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A nested longitudinal study within theAsymptomatic novel CORonavirus iNFfection study followed participants with positive nasopharyngeal swab to query for development of symptoms and assess duration of positive reverse transcription-polymerase chain reaction (RT-PCR) test results. Of the 91 participants initially testing positive, 86 participated in follow-up approximately 14 days after study enrollment; of those 86 participants, 19 (22.1%) developed at least one symptom at any time after the initial positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result. The median number of days to symptom development after their initial positive test result was 6 (range 1-29 days). No participants reported a SARS-CoV-2-related hospitalization. The most frequently reported symptoms were fatigue or muscle aches (10.5%), headache (9.3%), fever (5.8%), and shortness of breath (5.8%). Of the 78 participants who submitted a nasopharyngeal swab for repeat RT-PCR testing, 17 (21.8%) remained positive at Day 14, 4 of which continued to test positive at Day 28. These findings reinforce the probable role of silent SARS-CoV-2 infections in community transmission, and that reliance on symptom development will miss a large proportion of infections. Broad testing programs not limited to individuals presenting with symptoms are critical for identifying persons with SARS-CoV-2 infection and ultimately slowing transmission.
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Infecciones Asintomáticas/epidemiología , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/fisiopatología , SARS-CoV-2/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Prueba de Ácido Nucleico para COVID-19 , Prueba de COVID-19 , Estudios Transversales , Disnea/epidemiología , Fatiga/epidemiología , Femenino , Fiebre/epidemiología , Estudios de Seguimiento , Cefalea/epidemiología , Hospitalización , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Prevalencia , SARS-CoV-2/genética , Manejo de Especímenes , Carga Viral , Adulto JovenRESUMEN
The Asymptomatic novel CORonavirus iNfection (ACORN) study was designed to investigate the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the asymptomatic adult population of the Indianapolis metropolitan area, to follow individuals testing positive for the development of symptoms, and to understand duration of positive test results. ACORN is a cross-sectional community-based observational study of adult residents presenting asymptomatic for COVID-like illness, defined as the self-reported absence of the following three symptoms in the last 7 days: fever (≥100°F), new-onset or worsening cough, and new-onset or worsening shortness of breath. SARS-CoV-2 infection was determined by real-time reverse transcription-polymerase chain reaction in nasopharyngeal swab samples. SARS-CoV-2 infection prevalence was expressed as a point estimate with 95% confidence interval (CI). Test results are reported for 2953 participants who enrolled and underwent nasopharyngeal swab testing between 7 April 2020 and 16 May 2020. Among tested participants, 91 (3.1%; 95% CI: 2.5%-3.7%) were positive for SARS-CoV-2. Overall, baseline characteristics, medical history, and infection risk factors were comparable between SARS-CoV-2 positive and negative participants. Within the ongoing 14-day follow-up period for positive participants, 58 (71.6%) of 81 assessed participants remained asymptomatic while others (n = 23, 28.4%) reported one or more symptoms. Indiana had "Stay-at-Home" orders in place during nearly the entire test period reported here, yet 3.1% of asymptomatic participants tested positive for SARS-CoV-2. These results indicate screening questions had limited predictive utility for testing in an asymptomatic population and suggest broader testing strategies are needed. Importantly, these findings underscore that more research is needed to understand the viral transmission and the role asymptomatic and presymptomatic individuals play in this global pandemic.
