Pipeline Therapies for Gout.

PURPOSE OF REVIEW: Despite effective available treatments, gout management is often unsuccessful in getting patients to target serum urate goal and in managing flares in the setting of comorbidities. Studies addressing future treatment options for short- and long-term management are reviewed. RECENT FINDINGS: URAT-1 blocking agents have been helpful but have had limitations related to effects on renal function, lack of efficacy with renal impairment, and potential to increase renal stones. Dotinurad may function in the setting of decreased renal function. Arhalofenate has anti-URAT-1 activity and may also blunt gout flares. A new xanthine oxidase inhibitor (XOI), tigulixostat, is under study. New uricase treatments manufactured in combination with agents that can reduce immunogenicity may make uricase treatment simpler. A unique strategy of inhibiting gut uricase may offer the benefits of avoiding systemic absorption. For gout flares, IL-1ß inhibitor studies in progress include different dosing schedules. Dapansutrile, an oral agent under investigation, inhibits activation of the NLRP3 inflammasome and may be an effective anti-inflammatory. New treatments for gout that are under study may work in the setting of comorbidities, simplify management, utilize new mechanisms, or have reduced side effects.

Association of COVID-19 Vaccinations With Flares of Systemic Rheumatic Disease: A Case-Crossover Study.

OBJECTIVE: We aimed to determine the association of COVID-19 vaccination with flares of systemic rheumatic disease (SRD). METHODS: Adults with systemic rheumatic disease (SRD) in a single-center COVID-19 Rheumatology Registry were invited to enroll in a study of flares. COVID-19 vaccine information from March 5, 2021, to September 6, 2022, was obtained from chart review and self-report. Participants self-reported periods of SRD flare and periods without SRD flare. "Hazard periods" were defined as the time before a self-report of flare and "control periods" as the time before a self-report of no flare. The association between flare and COVID-19 vaccination was evaluated during hazard and control periods through univariate conditional logistic regression stratified by participant, using lookback windows of 2, 7, and 14 days. RESULTS: A total of 434 participants (mean ± SD age 59 ± 13 years, 84.1% female, 81.8% White, 64.5% with inflammatory arthritis, and 27.0% with connective tissue diseases) contributed to both the hazard and control periods and were included in analysis. A total of 1,316 COVID-19 vaccinations were identified (58.5% Pfizer-BioNTech, 39.5% Moderna, and 1.4% Johnson & Johnson); 96.1% of participants received at least one dose and 93.1% at least two doses. There was no association between COVID-19 vaccination and flares in the subsequent 2, 7, or 14 days (odds ratio [OR] 1.46, 95% confidence interval [CI] 0.86-2.46; OR 1.09, 95% CI 0.76-1.55; and OR 0.85, 95% CI 0.64-1.13, respectively). Analyses stratified on sex, age, SRD subtype, and vaccine manufacturer similarly showed no association between vaccination and flare. CONCLUSION: COVID-19 vaccination was not associated with flares in this cohort of participants with SRD. These data are reassuring and can inform shared decision-making on COVID-19 immunization.

Tapering biologic DMARDs in rheumatoid arthritis.

With the arrival of biologics and the shift toward treat-to-target therapy, the possibility of a sustained clinical response has become an achievable goal for many patients with rheumatoid arthritis (RA). Although biologics have revolutionized the treatment of RA, they are costly, potentially inconvenient, and carry risks of side effects. Whether they can or should be tapered in patients with tight disease control is a matter of clinical uncertainty. The major international rheumatology professional societies have all issued guidelines on this question, but across recommendations, consensus is lacking on how and when to consider therapy de-escalation. Recent evidence suggests that sustained remission or low disease activity is more attainable with dose reduction as opposed to outright discontinuation of biologic therapy, and certain predictors of successful taper have begun to be described. This article will (1) summarize the current evidence base for biologic tapering in RA, (2) outline real-world outcomes findings, (3) review important contextual factors relevant to therapy de-escalation, such as cost-effectiveness considerations and patient perspectives, and (4) conclude by summarizing current guidelines.

Fatal COVID-19 in an MS patient on natalizumab: A case report.

