Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy.

BACKGROUND: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described. METHODS: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation. RESULTS: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20). CONCLUSIONS: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada.

BACKGROUND: Integrase strand transfer inhibitor (INSTI)-based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). METHODS: cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. RESULTS: Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92-1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07-1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06-1.91]) vs NNRTI initiators. The INSTI-DM association was attenuated (HR, 1.03 [95% CI, .71-1.49] vs NNRTIs) when accounting for 12-month weight. CONCLUSIONS: Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.

Efficacy and safety of dapagliflozin in acute heart failure: Rationale and design of the DICTATE-AHF trial.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure. OBJECTIVE: The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care. METHODS: DICTATE-AHF is a prospective, multicenter, open-label, randomized trial enrolling a planned 240 patients in the United States. Patients with type 2 diabetes hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 mL/min/1.73m2 are eligible for participation. Patients are randomly assigned 1:1 to dapagliflozin 10 mg once daily or structured usual care until day 5 or hospital discharge. Both treatment arms receive protocolized diuretic and insulin therapies. The primary endpoint is diuretic response expressed as the cumulative change in weight per cumulative loop diuretic dose in 40 mg intravenous furosemide equivalents. Secondary and exploratory endpoints include inpatient worsening AHF, 30-day hospital readmission for AHF or diabetic reasons, change in NT-proBNP, and measures of natriuresis. Safety endpoints include the incidence of hyper/hypoglycemia, ketoacidosis, worsening kidney function, hypovolemic hypotension, and inpatient mortality. CONCLUSIONS: The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

Quality of physician care coordination during inter-facility transfer for cardiac arrest patients.

AIM: We sought to evaluate whether the quality of coordination between physicians transferring comatose cardiac arrest survivors to a high-volume cardiac arrest center for targeted temperature management (TTM) was associated with timeliness of care. METHODS: We conducted a retrospective analysis of inter-facility transfers to Vanderbilt University Medical Center for TTM between October 2016 and October 2018. We examined the relationship between Relational Coordination (RC) - a measure of communication and relationship quality - during phone conversations between transferring physicians and time-to-acceptance. RESULTS: We identified 18 patients meeting criteria. TTM was initiated or continued in 72%, and in-hospital mortality was 75%. Median time-to-acceptance was 2.77 (interquartile range [IQR] 2.0, 4.1) minutes, and duration of calls was 3.95 (IQR 2.7, 5.2) minutes. Interrater reliability for overall RC was high (rho = 0.87). The correlation between RC and the time-to-acceptance was significant in univariate analyses (adjusted relative risk = 0.96, 95%CI 0.93, 1.0, p = 0.05). Secondary analyses did not find a significant relationship between RC and timeliness measures. CONCLUSION: In this sample of patients transferred for TTM, we found that RC as a measure of care coordination, was reliable. Higher quality care coordination for cardiac arrest survivors was associated with faster physician acceptance. Future work using a larger cohort should explore if higher RC among a broader set of stakeholders (physicians, EMS, families, etc.) is associated with timeliness measures after adjusting for other factors, to better understand how the quality of care coordination impacts timeliness of care and patient outcomes.

Emergency department provider and facility variation in opioid prescriptions for discharged patients.

STUDY OBJECTIVE: To study the variation in opioid prescribing among emergency physicians and facilities for discharged adult ED patients. METHODS: We conducted a retrospective analysis of ED visits from five U.S. hospitals between January and May 2014 using records from Data to Intelligence (D2i). We examined physician- and facility-level variation in opioid prescription rates for discharged ED patients. We calculated unadjusted opioid prescription rates at the physician and facility levels and used a multivariable mixed-effect logistic regression model to examine within-facility physician variation in opioid prescription adjusting for patient and situational factors including time of presentation, ED census, and physician workload. RESULTS: In 47,304 visits across five EDs, median patient age was 40 years old (IQR 28,55), and 89% had some form of insurance. There were 17,098 (36%) ED discharges with at least one opioid prescription. The unadjusted facility-level opioid prescription rate ranged from 24%-46%. Among 253 ED physicians, the adjusted opioid prescription rate varied from 22%-76%. Increased physician workload is related to decreased odds of opioid prescription at ED discharge for the lowest (<3 patients) and moderate (6-9 patients) physician workload levels, while the association weakened with increasing levels of workload. CONCLUSION: There was substantial physician and facility variation in opioid prescription for discharged adult ED patients. Emergency physicians were less likely to prescribe opioids when their workload was lower, and this effect diminished at high workload levels. Understanding situational and other factors that explain this variation is important given the rising U.S. opioid epidemic and the need for urgent intervention.

