Neutrophil Activation and Adhesiveness in Coronary Artery Disease: Results From the COLCHICINE-PCI Biomarker Substudy.

Registration URL: https://clinicaltrials.gov. Unique identifier: NCT02594111.

Patient Experience with Chronic Refractory Gout and Its Impact on Health-Related Quality of Life: Literature Review and Qualitative Analysis.

INTRODUCTION: Patients with chronic refractory gout face a considerable burden of disease due to unexpected flares characterized by severe and debilitating pain, which can lead to chronic pain and joint damage. This study aimed to understand the symptoms and impacts of chronic refractory gout on health-related quality of life (HRQoL). METHODS: A targeted literature review was conducted to identify and review key articles describing the symptoms and impacts of gout, and articles examining the psychometric performance of the Medical Outcomes Survey Short Form-36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in gout. Qualitative interviews were conducted with 20 participants with chronic refractory gout. The results were used to develop the conceptual model and determine the appropriateness of the SF-36 and HAQ-DI in evaluating HRQoL in this population. RESULTS: Most frequently reported symptoms included bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%). Most frequently reported impacts were difficulties climbing a flight (n = 20, 100.0%) or several flights of stairs (n = 20, 100.0%), climbing five steps (n = 19, 95.0%), completing chores (n = 19, 95.0%), and running errands and shopping (n = 19, 95.0%). All assessed items from SF-36 and HAQ-DI were reported by ≥ 25% (n = 5) of participants and mapped sufficiently to concepts elicited by participants. CONCLUSIONS: Patients with chronic refractory gout report symptoms and impacts that are highly bothersome and burdensome to everyday life. Items included in the HAQ-DI and SF-36 mapped directly to these symptoms and impacts and are relevant to understand the burden of disease of chronic refractory gout.

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.

OBJECTIVE: Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. METHODS: This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. RESULTS: Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. CONCLUSION: These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial.

RATIONALE & OBJECTIVE: We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). STUDY DESIGN: Prespecified subcohort analysis of a randomized controlled trial. SETTING & PARTICIPANTS: A substudy of the STOP Gout Trial in participants with CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) 30-59mL/min/1.73m2 at baseline. EXPOSURE: Trial participants with CKD and gout and serum urate (SUA) concentration of≥6.8mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate-lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal SUA of<6.0mg/dL (<5.0mg/dL with tophi) (phase 1) and maintained during weeks 25-48 (phase 2). Gout flare was assessed between weeks 49-72 (phase 3). OUTCOME: Gout flare between weeks 49-72 (phase 3) was the primary outcome. Secondary outcomes included SUA goal achievement and ULT dosing at end of phase 2, and serious adverse events. ANALYTICAL APPROACH: Outcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm. RESULTS: CKD was present in 351 of 940 participants; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; P=0.02) despite similar attainment of the SUA goal (79% vs 81%; P=0.6) by the end of phase 2. Acute kidney injury was more common in participants with stage 3 CKD randomized to allopurinol compared with febuxostat. LIMITATIONS: Limited power to assess infrequent safety events, largely male, older population. CONCLUSIONS: Allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen with lower incidence of gout flares in participants randomized to allopurinol. PLAIN-LANGUAGE SUMMARY: The STOP Gout Trial was a multicenter, randomized, double-blind, noninferiority, comparative effectiveness trial, which found that allopurinol was noninferior to febuxostat in gout flare prevention and that both medications were similarly efficacious in reaching a serum urate goal when used as part of a treat-to-target approach. A significant proportion of patients with chronic kidney disease (CKD) are afflicted by gout, yet there is a lack of high-quality comparative effectiveness data comparing allopurinol and febuxostat in these patients. We evaluated the efficacy and safety of allopurinol and febuxostat in the subgroup of STOP Gout Trial participants with stage 3 CKD and found that allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen, with lower incidence of gout flares in participants randomized to allopurinol.

Skeletal muscle mass and quality in gout patients versus non-gout controls: A computed tomography imaging study.