We report a fatal case of COVID-19 in a 51-year-old African American woman with multiple sclerosis on natalizumab. She had multiple risk factors for severe COVID-19 disease including race, obesity, hypertension, and elevated inflammatory markers, but the contribution of natalizumab to her poor outcome remains unknown. We consider whether altered dynamics of peripheral immune cells in the context of natalizumab treatment could worsen the cytokine storm syndrome associated with severe COVID-19. We discuss extended interval dosing as a risk-reduction strategy for multiple sclerosis patients on natalizumab, and the use of interleukin-6 inhibitors in such patients who contract COVID-19.

Prevalence of coronary artery calcification in young patients with SLE of predominantly Hispanic and African-American descent.

OBJECTIVES: Cardiovascular disease (CVD) is a leading cause of death in SLE. Coronary artery calcium (CAC) scores predict CVD events, independent of traditional risk factors. Patients with SLE aged >45 years have an increased prevalence of CAC in a predominantly white population. Little is known about CAC in younger patients with SLE. We evaluated CAC in younger patients with SLE of predominantly African-American and Hispanic ancestry, compared with healthy controls. METHODS: We identified 76 patients with SLE meeting 1997 American College of Rheumatology classification criteria, without known coronary artery disease and who had a non-contrast chest CT performed as part of their clinical care, with images retrievable for calculation of CAC scores. Demographics, disease characteristics and comorbidities were ascertained and adjusted for. RESULTS: 42.1% of patients with SLE (mean age 40±13 years, 90% female, 33% Hispanic and 40% African-American) had CAC>0, 32% for age ≤45 years and 61.6% for age >45. Patients with SLE with CAC>0 were older and had more comorbid hypertension. Women with SLE aged ≤45 years, had a 12.6-fold higher adjusted odds of CAC>0 compared with age-matched and sex-matched controls (95% CI 5.2 to 30.7, p<0.001). Furthermore, 29% of patients with SLE aged 18-32 years (median disease duration of 5 years) had CAC>0. CONCLUSION: Patients with SLE aged ≤45 years have an increased prevalence of detectable CAC compared with the general population. Our data suggest that subclinical atherosclerosis in SLE develops early and warrants timely screening and cardioprotective interventions.

Ethical Issues in Contemporary Clinical Genetics.

As genetic sequencing capabilities become more powerful and costs decline, the reach of genomics is expanding beyond research laboratories to the wards, outpatient clinics, and, with the marketing of direct-to-consumer testing services, patients' homes. Increasingly, patients receiving various diagnoses-from cancer to cardiomyopathy-can reasonably expect to have conversations with their providers about indications for genetic testing. In this dynamic context, a grasp of the ethical principles and history underlying clinical genetics will provide clinicians with the tools to guide their practice and help patients navigate complex medical-psychosocial terrain. This article provides an overview of the salient ethical concerns pertaining to clinical genetics. The subject is approached with an emphasis on clinical practice, but consideration is also given to research. The review is organized around the temporal and informational sequence of issues commonly arising during the course of pretesting, testing, and posttesting phases of patient care. Drawing from medical, legal, and historical perspectives, this review covers the following topics: (1) informed consent, (2) return of results, and (3) privacy and confidentiality, and intends to equip readers with an appropriate foundation to apply ethical principles to genetic testing paradigms with an understanding of the contextual landscape against which these situations occur.

Finding the Words: Medical Students' Reflections on Communication Challenges in Clinic.

BACKGROUND AND OBJECTIVES: Interpersonal communication is essential to providing excellent patient care and requires ongoing development. Although aspects of medical student interpersonal communication may degrade throughout career progression, it is unknown what specific elements pose challenges. We aimed to characterize clerkship students' perspectives on communication challenges in the outpatient setting to help inform curricular development. METHODS: Third-year medical students in a required family medicine clerkship were asked to describe a communication challenge they encountered. Open-ended written responses were collected through a mandatory post-clerkship survey. Responses were qualitatively coded using an a priori framework for teaching and assessing communication skills (The SEGUE Framework for Teaching and Assessing Communication Skills) with data-derived additions to the framework, followed by a team-based thematic analysis. RESULTS: We collected 799 reflections written by 518 students from 2007-2014. Three dominant themes emerged from the analysis: challenges with (1) effectively exchanging information with patients, (2) managing emotional aspects of the patient encounter, and (3) negotiating terms of the encounter. CONCLUSIONS: Communication curricula focus on content and process of the medical interview, but insufficient time and energy are devoted to psychosocial factors, including aspects of the encounter that are emotionally charged or conflicting. While gaps in students' communication skillsets may be anticipated or observed by educators, this study offers an analysis of students' own perceptions of the challenges they face.