Mortality in Children with Human Immunodeficiency Virus Initiating Treatment: A Six-Cohort Study in Latin America.

OBJECTIVES: To assess the risks of and factors associated with mortality, loss to follow-up, and changing regimens after children with HIV infected perinatally initiate combination antiretroviral therapy (cART) in Latin America and the Caribbean. STUDY DESIGN: This 1997-2013 retrospective cohort study included 1174 antiretroviral therapy-naïve, perinatally infected children who started cART age when they were younger than 18 years of age (median 4.7 years; IQR 1.7-8.8) at 1 of 6 cohorts from Argentina, Brazil, Haiti, and Honduras, within the Caribbean, Central and South America Network for HIV Epidemiology. Median follow-up was 5.6 years (IQR 2.3-9.3). Study outcomes were all-cause mortality, loss to follow-up, and major changes in cART. We used Cox proportional hazards models stratified by site to examine the association between predictors and times to death or changing regimens. RESULTS: Only 52% started cART at younger than 5 years of age; 19% began a protease inhibitor. At cART initiation, median CD4 count was 472 cells/mm3 (IQR 201-902); median CD4% was 16% (IQR 10-23). Probability of death was high in the first year of cART: 0.06 (95% CI 0.04-0.07). Five years after cART initiation, the cumulative mortality incidence was 0.12 (95% CI 0.10-0.14). Cumulative incidences for loss to follow-up and regimen change after 5 years were 0.16 (95% 0.14-0.18) and 0.30 (95% 0.26-0.34), respectively. Younger children had the greatest risk of mortality, whereas older children had the greatest risk of being lost to follow-up or changing regimens. CONCLUSIONS: Innovative clinical and community approaches are needed for quality improvement in the pediatric care of HIV in the Americas.

Comparing results from multiple imputation and dynamic marginal structural models for estimating when to start antiretroviral therapy.

Optimal timing of initiating antiretroviral therapy has been a controversial topic in HIV research. Two highly publicized studies applied different analytical approaches, a dynamic marginal structural model and a multiple imputation method, to different observational databases and came up with different conclusions. Discrepancies between the two studies' results could be due to differences between patient populations, fundamental differences between statistical methods, or differences between implementation details. For example, the two studies adjusted for different covariates, compared different thresholds, and had different criteria for qualifying measurements. If both analytical approaches were applied to the same cohort holding technical details constant, would their results be similar? In this study, we applied both statistical approaches using observational data from 12,708 HIV-infected persons throughout the USA. We held technical details constant between the two methods and then repeated analyses varying technical details to understand what impact they had on findings. We also present results applying both approaches to simulated data. Results were similar, although not identical, when technical details were held constant between the two statistical methods. Confidence intervals for the dynamic marginal structural model tended to be wider than those from the imputation approach, although this may have been due in part to additional external data used in the imputation analysis. We also consider differences in the estimands, required data, and assumptions of the two statistical methods. Our study provides insights into assessing optimal dynamic treatment regimes in the context of starting antiretroviral therapy and in more general settings. Copyright © 2016 John Wiley & Sons, Ltd.

Association of atrial fibrillation risk alleles and response to acute rate control therapy.

