Barriers to increasing paid parental leave in U.S. neurology residencies: a survey of program directors.

BACKGROUND: The American Board of Psychiatry and Neurology (ABPN) and the Accreditation Council for Graduate Medical Education (ACGME) require that residency programs allow at least 6 weeks of parental leave. The American Medical Association (AMA) recommends 12 weeks of paid parental leave. Despite these recommendations, there is little information about parental leave policies across U.S. neurology residencies. The objective of our study was to assess parental leave policies in U.S. adult neurology residencies and barriers to increasing the duration of leave. METHODS: We distributed an anonymous online survey to U.S. adult neurology program directors (PDs) to assess demographics, components and length of parental leave, perceived impact on residents' clinical training and academic development, and barriers to increasing the length of leave. RESULTS: We contacted 163 PDs and received 54 responses (response rate of 33%). 87% reported policies for both childbearing and non-childbearing residents. The average maximal length of leave allowed without extension of training was 8.5 weeks (range 0-13) for childbearing and 6.2 weeks (range 0-13) for non-childbearing residents. Most PDs felt that parental leave had a positive impact on resident wellness and neutral impact on clinical competency, academic opportunities, and career development. The most common barriers to providing a 12-week paid policy were concerns about equity in the program (82%), staffing of clinical services (80%), and impact on clinical training (78%). CONCLUSIONS: Although most programs in our study have parental leave policies, there is significant variability. Policies to improve parental leave should focus on addressing common barriers, such as additional solutions to staffing clinical services.

Neurologic disease activity in people with multiple sclerosis treated with immune checkpoint inhibitors.

BACKGROUND: There is concern that immune checkpoint inhibitors (ICPIs) can provoke relapses in people with multiple sclerosis (pwMS). OBJECTIVE: Analyze outcomes of pwMS who received ICPI treatment for malignancy. METHODS: We electronically identified pwMS who received ICPI treatment at Mass General Brigham hospital system. We retrospectively obtained information about patients' MS, cancer, treatment, and outcomes. RESULTS: Sixteen patients were identified with an average (standard deviation (SD)) age of 67.4 (11.9) years. Eleven (68.8%) had no relapses since MS diagnosis. None had MS relapses after ICPI treatment or new MS lesions. CONCLUSION: ICPI use was not associated with increased clinical disease activity in this cohort of older patients with inactive MS.

Central Nervous System Neuroimmunologic Complications of COVID-19.

Autoimmune disorders of the central nervous system following COVID-19 infection include multiple sclerosis (MS), neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune encephalitis, acute disseminated encephalomyelitis, and other less common neuroimmunologic disorders. In general, these disorders are rare and likely represent postinfectious phenomena rather than direct consequences of the SARS-CoV-2 virus itself. The impact of COVID-19 infection on patients with preexisting neuroinflammatory disorders depends on both the disorder and disease-modifying therapy use. Patients with MS do not have an increased risk for severe COVID-19, though patients on anti-CD20 therapies may have worse clinical outcomes and attenuated humoral response to vaccination. Data are limited for other neuroinflammatory disorders, but known risk factors such as older age and medical comorbidities likely play a role. Prophylaxis and treatment for COVID-19 should be considered in patients with preexisting neuroinflammatory disorders at high risk for developing severe COVID-19.

Academic Medical Centers and Federally Qualified Health Centers: Collaboration for the Care of Underserved Communities.

Academic Medical Centers (AMCs) and Federally Qualified Health Centers (FQHCs) are similarly tasked with managing the health of their local community, yet they each face unique challenges in their ability to do so. Integrating AMCs and FQHCs into novel care delivery models can leverage both organizations strengths, providing care in a comprehensive and sustainable fashion. Johns Hopkins Medicine (JHM) implemented this model with a large East Baltimore medical center, creating an AMC-FQHC collaboration focused on providing care to the East Baltimore patient population. This system provided various improvements in care delivery, including increased staffing, new wraparound services, improved access to funding dollars, and decreased out of pocket costs for patients qualifying for financial assistance. The academic missions of research and training were preserved, serving as the primary continuity clinic for several residency programs and as a community site for research. These changes resulted in more robust care for patients while improving the financial standing of the clinic. Through AMC and FQHC partnership, progress can be made toward providing holistic and financially sustainable primary care services in underserved areas while preserving the tripartite mission of academic medicine, with significant pedagogical and research opportunities.

