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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Circulation. Author manuscript; available in PMC Jul 10, 2010.
Published in final edited form as:
PMCID: PMC2901546
NIHMSID: NIHMS213438
Physician Alerts to Prevent Symptomatic Venous Thromboembolism in Hospitalized Patients
Gregory Piazza, MD,i Erin J. Rosenbaum, BA,ii William Pendergast, MD,iii Joseph O. Jacobson, MD,iv Robert C. Pendleton, MD,v Gordon D. McLaren, MD,vi C. Gregory Elliott, MD,vii Scott M. Stevens, MD,viii William F. Patton, MD,ix Ousama Dabbagh, MD,x Marilyn D. Paterno, MBI,xi Elaine Catapane, MEd, MT,xii Zhongzhen Li, MD,xiii and Samuel Z. Goldhaber, MDxiv
iCardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
iiCardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
iiiDepartment of Internal Medicine, The Washington Hospital, Washington, PA, USA
ivDepartment of Medicine, North Shore Medical Center, Salem, MA, Harvard Medical School, Boston, MA, USA
vDepartment of Internal Medicine, University of Utah Health Sciences, Salt Lake City, UT, USA
viDepartment of Veterans Affairs Long Beach Healthcare System, Long Beach, CA, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, CA, USA
viiDepartment of Medicine, Intermountain Medical Center, Murray, UT, University of Utah School of Medicine, Salt Lake City, UT, USA
viiiDepartment of Medicine, Intermountain Medical Center, Murray, UT, University of Utah School of Medicine, Salt Lake City, UT, USA
ixDepartment of Internal Medicine, St. Joseph Mercy Health System, Ann Arbor, MI, USA
xDivision of Pulmonary, Critical Care and Environmental Medicine, Department of Internal Medicine, University of Missouri-Columbia, Columbia, MO
xiInformation Systems/Clinical Informatics Research & Development, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
xiiHarvard Clinical Research Institute, Harvard University, Boston, MA, USA
xiiiHarvard Clinical Research Institute, Harvard University, Boston, MA, USA
xivCardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
Address for Correspondence: Gregory Piazza, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115, Tel: (857) 307-1932, Fax: (857) 307-1955, gpiazza/at/partners.org
Background
Venous thromboembolism (VTE) prophylaxis remains underutilized among hospitalized patients. We designed and carried out a large multicenter randomized controlled trial to test the hypothesis that an alert from a hospital staff member to the Attending Physician will reduce the rate of symptomatic VTE among high-risk patients not receiving prophylaxis.
Methods and Results
We enrolled patients using a validated point score system to detect hospitalized patients at high risk for symptomatic VTE who were not receiving prophylaxis. 2,493 patients (82% on Medical Services) from 25 study sites were randomized to the intervention group (n=1,238), in which the responsible physician was alerted by another hospital staff member, versus the control group (n=1,255), in which no alert was issued. The primary end point was symptomatic, objectively confirmed VTE within 90 days. Patients whose physicians were alerted were more than twice as likely to receive VTE prophylaxis as controls (46.0% versus 20.6%, p<0.0001). The symptomatic VTE rate was lower in the intervention group (2.7% versus 3.4%; hazard ratio, 0.79; 95% confidence interval, 0.50 to 1.25), but the difference did not achieve statistical significance. The rate of major bleeding at 30 days in the alert group was similar to the control group (2.1% versus 2.3%, p=0.68).
Conclusions
A strategy of direct staff member to physician notification increases prophylaxis utilization and leads toward reducing the rate of symptomatic VTE in hospitalized patients. However, VTE prophylaxis continues to be underutilized even after physician notification, especially among Medical Service patients.
