Prediction of Critical Illness During Out-of-Hospital Emergency Care

CONTEXT: Early identification of nontrauma patients in need of critical care services in the emergency setting may improve triage decisions and facilitate regionalization of critical care. OBJECTIVES: To determine the out-of-hospital clinical predictors of critical illness and to characterize the performance of a simple score for out-of-hospital prediction of development of critical illness during hospitalization. DESIGN AND SETTING: Population-based cohort study of an emergency medical services (EMS) system in greater King County, Washington (excluding metropolitan Seattle), that transports to 16 receiving facilities. PATIENTS: Nontrauma, non-cardiac arrest adult patients transported to a hospital by King County EMS from 2002 through 2006. Eligible records with complete data (N = 144,913) were linked to hospital discharge data and randomly split into development (n = 87,266 [60%]) and validation (n = 57,647 [40%]) cohorts. MAIN OUTCOME MEASURE: Development of critical illness, defined as severe sepsis, delivery of mechanical ventilation, or death during hospitalization. RESULTS: Critical illness occurred during hospitalization in 5% of the development (n = 4835) and validation (n = 3121) cohorts. Multivariable predictors of critical illness included older age, lower systolic blood pressure, abnormal respiratory rate, lower Glasgow Coma Scale score, lower pulse oximetry, and nursing home residence during out-of-hospital care (P < .01 for all). When applying a summary critical illness prediction score to the validation cohort (range, 0-8), the area under the receiver operating characteristic curve was 0.77 (95% confidence interval [CI], 0.76-0.78), with satisfactory calibration slope (1.0). Using a score threshold of 4 or higher, sensitivity was 0.22 (95% CI, 0.20-0.23), specificity was 0.98 (95% CI, 0.98-0.98), positive likelihood ratio was 9.8 (95% CI, 8.9-10.6), and negative likelihood ratio was 0.80 (95% CI, 0.79- 0.82). A threshold of 1 or greater for critical illness improved sensitivity (0.98; 95% CI, 0.97-0.98) but reduced specificity (0.17; 95% CI, 0.17-0.17). CONCLUSIONS: In a population-based cohort, the score on a prediction rule using out-of-hospital factors was significantly associated with the development of critical illness during hospitalization. This score requires external validation in an independent populationPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85143/1/Seymour - JAMA-2010-747-54.pdf11

Modifiable predictors of ventricular ectopy in the community

Background Premature ventricular contractions (PVCs) predict heart failure and death. Data regarding modifiable risk factors for PVCs are scarce. Methods and Results We studied 1424 Cardiovascular Health Study participants randomly assigned to 24-hour Holter monitoring. Demographics, comorbidities, habits, and echocardiographic measurements were examined as predictors of PVC frequency and, among 845 participants, change in PVC frequency 5 years later. Participants exhibited a median of 0.6 (interquartile range, 0.1-7.1) PVCs per hour. Of the more directly modifiable characteristics and after multivariable adjustment, every SD increase in systolic blood pressure was associated with 9% more PVCs (95% confidence interval [CI], 2%-17%; P=0.01), regularly performing no or low-intensity exercise compared with more physical activity was associated with ≈15% more PVCs (95% CI, 3-25%; P=0.02), and those with a history of smoking exhibited an average of 18% more PVCs (95% CI, 3-36%; P=0.02) than did never smokers. After 5 years, PVC frequency increased from a median of 0.5 (IQR, 0.1-4.7) to 1.2 (IQR, 0.1-13.8) per hour ( P&lt;0.0001). Directly modifiable predictors of 5-year increase in PVCs, described as the odds per each quintile increase in PVCs, included increased diastolic blood pressure (odds ratio per SD increase, 1.16; 95% CI, 1.02-1.31; P=0.02) and a history of smoking (OR, 1.31; 95% CI, 1.02-1.68; P=0.04). Conclusions Enhancing physical activity, smoking cessation, and aggressive control of blood pressure may represent fruitful strategies to mitigate PVC frequency and PVC-associated adverse outcomes

NT -pro BNP as a Mediator of the Racial Difference in Incident Atrial Fibrillation and Heart Failure.

