Evaluating Factors Associated With Telehealth Appropriateness in Outpatient Rheumatoid Arthritis Encounters Using the Encounter Appropriateness Score for You (EASY).

OBJECTIVE: Telehealth has been proposed as a safe and effective alternative to in-person care for rheumatoid arthritis (RA). The purpose of this study was to evaluate factors associated with telehealth appropriateness in outpatient RA encounters. METHODS: A prospective cohort study (January 1, 2021, to August 31, 2021) was conducted using electronic health record data from outpatient RA encounters in a single academic rheumatology practice. Rheumatology providers rated the telehealth appropriateness of their own encounters using the Encounter Appropriateness Score for You (EASY) immediately following each encounter. Robust Poisson regression with generalized estimating equations modeling was used to evaluate the association of telehealth appropriateness with patient demographics, RA clinical characteristics, comorbid noninflammatory causes of joint pain, previous and current encounter characteristics, and provider characteristics. RESULTS: During the study period, 1823 outpatient encounters with 1177 unique patients with RA received an EASY score from 25 rheumatology providers. In the final multivariate model, factors associated with increased telehealth appropriateness included higher average provider preference for telehealth in prior encounters (relative risk [RR] 1.26, 95% CI 1.21-1.31), telehealth as the current encounter modality (RR 2.27, 95% CI 1.95-2.64), and increased patient age (RR 1.05, 95% CI 1.01-1.09). Factors associated with decreased telehealth appropriateness included moderate (RR 0.81, 95% CI 0.68-0.96) and high (RR 0.57, 95% CI 0.46-0.70) RA disease activity and if the previous encounters were conducted by telehealth (RR 0.83, 95% CI 0.73-0.95). CONCLUSION: In this study, telehealth appropriateness was most associated with provider preference, the current and previous encounter modality, and RA disease activity. Other factors like patient demographics, RA medications, and comorbid noninflammatory causes of joint pain were not associated with telehealth appropriateness.

Evaluating Provider Perceptions of Telehealth Utility in Outpatient Rheumatology Telehealth Encounters.

OBJECTIVE: This study aims to explore the factors associated with rheumatology providers' perceptions of telehealth utility in real-world telehealth encounters. METHODS: From September 14, 2020 to January 31, 2021, 6 providers at an academic medical center rated their telehealth visits according to perceived utility in making treatment decisions using the following Telehealth Utility Score (TUS) (1 = very low utility to 5 = very high utility). Modified Poisson regression models were used to assess the association between TUS scores and encounter diagnoses, disease activity measures, and immunomodulatory therapy changes during the encounter. RESULTS: A total of 481 telehealth encounters were examined, of which 191 (39.7%) were rated as "low telehealth utility" (TUS 1-3) and 290 (60.3%) were rated as "high telehealth utility" (TUS 4-5). Encounters with a diagnosis of inflammatory arthritis were significantly less likely to be rated as high telehealth utility (adjusted relative risk [aRR], 0.8061; p = 0.004), especially in those with a concurrent noninflammatory musculoskeletal diagnosis (aRR, 0.54; p = 0.006). Other factors significantly associated with low telehealth utility included higher disease activity according to current and prior RAPID3 scores (aRR, 0.87 and aRR, 0.89, respectively; p < 0.001) and provider global scores (aRR, 0.83; p < 0.001), as well as an increase in immunomodulatory therapy (aRR, 0.70; p = 0.015). CONCLUSIONS: Provider perceptions of telehealth utility in real-world encounters are significantly associated with patient diagnoses, current and prior disease activity, and the need for changes in immunomodulatory therapy. These findings inform efforts to optimize the appropriate utilization of telehealth in rheumatology.

Trends in Oral Anticoagulant Use Among 436 864 Patients With Atrial Fibrillation in Community Practice, 2011 to 2020.