Keywords: Deep vein thrombosis, Prevention, Prophylaxis, Pulmonary embolism, Venous thromboembolism
In 2005, we described a new system utilizing electronic alerts to prevent symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients.1 First, we devised a point score system to detect hospitalized patients at high risk for developing DVT or PE. Next, we created a computer program linked to the patient database to identify consecutive hospitalized patients at high risk for venous thromboembolism (VTE) who were not receiving prophylaxis. Finally, we programmed the hospital computer system as a Quality Improvement initiative to randomize the notification (versus no notification) of physicians caring for 2,506 high-risk patients not receiving any VTE prophylaxis. The physicians in the intervention group received electronic alerts, which resulted in a 41% reduction in symptomatic VTE at 90 days compared with the control group.1
We designed the current multicenter randomized trial with an eye toward applying the alert strategy to a broad array of hospitals across the United States. As we organized participating centers, we learned that replication of our electronic alerting system was not feasible for many hospitals because it requires an electronic medical record, sophisticated Information Technology infrastructure, and considerable financial resources. Therefore, we crafted a strategy that employed a “human” rather than electronic alerting system. The physician alert consists of a direct page from a hospital staff member to the Attending Physician. The primary end point is reduction in symptomatic VTE within 90 days of randomization.
Study Design
From July 2006 to November 2007, we identified 2,493 consecutive patients admitted to Medical or Surgical Services who were at least 18 years of age, at high risk of VTE based upon our score point system, and not receiving any VTE prophylaxis (Figure 1). Patients on the Neurology Service, the Newborn Service, Neonatal Intensive Care Unit, Rehabilitation Units, and those receiving mechanical or pharmacological prophylaxis were excluded. Patients who were not at increased risk for developing VTE were also excluded. Patients were enrolled from 25 medical centers throughout the U.S., including urban, non-urban, teaching, and non-teaching hospitals. Institutional Review Board approval was obtained from all 25 study sites.
Figure 1
Figure 1
Flow of patients through each stage of the trial.
Identification of Patients at Risk for Venous Thromboembolism
Patients who were admitted overnight were screened for VTE risk by research nurses, pharmacists, physicians, or other professional staff. Our previously established scoring system was used to identify patients at increased risk for VTE.1 Each risk factor was weighted according to a point scale. Major risk factors of cancer, prior VTE, and hypercoagulability were assigned 3 points each; an intermediate risk factor of major surgery was assigned a score of 2 points; and minor risk factors of advanced age, obesity, bed rest, and use of hormone-replacement therapy or oral contraceptives were assigned 1 point each. An increased risk of VTE was defined as a cumulative risk score of at least 4 points.1
At each study site, designated screeners used current lists of inpatient diagnoses to identify patients with the following types of cancer: cervical, ovarian, uterine, prostate, esophageal, gastric, colorectal, pancreatic, liver, lung, renal, thyroid, brain, head and neck, sarcoma, and melanoma. In addition, admitting diagnoses were screened to identify cancer coded according to the International Classification of Diseases, 9th Revision (ICD-9), as codes 149.0 to 172.99 and 174.0 to 209.99. Inpatient and outpatient medical records were reviewed to identify patients with a previous history of DVT or PE, as well as those with a history of VTE, as indicated by ICD-9 codes 415.1, 415.19, 453.9, and 671.31 to 671.50.
Hypercoagulable states were identified on the basis of available laboratory test results (not all patients were tested), including the presence of factor V Leiden mutation, prothrombin gene mutation, lupus anticoagulant, anticardiolipin antibodies, and deficiencies of protein C, protein S, and antithrombin III. Major surgery was defined as any surgical procedure lasting more than 60 minutes. Bed rest was defined as an active order for bed rest not related to surgery. Advanced age was defined as an age greater than 70 years. If data on weight and height were available, body mass index (BMI) (weight in kilograms divided by the square of height in meters) was calculated. Obesity was defined as a BMI of greater than 29. If weight and height were unavailable, inpatient and outpatient records were screened for a diagnosis of obesity and for the ICD-9 code for obesity (278.0). Ongoing use of hormone-replacement therapy or oral contraceptives was identified by reviewing patients’ active medications.
Screening for Venous Thromboembolism Prophylaxis
If the cumulative VTE risk score was at least 4 points, the patient was defined as high risk for developing VTE, and the screener reviewed orders to identify the ongoing use of any pharmacological or mechanical prophylaxis. Active medication orders were screened for pharmacological prophylaxis, including unfractionated heparin, enoxaparin, dalteparin, tinzaparin, fondaparinux, and warfarin. Orders were also searched for mechanical prophylactic measures, including the use of graduated compression stockings or intermittent pneumatic compression devices. Patients with orders for VTE prophylaxis were excluded. However, control patients could receive VTE prophylaxis in the 2 days between randomization and our in-hospital follow-up.
