Identification of an ANCA-Associated Vasculitis Cohort Using Deep Learning and Electronic Health Records.

Background: ANCA-associated vasculitis (AAV) is a rare but serious disease. Traditional case-identification methods using claims data can be time-intensive and may miss important subgroups. We hypothesized that a deep learning model analyzing electronic health records (EHR) can more accurately identify AAV cases. Methods: We examined the Mass General Brigham (MGB) repository of clinical documentation from 12/1/1979 to 5/11/2021, using expert-curated keywords and ICD codes to identify a large cohort of potential AAV cases. Three labeled datasets (I, II, III) were created, each containing note sections. We trained and evaluated a range of machine learning and deep learning algorithms for note-level classification, using metrics like positive predictive value (PPV), sensitivity, F-score, area under the receiver operating characteristic curve (AUROC), and area under the precision and recall curve (AUPRC). The deep learning model was further evaluated for its ability to classify AAV cases at the patient-level, compared with rule-based algorithms in 2,000 randomly chosen samples. Results: Datasets I, II, and III comprised 6,000, 3,008, and 7,500 note sections, respectively. Deep learning achieved the highest AUROC in all three datasets, with scores of 0.983, 0.991, and 0.991. The deep learning approach also had among the highest PPVs across the three datasets (0.941, 0.954, and 0.800, respectively). In a test cohort of 2,000 cases, the deep learning model achieved a PPV of 0.262 and an estimated sensitivity of 0.975. Compared to the best rule-based algorithm, the deep learning model identified six additional AAV cases, representing 13% of the total. Conclusion: The deep learning model effectively classifies clinical note sections for AAV diagnosis. Its application to EHR notes can potentially uncover additional cases missed by traditional rule-based methods.

Enhancing Faculty Development Through Compiled Verbal Feedback on Clinical Teaching From Trainees.

OBJECTIVE: Feedback from fellows-in-training (FITs) is important for faculty development and to enrich clinical teaching. We sought to evaluate the effectiveness of traditional online evaluations and a novel compiled verbal feedback mechanism. METHODS: An annual feedback system was implemented in our rheumatology division in which FITs provided verbal feedback on all faculty to a facilitator who compiled, deidentified, and shared the feedback with individual faculty members. FITs also completed standard online annual evaluations of faculty. FITs and faculty completed surveys assessing the perceived effectiveness and confidentiality of each feedback mechanism. RESULTS: Thirteen of 15 eligible faculty and all 4 eligible FITs completed both surveys. Responses by FITs and faculty regarding the quality of online evaluations were generally unfavorable or neutral. Faculty responses regarding compiled verbal feedback were more favorable in all questions and significantly more favorable with respect to the feedback's ability to explain strengths (54% favorable for online evaluations vs 100% for compiled verbal feedback), the feedback's specificity (0% vs 54%), and the feedback's actionable nature (15% vs 62%). All FITs' responses regarding quality of compiled verbal feedback were favorable. FITs had concerns regarding confidentiality with both online evaluations (0% favorable) and compiled verbal feedback (25% favorable), though FITs had less concern for future faculty interactions with compiled verbal feedback (100% favorable) than with online evaluations (0% favorable). CONCLUSION: Compiled verbal feedback by FITs produced more actionable and effective feedback for faculty, with less concerns regarding future faculty interactions compared with traditional online evaluations. Further study of this method across different programs and institutions is warranted.

Steroid sparing in vasculitis: Myth or reality?

Glucocorticoids are the cornerstone of therapy for all forms of vasculitis. However, glucocorticoid treatment carries with it the risk of glucocorticoid toxicity. Recent research efforts in vasculitis have emphasized investigation into strategies that reduce glucocorticoid exposure. These strategies include the adoption of rapid-acting steroid-sparing agents, reduced-dose glucocorticoid induction regimens, the early introduction of steroid-sparing agents for maintenance therapy, and the extension of maintenance therapy to minimize glucocorticoid exposure associated with disease relapse. These are critical advances to move us toward the goal of glucocorticoid-free treatment of vasculitis. The evidence supporting each of these strategies and directions for future research are explored.

