The COVID-19 crisis has had an unprecedented impact on resident education and well-being: social distancing guidelines have limited patient volumes and forced virtual learning, while personal protective equipment (PPE) shortages, school/daycare closures, and visa restrictions have served as additional stressors. Our study aimed to analyze the effects of COVID-19 crisisrelated stressors on residents' professional and personal lives. In April 2020, we administered a survey to residents at a large academic hospital system in order to assess the impact of the pandemic on residency training after >6 weeks of a modified schedule. The primary outcome was to determine which factors or resident characteristics were related to stress during the pandemic. Our secondary goals were to examine which resident characteristics were related to survey responses. Data were analyzed with regression analyses. Ninety-six of 205 residents completed the survey (47% response rate). For our primary outcome, anxiety about PPE (P < 0.001), female gender (P = 0.03), and the interaction between female gender and anxiety about PPE (P = 0.04) were significantly related to increased stress during the COVID-19 pandemic. Secondary analyses suggested that medicine residents were more comfortable than surgical residents using telemedicine (P > 0.001). Additionally, compared to juniors, seniors believed that the pandemic was more disruptive, modified schedules were effective, and virtual meetings were less effective while virtual lectures were more effective (all P ≤ 0.05) Furthermore, the pandemic experience has allowed seniors in particular to feel more confident to lead in future health crises (P ≤ 0.05). Medicine and surgery residency programs should be cognizant of and closely monitor the effects of COVID-19 crisis-related factors on residents' stress and anxiety levels. Transparent communication, telemedicine, online lectures/meetings, procedure simulations, advocacy groups, and wellness resources may help to mitigate some of the challenges posed by the pandemic.

Severe relapse in a multiple sclerosis patient associated with ipilimumab treatment of melanoma Dear EditorWe are writing about a case of relapse in a patient with previously stable relapsing-remitting multiple sclerosis (RRMS) after treatment with ipilimumab (BristolMyers Squibb Co., New York, NY) for metastatic melanoma. Ipilimumab is a humanized monoclonal antibody for treatment of malignant melanoma. The mechanism of action involves blocking CTLA-4, a cell surface molecule on T cells that downregulates T cell activation by binding CD80 and CD86. Ipilimumab enhances the anti-tumoral response while increasing the likelihood of autoimmunity. 1 Adverse effects include colitis and dermatitis and there are recent reports of neurological complications, but none affecting MS. [2][3][4]

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The degree to which relapses with incomplete recovery (RW) contribute to the overall picture of worsening disability in relapse-onset multiple sclerosis (RMS) remains unclear. 1,2 Clarification of this issue may determine the extent to which elimination of relapses through immunotherapy can result in long-term benefits. Incomplete recovery from relapses implies a contribution of these circumscribed events to the irreversible process of tissue destruction. 3,4 Better understanding of the impact of relapses vs slow progression may also help us understand the complex relationship between inflammation vs degeneration, which evolves over a lifetime of RMS. Some epidemiologists opine that the majority of disability accumulated in MS over time results from a more or less degenerative process involving slow progression, whereas relapses contribute little to the long-term picture. 5 This view is challenged in more recent studies. 6,7 We sought to calculate the frequency of RW in the first 15 years of longitudinally followed RMS patients, using a clinical definition of incomplete recovery from relapse, and to compare the frequency of year-to-year slow progressive worsening (PW). Furthermore, we Background: Treatments affect both relapse-related disability and short-term disability change, but measurements of their impact on long-term outcomes remain a challenge.Objective: To ascertain the contribution of relapse-associated disability to overall disability in relapse-onset multiple sclerosis (RMS) using long-term data collected in our clinic. Materials and Methods: Retrospective study of a cohort of newly diagnosed patients with RMS, (n = 176) was undertaken, measuring all confirmed changes in disability up to 15 years after onset. Worsening was assessed yearly and in 5-year epochs and was attributed to either relapse (RW) or slow progression (PW). Results: At data lock, 139/176 (81%) of patients were still actively followed, with Expanded Disability Status Scale (EDSS) available for 10 years post-onset in 145/176 (82%) patients and 15 years post-onset EDSS in 83 patients (mean follow-up entire group 12.7 years post-onset). RW accounted for a large amount of worsening seen in the first 15 years of RMS. RW was less frequent over time, but accounted for most EDSS changes in the first decade of MS (167/267, 63% of EDSS changes), and remained important even in years 11-15 (17/50, 34% of EDSS changes). Median change in disability due to RW vs PW was similar over the entire 15 years.Conclusions: Worsening of treated MS was associated with relapses in many RMS patients throughout the first 15 years after onset, suggesting an opportunity for long-term benefit through relapse reduction. K E Y W O R D S expanded disability status scale, MS, progression, relapse | 337 SCOTT eT al.

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Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups.