Putting the Heme Back in Heme-Onc: an Evaluation of the Redesigned Hematology Track within the Dana Farber/Mass General Brigham Hematology-Oncology Fellowship.

In 2019, the Dana Farber/Mass General Brigham Hematology-Oncology Fellowship redesigned the 6-month Hematology training track/curriculum required for all fellows seeking to double board in hematology and oncology. Responding to both national and local trends suggesting a future shortage of hematologists, the goal of the redesign was to create a new curriculum that would increase fellow interest in hematology, improve fellows' clinical knowledge of hematology, and serve as an example to other Hematology-Oncology programs across the country. The revised track has now been in place for four years, and, in this paper, the authors present the fellow experience with the first four years of the redesigned curriculum. Based on the number of fellows who chose to complete the new curriculum, as well as the fellow evaluations and performance on the Hematology In-Training Exam, the authors conclude that the new curriculum has successfully increased both fellow interest in and knowledge of hematology.

Thrombophilia evaluation in pulmonary embolism.

PURPOSE OF REVIEW: Patients with pulmonary embolism commonly undergo thrombophilia evaluation for a variety of reasons including risk stratification for recurrent venous thromboembolism (VTE) and treatment planning. However, the utility of thrombophilia testing in many clinical scenarios remains unclear. This review evaluates current recommendations for thrombophilia testing described in consensus VTE guidelines, recent literature on the clinical application of these recommendations, novel genetic assessments for hereditary thrombophilias, and studies evaluating use of direct oral anticoagulants (DOACs) in VTE patients with thrombophilias. RECENT FINDINGS: Current VTE guidelines advise limited use of thrombophilia testing, recognizing that testing may be misinterpreted and frequently does not lead to a change in management. Testing and test results are not necessarily benign, are frequently misinterpreted, and can lead to increased anxiety in both patients and clinicians. Recent studies have offered innovative techniques to better align clinical practice with these recommendations as well as expanded genomic assessments to improve the scope and predictive value of thrombophilia testing. There is also emerging literature on the appropriateness of direct oral anticoagulant therapy for VTE patients with hereditary thrombophilias or antiphospholipid syndrome. SUMMARY: Thrombophilia testing in its current form does not significantly impact clinical management or improve outcomes for most VTE patients. Therefore, it should be employed judiciously and only in patients for whom it is likely to alter clinical management. Novel expanded genomic thrombophilia testing approaches and additional studies evaluating optimal anticoagulant treatment in various thrombophilia subpopulations will make thrombophilia testing more useful for patients moving forward.

Enhanced perceptions of control and predictability reduce motion-induced nausea and gastric dysrhythmia.

Nausea is a debilitating condition that is typically accompanied by gastric dysrhythmia. The enhancement of perceived control and predictability has generally been found to attenuate the physiological stress response. The aim of the present study was to test the effect of these psychosocial variables in the context of nausea, motion sickness, and gastric dysrhythmia. A 2x2, independent-groups, factorial design was employed in which perceived control and predictability were each provided at high or low levels to 80 participants before exposure to a rotating optokinetic drum. Ratings of nausea were obtained throughout a 6-min baseline period and a 16-min drum rotation period. Noninvasive recordings of the electrical activity of the stomach called electrogastrograms were also obtained throughout the study. Nausea scores were significantly lower among participants with high control than among those with low control, and were significantly lower among participants with high predictability than among those with low predictability. Estimates of gastric dysrhythmia obtained from the EGG during drum rotation were significantly lower among participants with high predictability than among those with low predictability. A significant interaction effect of control and predictability on gastric dysrhythmia was also observed, such that high control was only effective for arresting the development of gastric dysrhythmia when high predictability was also available. Stronger perceptions of control and predictability may temper the development of nausea and gastric dysrhythmia during exposure to provocative motion. Psychosocial interventions in a variety of nausea contexts may represent an alternative means of symptom control.

Jewish physicians' beliefs and practices regarding religion/spirituality in the clinical encounter.

We used data from a 2003 survey of US physicians to examine differences between Jewish and other religiously affiliated physicians on 4-D of physicians' beliefs and practices regarding religion and spirituality (R/S) in the clinical encounter. On each dimension, Jewish physicians ascribed less importance to the effect of R/S on health and a lesser role for physicians in addressing R/S issues. These effects were partially mediated by lower levels of religiosity among Jewish physicians and by differences in demographic and practice-level characteristics. The study provides a salient example of how religious affiliation can be an important independent predictor of physicians' clinically-relevant beliefs and practices.

