Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. Interventions: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). Main Outcomes and Measures: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. Results: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. Conclusions and Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.

COVID-19 in a rural health system in New York - case series and an approach to management.

INTRODUCTION: Many rural hospitals and health systems in the USA lack sufficient resources to treat COVID-19. St Lawrence Health (SLH) developed a system for managing inpatient COVID-19 hospital admissions in St Lawrence County, an underserved rural county that is the largest county in New York State. METHODS: SLH used a hub-and-spoke system to route COVID-19 patients to its flagship hospital. It further assembled a small clinical team to manage admitted COVID-19 patients and to stay abreast of a quickly changing body of literature and standard of care. A review of clinical data was completed for patients who were treated by SLH's inpatient COVID-19 treatment team between 20 March and 22 May 2020. RESULTS: Twenty COVID-19 patients were identified. Sixteen patients (80%) met National Institutes of Health criteria for severe or critical disease. One patient died. No patients were transferred to other hospitals. CONCLUSION: During the first 2 months of the pandemic, the authors were able to manage hospitalized COVID-19 patients in their rural community. Development of similar treatment models in other rural areas should be considered.

Developing patient-centered outcomes research infrastructure in a rural community through patient and stakeholder engagement and education during the COVID-19 pandemic.

In addition to facing numerous healthcare disparities, rural America is chronically underrepresented in clinical research. This gap was made more evident during the COVID-19 pandemic. St Lawrence Health, located in rural Upstate New York, established its Clinical and Rural Health Research Department in 2015 to help close this gap. The research department then launched the DISRUPTS (Developing InfraStructure for Research to Utilize Patient-centered Techniques at St Lawrence Health System) program to build the infrastructure to conduct Patient-Centered Outcomes Research (PCOR). Together with a diverse committee, the team used proven methods and frameworks to develop a model for engagement, content creation, and education delivery that was successfully used to create educational programs on PCOR and COVID-19. The resulting DISRUPTS webinars had a combined total of over 450 live attendees and over 1,110 views on recordings. Furthermore, nearly one-third of those who participated in the COVID-19 vaccines webinar indicated they were more likely to receive a COVID-19 vaccine after taking part. DISRUPTS can serve as an important model for other rural communities that aim to increase access to and engagement in PCOR, and which hope to improve outreach and education efforts in their communities.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19. Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality. Results: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41- 0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo). Conclusions: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality. Trial registration: ClinicalTrials.gov ( NCT04593940 ).

Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care. Methods: We conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality. Results: A total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99-1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05-1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39-0.90). No differences in risk of serious adverse events including secondary infections. Conclusions: Infliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28- day mortality compared with standard of care. Trial registration: ClinicalTrials.gov ( NCT04593940 ).

Prevalence of Common Comorbidities in Rheumatoid Arthritis in Rural New York Compared With National Data.

Background Rheumatoid arthritis (RA) is a systemic autoimmune disease with multiple known comorbidities and risk factors. The rate and severity of different comorbidities among RA patients are influenced by various demographic, behavioral, and socioeconomic factors, which can vary widely between urban and rural areas. However, limited information is currently available regarding the association of comorbidities with RA in rural settings. In this study, we investigated the prevalence of common comorbidities and risk factors of RA among RA patients from a rural hospital located in rural northern New York and compared them against national patient records obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS). Methodology We compared de-identified patient records of 153 RA patients obtained from St. Lawrence Health (SLH) to 198 RA patients from the NHAMCS. After performing the descriptive analyses and removing outliers, two-sample tests of proportions were used for comparing the binary categories of sex, age, obesity, hypertension, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF) between the two datasets. These analyses were applied to both weighted and unweighted sets of national data, and a p-value of <0.05 was considered statistically significant. The differences were then explored at a greater resolution by binning body mass index, blood pressure (BP), COPD prevalence, and tobacco usage data across different age groups. Results A significantly higher rate of diastolic hypertension (χ2 = 17.942, w = 0.232, p < 0.001) and over two times higher prevalence of COPD (χ2 = 7.635, w = 0.147, p = 0.006) were observed among RA patients in the rural group. The rates of CHF were significantly different only when sample weighting was applied. When categorized by age groups, diastolic BP showed a peak at 40-49 years, coinciding with the age group for high tobacco smoking and peak disease activity in rural RA patients. Conclusions A higher prevalence of comorbidities of RA such as hypertension (diastolic) and COPD are observed in patients from northern rural New York compared to the national average. Our findings indicate that rural RA patients might have a distinct comorbidity burden, suggesting the need for larger-scale studies.

A bedside ultrasound sign of cardiac disease: the left atrium-to-aorta diastolic diameter ratio.

PURPOSE: This study evaluated a simple ultrasound method to detect left atrial (LA) enlargement by comparing the diameters of the LA and aortic root. PROCEDURES: The LA and aortic diameters, the LA volume index (LAVI), and significant echo findings were analyzed in 101 consecutive echocardiograms. Mean LAVI and the prevalence of an abnormal echo were compared between groups in which the ratio of the LA diameter to aortic diameter in diastole was >1 vs < or = 1. FINDINGS: Left atrial-to-aortic diameter ratio increased with LAVI (r = 0.64, P < .001). Left atrial-to-aortic diameter ratio >1 vs < or = 1 was noted in 45% vs 55% of patients and had a mean (+ or - SD) LAVI = 39 + or - 12 vs 27 + or - 7 mL/m(2) (P < .001) and a 78% vs 43% prevalence of an abnormal echo (P < .001). CONCLUSION: The left atrium-to-aorta diastolic diameter ratio can detect LA enlargement and may be useful as a quick bedside technique to screen for cardiac disease.

Lipid-associated rheumatologic syndromes.

Rheumatologic manifestations of hyperlipidemia and lipid-associated arthritis are rarely seen in the rheumatologist's office. On the other hand, a rheumatologist may be the clinician who identifies and initiates proper therapy for disorders related to hyperlipidemia when the musculoskeletal manifestations of these syndromes are recognized. In this article both the joint and tendon manifestations are reviewed, including the lesser known lipid liquid crystal form of arthritis. The relationship between gout and hyperuricemia is briefly discussed, as are the autoimmune manifestations of lipid-lowering therapy.

A perspective on diet and gout.

The epidemiology of gout has changed dramatically over the past century. Once thought of as a disease of the nobility, it is now an egalitarian disease that affects patients across the socioeconomic spectrum. The incidence of gout has also risen in recent years, to the point that we are now seeing what is regarded by some as a "second epidemic" of gout. This change coincides with a significant dietary shift for many Americans - in particular, the advent of high-fructose corn syrup as the most prominent sweetener in the modern American diet and what may be a related rise in obesity. Fructose is a powerful driver of ATP catabolism that, in turn, leads to the production of uric acid. The new epidemic of gout is likely secondary in significant part to the rise in fructose consumption, as well as to the increase in obesity, the endurance of other dietary and non-dietary gout risk factors such as consumption of meat and alcohol, the continued use of culprit medications and potentially to the under-recognition of the benefits of certain foods and drinks (such as dairy products and coffee). Though the exact reasons for the rise in gout are yet unproven, this reopens the opportunity for dietary control of hyperuricemia through restraints that curtail not only exogenous but also endogenous pathways of purine production.