvey; paired difference, -13.87; 95% CI, -17.38 to -9.50; P < .001) and work exhaustion scores (mean [SD], 1.95 [0.79] presurvey vs 1.62 [0.68] postsurvey; paired difference, -0.33; 95% CI, -0.50 to -0.17; P < .001). Conclusions and Relevance: In this quality improvement study of an early implementation of generative AI, there was notable adoption, usability, and improvement in assessments of burden and burnout. There was no improvement in time. Further code-to-bedside testing is needed to guide future development and organizational strategy.
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Centros Médicos Acadêmicos , Inteligência Artificial , Estados Unidos , Humanos , Estudos Prospectivos , Instituições de Assistência Ambulatorial , Esgotamento PsicológicoRESUMO
BACKGROUND: Physiatry is a specialty with high rates of burnout. Although organizational strategies to combat burnout are key, it is also important to understand strategies that individual physiatrists can use to address burnout. OBJECTIVE: To identify changes that resulted in improvement of occupational well-being of physiatrists over a 6- to 9-month period. DESIGN: We employed two quantitative surveys spaced 6 to 9 months apart to identify physiatrists who experienced meaningful improvement in occupational burnout and/or professional fulfillment between the two survey timepoints. These physiatrists were subsequently recruited to participate in a qualitative study using semi-structured interviews to identify changes that respondents felt contributed to improvements in burnout and professional fulfillment. SETTING: Online surveys and interviews. PARTICIPANTS: Physiatrists in the American Academy of Physical Medicine and Rehabilitation (AAPM&R) Membership Masterfile. MAIN OUTCOME MEASURE: Burnout and professional fulfillment were assessed using the Stanford Professional Fulfillment Index. RESULTS: One hundred twelve physiatrists responded to the baseline and follow-up surveys. Of these, 35 were eligible for interviews based on improvements in the Stanford Professional Fulfillment Index, and 23 (64%) agreed to participate. Themes from the qualitative interviews highlighted the importance of personal lifestyle choices, approaches to improve professional satisfaction, and strategies to foster work-life harmony. Personal lifestyle strategies included investing in wellness and mental health. Efforts to improve professional satisfaction included decreasing work intensity, prioritizing meaningful aspects of work, and building relationships with colleagues. Fostering work-life harmony also included making trade-offs in both domains, setting boundaries at work, setting expectations at home, and overcoming personal challenges. CONCLUSION: Our findings illustrate that, in addition to organizational strategies demonstrated to be effective, there are actions that individual physiatrists can take to recover from burnout and foster professional fulfillment.
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Esgotamento Profissional , Satisfação no Emprego , Fisiatras , Medicina Física e Reabilitação , Pesquisa Qualitativa , Humanos , Esgotamento Profissional/prevenção & controle , Esgotamento Profissional/psicologia , Masculino , Feminino , Fisiatras/psicologia , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Estados UnidosRESUMO
BACKGROUND: Physiatry is a specialty with high rates of burnout. Although organizational strategies to combat burnout are key, it is also important to understand strategies that individual physiatrists can use to address burnout. OBJECTIVE: The aim of the study is to identify changes that resulted in improvement of occupational well-being of physiatrists over a 6- to 9-mo period. DESIGN: We employed two quantitative surveys spaced 6-9 mos apart to identify physiatrists who experienced meaningful improvement in occupational burnout and/or professional fulfillment between the two survey time points. These physiatrists were subsequently recruited to participate in a qualitative study using semistructured interviews to identify changes that respondents felt contributed to improvements in burnout and professional fulfillment. SETTING: Online surveys and interviews. PARTICIPANTS: Physiatrists in the American Academy of Physical Medicine and Rehabilitation (AAPM&R) Membership Masterfile. MAIN OUTCOME MEASURE: Burnout and professional fulfillment were assessed using the Stanford Professional Fulfillment Index. RESULTS: One hundred twelve physiatrists responded to the baseline and follow-up surveys. Of these, 35 were eligible for interviews based on improvements in the Stanford Professional Fulfillment Index, and 23 (64%) agreed to participate. Themes from the qualitative interviews highlighted the importance of personal lifestyle choices, approaches to improve professional satisfaction, and strategies to foster work-life harmony. Personal lifestyle strategies included investing in wellness and mental health. Efforts to improve professional satisfaction included decreasing work intensity, prioritizing meaningful aspects of work, and building relationships with colleagues. Fostering work-life harmony also included making trade-offs in both domains, setting boundaries at work, setting expectations at home, and overcoming personal challenges. CONCLUSIONS: Our findings illustrate that in addition to organizational strategies demonstrated to be effective, there are actions that individual physiatrists can take to recover from burnout and foster professional fulfillment.