The Relationship Between Applicant Gender and Internal Medicine Residency Interview Scores.

BACKGROUND: Gender inequity is widespread in academic medicine, including in the promotion, academic recognition, and compensation of female faculty. OBJECTIVE: To assess whether these inequities extend to the GME intern selection process, this study examines differences in the interview scores assigned to male and female applicants at one large internal medicine residency program. METHODS: Subjects include 1399 applicants who completed 3099 interviews for internship positions for the Brigham and Women's Hospital internal medicine residency in Electronic Residency Application Service (ERAS) cycles 2015-2016, 2017-2018, 2018-2019, and 2019-2020. Unadjusted and multivariable linear regressions were used to assess the simultaneous effect of applicant gender, interviewer gender, and applicant academic characteristics on pre-interview, post-interview, and change in interview scores. RESULTS: Our analysis included 3027 interviews (97.7%) of 1359 applicants (97.1%). There were no statistically significant differences in the interview scores assigned to female versus male applicants. This was true across pre-interview scores (difference = 0.03, P = .61), post-interview scores (difference = 0.00, P = .98), and change in interview scores (difference = 0.01, P = .24) as well as when adjusting for the baseline academic characteristics of both male and female applicants. This was also true when analyzing individual application years, individual residency tracks, and accounting for the gender of the faculty interviewers. CONCLUSIONS: The findings do not support the presence of gender inequity in the interview scores assigned to male and female applicants included in this study.

Dana-Farber Cancer Institute/Mass General Brigham Fellowship Response to the COVID-19 Pandemic.

The coronavirus disease (COVID)-19 pandemic has affected graduate medical education training programs, including hematology-oncology fellowship programs, both across the United States and abroad. Within the Dana-Farber Cancer Institute/Mass General Brigham hematology-oncology fellowship program, fellowship leadership had to quickly reorganize the program's clinical, educational, and research structure to minimize the risk of COVID-19 spread to our patients and staff, allow fellows to assist in the care of patients with COVID-19, maintain formal didactics despite physical distancing, and ensure the mental and physical well-being of fellows. Following the first wave of patients with COVID-19, we anonymously surveyed the Dana-Farber Cancer Institute/Mass General Brigham first-year fellows to explore their perceptions regarding what the program did well and what could have been improved in the COVID-19 response. In this article, we present the feedback from our fellows and the lessons we learned as a program from this feedback. To our knowledge, this represents the first effort in the hematology-oncology literature to directly assess a hematology-oncology program's overall response to COVID-19 through direct feedback from fellows.

Targeting the mTOR pathway in idiopathic multicentric Castleman disease.

Idiopathic multicentric Castleman disease (iMCD) is a rare hematologic illness of systemic inflammation and organ dysfunction, with unknown etiology. Although therapies targeting IL-6 have been proven effective, a subset of patients with iMCD are resistant to this approach. In this issue of the JCI, Fajgenbaum et al. performed an in-depth analysis of serum inflammatory markers in three iMCD patients refractory to IL-6 blockade, and identified activation of the mTOR pathway associated with symptom flares. Treatment with sirolimus, an mTOR inhibitor, induced remission in all three patients. This study models a precision medicine approach to discovering therapies for rare diseases.

Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. Until recently, the complement inhibitor, eculizumab, was the only United States Food and Drug Administration (US FDA)-approved therapy for the treatment of PNH. Although effective, eculizumab requires a frequent dosing schedule that can be burdensome for some patients and increases the risk of breakthrough intravascular hemolysis. Ravulizumab, an eculizumab-like monoclonal antibody engineered to have a longer half-life, is intended to provide the same benefits as eculizumab but with a more convenient and effective dosing schedule. In two recently published phase III non-inferiority trials, ravulizumab was found to be non-inferior to eculizumab both in efficacy and safety for the treatment of patients with PNH. Based on these results, ravulizumab was approved by the US FDA on 21 December 2018 and is currently under regulatory review in both the European Union and Japan.

Fostering Meaning in Residency to Curb the Epidemic of Resident Burnout: Recommendations From Four Chief Medical Residents.

Burnout has become commonplace in residency training, affecting more than half of residents and having negative implications for both their well-being and their ability to care for patients. During the authors' year as chief medical residents at Brigham and Women's Hospital in 2017-2018, they became intimately familiar with the burnout epidemic in residency training. The authors argue that addressing resident burnout requires residency programs and teaching hospitals to focus not on the individual contributors to burnout but instead on fostering meaning within residency to help residents find purpose and professional satisfaction in their work. In this Perspective, they highlight 4 important elements of residency that provide meaning: patient care, intellectual engagement, respect, and community. Patient care, intellectual engagement, and community provide residents with a focus that is larger than themselves, while respect is necessary for a resident's sense of belonging. The authors provide examples from their own experiences and from the literature to suggest ways in which residency programs and teaching hospitals can strengthen each of these elements within residency and curb the epidemic of burnout.

Susceptibility to nausea and motion sickness as a function of the menstrual cycle.

PURPOSE: The present study examined whether susceptibility to nausea and other symptoms of vection-induced motion sickness vary as a function of phase of the menstrual cycle, as research findings in this area are sparse and contradictory. DESIGN: Ninety young women (42 current users of oral contraceptives) were exposed to a rotating optokinetic drum during the peri-menses or peri-ovulatory phase of the menstrual cycle in an independent-groups, quasi-experimental design. Nausea and motion sickness symptoms were assessed using the Nausea Profile (NP) and the Subjective Symptoms of Motion Sickness (SSMS) questionnaire. RESULTS: Among women not on oral contraceptives, reports of nausea and motion sickness by women in the peri-menses phase were more severe than reports by women in the peri-ovulatory phase. By contrast, among women taking oral contraceptives, reports of nausea and motion sickness did not differ by the same categorical phase of the menstrual cycle. CONCLUSIONS: We speculate that fluctuating estrogen levels over the course of the menstrual cycle may influence the experience of or susceptibility to nausea and motion sickness during illusory self-motion and other nauseogenic contexts.

The effects of manipulating expectations through placebo and nocebo administration on gastric tachyarrhythmia and motion-induced nausea.

BACKGROUND: Interest in the role of expectation in the development of nausea and other adverse conditions has existed for decades. The purpose of this study was to examine the effects of manipulating expectations through the administration of placebos and nocebos on nausea and gastric tachyarrhythmia provoked by a rotating optokinetic drum. METHOD: Seventy-five participants were assigned to one of three groups. Positive-expectancy group participants were given placebo pills that would allegedly protect them against the development of nausea and motion sickness. Negative-expectancy group participants were given the same pills as nocebos; they were led to believe there was a tendency for them to make nausea somewhat worse. Placebo-control group participants were told the pills were indeed placebos that would have no effect whatsoever. RESULTS: Subjective symptoms of motion sickness were significantly lower among negative-expectancy group participants than positive-expectancy and placebo-control group participants (p<0.05). Gastric tachyarrhythmia, the abnormal stomach activity that frequently accompanies nausea, was also significantly lower among negative-expectancy group participants than positive-expectancy and Placebo-Control Group participants during drum rotation (p<.05) [corrected] CONCLUSIONS: Inducing negative expectations through nocebo administration reduced nausea and gastric dysrhythmia during exposure to provocative motion, whereas positive placebos were ineffective for preventing symptom development. That manipulation of expectation affected gastric physiological responses as well as reports of symptoms, suggests an unspecified psychophysiological mechanism was responsible for the observed group differences. These results also suggest that patients preparing for difficult medical procedures may benefit most from being provided with detailed information about how unpleasant their condition may become.

The contribution of expectations to motion sickness symptoms and gastric activity.

OBJECTIVE: The goal of this investigation was to determine in healthy adults the effect of expectation manipulations on the development of motion sickness, as indicated by abnormal gastric myoelectric activity and subjective reports of symptoms of motion sickness. METHOD: Eighty participants, moderately susceptible to motion sickness, experienced one of four conditions created from a two-variable (Expectation, Drum), two-factor model (High/Low expectation for sickness; Rotating/Stable Drum). The electrogastrogram (EGG) was recorded 6 min prior to the expectation manipulation; 6 min following the expectation manipulation; 6 min before drum activation; and 16 min during drum activation. Self-report questionnaires indicating expectation for sickness (MSEx) and motion sickness symptoms (Nausea Profile [NP]) were obtained following the expectation manipulation and exposure to the drum, respectively. RESULTS: No significant differences were observed among expectation groups for retrospective reports of motion sickness (NP); however, significant differences in EGG responses to drum rotation were obtained. The unexpected results of a univariate analysis of variance (ANOVA) revealed significantly greater gastric tachyarrhythmia and less normal activity, an indication of motion sickness, in the low expectation for sickness conditions. CONCLUSION: These results suggest that inducing a high expectation for sickness in healthy individuals about to be exposed to provocative motion results in a protective effect from motion sickness following exposure to the stimulus, while low expectations may induce abnormal gastric activity.