Inflammatory vaginitis in women with multiple sclerosis: a retrospective analysis of B-cell depleting therapy compared to other disease modifying therapies.

This study investigates the occurrence of inflammatory vaginitis in women with Multiple Sclerosis (wwMS) undergoing B-cell depleting therapy versus other disease-modifying therapies (DMTs). Retrospective analysis of medical records from Stanford University between 2015-2023 shows similar rates of vaginitis in both groups, suggesting no significant association with B-cell therapy. Despite this, inflammatory vaginitis remains prevalent in both treatment groups, warranting further investigation into its mechanisms and management.

Tixagevimab/Cilgavimab does not prevent COVID-19 in patients with multiple sclerosis and related disorders on B-cell depleting therapies.

BACKGROUND: Patients with MS and related disorders (pwMSARD) on B-cell depleting treatments have attenuated immune responses to vaccination and were eligible to receive tixagevimab/cilgavimab. OBJECTIVES: Understand incidence and severity of COVID-19 in pwMSARD on B-cell depleting therapies who received tixagevimab/cilgavimab compared to an untreated group. METHODS: We conducted a retrospective medical records review of adult pwMSARD on B-cell depleting treatments who received tixagevimab/cilgavimab between 1/2022-1/2023. PwMSARD on B-cell depleting treatments who did not served as a control group (CG). We compared COVID-19 incidence and severity within 6 months of tixagevimab/cilgavimab or rituximab/ocrelizumab infusion for the CG. RESULTS: 210 patients were identified, 135 in the treatment group (TG) and 75 in the CG. In the TG, 24 (17.8 %) developed COVID-19 compared to 12 (16 %) in the CG. There was no difference in the odds of developing COVID-19 in an unadjusted logistic regression model (OR=1.14; 95 % CI: 0.53, 2.42; p = 0.74) or after adjusting for age and disease duration (OR=1.05; 95 % CI: 0.47, 2.37; p = 0.91). There was also no difference in COVID-19 severity between groups. CONCLUSIONS: There was no difference in COVID-19 infection rates or severity in pwMSARD on B-cell depleting treatments who received tixagevimab/cilgavimab compared to those who remained untreated.

Transforming Health Care from Volume to Value: Moving the Needle Through Population Health.

United States health systems face unique challenges in transitioning from volume-based to value-based care, particularly for academic institutions. Providing complex specialty and tertiary care dependent on servicing large geographic areas, and concomitantly meeting education and research academic missions may limit the time and resources available for focusing on the care coordination needs of complex local populations. Despite these challenges, academic medicine is well situated to capitalize on the promise of value-based care and to lead broad improvements in both teaching and nonteaching hospitals. If properly executed, value-based care and complex specialty care can be complementary and synergistic. We postulate that the transition from volume to value in population health requires all health care organizations to advance and formalize infrastructure in 3 core areas: organizational capabilities; provider engagement; and engagement of the patient, family, and community. Although these apply to all organizations, for academic health systems, this transition must also be interwoven with the other domains of the tripartite mission.

Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination. Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab. Results: After 2-vax, 8/33 (24.2%) patients in ocrelizumab group, 5/7 (71.4%) in fingolimod group, and 29/29 (100%) in HC group (P = 5.7 × 10-11) seroconverted. After 3-vax, 9/22 (40.9%) patients in ocrelizumab group, 19/21 (90.5%) in fingolimod group, and 7/7 (100%) in HC group seroconverted (P = 0.0003). The percentage of SARS-CoV-2 peptide reactive total CD4+ T cells increased in HC and ocrelizumab group but not in fingolimod group after 2-vax and 3-vax (P < 0.0001). The percentage of IFNγ and TNFα producing total CD4+ and CD8+ T cells increased in fingolimod group as compared to HC and ocrelizumab group after 2-vax and 3-vax (P < 0.0001). Conclusions: MS patients on ocrelizumab and fingolimod had attenuated humoral responses, but preserved cytokine producing T cell responses compared to HCs after SARS-CoV-2 mRNA vaccination. Clinical Trials Registration: NCT05060354.

COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders.

BACKGROUND: Neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 is not well understood. The objective of this study was to investigate neurologic outcomes in patients with MSRD post-COVID-19. METHODS: This was a retrospective medical records review study of adult patients with MSRD and COVID-19 infection at the Brigham MS Center. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudorelapse, new brain MRI activity, worsening of preexisting MSRD symptoms, or development of other long-term neurologic symptoms. RESULTS: 111 patients, 85 (76.6%) females, with a mean [SD] age of 49.3 [12.2] years and median [range] EDSS of 2.5 [0, 8.5] were identified. 41 patients (36.9%) had neurologic worsening post-COVID-19. Of those, 19 (46.3%) had pseudorelapses, 2 (4.8%) had relapses, and 24 (58.5%) patients reported worsening of preexisting MSRD symptoms, or other new long-term neurologic symptoms. Neurologic worsening was associated with hospitalized (moderate or severe) COVID-19 (p = 0.001), treatment for COVID-19 (p = 0.006), and incomplete COVID-19 recovery (p = 0.0267) but not with age, sex, MS type, race, disease duration, EDSS, vitamin D use, or disease modifying therapy use. CONCLUSIONS: COVID-19 severity and lack of complete systemic recovery were associated with new or worsening neurologic symptoms in 36.9% of MSRD patients.

Development and Impact of a Progressive Parental Leave Policy in a Neurology Residency.

Appropriate parental leave policies remain an unmet need in graduate medical education. Although legal and institutional guidelines allow for policies that support parental leave, there are many challenges and perceived barriers to consider in developing and implementing a successful policy. In 2018, we revised the parental leave policy for our neurology residency. Here we describe the development of our policy, measure its effects, and offer guidelines for other programs to develop a similar approach. We propose solutions to commonly encountered problems, focusing on training and education, staffing of clinical services, evolving legal requirements, resident well-being and equity, and financial support.

Peripartum disease activity in moderately and severely disabled women with multiple sclerosis.

Background: The effects of pregnancy on multiple sclerosis (MS) inflammatory activity are not well described in women with moderate to severe disabilities. Objective: To quantify the peripartum annualized relapse rate (ARR) in women with MS with an Expanded Disability Status Scale (EDSS) ≥ 3. Methods: We performed a retrospective cohort study of 85 pregnancies in 74 subjects with preconception EDSS ≥ 3. We quantified peripartum ARR and tested for risk factors predictive of peripartum relapses, postpartum brain magnetic resonance imaging activity (new T2 or gadolinium-enhancing lesions), and disability worsening. Results: There were 74 live births, with a 56% operative delivery rate. In subjects with relapsing-remitting MS, ARR decreased to 0.11 during the third trimester of pregnancy compared to 0.59 in the year preconception and increased to 1.22 in the 3 months postpartum. Women with a higher preconception EDSS had higher odds of postpartum relapses and clinically significant worsening of disability as compared to subjects with a lower EDSS. Conclusions: Moderately to severely disabled women with MS have a lower risk of relapse during pregnancy as compared to preconception, followed by a marked increase postpartum. Further studies are needed to identify ways to reduce peripartum inflammatory activity and disability progression in women with MS with moderate to severe disability.

Treatment outcomes of first-ever episode of severe optic neuritis.

