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Objective To determine whether electronic health record (EHR) data components could be identified and used to assess bone health quality indicators in patients with systemic lupus erythematosus as a foundation for population health management. Methods We identified patients in our EHR system who had diagnosis codes for lupus from 2012 to 2017 and characterized them based on the frequency and dosage of prescribed glucocorticoid medications. The medical records of patients who received repeated high-dose glucocorticoid orders were further reviewed for osteoporosis, osteoporotic fractures, receipt of appropriate preventive screening, and orders for protective medications based on established quality indicators. Descriptive statistics were calculated to summarize results. Results We identified 617 patients with a lupus diagnosis; 414 received glucocorticoid prescriptions, 189 received chronic, high-dose; and 83 received chronic, low-dose prescription orders. Of those with chronic high-dose glucocorticoid prescriptions, 14% had an osteoporosis diagnosis, 3% had an osteoporotic fracture, 51% received a prescription for calcium/vitamin D, 43% had bone mineral density screening orders, 20% received a spine radiograph order, 29% had a documented T-score, 12% received a prescription for osteoporosis medication, and 6% had a documented osteoporosis screening. We were able to identify data elements in the EHR for all nine components of the osteoporosis management quality indicator. Conclusions It is possible to identify data in the EHR for all attributes of the quality indicator for osteoporosis in lupus patients who receive chronic high-dose glucocorticoids. However, missing data and need to extract data from text-based notes may make development of population management tools challenging.

Rationale: Current guidelines recommend patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia receive empirical antibiotics for suspected bacterial superinfection on the basis of weak evidence. Rates of ventilator-associated pneumonia (VAP) in clinical trials of patients with SARS-CoV-2 pneumonia are unexpectedly low. Objectives: We conducted an observational single-center study to determine the prevalence and etiology of bacterial superinfection at the time of initial intubation and the incidence and etiology of subsequent bacterial VAP in patients with severe SARS-CoV-2 pneumonia. Methods: Bronchoscopic BAL fluid samples from all patients with SARS-CoV-2 pneumonia requiring mechanical ventilation were analyzed using quantitative cultures and a multiplex PCR panel. Actual antibiotic use was compared with guideline-recommended therapy. Measurements and Main Results: We analyzed 386 BAL samples from 179 patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. Bacterial superinfection within 48 hours of intubation was detected in 21% of patients. Seventy-two patients (44.4%) developed at least one VAP episode (VAP incidence rate = 45.2/1,000 ventilator days); 15 (20.8%) initial VAPs were caused by difficult-to-treat pathogens. The clinical criteria did not distinguish between patients with or without bacterial superinfection. BAL-based management was associated with significantly reduced antibiotic use compared with guideline recommendations. Conclusions: In patients with SARS-CoV-2 pneumonia requiring mechanical ventilation, bacterial superinfection at the time of intubation occurs in

BackgroundPatients with severe SARS-CoV-2 pneumonia experience longer durations of critical illness yet similar mortality rates compared to patients with severe pneumonia secondary to other etiologies. As secondary bacterial infection is common in SARS-CoV-2 pneumonia, we hypothesized that unresolving ventilator-associated pneumonia (VAP) drives the apparent disconnect between length-of-stay and mortality rate among these patients.MethodsWe analyzed VAP in a prospective single-center observational study of 585 mechanically ventilated patients with suspected pneumonia, including 190 patients with severe SARS-CoV-2 pneumonia. We developed CarpeDiem, a novel machine learning approach based on the practice of daily ICU team rounds to identify clinical states for each of the 12,495 ICU patient-days in the cohort. We used the CarpeDiem approach to evaluate the effect of VAP and its resolution on clinical trajectories.FindingsPatients underwent a median [IQR] of 4 [2,7] transitions between 14 clinical states during their ICU stays. Clinical states were associated with differential hospital mortality. The long length-of-stay among patients with severe SARS-CoV-2 pneumonia was associated with prolonged stays in clinical states defined by severe respiratory failure and with a lower frequency of transitions between clinical states. In all patients, including those with COVID-19, unresolving VAP episodes were associated with transitions to unfavorable states and hospital mortality.InterpretationCarpeDiem offers a machine learning approach to examine the effect of VAP on clinical outcomes. Our findings suggest an underappreciated contribution of unresolving secondary bacterial pneumonia to outcomes in mechanically ventilated patients with pneumonia, including due to SARS-CoV-2.Abstract FigureGraphical abstractDisentangling the contributions of ICU complications and interventions to ICU outcomes. (A) Traditional approaches evaluate the ICU stay as a black box with severity of illness measured on presentation and dichotomized survival at an arbitrary time point (e.g., day 28) or on ICU or hospital discharge. Hence, the effect of intercurrent complications and interventions cannot be easily measured, a problem that is compounded when ICU stays are long or significantly differ between groups. (B) Defining the ICU course by clinical features during each day in the ICU permits the association of a complication or intervention with transitions toward clinical states associated with favorable or unfavorable outcomes.

Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia2. Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation. Analysis of bronchoalveolar lavage fluid samples from patients with SARS-CoV-2-induced respiratory failure suggests that SARS-CoV-2 infects alveolar macrophages to cause release of T cell chemoattractants, thereby inducing local inflammatory cytokine release and further T cell activation, ultimately resulting in a positive feedback loop that drives alveolar inflammation.

BackgroundSevere community-acquired pneumonia secondary to SARS-CoV-2 is a leading cause of death. Current guidelines recommend patients with SARS-CoV-2 pneumonia receive empirical antibiotic therapy for suspected bacterial superinfection, but little evidence supports these recommendations.MethodsWe obtained bronchoscopic bronchoalveolar lavage (BAL) samples from patients with SARS-CoV-2 pneumonia requiring mechanical ventilation. We analyzed BAL samples with multiplex PCR and quantitative culture to determine the prevalence of superinfecting pathogens at the time of intubation and identify episodes of ventilator-associated pneumonia (VAP) over the course of mechanical ventilation. We compared antibiotic use with guideline-recommended care.ResultsThe 179 ventilated patients with severe SARS-CoV-2 pneumonia discharged from our hospital by June 30, 2020 were analyzed. 162 (90.5%) patients had at least one BAL procedure; 133 (74.3%) within 48 hours after intubation and 112 (62.6%) had at least one subsequent BAL during their hospitalization. A superinfecting pathogen was identified within 48 hours of intubation in 28/133 (21%) patients, most commonly methicillin-sensitive Staphylococcus aureus or Streptococcus species (21/28, 75%). BAL-based treatment reduced antibiotic use compared with guideline-recommended care. 72 patients (44.4%) developed at least one VAP episode. Only 15/72 (20.8%) of initial VAPs were attributable to multidrug-resistant pathogens. The incidence rate of VAP was 45.2/1000 ventilator days.ConclusionsWith use of sensitive diagnostic tools, bacterial superinfection at the time of intubation is infrequent in patients with severe SARS-CoV-2 pneumonia. Treatment based on current guidelines would result in substantial antibiotic overuse. The incidence rate of VAP in ventilated patients with SARS-CoV-2 pneumonia are higher than historically reported.

Introduction: Inflammation plays an important role in the pathogenesis of coronary heart disease (CHD). Chronic inflammatory diseases (CIDs) may serve as models to provide insights into the relationships between immune dysfunction, inflammation, and CHD. To investigate this further, we analyzed the risk of incident CHD across different CIDs. Methods: We created a cohort of individuals with CIDs and non-CID controls (frequency-matched on demographics and CHD risk factors), free of baseline CHD, receiving regular outpatient care in a large medical system from 2000 to 2019. CIDs included psoriasis, rheumatoid arthritis (RA), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and inflammatory bowel disease (IBD). CHD was defined as myocardial infarction (MI), angina, or coronary revascularization. We used adjusted hazards models to determine incident CHD risk for each CID relative to controls. We also analyzed incident CHD risk by severity of inflammation (baseline C-reactive protein) or immune dysfunction (baseline CD4 T cell level in HIV). Results: Of 18,129 individuals with CIDs and 18,988 controls, there were 1,011 incident CHD events over a median of 3.5 years. After adjusting for demographics and CHD risk factors, CHD risk was significantly elevated in SLE [hazard ratio (HR) 2.85, 95% confidence interval (CI) 2.19-3.71, p Conclusions: Our results show that SLE, SSc, HIV, and RA were associated with significantly elevated risks of incident CHD and MI. Higher levels of inflammation or immune dysfunction were associated with heightened CHD risk within CIDs.