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Infecciones Asintomáticas/epidemiología , COVID-19/epidemiología , Nasofaringe/virología , Salud Pública/estadística & datos numéricos , Adolescente , Adulto , Anciano , Prueba de Ácido Nucleico para COVID-19/estadística & datos numéricos , Ciudades/epidemiología , Tos/epidemiología , Estudios Transversales , Femenino , Fiebre/epidemiología , Humanos , Indiana/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
AIMS: Dulaglutide, a once weekly GLP-1 receptor agonist, is approved at two doses (1.5 and 0.75 mg) for treatment of type 2 diabetes (T2D). Two higher doses of dulaglutide (3.0 and 4.5 mg) were evaluated for safety and efficacy to determine whether these doses warrant further study for improved control of glucose and body weight. MATERIALS AND METHODS: This 18-week, double-blind, phase 2 trial randomized 318 patients with T2D using ≥1500 mg metformin, to receive subcutaneous injection of placebo (n = 82), dulaglutide 1.5 mg (n = 81), dulaglutide 3.0 mg (n = 79) or dulaglutide 4.5 mg (n = 76). The primary objective was superiority of dulaglutide doses over placebo in reduction of HbA1c at 18 weeks. Secondary objectives included superiority of dulaglutide over placebo in change from baseline in body weight and fasting serum glucose (FSG) at 18 weeks. Investigational doses of dulaglutide were compared to the 1.5 mg dose as an exploratory objective. RESULTS: HbA1c reduction at 18 weeks was significantly greater with dulaglutide vs placebo (placebo, -0.44% ± 0.10% [-4.8 ± 1.1 mmol/mol]; dulaglutide 1.5 mg, -1.23% ± 0.10% [-13.5 ± 1.1 mmol/mol]; dulaglutide 3.0 mg, -1.31% ± 0.10% [-14.3 ± 1.1 mmol/mol]; dulaglutide 4.5 mg, -1.40% ± 0.10% [-15.3 ± 1.1 mmol/mol]; P < 0.001, each dose), as were changes in body weight (placebo, -1.6 ± 0.39 kg; dulaglutide 1.5 mg, -2.8 ± 0.39 kg; dulaglutide 3.0 mg, -3.9 ± 0.39 kg; dulaglutide 4.5 mg, -4.1 ± 0.41 kg; P < 0.001, each dose). All three dulaglutide doses significantly reduced FSG from baseline (1.5 mg, -36.2 ± 4.7 mg/dL [-2.0 ± 0.3 mmol/L]; 3.0 mg, -34.5 ± 4.5 mg/dL [-1.9 ± 0.3 mmol/L]; 4.5 mg, -38.0 ± 4.7 mg/dL [-2.1 ± 0.3 mmol/L]) vs placebo (-12.4 ± 4.5 mg/dL [-0.7 ± 0.3 mmol/L]) (P < 0.001, all). Safety profiles of the higher doses were consistent with the established safety profile for dulaglutide. Gastrointestinal events were mostly mild to moderate, and was dose-related for nausea. CONCLUSION: All three dulaglutide doses were superior to placebo in improving glycaemic control and reducing body weight in participants with T2D using metformin. The potential for doses of dulaglutide of 3.0 and 4.5 mg to provide additional glycaemic benefit and weight reduction with an acceptable safety profile, compared with the 1.5 mg dose, warrants further study in a phase 3 trial.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/administración & dosificación , Fragmentos Fc de Inmunoglobulinas/administración & dosificación , Metformina/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Adulto , Anciano , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Método Doble Ciego , Quimioterapia Combinada , Femenino , Péptidos Similares al Glucagón/administración & dosificación , Hemoglobina Glucada/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Pérdida de Peso/efectos de los fármacosRESUMEN
In patients with type 2 dibetes and moderate-to-severe chronic kidney disease, dulaglutide treatment led to body weight (BW) loss and lesser eGFR decline compared to insulin glargine. As BW may affect muscle mass, creatinine-based eGFR can be altered independently of kidney function. Cystatin C-based eGFR is not affected by muscle mass. The objective of this post-hoc analysis was to determine whether the lesser eGFR decline with dulaglutide was related to BW loss. Baseline characteristics were similar between treatments ([mean ± SD] age, 64.6 ± 8.6 years; women, 48%; BW, 89.1 ± 17.7 kg; eGFR [CKD-EPI-cystatin C] 38 ± 14 mL/min/1.73m2 ). BW decreased with dulaglutide 1.5 and 0.75 mg and increased with insulin glargine ([LSM change (SE)], -2.66 [0.47] kg and -1.71 [0.45] vs 1.57 [0.43] kg; P < 0.001). Changes in eGFR were not significant with dulaglutide 1.5 and 0.75 mg, but eGFR significantly decreased with insulin glargine (eGFR-CKD-EPI-cystatin C [LSM change (95%CI)], -0.7 [-2.5, 1.0] and -0.7 [-2.4, 1.1] vs -3.3 [-5.1, -1.6] mL/min/1.73 m2 ; P ≤ 0.037 vs glargine). Changes in BW did not correlate with changes in eGFR-CKD-EPI-cystatin C (r = -0.041; n = 471; P = 0.379) or eGFR-CKD-EPI-creatinine (r = -0.074; n = 473; P = 0.106). In conclusion, the lesser decline in eGFR observed with dulaglutide was not influenced by BW loss.