Randomization and Physician Alerts
Randomization envelopes containing the statement “ALERT” (intervention group) or “NO ALERT” (control group) were provided by the Harvard Clinical Research Institute (HCRI) to randomize eligible patients. Among 2,493 eligible patients, 1,238 were assigned to the intervention group, and 1,255 were assigned to the control group. For patients randomized to the intervention group, the Attending Physician was paged and informed that: 1) his or her patient is at high risk for VTE, 2) the patient is not currently receiving VTE prophylaxis, and 3) VTE prophylaxis is recommended. A sample script was provided and read: “Hello, this is (name of hospital staff member, title, and department). I am calling to alert you that your patient, (patient’s name), is at high risk for deep vein thrombosis. This is based on a point scale of DVT risk factors and the absence of current prophylaxis orders.” One study center that enrolled 178 patients violated the study protocol and paged House Officers rather than the Attending Physicians. For patients in the control group, VTE prevention guidelines were available, but no specific communication regarding VTE risk or prophylaxis was issued.
Follow-Up
We conducted 90-day follow-up of all study patients by reviewing their medical records. Clinical events were identified using data from the index hospitalization, subsequent hospitalizations, and office visits, including discharge summaries, healthcare provider’s notes, laboratory test results, vascular laboratory reports, nuclear medicine reports, and radiology reports. If patient outcomes could not be determined by medical record review alone, study representatives contacted the responsible primary care provider for necessary information. Investigational Review Board approval was obtained at each site prior to any contact with primary care providers. In addition, the Social Security Death Index was used to identify patients who died during the 90-day follow-up period. Overall, 2,493 (100%) had follow-up data beyond the index hospitalization.
Data Collection
The primary end point was clinically diagnosed DVT or PE within 90 days of hospital discharge. For patients with more than one clinical event, only the first event was counted. Safety endpoints included total mortality and major bleeding events at 90 and 30 days, respectively. We defined major bleeding as intracranial, intraocular, retroperitoneal, or pericardial bleeding, or bleeding that required surgical intervention or clinically overt bleeding that resulted in a hemoglobin decrease of greater than 3 g/dL.2
DVT was diagnosed if there was loss of compressibility on venous ultrasonography3 or evidence of a filling defect on conventional contrast venography. PE was diagnosed on the basis of findings on contrast-enhanced chest computed tomography4, ventilation-perfusion lung scanning, or invasive pulmonary angiography. Events suspected clinically to be VTE-related were not counted unless objective diagnostic imaging evidence was obtained. All end points were adjudicated by investigators who were unaware of the patients’ group assignments.
Statistical Analysis
We estimated a 4.1% rate for the primary end point in the intervention group and a 7% rate for the primary end point in the control group, with an odds ratio of 0.59. We estimated a sample size of approximately 2,150 patients for the study to have 80% power to detect a difference between the intervention and control group (two-sided alpha of 5%). We aimed for trial enrollment of approximately 2,500 patients, to provide a “cushion” of about 350 patients for potential administrative problems such as improper randomization or withdrawal from the study.
We used Wilcoxon rank-sum tests to compare the distributions of continuous variables between groups and chi-square tests or Fisher’s exact tests to compare categorical variables. Freedom from DVT or PE at day 90 for the intervention and control groups was estimated using the Kaplan-Meier method. Standard errors were estimated using Greenwood’s formula. The comparison between the intervention and control groups was assessed by log-rank test. We employed the proportional-hazards model to estimate the relative hazard of clinical end points associated with the physician alert and obtained 95% confidence intervals from this model. All reported p-values are two-sided. The authors had full access to the data and take responsibility for its integrity. All authors have read and agree to the manuscript as written.