OBJECTIVE: Patients with gout are at elevated risk of multiple vascular and metabolic comorbidities. Whether they are also at risk of sarcopenia, which is known to affect patients with other rheumatic diseases, has not been previously assessed. We examined whether patients with gout have decreased lumbar muscle quality and quantity, indicating an association between gout and sarcopenia. METHODS: Fifty gout subjects and 25 controls, ages 45-80, underwent computed tomography imaging of the lumbosacral spine. We measured muscle quantity (skeletal muscle area [SMA] and index [SMI]) and quality (skeletal muscle radiation attenuation [SMRA] and intermuscular adipose tissue [IMAT] area and index [IMATI]) of the psoas and erector spinae muscles at the L3 level. RESULTS: Seventy subjects (45 gout and 25 controls) were included in the analysis. Gout subjects had higher BMI, more kidney disease and hypertension, lower exercise frequency, and higher mean serum urate and creatinine vs. controls. Lumbar SMRA was significantly lower in gout subjects vs. controls, indicating reduced muscle quality. Lumbar IMAT area was significantly higher in gout subjects vs. controls, as was lumbar IMATI, indicating increased muscle adiposity. These differences persisted after adjusting for potential confounders. In contrast, there was no significant difference between gout and control groups in lumbar SMA or lumbar SMI, suggesting that muscle quantity may not be routinely affected by the diagnosis of gout. CONCLUSIONS: Gout patients exhibit decreased lumbar muscle quality compared with controls, consistent with an association between gout and sarcopenia.

Knowledge of and Stated Adherence to the 2020 ACR Guideline for Gout Management: Results of a Survey of US Rheumatologists.

OBJECTIVE: This report evaluates rheumatologists' stated adherence to and agreement with the 2020 American College of Rheumatology (ACR) Guideline for the Management of Gout. METHODS: A 57-item questionnaire was administered to a sample of US rheumatologists. Stated adherence scores were based on several guideline recommendations reported to be followed by rheumatologists in practice, whereas stated agreement scores were based on whether respondents always followed the recommendations. RESULTS: All 201 rheumatologists approached completed the questionnaire. The mean overall stated adherence score was 11.5 (maximum 15), whereas the mean overall stated agreement score was 7.7 (maximum 14). Less experienced rheumatologists (≤ 8 yrs; n = 49) were likely to claim adherence to more individual ACR recommendations than those with more experience (> 8 yrs; n = 152; mean stated adherence score: 12.3 vs 11.3; P ≤ 0.05). Rheumatologists who claimed to see ≤ 75 patients with gout in 6 months (n = 66) had a mean stated adherence score of 12.1 vs 11.2 for those who claimed to have seen > 75 patients (P ≤ 0.05). Approximately 78% of rheumatologists claimed to follow the guideline for initiating urate-lowering therapy (ULT), and 89% were likely to prescribe allopurinol as a first-line ULT. Claimed adherence to recommendations for dosing was lower (febuxostat: 43%; allopurinol: 39%). Rheumatologists from academic settings were more likely to prescribe an interleukin-1 inhibitor for gout flares. CONCLUSION: The self-reported practice of the surveyed US rheumatologists was generally concordant with the 2020 ACR Guideline for the Management of Gout. However, there were gaps in guideline knowledge and stated adherence among rheumatologists, mainly concerning the dosing of treatment regimens.

Accuracy of Financial Disclosures in US-Based Rheumatology Journals.