OBJECTIVES: Given the sparse evidence for selection of first-line therapy for acute atrial fibrillation (AF) based on clinical factors alone, incorporation of genotype data may improve the effectiveness of treatment algorithms and advance the understanding of interpatient heterogeneity. We tested whether candidate nucleotide polymorphisms (SNPs) related to AF physiologic responses are associated with ventricular rate control after intravenous diltiazem in the emergency department (ED). METHODS: We conducted an analysis within a prospective observational cohort of ED patients with acute symptomatic AF, ventricular rate >110 beats per minute within the first 2 hours, initially treated with intravenous diltiazem, and who had DNA available for analysis. We evaluated 24 candidate SNPs that were grouped into 3 categories based on their phenotype response (atrioventricular nodal [AVN] conduction, resting heart rate, disease susceptibility) and calculated 3 genetic scores for each patient. Our primary outcome was maximum heart rate reduction within 4 hours of diltiazem administration. Multivariable regression was used to identify associations with the outcome while adjusting for age, sex, baseline heart rate, and diltiazem dose. RESULTS: Of the 142 patients, 127 had complete data for the primary outcome. None of the genetic scores for AVN conduction, resting heart rate, or AF susceptibility showed a significant association with maximal heart rate response. CONCLUSION: Using a candidate SNP approach, screening for genetic variants associated with AVN conduction, resting heart rate, or AF susceptibility failed to provide significant data for predicting successful rate control response to intravenous diltiazem for treating acute AF in the ED.

Validation of the Risk Estimator Decision Aid for Atrial Fibrillation (RED-AF) for predicting 30-day adverse events in emergency department patients with atrial fibrillation.

STUDY OBJECTIVE: In the United States, nearly 70% of emergency department (ED) visits for atrial fibrillation result in hospitalization. The incidence of serious 30-day adverse events after an ED evaluation for atrial fibrillation remains low. This study's goal was to prospectively validate our previously reported Risk Estimator Decision Aid for Atrial Fibrillation (RED-AF) model for estimating a patient's risk of experiencing a 30-day adverse event. METHODS: This was a prospective cohort study, which enrolled a convenience sample of ED patients presenting with atrial fibrillation. RED-AF, previously derived from a retrospective cohort of 832 patients, assigns points according to age, sex, coexisting disease (eg, heart failure, hypertension, chronic obstructive pulmonary disease), smoking, home medications (eg, ß-blocker, diuretic), physical examination findings (eg, dyspnea, palpitations, peripheral edema), and adequacy of ED ventricular rate control. Primary outcome was occurrence of greater than or equal to 1 atrial fibrillation-related adverse outcome (ED visits, rehospitalization, cardiovascular complications, death) within 30 days. We identified a clinically relevant threshold and measured RED-AF's performance in this prospective cohort, assessing its calibration, discrimination, and diagnostic accuracy. RESULTS: The study enrolled 497 patients between June 2010 and February 2013. Of these, 120 (24%) had greater than or equal to 1 adverse event within 30 days. A RED-AF score of 87 was identified as an optimal threshold, resulting in sensitivity and specificity of 96% (95% confidence interval [CI] 91% to 98%) and 19% (95% CI 15% to 23%), respectively. Positive and negative predictive values were 27% (95% CI 23% to 32%) and 93% (95% CI 85% to 97%), respectively. The c statistic for RED-AF was 0.65 (95% CI 0.59 to 0.71). CONCLUSION: In this separate validation cohort, RED-AF performed moderately well and similar to the original derivation cohort for identifying the risk of short-term atrial fibrillation-related adverse events in ED patients receiving a diagnosis of atrial fibrillation.

Hormonal Contraception and Risk of Cardiometabolic Disease in Women with HIV.

Objective: We sought to determine the association of hormonal contraception (HC) and cardiometabolic outcomes among women with human immunodeficiency virus (HIV). Methods: We included women with HIV aged 18-45 years in clinical care in the Southeastern United States between 1998 and 2018. Oral and injectable HC use was captured from medication records. Our outcomes included incident cardiovascular/thrombotic disease (CVD) (atherosclerosis, hypertension, cerebrovascular disease, thrombosis, and heart failure) and incident metabolic disorders (diabetes, dyslipidemia, obesity, and non-alcoholic steatohepatitis). We excluded women with prevalent conditions. We used multivariable marginal structural models to examine time-varying current and cumulative HC use and cardiometabolic outcomes in separate analyses, adjusting for age, race, smoking, time-varying comorbidities, CD4 cell count, HIV RNA, and antiretroviral use. Women with HC exposure were compared with women without HC exposure. Results: Among the 710 women included, 201 women (28%) used HC. CVD analyses included 603 women without prevalent CVD and 93 incident events; metabolic analyses included 365 women without prevalent metabolic disease and 150 incident events. Current and cumulative oral HC use was associated with increased odds of CVD, though this was not statistically significant (adjusted odds ratio [aOR] = 2.08, [95% confidence interval (CI): 0.80-5.43] and aOR = 1.24 [95% CI: 0.96-1.60] per year of use, respectively). Oral HC was not associated with risk of incident metabolic disorders. Depot medroxyprogesterone acetate (DMPA) was not associated with risk of incident CVD. Current and cumulative DMPA use was significantly associated with decreased odds of incident metabolic disorders (aOR = 0.48 [95% CI: 0.23, 1.00] and aOR = 0.65 [95% CI: 0.42-1.00] per year of use, respectively). Conclusion: Our results suggest that cardiovascular risk should be considered when selecting contraception for women with HIV.

Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure.

BACKGROUND: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. OBJECTIVES: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. METHODS: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. RESULTS: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period. CONCLUSIONS: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).

Comparison of visual inspection with acetic acid and cervical cytology to detect high-grade cervical neoplasia among HIV-infected women in India.

Human immunodeficiency virus (HIV)-infected women in India and other developing country settings are living longer on antiretroviral therapy, yet their risk for human papillomavirus (HPV)-induced cervical cancer remains unabated because of lack of cost-effective and accurate secondary prevention methods. Visual inspection after application of dilute acetic acid on the cervix (VIA) has not been adequately studied against the current standard: conventional cervical cytology (Pap smears) among HIV-infected women. We evaluated 303 nonpregnant HIV-infected women in Pune, India, by simultaneous and independent screening with VIA and cervical cytology with disease ascertainment by colposcopy and histopathology. At the cervical intraepithelial neoplasia (CIN2+) disease threshold, the sensitivity, specificity and positive and negative predictive value estimates of VIA were 80, 82.6, 47.6 and 95.4% respectively, compared to 60.5, 59.6, 22.4 and 88.7% for the atypical squamous cells of undetermined significance or severe (ASCUS+) cutoff on cytology, 60.5, 64.6, 24.8 and 89.4% for the low-grade squamous intraepithelial cells or severe (LSIL+) cutoff on cytology and 20.9, 96.0, 50.0 and 86.3% for high-grade squamous intraepithelial lesion or severe (HSIL+) cutoff on cytology. A similar pattern of results was found for women with the presence of carcinogenic HPV-positive CIN2+ disease, as well as for women with CD4+ cell counts <200 and <350 µL(-1) . Overall, VIA performed better than cytology in this study with biologically rigorous endpoints and without verification bias, suggesting that VIA is a practical and useful alternative or adjunctive screening test for HIV-infected women. Implementing VIA-based screening within HIV/acquired immunodeficiency syndrome care programs may provide an easy and practical means of complementing the highly anticipated low-cost HPV-based rapid screening tests in the near future, thereby contributing to improve program effectiveness of screening.

Dual analysis for mycobacteria and propionibacteria in sarcoidosis BAL.

PURPOSE: Sarcoidosis is a non-caseating granulomatous disease for which a role for infectious antigens continues to strengthen. Recent studies have reported molecular evidence of mycobacteria or propionibacteria. We assessed for immune responses against mycobacterial and propionibacterial antigens in sarcoidosis bronchoalveolar lavage (BAL) using flow cytometry, and localized signals consistent with microbial antigens with sarcoidosis specimens, using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS). METHODS: BAL cells from 27 sarcoidosis, 14 PPD- controls, and 9 subjects with nontuberculosis mycobacterial (NTM) infections were analyzed for production of IFN-γ after stimulation with mycobacterial ESAT-6 and Propionibacterium acnes proteins. To complement the immunological data, MALDI-IMS was performed to localize ESAT-6 and Propionibacterium acnes signals within sarcoidosis and control specimens. RESULTS: CD4+ immunologic analysis for mycobacteria was positive in 17/27 sarcoidosis subjects, compared to 2/14 PPD- subjects, and 5/9 NTM subjects (p = 0.008 and p = 0.71 respectively, Fisher's exact test). There was no significant difference for recognition of P. acnes, which occurred only in sarcoidosis subjects that also recognized ESAT-6. Similar results were also observed for the CD8+ immunologic analysis. MALDI-IMS localized signals consistent with ESAT-6 only within sites of granulomatous inflammation, whereas P. acnes signals were distributed throughout the specimen. CONCLUSIONS: MALDI-IMS localizes signals consistent with ESAT-6 to sarcoidosis granulomas, whereas no specific localization of P. acnes signals is detected. Immune responses against both mycobacterial and P. acnes are present within sarcoidosis BAL, but only mycobacterial signals are distinct from disease controls. These immunologic and molecular investigations support further investigation of the microbial community within sarcoidosis granulomas.