Baseline Demographic and Clinical Characteristics
The intervention and control groups were similar with regard to baseline characteristics, except that patients randomized to a physician alert were more likely to be older than 75 years (42.5% versus 37.8%, p = 0.02) (Table 1). The overall study population (intervention and control groups) was comprised of 46.1% women and 53.9% men. Nearly two-thirds of the study population had a VTE risk score of 4. The remaining 35.5% had a VTE risk score of 5 or greater. Overall, 18% of patients had undergone major surgery, and 82% were hospitalized for nonsurgical indications. Almost 30% of patients had suffered prior VTE, and nearly 75% had a history of cancer.
Table 1
Table 1
Baseline characteristics.*
Venous Thromboembolism Prophylaxis
Patients in the intervention group were more than twice as likely to receive VTE prophylaxis as those in the control group (46.0% versus 20.6%, respectively; 95% confidence interval [CI], 21.8% to 28.9%) (Table 2). The intervention group had a three-times higher rate of mechanical prophylaxis (20.8% versus 7.6%, 95% CI, 10.6% to 16.0%) and a two-times higher rate of pharmacological prophylaxis (27.7% versus 14.1%, 95% CI, 10.5% to 16.8%) than the control group. Urban sites were less likely to prescribe VTE prophylaxis after a physician alert than non-urban sites (43.3% versus 48.8%, p = 0.02). There was no difference in VTE prophylaxis rates after a physician alert between academic and nonacademic sites.
Table 2
Table 2
Venous thromboembolism prophylaxis.*
Study End Points
The primary end point of symptomatic DVT or PE at 90 days occurred in 32 patients in the intervention group (2.7%) compared with 41 patients in the control group (3.4%) (hazard ratio, 0.79; 95% CI, 0.50 to 1.25) (Table 3). There was a non-significant trend toward reduction in symptomatic proximal lower extremity DVT among patients in the intervention group (0.3% versus 1.0%; hazard ratio, 0.34; 95% CI, 0.11 to 1.04). Kaplan-Meier estimates of the absence of symptomatic DVT or PE at 90 days were 97.1% (95% CI, 96.1 to 98.1) in the intervention group and 96.3% (95% CI, 95.1 to 97.5) in the control group (Figure 2). There was no significant difference in the rate of VTE at 90 days between the intervention group and the control group in clinically important subgroups, including patients with a risk score of greater than 4, age greater than or equal to 70 years, cancer, major surgery or trauma, and prior VTE.
Table 3
Table 3
Study end points.
Figure 2
Figure 2
Kaplan-Meier estimates of the absence of symptomatic deep vein thrombosis or pulmonary embolism in the intervention group and the control group (p = 0.31 by the log-rank test for comparison of the outcome between groups at 90 days).
The overall rate of death at 90 days was similar between the intervention group and control group (Table 3). The rate of major bleeding at 30 days in the intervention group was similar to the control group (2.1% versus 2.3%, p=0.68).
We observed a 21% reduction in symptomatic VTE with the use of physician alerts. This rate trended toward but did not achieve statistical significance. The overall rate of VTE prophylaxis was low, despite fewer than half of patients in the intervention group receiving any preventive measures. However, patients for whom a physician alert was issued were more than twice as likely to receive VTE prophylaxis.
In our prior trial of electronic alerts, the reduction in symptomatic VTE was 41%, compared with 21% in the present study. This was surprising because the median age was 73 years in this study compared with 63 years in the electronic alert study. A history of VTE was present in 30% in this study compared with 20% in the electronic alert trial. The older patient population and higher rate of prior VTE should have provided the substrate for higher baseline VTE rates and for greater reductions in symptomatic DVT and PE than we observed. Based upon the event rate in this trial, we would have needed to enroll approximately 9,000 patients to detect a significant difference (with 80% power) in symptomatic VTE between the two groups.
The most likely explanation for the lesser reduction in symptomatic VTE in this trial is the fundamental difference between the two trials: human versus computer alerts. We had thought that the “personal touch” of direct staff communication with the Attending Physician might be more effective than an impersonal computer-generated alert in raising awareness of a patient’s VTE risk, encouraging prophylaxis utilization, and reducing symptomatic VTE events. However, based on our data, it is likely that a computer alerting system is inherently more effective. Computer-based systems can provide direct access to a wide range of decision-support tools, including evidence-based practice guidelines, that would not be possible through a human alerting system.5, 6 A computer-based alerting system, such as the one used in our previous trial, may be more difficult to ignore because it forces the clinician to acknowledge the alert before the clinician can continue using the electronic medical record or order entry program.7 Finally, computer-based alerting systems aimed at improving VTE prophylaxis may maintain effectiveness over time better than a human alerting system.8 Nevertheless, we do recognize that there were no direct comparisons between the two alerting modalities and that the setting of the two studies was different.