Ear, Nose, and Throat Manifestations of Vasculitis and Other Systemic Autoimmune Diseases: Otologic, Sinus, and Airway.

Auricular, nasal, and laryngeal manifestations occur frequently in rheumatic diseases. Inflammatory ear, nose, and throat (ENT) processes often result in organ damage and have profound effects on quality of life. Herein, we review the otologic, nasal, and laryngeal involvement of rheumatic diseases, focusing on their clinical presentation and diagnosis. ENT manifestations generally respond to treatment of the systemic disease, which is outside the scope of this review; however, adjunctive topical and surgical treatment approaches, as well as treatment of idiopathic inflammatory ENT manifestations will be reviewed.

Approach to laboratory ordering and interpretation in rheumatology.

Evaluation of suspected rheumatic disease is a significant challenge due to overlapping and sometimes non-specific clinical features. Most laboratory tests in rheumatic disease have incomplete sensitivity and specificity, leading to positive results without disease and negative results despite disease presence. Therefore, judicious ordering and correct interpretation of laboratory testing in rheumatology is critical in order to provide high-value care. Herein we review laboratory testing in rheumatology in the context of a framework for approaching rheumatic disease.

Development and Validation of a Simulation Model for Treatment to Maintain Remission in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: Fixed and tailored rituximab retreatment strategies to maintain remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are associated with tradeoffs. The current study was undertaken to develop a simulation model (AAV-Sim) to project clinical outcomes with these strategies. METHODS: We developed the AAV-Sim, a microsimulation model of clinical events among individuals with AAV initiating treatment to maintain remission. Individuals transition between health states of remission or relapse and are at risk for severe infection, end-stage renal disease, or death. We estimated transition rates from published literature, stratified by individual-level characteristics. We performed validation using the mean average percent error (MAPE) and the coefficient of variation of root mean square error (CV-RMSE). In internal validation, we compared model-projected outcomes over 28 months with outcomes observed in the Rituximab versus Azathioprine in ANCA-Associated Vasculitis 2 (MAINRITSAN2) trial, which compared fixed versus tailored retreatment. In external validation, we compared outcomes with fixed rituximab retreatment from the AAV-Sim to outcomes from the MAINRITSAN1 trial and an observational study. RESULTS: The AAV-Sim projected outcomes similar to those in the MAINRITSAN2 trial, including minor (AAV-Sim 6.0% fixed versus 7.3% tailored; MAINRITSAN2 6.2% versus 8.6%; MAPE 3% and 15%) and major relapse (AAV-Sim 3.5% versus 5.5%; MAINRITSAN2 3.7% versus 7.4%; MAPE 5% and 26%), severe infection (AAV-Sim 19.4% versus 11.1%; MAINRITSAN2 19.8% versus 10.2%; MAPE 2% and 9%), and relapse-free survival (AAV-Sim 84.8% versus 82.3%; MAINRITSAN2 86% versus 84%; CV-RMSE 2.3% and 2.5%). Similar performance was observed in external validation. CONCLUSION: The AAV-Sim projected a range of clinical outcomes for different treatment approaches that were validated against published data. The AAV-Sim has the potential to inform management guidelines and research priorities.

Pairing medical students on the wards: A multi-site analysis of pairing effect on clerkship performance.