Background: Immune regulation and inflammation play a role in the pathogenesis and progression of acute and chronic heart failure (HF). While overt inflammatory cardiomyopathy is a well-described clinical entity marked by acute cardiac dysfunction and relatively high rates of recovery, trajectories in cardiac function among people with chronically heightened systemic inflammation are less clear. We hypothesized that there are differences in trajectories of left ventricular ejection fraction among HF patients with different chronic inflammatory diseases (CIDs): human immunodeficiency virus (HIV), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. Methods: We analyzed serial echocardiographic data from people with CIDs and HF who had at least three echocardiograms (n=974) at a large academic medical center. We identified latent trajectories patterns of LVEF using latent class trajectory models, then described clinical differences across the different trajectories. We then used multinomial regression to test if CID type and other baseline variables were associated with different trajectories. Results: We observed three major LVEF trajectories which paralleled known HF subtypes: preserved/intermediate EF (HFp/iEF, 687, 70.5%), reduced EF (HFrEF, 255, 26.2%), and recovered EF (HFrecEF, 32, 3.3%). These trajectories corresponded closely to accepted clinical definitions. For example, 30/32 (94%) patients in the HFrecEF trajectory had LVEF Conclusions: Among people with HF and CIDs, different trajectories of LVEF are associated with different CIDs and clinical characteristics. This may have implications for therapy and prognosis of HF in CIDs.

Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation.This manuscript is accompanied by an online resource: https://www.nupulmonary.org/covid-19/One sentence summarySARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.

Introduction: Several chronic inflammatory diseases (CID) are associated with elevated risks for cardiovascular diseases (CVDs). However, the relative magnitude of elevated CVD risk may differ considerably between chronic inflammatory diseases. Hypothesis: We hypothesized that not all CIDs are associated with elevated risk for diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD), and that magnitudes of increased CVD risk differ considerably across CIDs. Methods: We estimated the incidence of DM and ASCVD in 18,373 patients with any of six CIDs [human immunodeficiency virus infection (HIV), Irritable bowel disease (IBD), psoriasis, rheumatoid arthritis (RA), scleroderma, and systemic lupus erythematosus (SLE)] in regular outpatient care, as well as controls without CIDs in regular primary care, in a large metropolitan health system since January 1 st , 2000. We assessed incidence of outcomes in patients with each CID compared to controls using quasi-Poisson regression adjusting for age, sex, insurance status, and common CVD risk factors. A 90-day blanking period was applied for identifying incident cases. Results: Psoriasis, HIV, male sex, black race, Hispanic ethnicity, and being on public insurance were all associated with significantly elevated risks for DM (Figure). HIV, RA, scleroderma, SLE, male sex, and public insurance were all associated with significantly elevated risks for ASCVD. The magnitude of increased risk for ASCVD was similarly high for HIV (incidence rate ratio 1.79, 95% confidence interval 1.57-2.05), scleroderma (1.79, 1.42-2.27), and SLE (1.95, 1.59-2.39). Conclusion: Several, but not all, CIDs are associated with elevated risks for DM and ASCVD, but the magnitude of risk elevation differs depending on the CID. These data demonstrate the importance of nuanced approaches to understanding CID- and inflammation-associated CVD risks.

Introduction: Clinicians widely use cardiac troponins I and T, sensitive and specific biomarkers of myocardial damage, as diagnostic criteria for myocardial infarction (MI). A common approach, dichotomizing based on whether troponin levels meet thresholds for MI, may miss meaningful heterogeneity in degree and pattern of troponin elevation, with wider clinical implications. Hypothesis: Using latent class trajectory modeling (LCTM) with patients’ patterns of troponin elevations will yield trajectories that represent clinically and prognostically distinct groups of patients. Methods: We used Northwestern Medicine’s Enterprise Data Warehouse to identify patients with at least 3 troponin measurements of which at least one was elevated during their inpatient stay. We built a LCTM to capture troponin trajectories from 13,432 patients with 65,162 measurements since 2000, using Bayesian Information Criterion to select the final model (# of classes varied from 3-7). We then described the clinical and prognostic factors associated with trajectory class membership. Results: LCTM identified 3 troponin trajectories: stable low (77.3%), moderate rise (9.5%), and severe rise-fall (13.2%). The average posterior probability of assignment was >0.95 for all classes. The low group had the most comorbidities vs moderate/severe groups, including cancer (21.9% vs 13.9%/11.3%), heart failure (12.6% vs 8.9%/7.5%), and COPD (15.0% vs 11.8%/10.1%). The moderate/severe rising trajectories had a greater rate of clinically-diagnosed MI than the stable group (34.5%/44.1% vs 5.6%), with relatively more ST-elevation MI in the severe group (19.8% vs 5.3%) and Non-ST-elevation MI in the moderate group (29.3% vs 24.3%). One-year mortality was greatest in the low group vs moderate/severe groups (25.5% vs 21.4%/18.8%). Conclusions: In a cohort of hospitalized patients with elevated troponins, LCTM identified 3 distinct, clinically interpretable troponin trajectories which were associated with differing clinical phenotypes.