OBJECTIVE: Transparency of disclosure in publication is necessary for readers to be aware of any potential conflicts of interest (PCOIs). Past studies of accuracy of disclosure in rheumatology journals have focused exclusively on clinical practice guidelines and not research works. We assessed discrepancy in reporting PCOIs in clinically oriented manuscripts published in the three top-ranked (by impact factor) US-based general rheumatology journals. METHODS: We reviewed disclosures provided by first, second, and last authors of 50 published clinically oriented articles in each of the three top-ranked general US rheumatology journals. For each author, we extracted payment reports from the Open Payments Database (OPD) related to consulting fees, honoraria, and speaker or faculty compensation. We defined a PCOI as a payment received from a company with an ongoing clinical trial or a medication on the market related to the manuscript's subject matter within the 36 months before the online publication date. We additionally analyzed each author individually to determine whether their reported disclosures matched PCOIs from the OPD. RESULTS: Of 150 articles analyzed, 101 included authors with PCOIs. Ninety-two of these 101 publications (92%) contained inaccurate (non- or under-) disclosures. Among 135 authors with PCOIs, 118 reported inaccurately (87%). All 14 articles that published clinical trial results (and all 23 of their qualifying authors) had disclosure inaccuracies. CONCLUSION: Inaccurate financial disclosure by authors remains an issue in clinically oriented research studies reported in top rheumatology journals. Improved community education and firmer expectations would permit readers to better assess any possible impact of PCOIs on publications.

Determinants of Achieving Serum Urate Goal with Treat-to-Target Urate-Lowering Therapy in Gout.

OBJECTIVE: Using trial data comparing treat-to-target allopurinol and febuxostat in gout, we examined participant characteristics associated with serum urate (SU) goal achievement. METHODS: Participants with gout and SU ≥6.8 mg/dL were randomized to allopurinol or febuxostat, titrated during weeks 0 to 24, and maintained weeks 25 to 48. Participants were considered to achieve SU goal if the mean SU from weeks 36, 42, and 48 was <6.0 mg/dL or <5 mg/dL if tophi were present. Possible determinants of treatment response were preselected and included sociodemographics, comorbidities, diuretic use, health-related quality of life (HRQoL), body mass index, and gout measures. Determinants of SU response were assessed using multivariable logistic regression with additional analyses to account for treatment adherence. RESULTS: Of 764 study participants completing week 48, 618 (81%) achieved SU goal. After multivariable adjustment, factors associated with a greater likelihood of SU goal achievement included older age (adjusted odds ratio [aOR] 1.40 per 10 years), higher education (aOR 2.02), and better HRQoL (aOR 1.17 per 0.1 unit). Factors associated with a lower odds of SU goal achievement included non-White race (aORs 0.32-0.47), higher baseline SU (aOR 0.83 per 1 mg/dL), presence of tophi (aOR 0.29), and the use of diuretics (aOR 0.52). Comorbidities including chronic kidney disease, hypertension, diabetes, and cardiovascular disease were not associated with SU goal achievement. Results were not meaningfully changed in analyses accounting for adherence. CONCLUSIONS: Several patient-level factors were predictive of SU goal achievement among patients with gout who received treat-to-target urate-lowering therapy (ULT). Approaches that accurately predict individual responses to treat-to-target ULT hold promise in facilitating personalized management and improving outcomes in patients with gout.

Major Adverse Cardiovascular Events After Colchicine Administration Before Percutaneous Coronary Intervention: Follow-Up of the Colchicine-PCI Trial.

Periprocedural inflammation is associated with major adverse cardiovascular events in patients who undergo percutaneous coronary intervention (PCI). In the contemporary era, 5% to 10% of patients develop restenosis, and in the acute coronary syndrome cohort, there remains a 20% major adverse cardiovascular events rate at 3 years, half of which are culprit-lesion related. In patients at risk of restenosis, colchicine has been shown to reduce restenosis when started within 24 hours of PCI and continued for 6 months thereafter, compared with placebo. The Colchicine-PCI trial, which randomized patients to a 1-time loading dose of colchicine or placebo 1 to 2 hours before PCI, showed a dampening of the inflammatory response to PCI but no difference in postprocedural myocardial injury. On mean follow-up of 3.3 years, the incidence of major adverse cardiovascular events did not differ between colchicine and placebo groups (32.5% vs 34.9%; hazard ratio 0.95 [0.68 to 1.34]).

Arthrocentesis and soft tissue aspiration and injection.