Background Among patients with nonvalvular atrial fibrillation (AF) and an elevated stroke risk, guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention. Changes in DOAC use over the past decade have not been well described. Methods and Results We evaluated trends in use of DOACs and warfarin from 2011 to 2020 among adults with AF and a CHA2DS2-VASc score ≥2 based on electronic health record data from 88 health systems in the United States contributing to Cerner Real World Data. The use of DOACs and warfarin was described over time, by age, sex, race, and ethnicity, and at the health-system level. We identified 436 864 patients with AF at risk for stroke (median age, 78 years; 52.1% men). From 2011 to 2020, overall anticoagulation rates increased from 56.3% to 64.7%, as DOAC use increased steadily (from 4.7% to 47.9%), while warfarin use declined (from 52.4% to 17.7%). DOAC uptake was similar across age, sex, and race and ethnicity groups but varied by health system. In 2020, the median health-system-level proportion of patients with AF on a DOAC was 49% (interquartile range, 40%-54%). Conclusions Over the past decade, anticoagulation rates for patients with AF have increased modestly as DOACs largely replaced warfarin, though significant gaps remain: One in 3 high-risk patients with AF is not on any anticoagulant. While DOAC adoption was generally consistent across major demographic groups, use between health systems remained highly variable, suggesting that provider and system factors influence DOAC uptake use more than patient-level factors.

Telehealth Made EASY: Understanding Provider Perceptions of Telehealth Appropriateness in Outpatient Rheumatology Encounters.

OBJECTIVE: The purpose of this study was to evaluate a novel scoring system, the Encounter Appropriateness Score for You (EASY), to assess provider perceptions of telehealth appropriateness in rheumatology encounters. METHODS: The EASY scoring system prompts providers to rate their own encounters as follows: in-person or telehealth acceptable, EASY = 1; in-person preferred, EASY = 2; or telehealth preferred, EASY = 3. Assessment of the EASY scoring system occurred at a single academic institution from January 1, 2021, to August 31, 2021. Data were collected in three rounds: 1) initial survey (31 providers) assessing EASY responsiveness to five hypothetical scenarios, 2) follow-up survey (34 providers) exploring EASY responsiveness to 11 scenario modifications, and 3) assessment of EASYs documented in clinic care. RESULTS: The initial and follow-up surveys demonstrated responsiveness of EASYs to different clinical and nonclinical factors. For instance, less than 20% of providers accepted telehealth when starting a biologic for active rheumatoid arthritis, although more than 35% accepted telehealth in the same scenario if the patient lived far away or was well known to the provider. Regarding EASY documentation, 27 providers provided EASYs for 12,381 encounters. According to these scores, telehealth was acceptable or preferred for 29.7% of all encounters, including 21.4% of in-person encounters. Conversely, 24.4% of telehealth encounters were scored as in-person preferred. CONCLUSION: EASY is simple, understandable, and responsive to changes in the clinical scenario. We have successfully accumulated 12,381 EASYs that can be studied in future work to better understand telehealth utility and optimize telehealth triage.

Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant. Plasma collected at enrollment was analyzed using aptamer-based proteomics (1305 proteins). Over a median follow-up of 30.4 months, there were 76 respiratory deaths and 26 lung transplants. In unadjusted univariable analyses, 61 proteins were significantly associated with the outcome (hazard ratio > 2 or < 0.5, corrected p ≤ 0.05). In multivariable analyses, a set of 4 clinical measures and 47 unique proteins predicted the probability of respiratory death or lung transplant with an optimism-corrected C-index of 0.76. Our results suggest that select circulating proteins strongly associate with the risk of mortality in patients with IPF and confer information independent of clinical measures.

The incremental value of angiographic features for predicting recurrent cardiovascular events: Insights from the Duke Databank for Cardiovascular Disease.