BACKGROUND: Medical students are often paired together on clinical teams during their clerkships. While this practice has multiple potential positive effects, evidence suggests that most students feel that their evaluation is impacted by the other student. This perception negatively impacts the learning environment. We set out to determine whether paired students had a measurable effect on each other's clerkship grade during the medicine sub-internship. METHOD: We examined 186 4th year student-pairs during the required medicine sub-internship at 3 hospital sites of Harvard Medical School from 2013-2017. Chi-square tests were used to determine whether pairing impacted the final clerkship grade. Subsequently we examined whether pairing impacted the sub-internship performance stratified by students' 3rd year core medicine clerkship grade to account for prior performance. FINDINGS: We found no significant deviation between the expected and observed distribution of student grades (chi-square 1.9, p = 0.39) among 186 student pairs, suggesting that pairing had no meaningful effect on the sub-internship grade. We also saw no significant effect of pairing when controlling for prior internal medicine clerkship performance (chi-square 10.9, p = 0.53). CONCLUSIONS: Despite concerns that students on the same medical team may impact each other's performance evaluation, our exploratory study demonstrated no significant effect of student pairing on grades in a medicine sub-internship. Further study of the complex relationship between students on a medical team are warranted to optimize this common practice and enhance the learning environment.

Use of rituximab in the treatment of mucous membrane pemphigoid: An analytic review.

Mucous Membrane Pemphigoid (MMP) is a potentially fatal mucocutaneous autoimmune blistering disease. Autoantibodies are produced against various components of the dermo-epidermal or mucosal-submucosal junction are referred to as basement membrane zone (BMZ). The hallmark is deposition of of Ig and C3 on the perilesional tissues and in some patients detection of anti-BMZ autoantibodies. A unique characteristic of MMP is that as the blisters or erosions heal, they leave irreversible scarring. This scarring results in serious and catastrophic sequelae that affect the quality of life. Conventional therapy consists of anti-inflammatory and immunosuppressive agents (ISA). In patients who fail conventional therapy or develop significant side effects to them, rituximab (RTX) has been used off label. In this review, the clinical outcomes of patients with MMP treated with RTX were studied. 124 patients were identified, 47.58% being male. 72 patients were treated by the Lymphoma Protocol and 51 by Rheumatoid Arthritis (RA) protocol. Follow up for the entire cohort was 36 months (range 0.5-72). On follow-up 64 patients (51.61%) achieved complete clinical remission (CR) off therapy, 25 patients (20.16%) were in CR on therapy, 5 patients (4.03%) were non-responders, and 9 patients (7.25%) were failures. 52 patients (41.93%) experienced a relapse, after 36 months follow-up. Duration between last RTX infusion and relapse was 10.5 months (range 1-30). Most patients with relapses were treated with additional RTX. A statistically significant better outcome was observed in patients treated with RTX as monotherapy compared to those who received RTX with ISA. Clinical outcomes in patients treated with Lymphoma protocol were better than RA protocol at a statistically significant level. Data on CD20+ B cell depletion and repopulation was limited. Interestingly relapses were seen in patients with CD20+ B cell depletion and after repopulation. In the final analysis, 89 patients (71.77%) were in complete remission. Data in this review indicated that RTX was a useful agent to treat MMP. While a randomized control trial may not be practically possible, better and disease specific protocols need to be developed. When publishing, authors should attempt to provide complete and detailed information. In doing so, they will benefit their colleagues and the patients with MMP they treat with RTX.

Advanced Integrated Science Courses: Building a Skill Set to Engage With the Interface of Research and Medicine.

Scientific research has been changing medical practice at an increasing pace. To keep up with this change, physicians of the future will need to be lifelong learners with the skills to engage with emerging science and translate it into clinical care. How medical schools can best prepare students for ongoing scientific change remains unclear. Adding to the challenge is reduced time allocated to basic science in curricula and rapid expansion of relevant scientific fields. A return to science with greater depth after clinical clerkships has been suggested, although few schools have adopted such curricula and implementation can present challenges. The authors describe an innovation at Harvard Medical School, the Advanced Integrated Science Courses (AISCs), which are taken after core clerkships. Students are required to take 2 such courses, which are offered in a variety of topics. Rather than factual content, the learning objectives are a set of generalizable skills to enable students to critically evaluate emerging research and its relationship to medical practice. Making these generalizable skills the defining principle of the courses has several important advantages: it allows standardization of acquired skills to be combined with diverse course topics ranging from basic to translational and population sciences; students can choose courses and projects aligned with their interests, thereby enhancing engagement, curiosity, and career relevance; schools can tailor course offerings to the interests of local faculty; and the generalizable skills delineate a unique purpose of these courses within the overall medical school curriculum. For the 3 years AISCs have been offered, students rated the courses highly and reported learning the intended skill set effectively. The AISC concept addresses the challenge of preparing students for this era of rapidly expanding science and should be readily adaptable to other medical schools.