Accessing a joint with a needle (arthrocentesis) to extract synovial fluid is a skill intrinsic to the rheumatologist's praxis. Joint aspirations are essential for diagnosing or excluding septic joints, are the gold standard for diagnosing acute crystal arthritis, and can provide valuable information about the nature of other forms of arthritis. In appropriate settings, injecting medications into joints can provide rapid, temporary, or even prolonged relief of pain and swelling and can provide a window of relief until other treatment modalities (anti-inflammatories, immunomodulators, and physical therapy) can enforce durable responses. Soft tissue aspirations (e.g., of bursae) and soft tissue injections (of bursae, tendons, trigger points, and areas of nerve compression) can provide similar relief, earning the practitioner the gratitude of the patient. Here, we provide a primary on joint and soft tissue aspiration and injection, including indications for and against procedures, preparing for procedures, and approaches to specific musculoskeletal structures.

Interleukin-1ß inhibitors for the management of acute gout flares: a systematic literature review.

OBJECTIVES: The objective of this systematic review was to assess the effects of interleukin-1ß (IL-1ß) inhibitors on gout flares. METHODS: Studies published between 2011 and 2022 that evaluated the effects of IL-1ß inhibitors in adult patients experiencing gout flares were eligible for inclusion. Outcomes including pain, frequency and intensity of gout flares, inflammation, and safety were assessed. Five electronic databases (Pubmed/Medline, Embase, Biosis/Ovid, Web of Science and Cochrane Library) were searched. Two independent reviewers performed study screening, data extraction and risk of bias assessments (Cochrane Risk of Bias Tool 2 for randomised controlled trials [RCTs] and Downs and Black for non-RCTs). Data are reported as a narrative synthesis. RESULTS: Fourteen studies (10 RCTs) met the inclusion criteria, with canakinumab, anakinra, and rilonacept being the three included IL-1ß inhibitors. A total of 4367 patients with a history of gout were included from the 14 studies (N = 3446, RCTs; N = 159, retrospective studies [with a history of gout]; N = 762, post hoc analysis [with a history of gout]). In the RCTs, canakinumab and rilonacept were reported to have a better response compared to an active comparator for resolving pain, while anakinra appeared to be not inferior to an active comparator for resolving pain. Furthermore, canakinumab and rilonacept reduced the frequency of gout flares compared to the comparators. All three medications were mostly well-tolerated compared to their comparators. CONCLUSION: IL-1ß inhibitors may be a beneficial and safe medication for patients experiencing gout flares for whom current standard therapies are unsuitable. REVIEW PROTOCOL REGISTRATION: PROSPERO ID: CRD42021267670.

Narrative Review: Peripheral Arterial Disease in Patients with Hyperuricemia and Gout.

PURPOSE OF REVIEW: To discuss what is currently known about the association and potential mechanistic interactions of hyperuricemia and gout with peripheral arterial disease (PAD). RECENT FINDINGS: Gout patients are at increased risk for coronary artery disease, but less is known about their risk for PAD. Studies suggest that the presence of gout and hyperuricemia are associated with PAD independent of known established risk factors. Moreover, higher SU was found to be associated with greater odds of having PAD and was independently associated with decreased absolute claudication distance. Urate's role in free radical formation, platelet aggregation, vascular smooth muscle proliferation, and impaired endothelial vasodilation may promote atherosclerotic progression. Studies suggest that patients with hyperuricemia or gout are at higher risk for developing PAD. Evidence is stronger for the relationship between elevated SU and PAD than for gout and PAD, but more data is needed. Whether elevated SU serves as a marker or cause of PAD remains to be investigated.

Monosodium urate deposition in the lumbosacral spine of patients with gout compared with non-gout controls: A dual-energy CT study.