Aims HIV-infected persons may have elevated risks for heart failure, but factors associated with heart failure in the modern era of HIV therapy are insufficiently understood. Despite substantial disagreement between physician-adjudicated heart failure and heart failure diagnosis codes, few studies of HIV cohorts have evaluated adjudicated heart failure. We evaluated associations of HIV viremia, immunosuppression, and cardiovascular risk factors with physician-adjudicated heart failure. Methods and results We analyzed clinical characteristics associated with heart failure in a cohort of 5041 HIV-infected patients receiving care at an urban hospital system between 2000 and 2016. We also evaluated characteristics of HIV-infected patients who screened negative for heart failure, screened positive for possible heart failure but did not have heart failure after adjudication, and had adjudicated heart failure. HIV-infected patients with heart failure ( N = 216) were older and more likely to be black, hypertensive, and have diabetes than HIV-infected patients without heart failure; heart failure with reduced ejection fraction was more common than heart failure with preserved ejection fraction. In our primary analyses restricted to HIV-infected patients whose heart failure diagnoses did not precede their HIV diagnoses ( N = 149), peak HIV viral load ≥100,000 copies/mL (odds ratio (OR) 2.12, 1.28-3.52) and nadir CD4 T-cell count200 cells/mm

The purpose of this study was to compare the risks of incident heart failure (HF) among a variety of chronic inflammatory diseases (CIDs) and to determine whether risks varied by severity of inflammation within each CID.Individuals with CIDs are at elevated risk for cardiovascular diseases, but data are limited regarding risk for HF.An electronic health records database from a large urban medical system was examined, comparing individuals with CIDs with frequency-matched controls without CIDs, all of whom were receiving regular outpatient care. Rates of incident HF were determined by using the Kaplan-Meier method and subsequently used multivariate-adjusted proportional hazards models to compare HF risks for each CID. Exploratory analyses determined HF risks by proxy measurement of CID severity.Of 37,636 patients (n = 18,278 patients with CIDs; and n = 19,358 controls without CIDs) there were 960 incident HF cases over a median of 3.6 years. Risks for incident HF were significantly or borderline significantly elevated for patients with systemic sclerosis (hazard ratio [HR]: 7.26; 95% confidence interval [CI]: 5.72 to 9.21; p 0.01), systemic lupus erythematosus (HR: 3.15; 95% CI: 2.41 to 4.11; p 0.01), rheumatoid arthritis (HR: 1.39; 95% CI: 1.13 to 1.71; p 0.01), and human immunodeficiency virus (HR: 1.28; 95% CI: 0.99 to 1.66; p = 0.06). There was no association between psoriasis or inflammatory bowel disease and incident HF, although patients with those CIDs with higher levels of C-reactive protein had higher risks for HF than controls.Systemic sclerosis and systemic lupus erythematosus were associated with the highest risks of HF, followed by rheumatoid arthritis and HIV. Measurements of inflammation were associated with HF risk across different CIDs.