While a smaller reduction in symptomatic VTE was noted with human alerts compared with computer alerts, VTE prophylaxis was ordered more often in the intervention group of the current trial (46%) compared with the intervention group of the prior study (33%). Although lower than expected, the reduction in symptomatic VTE may have reached significance if prophylaxis rates in the intervention group had been higher. For each 0.1% decrease in symptomatic VTE, the current study required a 4% increase in prophylaxis utilization. The trial would have achieved statistical significance if there had been an additional absolute decrease in symptomatic VTE of 0.6%, yielding a VTE rate of 2.1%. A prophylaxis rate of 74% rather than the observed 46% should have reduced the rate of symptomatic VTE to the target of 2.1%.
The decrease in the rate of symptomatic VTE in the control group of the current investigation may represent a possible time trend. There may be greater emphasis on early mobilization of hospitalized patients now compared with five years ago. At the conclusion of the previous electronic alert trial, we discontinued randomization and issued electronic alerts for all patients in a cohort of 866 patients who were high-risk for VTE and not receiving prophylaxis.9 The rate of symptomatic VTE within 90 days decreased to 5.1% in this follow-up cohort.9 In another study of hospitalized medical patients, the rate of clinically diagnosed DVT or PE within 90 days of hospital discharge was estimated to be as low as 1.6%.10
In the current trial, both the intervention and control groups had low rates of VTE prophylaxis, despite numerous studies demonstrating the safety and efficacy of pharmacological1115 and mechanical16, 17 modalities, as well as guidelines supporting the use of VTE prophylaxis in high-risk patients.18, 19 Patients in the intervention group received VTE prophylaxis less than half of the time, while those in the control group were prescribed prophylactic measures less than a quarter of the time. These findings are consistent with multiple recent studies demonstrating underutilization of VTE prophylaxis as an international public health crisis.2024
The majority of patients not receiving VTE prophylaxis and subsequently enrolled in the study (82%) were hospitalized medical patients. Similar to our previous trial, nearly 80% of these hospitalized medical patients had malignancy. Our observation of underutilization of VTE prophylaxis is consistent with previous data regarding VTE prevention among hospitalized patients on the Medical Service.25 In addition, 40% of patients enrolled in the study were older than 75 years, and VTE is particularly problematic in hospitalized elderly patients.26
The education of healthcare providers about the risk of VTE in hospitalized medical patients is critical.27 Hospital Grand Rounds, Continuing Medical Education courses, and Risk Management programs can increase VTE awareness among healthcare providers. Furthermore, VTE prevention in hospitalized patients is considered an important measure of healthcare quality.28, 29 Underutilization of VTE prophylaxis is a problem of such magnitude that organizations such as Medicare, the National Quality Forum, and the Joint Commission are focusing on a policy-based approach to VTE prevention. For example, the Centers for Medicare & Medicaid Services has announced that DVT or PE following total knee and hip replacement procedures are considered “never events”, and hospitals are no longer being reimbursed for this surgical complication, effective on October 1, 2008.30 Finally, patient advocacy groups, such as the North American Thrombosis Forum (www.natfonline.org), National Alliance for Thrombosis and Thrombophilia (www.stoptheclot.org), and the Coalition to Prevent DVT (www.preventdvt.org), increase public awareness and empower patients to participate in VTE prevention.