Sicca syndrome associated with immune checkpoint inhibitor therapy.

Cancer immunotherapy, which seeks to stimulate a patient's own immune system to combat cancer, is quickly becoming a central pillar of cancer therapeutics and has resulted in the development of many novel anticancer therapies. One subtype of cancer immunotherapy, immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment and changed the standard of care for multiple indications. However, the advent of ICIs has produced a wide variety of inflammatory side effects termed immune-related adverse events (IRAEs), including ICI-induced Sicca syndrome. This article outlines the clinical features of ICI-induced Sicca syndrome and assesses its reported incidence in clinical trials, case series, and case reports across numerous cancers and treatment modalities. Presentations of ICI-induced Sicca syndrome in patients with pre-existing SjÓ§gren's disease and with extra-glandular manifestations will also be explored. The pathophysiological mechanisms underlying IRAEs, including ICI-induced Sicca syndrome, will be evaluated through an examination of existing literature. Finally, the various treatment and management strategies as well as aims for future work will be discussed and reviewed.

Pairing students on the wards: The effect on the clerkship learning environment.

BACKGROUND: Medical students are often paired together on clinical teams during their clerkships, but the effect of this practice is unknown. We conducted a survey study to determine student perceptions and attitudes regarding being paired on the same team with a classmate. METHODS: We conducted semi-structured interviews and utilized thematic analysis to develop themes for survey design. We then designed and administered a survey to the graduating class of 2018 at Harvard Medical School. RESULTS: One hundred students participated in the survey (60% response). The majority of students perceived that pairing impacted their clerkship evaluations. Pairing was perceived to positively impact learning, adjustment to the clerkship, enjoyment, wellness and the overall clerkship experience. However, stress related to grading and evaluation as well as competition for patients were cited as negative impacts. Students in our sample were split on their preferences for working alone or with another student on a clinical team. CONCLUSION: Student pairing is a common practice that affects the learning environment in clinical clerkships. Further study of interactions between students on medical teams as well as interventions to raise the positive value of pairing while limiting its negative impact may enhance the clerkship learning environment.

Nodular Pachymeningitis Associated With Relapsing Polychondritis and Crohn Disease Responsive to Adalimumab and Prednisone.

OBJECTIVES: To review the previous literature on the associations of pachymeningitis with Crohn disease (CD) and relapsing polychondritis (RP) and to describe a new case occurring in association with both in addition to highlighting its positive response to steroid and adalimumab treatment. METHODS: We review the patient's clinical presentation, diagnostic workup (serum and CSF testing), and MRI findings in detail and chronicle the response of the pachymeningitis to intensive immunotherapy. We contrast this case against previous reports of pachymeningitis occurring in association with RP and inflammatory bowel disease that were found on PubMed. RESULTS: Only 2 cases of ulcerative colitis and 5 cases of RP were found in association with pachymeningitis; there were no cases in association with CD. Our patient presented with symptoms isolated to a steroid-responsive headache in the setting of normal neurologic and rheumatologic examinations. Her preceding history was notable for long-standing CD and increasingly active symptoms referable to RP. Focal nodular pachymeningitis was seen overlying the left hemisphere on brain MRI. An extensive serum and CSF workup and body fluorodeoxyglucose-PET scan failed to identify an alternative etiology beyond her underlying autoimmune inflammatory disorders. After adding prednisone and adalimumab to her preexisting treatment of methotrexate, she responded dramatically both clinically and radiographically. CONCLUSIONS: Although exceptionally rare, pachymeningitis may occur as a neuroinflammatory complication of CD and RP.