Background Blacks harbor more cardiovascular risk factors than whites, but experience less atrial fibrillation ( AF ). Conversely, whites may have a lower risk of heart failure ( CHF ). N-terminal pro-B-type natriuretic peptide ( NT -pro BNP) levels are higher in whites, predict incident AF , and have diuretic effects in the setting of increased ventricular diastolic pressures, potentially providing a unifying explanation for these racial differences. Methods and Results We used data from the CHS (Cardiovascular Health Study) to determine the degree to which baseline NT -pro BNP levels mediate the relationships between race and incident AF and CHF by comparing beta estimates between models with and without NT -pro BNP . The ARIC (Atherosclerosis Risk in Communities) study was used to assess reproducibility. Among 4731 CHS (770 black) and 12 418 ARIC (3091 black) participants, there were 1277 and 1253 incident AF events, respectively. Whites had higher baseline NT -pro BNP ( CHS : 40% higher than blacks; 95% CI , 29-53; ARIC : 39% higher; 95% CI , 33-46) and had a greater risk of incident AF compared with blacks ( CHS : adjusted hazard ratio, 1.60; 95% CI , 1.31-1.93; ARIC : hazard ratio, 1.93; 95% CI , 1.57-2.27). NT -pro BNP levels explained a significant proportion of the racial difference in AF risk ( CHS : 36.2%; 95% CI , 23.2-69.2%; ARIC : 24.6%; 95% CI , 14.8-39.6%). Contrary to our hypothesis, given an increased risk of CHF among whites in CHS (adjusted hazard ratio, 1.20; 95% CI , 1.05-1.47) and the absence of a significant association between race and CHF in ARIC (adjusted hazard ratio, 1.07; 95% CI , 0.94-1.23), CHF -related mediation analyses were not performed. Conclusions A substantial portion of the relationship between race and AF was statistically explained by baseline NT -pro BNP levels. No consistent relationship between race and CHF was observed

Ectopy on a single 12‐lead ECG, incident cardiac myopathy, and death in the community

BackgroundAtrial fibrillation and heart failure are 2 of the most common diseases, yet ready means to identify individuals at risk are lacking. The 12-lead ECG is one of the most accessible tests in medicine. Our objective was to determine whether a premature atrial contraction observed on a standard 12-lead ECG would predict atrial fibrillation and mortality and whether a premature ventricular contraction would predict heart failure and mortality.Methods and resultsWe utilized the CHS (Cardiovascular Health) Study, which followed 5577 participants for a median of 12&nbsp;years, as the primary cohort. The ARIC (Atherosclerosis Risk in Communities Study), the replication cohort, captured data from 15&nbsp;792 participants over a median of 22&nbsp;years. In the CHS, multivariable analyses revealed that a baseline 12-lead ECG premature atrial contraction predicted a 60% increased risk of atrial fibrillation (hazard ratio, 1.6; 95% CI, 1.3-2.0; P&lt;0.001) and a premature ventricular contraction predicted a 30% increased risk of heart failure (hazard ratio, 1.3; 95% CI, 1.0-1.6; P=0.021). In the negative control analyses, neither predicted incident myocardial infarction. A premature atrial contraction was associated with a 30% increased risk of death (hazard ratio, 1.3; 95% CI, 1.1-1.5; P=0.008) and a premature ventricular contraction was associated with a 20% increased risk of death (hazard ratio, 1.2; 95% CI, 1.0-1.3; P=0.044). Similarly statistically significant results for each analysis were also observed in ARIC.ConclusionsBased on a single standard ECG, a premature atrial contraction predicted incident atrial fibrillation and death and a premature ventricular contraction predicted incident heart failure and death, suggesting that this commonly used test may predict future disease

Alcohol consumption and leukocyte telomere length.

The relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation

Peripheral Arterial Disease and Risk of Atrial Fibrillation and Stroke: The Multi�Ethnic Study of Atherosclerosis

Background Peripheral arterial disease (PAD) shares several risk factors with atrial fibrillation (AF), and persons with PAD have an increased risk of stroke. It is unclear if PAD is associated with an increased risk for AF and whether this potential association explains the increased risk of stroke observed in those with PAD. Methods and Results We examined the association between PAD, measured by ankle�brachial index (ABI), and incident AF and incident stroke, separately, in 6568 participants (mean age 62±10 years, 53% women, 62% nonwhite) from the Multi�Ethnic Study of Atherosclerosis (MESA). ABI values 1.4 defined PAD. AF was ascertained through review of hospital discharge records and from Medicare claims data until December 31, 2010. An independent adjudication committee ascertained stroke events. Cox regression was used to estimate hazard ratios and 95% CIs for the association between PAD and AF and stroke. Over a median follow�up of 8.5 years, 301 (4.6%) participants developed AF and 140 (2.1%) developed stroke. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, PAD was associated with an increased risk of AF (hazard ratio 1.5, 95% CI 1.1 to 2.0). In a similar model, PAD was associated with incident stroke (hazard ratio 1.7, 95% CI 1.1 to 2.5), and the magnitude of risk was not different after inclusion of AF as a time�dependent covariate (hazard ratio 1.7, 95% CI 1.1 to 2.5). Conclusions PAD is associated with an increased risk of AF and stroke in MESA. Potentially, the relationship between PAD and stroke is not mediated by AF

Nonsteroidal Antiinflammatory Drug Use and Association With Incident Hypertension in Ankylosing Spondylitis.

ObjectiveNonsteroidal antiinflammatory drugs (NSAIDs) increase blood pressure and potentially cardiovascular burden, which may limit their use in ankylosing spondylitis (AS). Our objective was to determine the association of NSAID use with incident hypertension in a longitudinal AS cohort.MethodsAdults with AS were enrolled in a prospective cohort study of patient outcomes and examined every 4-6 months. Hypertension was defined by patient-reported hypertension; antihypertensive medication use; or, on 2 consecutive visits, systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. Continuous NSAID use was dichotomized based on the validated NSAID index. We assessed the association of NSAID use as a time-varying exposure with the incidence of hypertension using Cox proportional hazards models.ResultsOf the 1,282 patients in the cohort, 628 patients without baseline hypertension had at least 1 year of follow-up and were included in the analysis. Of these, 72% were male, the mean age at baseline was 39 ± 13 years, and 200 patients used NSAIDs continuously. On follow-up, 129 developed incident hypertension. After controlling for other variables, continuous NSAID use was associated with a hazard ratio of 1.12 for incident hypertension (95% confidence interval 1.04-1.20), compared to noncontinuous or no use. The association did not differ in subgroups defined by age, body mass index, biologic use, or disease activity.ConclusionIn our prospective, longitudinal AS cohort, continuous NSAID use was associated with a 12% increased risk for the development of incident hypertension, as compared to noncontinuous or no NSAID use

Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR)&nbsp;=&nbsp;1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR&nbsp;=&nbsp;0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR&nbsp;=&nbsp;2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research

Incremental value of rare genetic variants for the prediction of multifactorial diseases

Background: It is often assumed that rare genetic variants will improve available risk prediction scores. We aimed to estimate the added predictive ability of rare variants for risk prediction of common diseases in hypothetical scenarios.Methods: In simulated data, we constructed risk models with an area under the ROC curve (AUC) ranging between 0.50 and 0.95, to which we added a single variant representing the cumulative frequency and effect (odds ratio, OR) of multiple rare variants. The frequency of the rare variant ranged between 0.0001 and 0.01 and the OR between 2 and 10. We assessed the resulting AUC, increment in AUC, integrated discrimination improvement (IDI), net reclassification improvement (NRI(>0.01)) and categorical NRI. The analyses were illustrated by a simulation of atrial fibrillation risk prediction based on a published clinical risk model.Results: We observed minimal improvement in AUC with the addition of rare variants. All measures increased with the frequency and OR of the variant, but maximum increment in AUC remained below 0.05. Increment in AUC and NRI(>0.01) decreased with higher AUC of the baseline model, w