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Peso Corporal/efectos de los fármacos , Diabetes Mellitus Tipo 2 , Tasa de Filtración Glomerular/efectos de los fármacos , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes , Fragmentos Fc de Inmunoglobulinas , Proteínas Recombinantes de Fusión , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/farmacología , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéutico , Insuficiencia Renal Crónica/complicacionesRESUMEN
PURPOSE: The aims of this study were to use real-world treatment results to compare changes in estimated glomerular filtration rate (eGFR) and glycosylated hemoglobin (HbA1c) among patients with type 2 diabetes who initiated treatment with dulaglutide or insulin glargine and to determine the proportions of patients with renal impairment who initiate each treatment. METHODS: The study used data from the Practice Fusion electronic health records database from October 2013 through June 2017. Adults with type 2 diabetes who initiated dulaglutide or insulin glargine therapy and had multiple recorded serum creatinine and/or HbA1c laboratory test results were included in the study. The dulaglutide cohort (nâ¯=â¯1222) was matched to the insulin glargine cohort (nâ¯=â¯13,869) using Mahalanobis distance matching with propensity score calipers. Multivariable analyses of the matched cohorts of individuals with serum creatinine results (nâ¯=â¯1183 dulaglutide and 1183 insulin glargine) examined the association between intent-to-treat therapy and changes in eGFR. In addition, multivariable analyses were also conducted on a subset of these patients who also had recorded HbA1c tests (nâ¯=â¯1088 dulaglutide and 1088 insulin glargine) to examine the association between changes in HbA1c during the 1 year postperiod. FINDINGS: Among patients who initiated dulaglutide therapy, only 0.9% of patients had an index eGFR <30 and ≥15 mL/min/1.73 m2 and 0.1% had an index eGFR <15 mL/min/1.73 m2. In contrast, 4.1% of insulin glargine-treated patients had an index eGFR <30 and ≥15 mL/min/1.73 m2 and 1.2% had an index eGFR <15 mL/min/1.73 m2. Compared with patients who initiated therapy with insulin glargine, initiation of dulaglutide therapy was associated with a significantly smaller decrease in eGFR (-0.4 vs -0.9 mL/min/1.73 m2; Pâ¯=â¯0.0024), a significantly smaller likelihood of having a 30% or greater reduction in eGFR (3.3% vs 4.1%; P < 0.0001), and a significantly larger reduction in HbA1c (-0.5% vs -0.2%; P < 0.0001). IMPLICATIONS: In clinical practice, the use of dulaglutide was relatively more limited in patients with a higher degree of renal impairment compared with use of insulin glargine. However, initiation of dulaglutide therapy, compared with insulin glargine therapy, was associated with a significantly smaller decrease in eGFR and a larger reduction in HbA1c during the 1 year postperiod.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Tasa de Filtración Glomerular/efectos de los fármacos , Péptidos Similares al Glucagón/análogos & derivados , Hipoglucemiantes/farmacología , Fragmentos Fc de Inmunoglobulinas/farmacología , Insulina Glargina/farmacología , Proteínas Recombinantes de Fusión/farmacología , Insuficiencia Renal/fisiopatología , Anciano , Creatinina/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Insulina Glargina/uso terapéutico , Masculino , Persona de Mediana Edad , Proteínas Recombinantes de Fusión/uso terapéutico , Insuficiencia Renal/complicaciones , Resultado del TratamientoRESUMEN