BACKGROUND AND AIMS: Identifying patient subgroups with cardiovascular disease (CVD) at highest risk for recurrent events remains challenging. Angiographic features may provide incremental value in risk prediction beyond clinical characteristics. METHODS: We included all cardiac catheterization patients from the Duke Databank for Cardiovascular Disease with significant coronary artery disease (CAD; 07/01/2007-12/31/2012) and an outpatient follow-up visit with a primary care physician or cardiologist in the same health system within 3 months post-catheterization. Follow-up occurred for 3 years for the primary major adverse cardiovascular event endpoint (time to all-cause death, myocardial infarction [MI], or stroke). A multivariable model to predict recurrent events was developed based on clinical variables only, then adding angiographic variables from the catheterization. Next, we compared discrimination of clinical vs. clinical plus angiographic risk prediction models. RESULTS: Among 3366 patients with angiographically-defined CAD, 633 (19.2%) experienced cardiovascular events (death, MI, or stroke) within 3 years. A multivariable model including 18 baseline clinical factors and initial revascularization had modest ability to predict future atherosclerotic cardiovascular disease events (c-statistic = 0.716). Among angiographic predictors, number of diseased vessels, left main stenosis, left anterior descending stenosis, and the Duke CAD Index had the highest value for secondary risk prediction; however, the clinical plus angiographic model only slightly improved discrimination (c-statistic = 0.724; delta 0.008). The net benefit for angiographic features was also small, with a relative integrated discrimination improvement of 0.05 (95% confidence interval: 0.03-0.08). CONCLUSIONS: The inclusion of coronary angiographic features added little incremental value in secondary risk prediction beyond clinical characteristics.

Impact of the COVID-19 pandemic on patterns of outpatient cardiovascular care.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic brought about abrupt changes in the way health care is delivered, and the impact of transitioning outpatient clinic visits to telehealth visits on processes of care and outcomes is unclear. METHODS: We evaluated ordering patterns during cardiovascular telehealth clinic visits in the Duke University Health System between March 15 and June 30, 2020 and 30-day outcomes compared with in-person visits in the same time frame in 2020 and in 2019. RESULTS: Within the Duke University Health System, there was a 33.1% decrease in the number of outpatient cardiovascular visits conducted in the first 15 weeks of the COVID-19 pandemic, compared with the same time period in 2019. As a proportion of total visits initially booked, 53% of visits were cancelled in 2020 compared to 35% in 2019. However, patients with cancelled visits had similar demographics and comorbidities in 2019 and 2020. Telehealth visits comprised 9.3% of total visits initially booked in 2020, with younger and healthier patients utilizing telehealth compared with those utilizing in-person visits. Compared with in-person visits in 2020, telehealth visits were associated with fewer new (31.6% for telehealth vs 44.6% for in person) or refill (12.9% vs 15.6%, respectively) medication prescriptions, electrocardiograms (4.3% vs 31.4%), laboratory orders (5.9% vs 21.8%), echocardiograms (7.3% vs 98%), and stress tests (4.4% vs 6.6%). When adjusted for age, race, and insurance status, those who had a telehealth visit or cancelled their visit were less likely to have an emergency department or hospital encounter within 30 days compared with those who had in-person visits (adjusted rate ratios (aRR) 0.76 [95% 0.65, 0.89] and aRR 0.71 [95% 0.65, 0.78], respectively). CONCLUSIONS: In response to the perceived risks of routine medical care affected by the COVID-19 pandemic, different phenotypes of patients chose different types of outpatient cardiology care. A better understanding of these differences could help define necessary and appropriate mode of care for cardiology patients.

Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort.

BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play important roles in the turnover of extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study aimed to determine the utility of circulating MMPs and TIMPs in distinguishing patients with IPF from controls and to explore associations between MMPs/TIMPs and measures of disease severity in patients with IPF. METHODS: The IPF cohort (n = 300) came from the IPF-PRO Registry, an observational multicenter registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Controls (n = 100) without known lung disease came from a population-based registry. Generalized linear models were used to compare circulating concentrations of MMPs 1, 2, 3, 7, 8, 9, 12, and 13 and TIMPs 1, 2, and 4 between patients with IPF and controls, and to investigate associations between circulating levels of these proteins and measures of IPF severity. Multivariable models were fit to identify the MMP/TIMPs that best distinguished patients with IPF from controls. RESULTS: All the MMP/TIMPs analyzed were present at significantly higher levels in patients with IPF compared with controls except for TIMP2. Multivariable analyses selected MMP8, MMP9 and TIMP1 as top candidates for distinguishing patients with IPF from controls. Higher concentrations of MMP7, MMP12, MMP13 and TIMP4 were significantly associated with lower diffusion capacity of the lung for carbon monoxide (DLCO) % predicted and higher composite physiologic index (worse disease). MMP9 was associated with the composite physiologic index. No MMP/TIMPs were associated with forced vital capacity % predicted. CONCLUSIONS: Circulating MMPs and TIMPs were broadly elevated among patients with IPF. Select MMP/TIMPs strongly associated with measures of disease severity. Our results identify potential MMP/TIMP targets for further development as disease-related biomarkers.