Background HIV is associated with elevated risk of heart failure ( HF ). Despite poor agreement between automated, administrative code–based HF definitions and physician‐adjudicated HF , no studies have evaluated incident adjudicated HF for people living with HIV ( PLWH ). Methods and Results We analyzed PLWH and uninfected controls receiving care in an urban medical system from January 1, 2000, to July 12, 2016. Physicians reviewed data from medical records to adjudicate HF diagnoses. We used multivariable‐adjusted Cox models to analyze incident HF for PLWH versus controls and HIV ‐related factors associated with incident HF . We also analyzed the performance of automated versus physician‐adjudicated HF definitions. Incident adjudicated HF occurred in 97 of 4640 PLWH (2.1%; mean: 6.8 years to HF ) and 55 of 4250 controls (1.3%; mean: 6.7 years to HF ; multivariable‐adjusted hazard ratio: 2.10; 95% confidence interval, 1.38–3.21). Among PLWH , higher HIV viral load ( hazard ratio per log 10 higher time‐updated viral load: 1.22; 95% confidence interval, 1.11–1.33) was associated with greater HF risk and higher CD 4+ T cell count was associated with lower HF risk ( hazard ratio per 100 cells/mm 3 higher time‐updated CD 4 count: 0.80; 95% confidence interval, 0.69–0.92). In exploratory analyses, the most accurate automated HF definitions had sensitivities of 67% to 75% and positive predictive values of 54% to 60%. Conclusions In a cohort with rigorous HF adjudication, PLWH had greater risks of HF than uninfected people after adjustment for demographics and cardiovascular risk factors. Higher HIV viral load and lower CD 4+ T cell count were associated with higher HF risk among PLWH . Automated methods of HF ascertainment exhibited poor accuracy for PLWH and uninfected people.

Background: Persons living with HIV (PLWH) have greater risks for atherosclerotic cardiovascular disease (ASCVD) than uninfected persons. However, data are sparse regarding HIV-specific factors associated with coronary atherosclerosis. Methods: HIVE-4CVD is an electronic data repository of demographic and clinical data collected during the routine clinical care of 5041 PLWH and 10082 uninfected controls frequency matched on age, sex, race, zip code, and clinic location receiving care at Northwestern Medicine from 1/1/2000 to 5/17/2017. Using validated natural language extraction algorithms, we analyzed data on coronary stenosis severity for the 286 PLWH and 266 uninfected controls in HIVE-4CVD who underwent coronary angiography. Stenosis severity was recorded as the highest percentage of stenosis noted for each patient in each artery (LAD, LCx, RCA). Multivariable logistic regression models adjusted for demographics and CVD risk factors were used to evaluate odds of significant (≥50%) coronary stenosis (1) for PLWH versus uninfected controls and (2) across different levels of HIV viremia and immune suppression among PLWH. Results: Of the 286 PLWH and 266 uninfected controls undergoing coronary angiography, 205 (55.4%) PLWH vs. 165 (44.6%) uninfected controls had diagnoses of myocardial infarction (p=0.02). The location and severity of coronary stenoses did not differ significantly for PLWH vs. uninfected controls; mean maximal overall stenosis and mean maximal LAD, RCA, and LCx stenoses were 52.3% vs. 50.2% (p=0.52), 44.5% vs. 42.3% (p=0.48), 37.0% vs. 36.1% (p=0.78) and 31.4% vs. 31.6% (p=0.95) respectively. There was no significant difference in odds of having significant coronary stenosis for PLWH vs. uninfected controls (multivariable-adjusted OR 1.15, 95% CI 0.79-1.70). Among PLWH, peak HIV viral load was associated with borderline significantly greater odds of ≥50% coronary stenosis after adjustment for demographics, CVD risk factors, and HIV therapies (OR 1.07 per 10-fold greater peak HIV viral load, 95% CI 1.00-1.14, p=0.04), but lower Nadir CD4+ T cell count (3 ) was not (OR 1.05, 95% CI 0.74-1.48, p=0.79). Conclusions: There was no consistent or significant difference in severity of coronary artery stenosis among PLWH and uninfected controls undergoing invasive coronary angiography in the course of routine clinical care. Higher peak HIV viral load is associated with borderline significantly greater odds of having significant coronary stenosis among PLWH undergoing invasive coronary angiography.