Prehospital Systolic Blood Pressure Thresholds: A Community‐based Outcomes Study

Objectives Emergency medical services (EMS) personnel commonly use systolic blood pressure ( sBP ) to triage and treat acutely ill patients. The definition of prehospital hypotension and its associated outcomes are poorly defined. The authors sought to determine the discrimination of prehospital sBP thresholds for 30‐day mortality and to compare patient classification by best‐performing thresholds to traditional cutoffs. Methods In a community‐based cohort of adult, nontrauma, noncardiac arrest patients transported by EMS between 2002 and 2006, entries to state hospital discharge data and death certificates were linked. Prehospital sBP thresholds between 40 and 140 mm Hg in derivation ( n =  132,624) and validation ( n =  22,020) cohorts and their discrimination for 30‐day mortality, were examined. Cutoffs were evaluated using the 0/1 distance, Youden index, and adjusted Z‐statistics from multivariable logistic regression models. Results In the derivation cohort, 1,594 (1.2%) died within 24 hours, 7,404 (6%) were critically ill during hospitalization, and 6,888 (5%) died within 30 days. The area under the receiver operating characteristic (ROC) curve for sBP was 0.60 (95% confidence interval [CI] = 0.59, 0.61) for 30‐day mortality and 0.64 (95% CI = 0.62 0.66) for 24‐hour mortality. The 0/1 distance, Youden index, and adjusted Z‐statistics found best‐performing sBP thresholds between 110 and 120 mm Hg. When compared to an sBP ≤ 90 mm Hg, a cutoff of 110 mm Hg would identify 17% ( n =  137) more deaths at 30 days, while overtriaging four times as many survivors. Conclusions Prehospital sBP is a modest discriminator of clinical outcomes, yet no threshold avoids substantial misclassification of 30‐day mortality among noninjured patients. Resumen Los Umbrales de la Presión Arterial Sistólica Prehospitalaria: Un Estudio de Base Comunitaria Acerca de la Evolución de los Pacientes Objetivos El personal de los sistemas de emergencias médicas ( SEM ) usa frecuentemente la presión arterial sistólica ( PAS ) para clasificar y tratar a los pacientes agudos. Las definiciones de hipotensión prehospitalaria y sus resultados asociados están pobremente definidos. Se determinó la discriminación de los umbrales de PAS prehospitalaria para la mortalidad a los 30 días, y se comparó la clasificación del paciente por los mejores umbrales con los puntos de corte tradicionales. Metodología Estudio de cohorte de base comunitaria de pacientes adultos no traumatológicos ni con paradas cardiorrespiratorias transportados por los SEM entre 2002 y 2006, cuyas historias estaban vinculadas con los datos de alta hospitalaria y los certificados de mortalidad. Se examinaron los umbrales de PAS prehospitalaria entre 40 mm Hg y 140 mm Hg en las cohortes de derivación ( n =  132.624), y validación ( n =  22,020), y su discriminación para la mortalidad a los 30 días. Los puntos de corte se evaluaron usando la distancia 0/1, el índice de Youden y los estadísticos Z ajustados de los modelos de regresión logística multivariable. Resultados: En la cohorte de derivación, 1.594 (1,2%) fallecieron en las primeras 24 horas, 7.404 (6%) estuvieron críticamente enfermos durante el ingreso y 6.888 (5%) fallecieron en los 30 primeros días. El área bajo la curva de la ROC para PAS fue 0,60 ( IC 95% = 0,59–0,61) para la mortalidad a los 30 días y 0,64 ( IC 95% = 0,62–0,66) para la mortalidad a las 24 horas. La distancia 0/1, el índice de Youden y las estadísticas Z ajustadas hallaronque los mejores umbrales de PAS estaban entre 110 y 120 mm Hg. Cuando se comparó con una PAS ≤ 90 mm Hg, un punto de corte de 110 mm Hg identificaría un 17% ( n =  137) más de muertes a los 30 días, mientras que sobreclasificaría cuatro veces más a los supervivientes. Conclusiones La presión arterial sistólica es un discriminador modesto de resultados clínicos. No obstante, ningún umbral evita una mala clasificación de la mortalidad a los 30 días entre los pacientes no traumatológicos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/1/acem12142-sup-0002-DataSupplementS2_FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/2/acem12142-sup-0007-DataSupplementS7_FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/3/acem12142-sup-0006-DataSupplementS6_FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/4/acem12142-sup-0009-DataSupplementS9_TableS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/5/acem12142-sup-0003-DataSupplementS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/6/acem12142-sup-0008-DataSupplementS8_TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/7/acem12142-sup-0004-DataSupplementS4_TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/8/acem12142-sup-0001-DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/9/acem12142.pd