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Esgotamento Profissional , Satisfação no Emprego , Fisiatras , Medicina Física e Reabilitação , Pesquisa Qualitativa , Humanos , Esgotamento Profissional/psicologia , Masculino , Feminino , Fisiatras/psicologia , Adulto , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Background: The use of an artificial intelligence electrocardiography (AI-ECG) algorithm has demonstrated its reliability in predicting the risk of atrial fibrillation (AF) within the general population. Objectives: This study aimed to determine the effectiveness of the AI-ECG score in identifying patients with chronic lymphocytic leukemia (CLL) who are at high risk of developing AF. Methods: We estimated the probability of AF based on AI-ECG among patients with CLL extracted from the Mayo Clinic CLL database. Additionally, we computed the Mayo Clinic CLL AF risk score and determined its ability to predict AF. Results: Among 754 newly diagnosed patients with CLL, 71.4% were male (median age = 69 years). The median baseline AI-ECG score was 0.02 (range = 0-0.93), with a value ≥0.1 indicating high risk. Over a median follow-up of 5.8 years, the estimated 10-year cumulative risk of AF was 26.1%. Patients with an AI-ECG score of ≥0.1 had a significantly higher risk of AF (HR: 3.9; 95% CI: 2.6-5.7; P < 0.001). This heightened risk remained significant (HR: 2.5; 95% CI: 1.6-3.9; P < 0.001) even after adjusting for the Mayo CLL AF risk score, heart failure, chronic kidney disease, and CLL therapy. In a second cohort of CLL patients treated with a Bruton tyrosine kinase inhibitor (n = 220), a pretreatment AI-ECG score ≥0.1 showed a nonsignificant increase in the risk of AF (HR: 1.7; 95% CI: 0.8-3.6; P = 0.19). Conclusions: An AI-ECG algorithm, in conjunction with the Mayo CLL AF risk score, can predict the risk of AF in patients with newly diagnosed CLL. Additional studies are needed to determine the role of AI-ECG in predicting AF risk in CLL patients treated with a Bruton tyrosine kinase inhibitor.
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ABSTRACT: High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL. We sequenced DNA from 371 individuals with HCMBL using a targeted sequencing panel of 59 recurrently mutated genes in CLL to identify high-impact mutations. We compared the sequencing results with that of our treatment-naïve CLL cohort (N = 855) and used Cox regression to estimate hazard ratios and 95% confidence intervals (CIs) for associations with TTFT. The frequencies of any mutated genes were lower in HCMBL (52%) than CLL (70%). At 10 years, 37% of individuals with HCMBL with any mutated gene had progressed requiring treatment compared with 10% among individuals with HCMBL with no mutations; this led to 5.4-fold shorter TTFT (95% CI, 2.6-11.0) among HCMBL with any mutated gene vs none, independent of CLL-IPI. When considering individuals with low risk of progression according to CLL-IPI, those with HCMBL with any mutations had 4.3-fold shorter TTFT (95% CI, 1.6-11.8) vs those with none. Finally, when considering both CLL-IPI and any mutated gene status, we observed individuals with HCMBL who were high risk for both prognostic factors had worse prognosis than patients with low-risk CLL (ie, 5-year progression rate of 32% vs 21%, respectively). Among HCMBL, the frequency of somatically mutated genes at diagnosis is lower than that of CLL. Accounting for both the number of mutated genes and CLL-IPI can identify individuals with HCMBL with more aggressive clinical course.
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Linfócitos B , Progressão da Doença , Leucemia Linfocítica Crônica de Células B , Linfocitose , Mutação , Humanos , Linfocitose/genética , Linfocitose/diagnóstico , Linfocitose/terapia , Prognóstico , Masculino , Feminino , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/terapia , Pessoa de Meia-Idade , Idoso , Linfócitos B/metabolismo , Linfócitos B/patologia , Adulto , Idoso de 80 Anos ou mais , Contagem de LinfócitosRESUMO
Physicians spend a large amount of time with the electronic health record (EHR), which the majority believe contributes to their burnout. However, there are limitedstandardized measures of physician EHR time. Vendor-derived metrics are standardized but may underestimate real-world EHR experience. Investigator-derived metrics may be more reliable but not standardized, particularly with regard to timeout thresholds defining inactivity. This study aimed to enable standardized investigator-derived metrics using conversion factors between raw event log-derived metrics and Signal (Epic System's standardized metric) for primary care physicians. This was an observational, retrospective longitudinal study of EHR raw event logs and Signal data from a quaternary academic medical center and its community affiliates in California, over a 6-month period. The study evaluated 242 physicians over 1370 physician-months, comparing 53.7 million event logs to 6850 Signal metrics, in five different time based metrics. Results show that inactivity thresholds for event log metric derivation that most closely approximate Signal metrics ranged from 90 seconds (Visit Navigator) to 360 seconds ("Pajama time") depending on the metric. Based on this data, conversion factors for investigator-derived metrics across a wide range of inactivity thresholds, via comparison with Signal metrics, are provided which may allow researchers to consistently quantify EHR experience.