INTRODUCTION: The study characterizes the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) with and without renal impairment and examines the effects of such use on the clinical outcomes of estimated glomerular filtration rate (eGFR) and glycated hemoglobin (A1c). METHODS: Data from the Practice Fusion electronic health records database from 1 January 2012 through 30 April 2015 were used. Adults with T2D who received serum creatinine laboratory tests and initiated therapy with a GLP-1 RA (N = 3225) or other glucose-lowering agent (GLA) (N = 37,074) were included in the analysis. The GLP-1 RA cohort was matched to cohorts initiating therapy any other GLA, and multivariable analyses examined the association between GLP-1 RA use and changes in eGFR or A1c at 1 year after therapy initiation. RESULTS: In this study, only 5.7% of patients with an eGFR of < 30 and ≥ 15 mL/min/1.73 m2 and 3.6% of patients with an eGFR of < 15 mL/min/1.73 m2 initiated therapy with a GLP-1 RA. Compared to other GLAs, at 1-year after initiation of therapy the use of a GLP-1 RA was associated with a significantly smaller decline in eGFR (- 0.80 vs. - 1.03 mL/min/1.73 m2; P = 0.0005), a significantly smaller likelihood of having a ≥ 30% reduction in eGFR (2.19 vs. 3.14%; P < 0.0001), and a significantly larger reduction in A1c (- 0.48 vs. - 0.43; P = 0.0064). CONCLUSION: In clinical practice, the use of GLP-1 RAs in patients with a higher degree of renal impairment disease was limited. Compared to other GLAs, the use of GLP-1 RAs was associated with a significantly smaller decline in eGFR and a larger reduction in A1c over the 1 year following therapy initiation. FUNDING: Eli Lilly and Company.
RESUMEN
BACKGROUND: Patients with community-acquired pneumonia (CAP) comprised 35.6% of the overall phase 3 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study and 33.1% of the placebo arm. We investigated the use of CURB-65, the Pneumonia Severity Index (PSI), and Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction scores to identify the CAP population from the PROWESS placebo arm at the greatest mortality risk. METHODS: Patients were classified as having CAP if the lung was the primary infection site and the patient originated from home. The abilities of CURB-65, PSI, and APACHE II scores to determine the 28-day and in-hospital mortality were compared using receiver operator characteristic (ROC) curves and the associated areas under the curve. RESULTS: PROWESS enrolled 278 patients with CAP in the placebo arm. The areas under the ROC curves for PSI = 5, CURB-65 ≥ 3, and APACHE II ≥ 25 for predicting 28-day (c = 0.65, 0.66, and 0.64, respectively) and in-hospital mortality (c = 0.65, 0.65, and 0.64, respectively) were not statistically different from each other. The 28-day mortality of patients with a PSI score of 5, CURB-65 ≥ 3, and APACHE II ≥ 25 was 41.6%, 37.9%, and 43.5%, respectively. CONCLUSIONS: Despite early diagnosis and appropriate antibiotic therapy, conventionally treated CAP with PSI = 5, CURB-65 3, or APACHE II 25 has an unacceptably high mortality. In this study, PSI, CURB-65, and APACHE II scoring systems perform similarly in predicting the 28-day and in-hospital mortality; however, differences in the categorization of severe CAP were observed and there was a significant mortality in patients with a CURB-65 <3 and PSI <5.