BACKGROUND: Gout is the most common cause of inflammatory arthritis in adults. Gout predominantly affects the peripheral joints, but an increasing number of published cases report gout affecting the spine. We used dual-energy CT (DECT) to assess the prevalence of monosodium urate (MSU) deposition in the spine of gout patients compared to controls, and to investigate whether gout or spinal MSU deposition is associated with low back pain. METHODS: 25 controls and 50 gout subjects (non-tophaceous and tophaceous) were enrolled. Demographics, gout history, Aberdeen back pain score, serum urate (sU), ESR and CRP were ascertained. Subjects underwent DECT of the lumbosacral spine, which was analyzed using manufacturer's default post-processing algorithm for MSU deposition as well as a maximally-specific algorithm to exclude potential artifact. FINDINGS: 72 subjects were analyzed (25 control, 47 gout). Gout subjects had greater BMI, serum creatinine, sU, CRP, and ESR versus controls. Using the default algorithm, MSU-coded volumes in the lumbosacral spines were significantly higher among the gout subjects vs controls (p = 0.018). 34% of gout subjects vs 4% of controls had spinal MSU-coded deposition (p = 0.0036). Applying the maximally-specific DECT post-processing algorithm, 18% of gout patients vs 0% of controls continued to demonstrate spinal MSU-coded deposition (p = 0.04). Non-tophaceous and tophaceous subjects did not differ in spinal MSU-coded deposition or sU. Gout patients had more back pain than controls. INTERPRETATION: A significant subpopulation of gout patients have spinal MSU-coded lesions. Default and maximally-specific MSU post-processing algorithms yielded different absolute MSU-coded volumes, but similar patterns of results. Gout patients had more back pain than controls. Spinal MSU deposition in gout patients may have implications for clinical picture and treatment.

Lowering and Raising Serum Urate Levels: Off-Label Effects of Commonly Used Medications.

Drug-induced hyperuricemia and gout present an increasingly prevalent problem in clinical practice. Herein, we review the urate-lowering or urate-raising effects of commonly used agents. We performed a PubMed search using the terms gout, urate, and medication, along with the specific agents/classes described herein. Reports were reviewed until 2022, and original studies were considered if they primarily or secondarily reported the effects of 1 or more drugs on serum urate level. Previous reviews were assessed for references to additional studies that described urate-altering effects of medications. Urate-changing drugs are summarized regarding their magnitude of effect, mechanism of action, and clinical significance. Potentially urate-lowering drugs include angiotensin II receptor blockers, calcium channel blockers, high-dose aspirin and salicylates, some nonsalicylate nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, sodium-glucose cotransporter 2 inhibitors, statins, and fenofibrate. Potentially urate-increasing drugs discussed include diuretics, ß-blockers, insulin, pyrazinamide, ethambutol, calcineurin inhibitors, low-dose aspirin, testosterone, and lactate. In patients who have or are at risk for hyperuricemia or gout, an increased awareness of drugs that affect serum urate level may allow for prescribing that effectively treats the indicated problem while minimizing adverse effects on hyperuricemia and gout.

Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management.

BACKGROUND: The relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues. METHODS: Participants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events. RESULTS: This study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P<0.001 for noninferiority). Overall, 80% of participants achieved mean target urates during phase 2 with no differences by treatment. There were no treatment differences (including cardiovascular events) in serious adverse events. CONCLUSIONS: Allopurinol and febuxostat achieved serum urate goals in patients with gout; allopurinol was noninferior to febuxostat in controlling flares. Similar outcomes were noted in participants with stage 3 chronic kidney disease. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; ClinicalTrials.gov identifier, NCT02579096.).

An NHC-Mediated Metal-Free Approach towards an NHC-Coordinated Endocyclic Disilene.

A convenient metal-free approach towards an N-heterocyclic carbene (NHC)-coordinated disilene 2 is described. Compound 2, featuring the disilene incorporated in cyclopolysilane framework, was obtained in good yield and characterized using NMR spectroscopy and X-ray crystallography. Density functional theory (DFT) calculations of the reaction mechanism provide a rationale for the observed reactivity and give detailed information on the bonding situation of the base-stabilized disilene. Compound 2 undergoes thermal or light- induced (λ=456 nm) NHC loss, and a dimerization process to give a corresponding dimer with a Si10 skeleton. In order to shed light on the dimerization mechanism, DFT calculations were performed. Moreover, the reactivity of 2 was examined with selected examples of transition metal carbonyl compounds.