Our study may be limited by the possibility of diagnostic bias because the administration of prophylaxis was not blinded, and testing for VTE was not routinely performed unless symptoms were present. It is possible that physicians were more likely to pursue diagnostic testing for VTE for patients with symptoms who had not received prophylaxis than for those who had received prophylaxis. In addition, diagnostic testing may not have been performed in symptomatic patients with a limited life expectancy or contraindications to anticoagulation, resulting in an underestimation of events. Since most physicians treated both intervention and control patients, it is possible that receiving a physician alert for patients in the intervention group also affected the utilization of prophylaxis in the control group. In both the previous study of electronic alerts and our current trial, we wanted to select a study population in which there would be 100% consensus that every selected patient should receive VTE prophylaxis. Therefore, we utilized a VTE risk score that would permit us to capture an unequivocally high-risk population (cumulative risk score of at least 4 points). We acknowledge that a subset of patients with lower cumulative VTE risk scores would also be considered appropriate for VTE prophylaxis in clinical practice.
Our data suggest that a strategy of manually screening patients for VTE risk and alerting healthcare providers about high-risk patients who are not receiving prophylactic measures increases prophylaxis utilization and trends toward reduction of symptomatic VTE. However, a human alerting system does not appear to be as effective as a computer-based decision support strategy. Increasing resources for computer-based decision support strategies and medical informatics may enhance effectiveness of VTE prevention measures.
CLINICAL PERSPECTIVE
Despite published guidelines for VTE prevention, underutilization of prophylaxis in hospitalized patients remains problematic. We previously described a novel system utilizing electronic alerts to prevent symptomatic VTE in hospitalized patients. We created a computer program linked to the patient database to identify hospitalized patients at high risk for VTE who were not receiving prophylaxis and randomize notification (versus no notification) of physicians caring for these patients. The physicians in the intervention group received electronic alerts urging them to order prophylaxis. This resulted in a 41% reduction in symptomatic VTE at 90 days compared with the control group. Because it required an intricate electronic notification system and medical informatics support, this strategy could not be easily implemented by most hospitals. Therefore, we devised a clinical trial that employed a “human,” rather than electronic, alerting system. 2,493 patients were randomized to the intervention group, in which the Attending Physician was alerted by another hospital staff member by direct page, versus the control group, in which no alert was issued. Patients whose physicians were alerted were more than twice as likely to receive VTE prophylaxis. Although a “human” alerting system more than doubled VTE prophylaxis utilization, the ensuing 21% reduction in symptomatic VTE at 90 days did not achieve statistical significance (p=0.31). Increasing resources for computer-based decision support strategies may enhance effectiveness of VTE prevention measures.
Supplementary Material
Supp1
Acknowledgments
FUNDING SOURCES
This investigator-initiated study was funded, in part, by an unrestricted research grant from sanofi-aventis.
ABBREVIATIONS
BMIbody mass index
CIconfidence interval
DVTdeep vein thrombosis
PEpulmonary embolism
VTEvenous thromboembolism

Footnotes
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Journal Subject Codes: 18, 121, 122, 173
CONFLICT OF INTEREST DISCLOSURES
Gregory Piazza, MD- none
Erin J. Rosenbaum, BA- none
William Pendergast, MD- sanofi-aventis (Research Grant > $10,000, Speaker’s Bureau > $10,000, Consultant/Advisory Board < $10,000); Pfizer (Speaker’s Bureau < $10,000); Novartis (Speaker’s Bureau < $10,000)
Joseph O. Jacobson, MD- none
Robert C. Pendleton, MD- none
Gordon D. McLaren, MD- sanofi-aventis (Research Grant > $10,000); Bristol-Myers Squibb (Research Grant > $10,000)
C. Gregory Elliott, MD- none
Scott M. Stevens, MD- none
William F. Patton, MD- St. Joseph Mercy Health System (Honoraria < $10,000) Ousama Dabbagh, MD- Bristol-Myers Squibb (Research Grant > $10,000); Pfizer (Research Grant > $10,000); Missouri Society of Respiratory Therapists (Honoraria < $10,000)
Marilyn D. Paterno, MBI- none
Elaine Catapane, MEd, MT- none
Zhongzhen Li, MD- none
Samuel Z. Goldhaber, MD- sanofi-aventis (Research Grant > $10,000, Consultant/Advisory Board < $10,000); Eisai (Research Grant > $10,000, Consultant/Advisory Board < $10,000); Boehringer Ingelheim (Research Grant > $10,000, Consultant Advisory Board < $10,000); Bristol-Myers Squibb (Consultant Advisory Board < $10,000)
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