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APACHE , Neumonía/diagnóstico , Medición de Riesgo/métodos , Sepsis/diagnóstico , Índice de Severidad de la Enfermedad , Anciano , Antiinfecciosos/uso terapéutico , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/mortalidad , Método Doble Ciego , Mortalidad Hospitalaria , Humanos , Persona de Mediana Edad , Neumonía/tratamiento farmacológico , Neumonía/mortalidad , Curva ROC , Proteínas Recombinantes/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Estadísticas no Paramétricas , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Research has focused on improvement of erectile function during treatment with phosphodiesterase type 5 (PDE5) inhibitors, but less is known about what occurs after treatment cessation. AIM: The aim of this retrospective analysis was to examine durability of response, defined as sustainability of erectogenic benefits following treatment cessation, in men with erectile dysfunction (ED) following long-term treatment with daily tadalafil. METHODS: The subjects (N=160) had participated in a 12-week double-blind trial followed by a one-year, open-label extension of tadalafil 5mg once daily. The extension was followed by a 4-week, treatment-free follow-up period. A total of 158 subjects completed International Index of Erectile Function-Erectile Function (IIEF-EF) domain score and were included in this analysis. MAIN OUTCOME MEASURES: The primary measures for this analysis were changes in ED severity category as captured by the IIEF-EF domain score. RESULTS: At the end of the 1-year open-label treatment period, a majority (86.1%, n=136) of subjects had either improved by at least one ED severity category (e.g., Severe to Moderate) (n=128), or maintained Normal erectile function (EF domain score ≥26) (n=8), compared to baseline. Following the 4-week, treatment-free period, 63 of those subjects (46.3% of the 136 subjects) had continued improvement of at least one ED severity category (n=61) or maintained scores in the Normal category (n=2) compared with baseline. Subjects who showed a sustained benefit of treatment were considered to have demonstrated a "durable response." Seventy-three subjects (53.7%) did not have a durable response following treatment cessation. A few patient characteristics were associated with durability of response. CONCLUSIONS: Of those men who demonstrated improved erectile function while taking tadalafil 5mg once daily for 1 year, 46.3% continued to show improvement compared with baseline following a 4-week treatment free period. Durability of response should be a focus of future research.
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Carbolinas/uso terapéutico , Disfunción Eréctil/tratamiento farmacológico , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Carbolinas/administración & dosificación , Método Doble Ciego , Esquema de Medicación , Humanos , Masculino , Persona de Mediana Edad , Erección Peniana/efectos de los fármacos , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Estudios Retrospectivos , Tadalafilo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Use of pharmacologic agents in clinical practice may differ from the manner in which they were studied in rigorous randomized clinical trials. This was a prospective, observational, noninterventional study to determine the profile of patients receiving drotrecogin alfa (activated) in clinical practice, provide additional outcome and safety data, and allow for a comparison to patients studied in the phase 3 Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial. METHODS: A total of 548 adult patients with severe sepsis were enrolled from 61 nonteaching or academically affiliated hospitals in the United States. Patients received drotrecogin alfa (activated) as part of physician-directed therapy for severe sepsis. RESULTS: The Xigris Use in the United States (XEUS) patients were younger (58 vs 63 years of age), had more comorbidities, and more sepsis-induced organ dysfunction at baseline compared to high-risk (Acute Physiology and Chronic Health Evaluation II score ≥ 25) PROWESS patients who received drotrecogin alfa (activated), (cardiovascular, 85.0% vs 79.7%; hematologic, 22.3% vs 16.4%; and renal, 57.9% vs 50.7%) (all P < .05). The XEUS patients had a higher mortality rate compared to high-risk PROWESS patients receiving drotrecogin alfa (activated) (36.7% vs 30.9%; P = .062) but a similar safety profile (infusion period serious bleeding, 2.7% vs 2.2%; P = .579; 28-day serious bleeding, 3.1% vs 3.9%; P = .520). The rate of intracranial hemorrhage in XEUS was 0.2%. CONCLUSIONS: Patients receiving drotrecogin alfa (activated) in clinical practice were more acutely ill, had a higher mortality rate, but a similar safety profile with respect to serious bleeding events compared to the PROWESS trial.