BACKGROUND: Severe optic neuritis (ON) is an acute inflammatory attack of the optic nerve(s) leading to severe visual loss that may occur in isolation or as part of a relapsing neuroinflammatory disease, such neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD), or more rarely multiple sclerosis (MS). In cases of first-ever severe ON of uncertain etiology best treatment strategies remain unclear. METHODS: We reviewed records of all patients with a documented diagnosis of ON between 2004 and 2019 at Mass General Brigham (MGB) and Johns Hopkins University (JHU) hospitals. Out of 381 patients identified, 90 (23.6%) satisfied the study criteria for severe ON with visual acuity (VA) equal to or worse than 20/200 (logMAR=1) at nadir in the affected eye and had sufficient follow-up data. Treatment strategies with corticosteroids only or treatment escalation with therapeutic plasma exchange (PLEX) after steroids were compared and evaluated for differences in visual outcomes at follow-up. RESULTS: Of the 90 patients with severe optic neuritis, 71(78.9%) received corticosteroids only, and 19 (17.0%) underwent PLEX following corticosteroids. Of the 71 patients who received steroids without escalation to PLEX, 30 patients (42.2%) achieved complete recovery (VA 20/20 on the affected eye), whereas 35 (49.3%) had a partial recovery and 6 (8.4%) had no recovery. Among the 19 corticosteroid non-responders patients who underwent escalation treatment, 13 (68.4%) made complete recovery, 6 (31.6%) had partial visual recoveries (p=0.0434). The median delta logMAR of patients who underwent escalation of care was -1.2 compared with 2.0 for the ones who did not (p=0.0208). A change of delta logmar 2.0 is equivalent of going from hand motion to light perception and the positive delta value refers to intra-attack worsening. Other than not responding to steroids, patients who underwent PLEX tended to have more severe ON with significantly worse nadir visual acuity compared with those who received corticosteroids alone (logMAR 3.12 (min 2.0 - max 5.0) vs. 2.17 (min 1.3 - max 3.0); p=0.004). CONCLUSION: In our cohort of first-ever severe optic neuritis of unknown etiology, patients that did not respond adequately to corticosteroids benefited from treatment escalation to PLEX, followed in most cases by Rituximab, regardless of final etiology. Randomized controlled trials are needed to confirm the best treatment strategies.

A multi-site review of second hip fractures across 6 Dublin teaching hospitals.

INTRODUCTION: Fragility hip fractures are common and costly. Secondary fracture prevention is a treatment goal following hip fracture; however, the number of those that proceed to fracture their contralateral hip in Ireland is unknown. There are plans to introduce a Fracture Liaison Service Database in Ireland which will aim to prevent secondary fractures. To establish a baseline figure for secondary hip fractures, the injury radiographs of 1284 patients from 6 teaching hospitals over a 1-year period were reviewed. METHODS: Irish Hip Fracture Datasheets and corresponding injury radiographs were reviewed locally for all hip fractures within each respective teaching hospital for a 1-year period (2019). RESULTS: A total of 8.7% of all fragility hip fractures across the 6 hospitals were secondary hip fractures (range 4.9-11.5%). 46% occurred within years 1 to 3 following index hip fracture. Forty-eight per cent of patients were started on bone protection medications following their second hip fracture. DISCUSSION/CONCLUSION: Approximately 1 in 11 hip fractures treated across the 6 teaching hospitals assessed in 2019 was a patient's second hip fracture. We advocate for the widespread availability of Fracture Liaison Services to patients throughout Ireland to assist secondary fracture prevention.

Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) on some disease modifying therapies (DMTs), particularly anti-CD20 and sphingosine-1-phosphate (S1P) modulators, are at increased risk of severe Coronavirus Disease 19 (COVID-19) and death. COVID-19 vaccinations are effective in preventing infection and severe disease, but humoral response to vaccination and outcomes of COVID-19 infection after vaccination in MS patients on DMTs remain less understood. METHODS: In this retrospective single-center study, patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital) study and biorepository who had been vaccinated against COVID-19 and had SARS-CoV-2 spike antibody (anti-SARS-CoV-2 S Roche-Elecsys) testing were identified and compared to healthy controls. Demographic data, serum immune profiles including lymphocyte count, B-cell count, and immunoglobulins, and clinical outcome of COVID-19 infection were collected. RESULTS: 254 patients (73.2% female, mean (SD) age 52.9 (11.2) years) were identified. When controlling for age, time since vaccination, and vaccine type, patients on fingolimod, ocrelizumab, rituximab, mycophenolate mofetil, natalizumab and teriflunomide had significantly lower levels of spike antibodies compared to healthy controls (n = 34). Longer duration of treatment was associated with lower spike antibody levels in patients on anti-CD20 therapy (p = 0.016) and S1P modulators (p = 0.016) compared to healthy controls. In patients on anti-CD20 therapy, higher spike antibody levels were associated with higher CD20 cell count (p<0.001), and longer time since last anti-CD20 therapy infusion (p<0.001). 92.8% (13/14) vaccine responders (spike antibody titer >100 ug/dL) on anti-CD20 therapy demonstrated B-cell reconstitution (mean CD20 3.6%). Only 1 out of 86 patients with CD20 of 0% had a measurable spike antibody response to vaccination. During follow-up (mean 270 days), five patients were diagnosed with COVID-19 after vaccination (incidence 1.9%), all of whom had spike antibody < 20 ug/dL. No patients required ICU care or died. CONCLUSIONS: Patients on some DMTs demonstrate reduced humoral immunity after Sars-CoV-2 vaccination. Longer duration of anti-CD20 therapy and reduced CD20 cell count is associated with blunted humoral response to vaccination. CD20 reconstitution >0.1% appears necessary, but not always sufficient, for humoral response to vaccination. Breakthrough COVID-19 infection in our cohort of MS patients on DMT was higher than in population studies. We propose that adjustment of B-cell therapy administration to allow for B-cell reconstitution prior to vaccination should be considered.

A Targeted "Top 100" High-Risk Care Management Program Improves Adherence to Best Practices.

Care management programs for high-risk patients have yielded inconsistent results in reducing health care expenditures. We reviewed the most successful programs and identified 5 best practice areas: (1) in-person patient meetings; (2) direct care manager/physician interaction; (3) provide transitional care services; (4) educate patients; and (5) provide medication review. We measured adherence to the best practices at baseline and at 6 and 9 months into the program for the highest-risk patients. The program increased adherence from baseline to each best practice area. Program enrollment increased at the 6-month follow-up but fell at the 9-month follow-up.

Intermediate to Long-Term Follow-up of Distal Femoral Replacements in the Treatment of Neoplastic Disease About the Knee.

BACKGROUND: Limb salvage procedures have become more prevalent in orthopedic oncology. Endoprostheses have been used successfully to reconstruct large skeletal deficits. The aim was to review intermediate to long-term follow-up of distal femoral replacements in the setting of neoplastic disease about the knee. METHODS: This was a single-center retrospective cohort study from 1997 to 2018 in a national referral center for oncology. The secondary objectives were to describe morbidity and mortality in this cohort. We recorded the modes of failure using Henderson classification system, complications, revisions, and all further operations. RESULTS: Seventy-two distal femoral replacements were performed. Osteosarcoma was the most common indication (55 patients). Other indications included chondrosarcoma (7 patients), giant cell tumor (5 patients), Ewing's sarcoma (2 patients), metastatic spread (2 patients), and leiomyosarcoma (1 patient). One-year mortality was 1.38% with an overall mortality of 13.8%, at the end of the study period. The 1-year revision rate was 4.2%, 30.5% for 10 years, and 38.8% for more than 15 years. The overall implant survival rate was 63.8%. The most common reasons for failure included aseptic loosening (16.6%), infection (16.6%), and local recurrence (9.7%) with an amputation rate of 6.9% in the cohort. CONCLUSION: Neoplastic disease of the lower limb is associated with significant morbidity. Aseptic loosening (16.6%) and infection (16.6%) were the most common reasons for failure in this cohort.

Increased P450 aromatase levels in post-menopausal women after acute ischemic stroke.