Peripheral blood proteomic profiling of idiopathic pulmonary fibrosis biomarkers in the multicentre IPF-PRO Registry.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease for which diagnosis and management remain challenging. Defining the circulating proteome in IPF may identify targets for biomarker development. We sought to quantify the circulating proteome in IPF, determine differential protein expression between subjects with IPF and controls, and examine relationships between protein expression and markers of disease severity. METHODS: This study involved 300 patients with IPF from the IPF-PRO Registry and 100 participants without known lung disease. Plasma collected at enrolment was analysed using aptamer-based proteomics (1305 proteins). Linear regression was used to determine differential protein expression between participants with IPF and controls and associations between protein expression and disease severity measures (percent predicted values for forced vital capacity [FVC] and diffusion capacity of the lung for carbon monoxide [DLco]; composite physiologic index [CPI]). Multivariable models were fit to select proteins that best distinguished IPF from controls. RESULTS: Five hundred fifty one proteins had significantly different levels between IPF and controls, of which 47 showed a |log2(fold-change)| > 0.585 (i.e. > 1.5-fold difference). Among the proteins with the greatest difference in levels in patients with IPF versus controls were the glycoproteins thrombospondin 1 and von Willebrand factor and immune-related proteins C-C motif chemokine ligand 17 and bactericidal permeability-increasing protein. Multivariable classification modelling identified nine proteins that, when considered together, distinguished IPF versus control status with high accuracy (area under receiver operating curve = 0.99). Among participants with IPF, 14 proteins were significantly associated with FVC % predicted, 23 with DLco % predicted, 14 with CPI. Four proteins (roundabout homolog-2, spondin-1, polymeric immunoglobulin receptor, intercellular adhesion molecule 5) demonstrated the expected relationship across all three disease severity measures. When considered in pathways analyses, proteins associated with the presence or severity of IPF were enriched in pathways involved in platelet and haemostatic responses, vascular or platelet derived growth factor signalling, immune activation, and extracellular matrix organisation. CONCLUSIONS: Patients with IPF have a distinct circulating proteome and can be distinguished using a nine-protein profile. Several proteins strongly associate with disease severity. The proteins identified may represent biomarker candidates and implicate pathways for further investigation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01915511).

The relationship between baseline and follow-up left ventricular ejection fraction with adverse events among primary prevention ICD patients.

BACKGROUND: Left ventricular ejection fraction (LVEF) is used to select patients for primary prevention implantable cardioverter defibrillators (ICDs). The relationship between baseline and long-term follow-up LVEF and clinical outcomes among primary prevention ICD patients remains unclear. METHODS: We studied 195 patients with a baseline LVEF ≤35% ≤6 months prior to ICD implantation and follow-up LVEF 1-3 years after ICD implantation without intervening left ventricular assist device (LVAD) or transplant. The co-primary study endpoints were: (1) a composite of time to death, LVAD, or transplant and (2) appropriate ICD therapy. We examined multivariable Cox proportional hazard models with a 3-year post-implant landmark view; the LVEF closest to the 3-year mark was considered the follow-up LVEF for analyses. Follow-up LVEF was examined using 2 definitions: (1) ≥10% improvement compared to baseline or (2) actual value of ≥40%. RESULTS: Fifty patients (26%) had a LVEF improvement of ≥10% and 44 (23%) had a follow-up LVEF ≥40%. Neither baseline nor follow-up LVEF was significantly associated with the composite endpoint. In contrast, both baseline and follow-up LVEF were associated with risk for long-term ICD therapies, whether follow-up LVEF was modeled as a ≥10% absolute improvement (baseline LVEF HR 0.87, CI 0.91-0.93, P < .001; follow-up LVEF HR 0.18, CI 0.06-0.53, P = .002) or a ≥40% follow-up value (baseline LVEF HR 0.89, CI 0.83-0.96, P = .001, follow-up LVEF HR 0.26, CI 0.08-0.87, P = .03). CONCLUSIONS: Among primary prevention ICD recipients, both baseline and follow-up LVEF were independently associated with long-term risk for appropriate ICD therapy, but they were not associated with time to the composite of LVAD, transplant, or death.