Risk stratification in acute heart failure: rationale and design of the STRATIFY and DECIDE studies.

BACKGROUND: A critical challenge for physicians facing patients presenting with signs and symptoms of acute heart failure (AHF) is how and where to best manage them. Currently, most patients evaluated for AHF are admitted to the hospital, yet not all warrant inpatient care. Up to 50% of admissions could be potentially avoided and many admitted patients could be discharged after a short period of observation and treatment. Methods for identifying patients that can be sent home early are lacking. Improving the physician's ability to identify and safely manage low-risk patients is essential to avoiding unnecessary use of hospital beds. METHODS: Two studies (STRATIFY and DECIDE) have been funded by the National Heart Lung and Blood Institute with the goal of developing prediction rules to facilitate early decision making in AHF. Using prospectively gathered evaluation and treatment data from the acute setting (STRATIFY) and early inpatient stay (DECIDE), rules will be generated to predict risk for death and serious complications. Subsequent studies will be designed to test the external validity, utility, generalizability and cost-effectiveness of these prediction rules in different acute care environments representing racially and socioeconomically diverse patient populations. RESULTS: A major innovation is prediction of 5-day as well as 30-day outcomes, overcoming the limitation that 30-day outcomes are highly dependent on unpredictable, post-visit patient and provider behavior. A novel aspect of the proposed project is the use of a comprehensive cardiology review to correctly assign post-treatment outcomes to the acute presentation. CONCLUSIONS: Finally, a rigorous analysis plan has been developed to construct the prediction rules that will maximally extract both the statistical and clinical properties of every data element. Upon completion of this study we will subsequently externally test the prediction rules in a heterogeneous patient cohort.

Prevalence of validated risk factors for developing atrial fibrillation--can we identify high-risk ED patients?

OBJECTIVE: The aim of this study was to investigate whether emergency department (ED) patients who were newly diagnosed with atrial fibrillation (AF) displayed risk factors for incident AF on prior ED visits. METHODS: This was a secondary analysis of a retrospective cohort study of ED patients with symptomatic AF at a tertiary referral center. We selected patients who were newly diagnosed with AF between July 1, 2005, and August 31, 2008, and had at least 1 ED visit before their diagnosis. We calculated the Framingham Heart Study AF risk score for each visit by documenting the presence of the risk factors (age, sex, body mass index, systolic blood pressure, hypertension treatment, PR interval, and ages of clinically significant cardiac murmur and heart failure diagnosis). RESULTS: Of the 296 patients newly diagnosed with AF, 115 (39%) had at least 1 prior ED visit resulting in 454 ED visits for analysis. The median time from first to last visit was 4 years (interquartile range [IQR], 2.1-5.9). The median age was 66 years (IQR, 49-79 years). Home medications included antihypertensives in 81% of visits, and 60% of visits with available electrocardiograms had a PR interval of 160 milliseconds or more. Heart failure history was reported in 23% of visits. The median AF risk score was 8 (IQR, 4-10) corresponding to a 16% 10-year predicted risk. CONCLUSIONS: Nearly 40% of patients diagnosed with new AF had previous ED visits and displayed validated risk factors for incident AF. The ED provides an opportunity to identify and educate these patients as well as refer them for primary prevention interventions.

Assessment of the Framingham risk factors among ED patients with newly diagnosed atrial fibrillation.