BACKGROUND: Sex differences in stroke have been attributed to the neuroprotective effects of estrogen, yet most clinical trials of estrogen supplementation for stroke prevention have failed. The contribution of sex hormones to stroke outcome remains a subject of debate. Aromatization of testosterone to estradiol in neural tissue leads to sexual differentiation. Emerging data suggests aromatase activity increases in response to brain injury, and increased aromatase expression is seen in the ischemic penumbra in animal models. The objective of this study was to examine the levels of endogenous sex steroids after acute ischemic stroke and determine if levels of sex steroids were associated with acute stroke outcomes. METHODS: Peripheral blood from ischemic stroke patients and controls was collected under an approved IRB within 24 h of symptom onset. 17ß-estradiol, testosterone, and aromatase levels were measured in the serum of both men and women using ELISA. Hormone levels were compared in men vs. women in stroke and control groups and correlated with outcomes (NIHSS and change in the modified Rankin Scale (mRS), defined as the difference of premorbid and discharge mRS) using multivariate regression. RESULTS: We found no significant difference in estradiol levels 24 h after stroke in men (p = 0.86) or women (p = 0.10). In men, testosterone significantly decreased after stroke as compared with controls (1.83 ± 0.12 vs. 2.86 ± 0.65, p = 0.01). Aromatase levels were significantly increased in women after stroke as compared with controls (2.27 ± 0.22 vs. 0.97 ± 0.22, p = 0.002), but not in men (p = 0.84). Estradiol levels positively correlated with change in mRS in both women (r = 0.38, p = 0.02) and men (r = 0.3, p = 0.04). CONCLUSIONS: Estradiol levels correlated with functional outcomes (change in mRS) in both men and women, at least in the acute phase (24 h) of stroke. However, no significant difference in estradiol levels is seen 24 h post-stroke in men or women. Testosterone levels decrease at 24 h after stroke in men. As seen in animal models, aromatase levels increase after acute ischemic stroke, but this was only true for women. These indicate an active aromatization process in post-menopausal women after acute ischemic stroke.

Population Health and Academic Medical Centers: High Cost Meets High Efficiency.

Academic medicine is at an inflection point with the changing priorities of health care to focus more on population health. In this new model of care, the academic medical center (AMC) tripartite mission needs to be reworked into a new framework that prioritizes management of populations, integration, adaptability, and rapid learning. To complete this change, AMCs will have to undergo the hard work of culture change, which will be facilitated by restructuring governance and organizational structures to fund and champion the population health view. Care coordination and fund health information technology enhancements will be needed to support this work.

Patient isolation for infection control and patient experience.

OBJECTIVE: Hospitalized patients placed in isolation due to a carrier state or infection with resistant or highly communicable organisms report higher rates of anxiety and loneliness and have fewer physician encounters, room entries, and vital sign records. We hypothesized that isolation status might adversely impact patient experience as reported through Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys, particularly regarding communication. DESIGN: Retrospective analysis of HCAHPS survey results over 5 years. SETTING: A 1,165-bed, tertiary-care, academic medical center. PATIENTS: Patients on any type of isolation for at least 50% of their stay were the exposure group. Those never in isolation served as controls. METHODS: Multivariable logistic regression, adjusting for age, race, gender, payer, severity of illness, length of stay and clinical service were used to examine associations between isolation status and "top-box" experience scores. Dose response to increasing percentage of days in isolation was also analyzed. RESULTS: Patients in isolation reported worse experience, primarily with staff responsiveness (help toileting 63% vs 51%; adjusted odds ratio [aOR], 0.77; P = .0009) and overall care (rate hospital 80% vs 73%; aOR, 0.78; P < .0001), but they reported similar experience in other domains. No dose-response effect was observed. CONCLUSION: Isolated patients do not report adverse experience for most aspects of provider communication regarded to be among the most important elements for safety and quality of care. However, patients in isolation had worse experiences with staff responsiveness for time-sensitive needs. The absence of a dose-response effect suggests that isolation status may be a marker for other factors, such as illness severity. Regardless, hospitals should emphasize timely staff response for this population.