Morbidity and Mortality Conference for Percutaneous Coronary Intervention.

BACKGROUND: Morbidity and mortality conference is a common educational and quality improvement activity performed in cardiac catheterization laboratories, but best practices for case selection and for maximizing the effectiveness of peer review have not been determined. METHODS AND RESULTS: We reviewed the 10-year percutaneous coronary intervention morbidity and mortality conference experience of an academic medical center. Cases were triggered for review by the occurrence of prespecified procedural events. Summary reports from morbidity and mortality conference discussions were linked to clinical data from the Duke Databank for Cardiovascular Disease to compare baseline and procedural characteristics and to assess postdischarge outcomes. Of 11 786 procedures, from 2004 to 2013, 157 (1.3%) were triggered for review. The most frequent triggering events were cardioversion/defibrillation (72, 0.6%), unplanned use of mechanical circulatory support (64, 0.5%), and major dissection (41, 0.3%). Selected procedures were more likely to include high-risk features, such as ST-segment-elevation myocardial infarction, cardiogenic shock, and multivessel disease, and were associated with higher mortality at 30 days. Only a minority of triggering events were caused by controversial or unacceptable physician behavior. CONCLUSIONS: This 10-year experience outlines the processes for conduct of an effective percutaneous coronary intervention morbidity and mortality conference, including a novel approach to case selection and structured peer review leading to actionable quality interventions. The prespecified clinical triggers, captured in the natural workflow by laboratory staff, identified complex cases that were associated with poor patient outcomes.

Temperature-dependent effects of cadmium and purine nucleotides on mitochondrial aconitase from a marine ectotherm, Crassostrea virginica: a role of temperature in oxidative stress and allosteric enzyme regulation.

Temperature and heavy metals such as cadmium (Cd) are important environmental stressors that can strongly affect mitochondrial function of marine poikilotherms. In this study, we investigated the combined effects of temperature (20 degrees C and 30 degrees C) and Cd stress on production of reactive oxygen species (ROS) and oxidative stress in a marine poikilotherm Crassostrea virginica (the eastern oyster) using mitochondrial aconitase as a sensitive biomarker of oxidative damage. We also assessed potential involvement of mitochondrial uncoupling proteins (UCPs) in antioxidant protection in oyster mitochondria using purine nucleotides (GDP, ATP and ADP) as specific inhibitors, and free fatty acids as stimulators, of UCPs. Our results show that exposure to Cd results in elevated ROS production and oxidative damage as indicated by aconitase inactivation which is particularly pronounced at elevated temperature. Unexpectedly, oyster mitochondrial aconitase was inhibited by physiologically relevant levels of ATP (IC(50)=1.93 and 3.04 mmol l(-1) at 20 degrees C and 30 degrees C, respectively), suggesting that allosteric regulation of aconitase by this nucleotide may be involved in regulation of the tricarboxylic acid flux in oysters. Aconitase was less sensitive to ATP inhibition at 30 degrees C than at 20 degrees C, consistent with the elevated metabolic flux at higher temperatures. ADP and GDP also inhibited mitochondrial aconitase but at the levels well above the physiological concentrations of these nucleotides (6-11 mmol l(-1)). Our study shows expression of at least three UCP isoforms in C. virginica gill tissues but provides no indication that UCPs protect mitochondrial aconitase from oxidative inactivation in oysters. Overall, the results of this study indicate that temperature stress exaggerates toxicity of Cd leading to elevated oxidative stress in mitochondria, which may have important implications for survival of poikilotherms in polluted environments during seasonal warming and/or global climate change, and suggest a novel temperature-dependent mechanism of allosteric regulation of TCA flux in oyster mitochondria.