Spatial task performance, sex differences, and motion sickness susceptibility.

There are substantial individual differences in susceptibility to motion sickness, yet little is known about what mediates these differences. Spatial ability and sex have been suggested as possible factors in this relationship. 89 participants (57 women) were administered a Motion Sickness Questionnaire that assesses motion sickness susceptibility, a Water-level Task that gauges sensitivity to gravitational upright, and a Mental Rotation Task that tests an individual's awareness of how objects typically move in space. Significant sex differences were observed in performance of both the Water-level Task (p<.01), and the Mental Rotation Task (p<.005), with women performing less accurately than men. Women also had significantly higher scores on the Motion Sickness Questionnaire (p<.005). Among men, but not women, significant negative relationships were observed between Water-level Task performance and Motion Sickness Questionnaire score (p<.001) and between Mental Rotation Task performance and Motion Sickness Questionnaire score (p<.005). In conclusion, women performed significantly more poorly than men did on the spatial ability tasks and reported significantly more bouts of motion sickness. In addition, men showed a significant negative relationship between spatial ability and motion sickness susceptibility.

Protein and ginger for the treatment of chemotherapy-induced delayed nausea.

BACKGROUND: Nausea that develops during the period that begins 24 hours after the administration of chemotherapy is called delayed nausea, and occurs in many patients with cancer. Meals high in protein decrease the nausea of motion sickness and pregnancy, possibly by reducing gastric dysrhythmias. Ginger also has antinausea properties. OBJECTIVES: To explore the use of protein meals with ginger for the treatment of the delayed nausea of chemotherapy. DESIGN: Twenty-eight (28) patients with cancer receiving chemotherapy for the first time were assigned to 1 of 3 groups. For 3 days beginning the day after their chemotherapy, Control Group patients continued with their normal diet, Protein Group patients consumed a protein drink and ginger twice daily, and High Protein Group patients consumed a protein drink with additional protein and ginger twice daily. OUTCOME MEASURES: Patients recorded in a diary each day whether they had experienced nausea, whether their nausea had been frequent, whether their nausea had been bothersome, and whether they had needed any antiemetic medication. Gastric myoelectrical activity was assessed in 5 patients before and after ingestion of a high protein meal and ginger. RESULTS: Reports of nausea, frequent nausea, and bothersome nausea were significantly less common among High Protein Group patients than among Control and Protein Group patients. Furthermore, significantly fewer patients in the High Protein Group used antiemetic medication. Differences between the Protein and Control groups were not statistically significant. In the 5 patients who had tests of gastric myoelectrical activity performed, a significant decrease in gastric dysrhythmia occurred after ingestion of the protein and ginger. CONCLUSIONS: High protein meals with ginger reduced the delayed nausea of chemotherapy and reduced use of antiemetic medications. Protein with ginger holds the potential of representing a novel, nutritionally based treatment for the delayed nausea of chemotherapy.

Changes in gastric myoelectric activity during space flight.

The purpose of the present study was to examine postprandial myoelectric activity of the stomach and gastric activity associated with space motion sickness using electrogastrography. Three crewmembers participated in this investigation. Preflight, subjects exhibited normal postprandial responses to the ingestion of a meal. Inflight, crewmembers exhibited an abnormal decrease in the power of the normal gastric slow wave after eating on flight day 1, but had a normal postprandial response by flight day 3. Prior to and during episodes of nausea and vomiting, the electrical activity of the stomach became dysrhythmic with 60-80% of the spectral power in the bradygastric and tachygastric frequency ranges. These findings indicate that gastric motility may be decreased during the first few days of space flight. In addition, changes in the frequency of the gastric slow wave associated with space motion sickness symptoms are consistent with those reported for laboratory-induced motion sickness.