STUDY OBJECTIVE: Atrial fibrillation (AF) is often first diagnosed in the emergency department (ED) and accounts for nearly 1% of all emergency department (ED) visits. Our objective was to assess the Framingham Heart Study risk score for AF development in ED patients with newly diagnosed AF. METHODS: We systematically reviewed the electronic medical records of ED patients with newly diagnosed AF between August 2005 and July 2008. We measured the frequency of the Framingham Heart Study predictors and calculated each patient's risk score. RESULTS: During the 3-year study period, 914 patients had 1228 ED visits. New AF was diagnosed in 296 (32%) patients. Among these patients, 107 (36%) were female, 127 (43%) had prior ED visits since 2003, 189 (64%) were taking hypertension medications and 170 (57.4%) had previous electrocardiograms with measurable PR intervals. The median PR interval was 166 ms (151 to 180) and 60% of available PR intervals were 160 ms or greater. The median (interquartile range) age, body mass index, and systolic blood pressure were 66 years (53-77), 27 (23-31), and 134 mm Hg (118-151), respectively. Median risk score was 7 (3-9) indicating high predicted risk. Heart failure and cardiac murmurs were previously diagnosed in 45 (15%) and 32 (11%) of these patients, respectively. CONCLUSIONS: The Framingham risk factors for AF are commonly encountered among ED patients with newly diagnosed AF. The ED might provide an opportunity to identify patients at high risk for AF and refer them for primary prevention interventions.

Acute kidney injury after placement of an antibiotic-impregnated cement spacer during revision total knee arthroplasty.

We performed a retrospective cohort study of 84 patients to determine the incidence and predictors of acute kidney injury after antibiotic-impregnated cement spacer (ACS) placement for infected total knee arthroplasties. Acute kidney injury was defined as a more than 50% rise in serum creatinine from a preoperative baseline to a level greater than 1.4 mg/dL within 90 days postoperatively. Total incidence was 17% (n = 14; 95% confidence interval [CI], 10%-26%), and acute kidney injury was significantly associated with ACS tobramycin dose as both a dichotomous variable (>4.8 g; odds ratio, 5.87; 95% CI, 1.43-24.19; P = .01) and linear variable (odds ratio, 1.24 for every 1-g increase; 95% CI, 1.00-1.52; P = .049). Routine monitoring of serum creatinine and measurement of serum aminoglycoside levels in response to a threshold creatinine rise may be warranted after the placement of an aminoglycoside-containing ACS.

Predictors of ambulance transport in patients with ST-elevation myocardial infarction.

INTRODUCTION: Despite intense public awareness campaigns, many patients with ST-elevation myocardial infarction (STEMI) do not utilize Emergency Medical Services (EMS) transportation to the Emergency Department (ED). Predictors for mode of transport by EMS versus private vehicle in patients with an acute STEMI were investigated. Hypothesis It was hypothesized that patient characteristics, specifically older age, male sex, and a history of a prior cardiac intervention, would be associated with a higher likelihood of EMS utilization. METHODS: A retrospective, observational cohort study was performed for all STEMI patients treated from April 1, 2007 through June 30, 2010 at an urban, academic ED with 24-hour cardiac catheterization available. Multivariable analyses with predetermined predictors (age, sex, prior cardiac intervention, weekend/evening arrival) were performed to investigate associations with mode of transport. Door-to-balloon (D2B) times were calculated. RESULTS: Of the 209 STEMI patients, 11 were excluded, leaving 198 for analysis. Median age was 60 years (IQR: 53-70), 138 (70%) arrived by private vehicle, and 60 (30%) by EMS. The primary analysis did not identify significant predictors for EMS, but a post-hoc model found that private insurance (OR 0.18; 95% CI, 0.07-0.45) was associated with fewer EMS transports. Although not statistically significant due to the great variability in time of arrival for STEMI patients transported by private vehicle, EMS transports had shorter D2B times. During business hours and weekend/evenings, EMS had D2B times of 50 (IQR: 42-61) and 58 minutes (IQR: 47-63), respectively, while private vehicle transports had median D2B times of 62 (IQR: 50-74) and 78 minutes (IQR: 66-106). Conclusion No associations between mode of transport and patient age, sex, weekend/evening presentation and history of a prior cardiac intervention were identified. Privately insured patients were less likely to use EMS when experiencing a STEMI. More effective ways are needed to educate the public on the importance of EMS activation when one is concerned for acute coronary syndrome.