Chasing the storm: Recruiting non-hospitalized patients for a multi-site randomized controlled trial in the United States during the COVID-19 pandemic.

Randomized controlled trials (RCTs) remain the gold standard to evaluate clinical interventions, producing the highest level of evidence while minimizing potential bias. Inadequate recruitment is a commonly encountered problem that undermines the completion and generalizability of RCTs-and is even more challenging when enrolling amidst a pandemic. Here, we reflect on our experiences with virtual recruitment of non-hospitalized patients in the United States for ColCorona, an international, multicenter, randomized, placebo-controlled coronavirus disease 2019 (COVID-19) drug trial. Recruitment challenges during a pandemic include constraints created by shelter-in-place policies and targeting enrollment according to national and local fluctuations in infection rate. Presenting a study to potential participants who are sick with COVID-19 and may be frightened, overwhelmed, or mistrusting of clinical research remains a challenge. Strategies previously reported to improve recruitment include transparency, patient and site education, financial incentives, and person-to-person outreach. Active measures taken during ColCorona to optimize United States recruitment involved rapid expansion of sites, adjustment of recruitment scripts, assessing telephone calls versus text messages for initial contact with participants, institutional review board-approved financial compensation, creating an infrastructure to systematically identify potentially eligible patients, partnering with testing sites, appealing to both self-interest and altruism, and large-scale media efforts with varying degrees of success.

Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease.

Over the last decade, evidence has demonstrated that long-term, low-dose colchicine (0.5 mg daily) is effective for preventing gout flare and cardiovascular (CV) events in a wide range of patients. Given the potentially expanding use of colchicine in CV disease, we here review and update the biologic effects and safety of colchicine based on recent data gathered from bench and pharmacodynamic studies, clinical reports, controlled clinical trials, and meta-analyses, integrated with important studies over the last 50 years, to offer a consensus perspective by experts from multiple specialties familiar with colchicine's long-term use. We conclude that the clinical benefits of colchicine in gout and CV disease achieved at low dose do not sustain serum levels above the upper limit of safety when used in patients without advanced renal or liver disease or when used concomitantly with most medications. Further, data accrued over the last 50 years strongly suggest that the biologic effects of long-term colchicine do not increase the risk of cancer, sepsis, cytopenia, or myotoxicity.

Mentoring Underrepresented Minority Physician-Scientists to Success.

As the nation seeks to recruit and retain physician-scientists, gaps remain in understanding and addressing mitigatable challenges to the success of faculty from underrepresented minority (URM) backgrounds. The Doris Duke Charitable Foundation Fund to Retain Clinical Scientists program, implemented in 2015 at 10 academic medical centers in the United States, seeks to retain physician-scientists at risk of leaving science because of periods of extraordinary family caregiving needs, hardships that URM faculty-especially those who identify as female-are more likely to experience. At the annual Fund to Retain Clinical Scientists program directors conference in 2018, program directors-21% of whom identify as URM individuals and 13% as male-addressed issues that affect URM physician-scientists in particular. Key issues that threaten the retention of URM physician-scientists were identified through focused literature reviews; institutional environmental scans; and structured small- and large-group discussions with program directors, staff, and participants. These issues include bias and discrimination, personal wealth differential, the minority tax (i.e., service burdens placed on URM faculty who represent URM perspectives on committees and at conferences), lack of mentorship training, intersectionality and isolation, concerns about confirming stereotypes, and institutional-level factors. The authors present recommendations for how to create an environment in which URM physician-scientists can expect equitable opportunities to thrive, as institutions demonstrate proactive allyship and remove structural barriers to success. Recommendations include providing universal training to reduce interpersonal bias and discrimination, addressing the consequences of the personal wealth gap through financial counseling and benefits, measuring the service faculty members provide to the institution as advocates for URM faculty issues and compensating them appropriately, supporting URM faculty who wish to engage in national leadership programs, and sustaining institutional policies that address structural and interpersonal barriers to inclusive excellence.