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Antiinfecciosos/uso terapéutico , Pautas de la Práctica en Medicina , Proteína C/uso terapéutico , Sepsis/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Antiinfecciosos/efectos adversos , Ensayos Clínicos Fase III como Asunto , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Estudios Prospectivos , Proteína C/efectos adversos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Factores de Riesgo , Sepsis/complicaciones , Sepsis/mortalidad , Resultado del Tratamiento , Estados UnidosRESUMEN
Drotrecogin alfa (activated) (DrotAA), or recombinant human activated protein C, represents the only Food and Drug Administration-approved therapy for mortality reduction in adult patients with severe sepsis. Drotrecogin alfa (activated) has properties that address microvascular injury in severe sepsis through its direct effects on endothelial cells and leukocytes while also having antithrombotic and indirect profibrinolytic properties. Sepsis bundle and guideline implementation has been associated with improved survival and includes DrotAA administration in appropriate patients. Several DrotAA postapproval clinical studies have yielded additional outcome and safety data, better defining its benefit/risk profile. Bleeding is more common in DrotAA-treated patients; therefore, a careful assessment of bleeding risk and an understanding of the safety profile is required. This summary provides a detailed review of safety data and outcomes of patients treated with DrotAA in recent clinical studies enrolling more than 7000 adult patients.
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Enfermedad Crítica , Hemorragia/inducido químicamente , Proteína C/uso terapéutico , Sepsis/tratamiento farmacológico , Anciano , Ensayos Clínicos como Asunto , Femenino , Heparina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Proteína C/efectos adversos , Proteína C/metabolismo , Tiempo de Protrombina , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéuticoRESUMEN
OBJECTIVE: To compare characteristics and outcomes of patients treated with drotrecogin alfa (activated) (DrotAA) in clinical practice to those treated in a phase III randomized controlled trial (PROWESS). DESIGN: Observational data were collected retrospectively from patients who received DrotAA as part of physician-directed treatment. SETTING: Intensive care units of five teaching institutions. PATIENTS: Patients were > or = 18 yrs old, had severe sepsis (confirmed/suspected infection with one or more sepsis-induced organ dysfunctions), and received DrotAA. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, severity of illness, time from organ dysfunction onset to DrotAA treatment, daily assessment of organ dysfunction, serious bleeding events, and in-hospital mortality were reported. Timing from severe sepsis documentation to start of DrotAA infusion was categorized: day 0 (same calendar day); day 1 (next calendar day); and day > or = 2 (second calendar day or later). Clinical practice patients (n = 274) were younger, had more comorbidities, had higher severity of illness (as measured by organ dysfunction or greater vasopressor/ventilator use), and received DrotAA later than PROWESS patients (all p < .05). Overall hospital mortality for clinical practice patients was 42%, compared with 37% for DrotAA-treated PROWESS patients with Acute Physiology and Chronic Health Evaluation II score > or = 25. Mortality for day 0, day 1, and day > or = 2 groups was 33%, 40%, and 52%, respectively. In PROWESS, the vast majority were treated on day 0 or day 1. Serious bleeding events during infusion were noted in 4.0% of clinical practice patients compared with 2.2% of PROWESS DrotAA-treated patients with Acute Physiology and Chronic Health Evaluation II score > or = 25. CONCLUSIONS: Patients treated in clinical practice differed from those in PROWESS. Patients were younger, had more comorbidities, had greater severity of illness, and had longer mean time from severe sepsis onset to the start of DrotAA. Hospital mortality for patients treated within 1 day of severe sepsis onset was similar to DrotAA-treated PROWESS patients. While the low number of serious bleeding events precludes a definitive assessment, the observed incidence of serious bleeding events in clinical practice patients was numerically higher than in DrotAA-treated PROWESS patients.