Background: Real-world clinical data on statin use and intensity among PLWH are sparse. We hypothesized that significant differences exist regarding statin utilization and dosing as well as on-statin total cholesterol (TC) lowering for PLWH compared with uninfected controls. Methods: HIVE-4CVD is an electronic data repository of 5,041 PLWH and 10,082 uninfected controls frequency matched on age, sex, race, zip code, and clinic location receiving care at Northwestern Medicine from 1/1/2000 to 5/17/2017. Medication administration records, prescription data, and validated natural language extraction algorithms were used to extract statin utilization information. Statins were categorized by generic name and intensity (high, moderate, and low). Lipid values were analyzed and categorized as before or after statin initiation. We compared statin utilization for PLWH vs. controls and used multivariable-adjusted regression models to compare changes in TC levels after statin initiation for PLWH vs. controls. Results: Among people on statins, PLWH were more likely than controls to have ever taken pravastatin (34.8% vs. 12.3%, p < 0.001) and atorvastatin (72.2% vs. 65.6%, p = 0.002), and less likely to have ever taken simvastatin (14.2% vs. 39.5%, p < 0.001). PLWH on statins were more likely to have their intensity reduced (14.6% vs. 11.2%, p = 0.034); this pattern was more apparent when analyses were restricted to patients on high-intensity statins (63.6% vs. 36.4%, p = 0.030). Although PLWH had borderline significantly less TC reduction after statin initiation than controls (-22.9 mg/dL vs. -28.5 mg/dL, p = 0.058; Figure 1), this association was attenuated after adjustment for age, sex, race, and pre-statin TC level (4.2 mg/dL greater TC lowering for controls than PLWH; p = 0.16). Conclusions: Significant differences exist in type and intensity of statin utilized for PLWH compared with uninfected controls. Studies of patient and provider knowledge and preferences are needed to understand reasons underlying these differences.

Background: Few studies have evaluated utilization of ASCVD-preventive therapies, such as statins, among PLWH. Although disparities by race, sex, and insurance status in statin utilization exist in the general population, the extent to which these disparities exist among PLWH - a population with a distinct demographic and risk factor profile - is unknown. Methods: We compared statin utilization rates by race for the 3252 black and white PLWH in HIVE-4CVD who received care at Northwestern Medicine between 1/1/2000 and 5/17/2017. Persons were considered as having an indication for statin therapy if they had one or more of the following: (1) diabetes mellitus; (2) coronary heart disease; (3) a total cholesterol level of ≥240 mg/dL; and/or (4) calculated 10-year ASCVD risk of ≥7.5%. We compared statin utilization between black and white PLWH overall and stratified by insurance status. Multivariable-adjusted logistic regression adjusted for age, sex, and insurance status then was used to compare statin utilization for black vs. white PLWH with statin indications. Results: Of 1680 white PLWH and 1572 black PLWH, 610 whites (36.3%) and 508 blacks (32.3%) had at least one indication for statin therapy. Among PLWH with statin indications, whites were significantly more likely than blacks to be taking statins (60.0% vs. 42.1%, p Conclusions: Among PLWH with indications for statin use, blacks were significantly less likely than whites to be taking statins, even after adjustment for age, sex, and insurance status. Further studies of real-world statin use among PLWH are needed to understand reasons for disparities.

Background Prophylaxis with valganciclovir reduces the incidence of cytomegalovirus (CMV) infection following solid organ transplant (SOT). Under-dosing of valganciclovir is associated with an increased risk of CMV infection and development of ganciclovir-resistant CMV. Methods An automated electronic health record (EHR)-based, pharmacist-driven program was developed to optimize dosing of valganciclovir in solid organ transplant recipients at a large transplant center. Two cohorts of kidney, pancreas-kidney, and liver transplant recipients from our center pre-implementation (April 2011-March 2012, n = 303) and post-implementation of the optimization program (September 2012-August 2013, n=263) had demographic and key outcomes data collected for 1 year post-transplant. Results The 1-year incidence of CMV infection dropped from 56 (18.5%) to 32 (12.2%, P = .05) and the incidence of breakthrough infections on prophylaxis was cut in half (61% vs 34%, P = .03) after implementation of the dose optimization program. The hazard ratio of developing CMV was 1.64 (95% CI 1.06-2.60, P = .027) for the pre-implementation group after adjusting for potential confounders. The program also resulted in a numerical reduction in the number of ganciclovir-resistant CMV cases (2 [0.7%] pre-implementation vs 0 post-implementation). Conclusions An EHR-based, pharmacist-driven valganciclovir dose optimization program was associated with reduction in CMV infections.

HIV-infected persons develop coronary artery disease (CAD) more commonly and earlier than uninfected persons; however, the role of non-invasive testing to stratify CAD risk in HIV is not well defined. Patients were selected from a single-center electronic cohort of HIV-infected patients and uninfected controls matched 1:2 on age, sex, race, and type of cardiovascular testing performed. Patients with abnormal echocardiographic or nuclear stress testing who subsequently underwent coronary angiography were included. Logistic regressions were used to assess differences by HIV serostatus in two co-primary endpoints: (1) severe CAD (≥70% stenosis of at least one coronary artery) and (2) performance of percutaneous coronary intervention (PCI). HIV-infected patients (N = 189) were significantly more likely to undergo PCI following abnormal stress test when compared with uninfected persons (N = 319) after adjustment for demographics, CAD risk factors, previous coronary intervention, and stress test type (OR 1.85, 95% CI 1.12-3.04, P = 0.003). No associations between HIV serostatus and CAD were statistically significant, although there was a non-significant trend toward greater CAD for HIV-infected patients. HIV-infected patients with abnormal cardiovascular stress testing who underwent subsequent coronary angiography did not have a significantly greater CAD burden than uninfected controls, but were significantly more likely to receive PCI.

Background Human Immunodeficiency Virus-Infected (HIV+) persons have elevated risks for various manifestations of cardiovascular disease (CVD). No studies to our knowledge have compared atrial fibrillation (AF) and atrial flutter (AFL) prevalence and associated characteristics for HIV+ persons and matched uninfected controls. Methods and findings Persons with diagnoses of HIV receiving care at a large urban academic medical center were frequency-matched 1:2 on age, sex, race, zip code, and clinic location with uninfected persons. Possible AF/AFL was screened for using administrative codes and diagnoses of AF/AFL were subsequently adjudicated using electrocardiography and physician notes; adjudication was performed given the inconsistent validity of administrative code-derived AF diagnoses found in previous studies. There were 101 confirmed AF/AFL cases (2.00%) among 5,052 HIV+ patients and 159 confirmed AF/AFL cases (1.57%) among 10,121 uninfected controls [Odds Ratio (OR) 1.27, 95% Confidence Interval (CI) 0.99–1.64; p = 0.056]. The association between HIV serostatus and AF/AFL was attenuated after adjustment for demographics and CVD risk factors. Among HIV+ persons, nadir CD4+ T cell count

Background: HIV+ persons appear to have elevated risks for HF. However, few studies have evaluated clinical characteristics of HF in HIV and none has adjudicated HF diagnoses. Thus, the extent to which traditional and HIV-specific risk factors contribute to HF in HIV remains unclear. We hypothesized

Background: HIV+ persons have elevated risks for various manifestations of cardiovascular disease (CVD), but no studies to our knowledge have evaluated AF and AFL for HIV+ persons and matched uninfected controls. Methods: Patients from an electronic cohort of 5,052 HIV+ patients and 10,121

Activation of the hypoxia inducible transcription factor HIF and the NF-ĸB pathway promotes inflammation-mediated tumor progression. The cellular transcription factor ZNF395 has repeatedly been found overexpressed in various human cancers, particularly in response to hypoxia, implying a functional relevance. To understand the biological activity of ZNF395, we identified target genes of ZNF395 through a genome-wide expression screen. Induced ZNF395 expression led to the upregulation of genes known to play a role in cancer as well as a subset of interferon (IFN)-stimulated genes (ISG) involved in antiviral responses such as IFIT1/ISG56, IFI44 and IFI16. In cells that lack ZNF395, the IFN-α-mediated stimulation of these factors was impaired, demonstrating that ZNF395 is required for the full induction of these antiviral genes. Transient transfections revealed that ZNF395-mediated activation of the IFIT1/ISG56 promoter depends on the two IFN-stimulated response elements within the promoter and on the DNA-binding domain of ZNF395, a so-called C-clamp. We also show that IĸBα kinase (IKK)-signaling is necessary to allow ZNF395 to activate transcription and simultaneously enhances its proteolytic degradation. Thus, ZNF395 becomes activated at the level of protein modification by IKK. Moreover, we confirm that the expression of ZNF395 is induced by hypoxia. Our results characterize ZNF395 as a novel factor that contributes to the maximal stimulation of a subset of ISGs. This transcriptional activity depends on IKK signaling further supporting a role of ZNF395 in the innate immune response. Given these results it is possible that under hypoxic conditions, elevated levels of ZNF395 may support inflammation and cancer progression by activating the target genes involved in the innate immune response and cancer.