Protection of the Medicare program has reached new heights in recent years. One of the most important ways hospitalist groups can protect their Medicare funding is the discovery and recovery of improper contractor payments of Medicare claims.

The Centers for Medicare and Medicaid Services (CMS) reviews various types of contractors—Medicare administrative contractors (MACs),  carriers, durable medical equipment regional carriers (DMERCs), fiscal intermediaries (FIs), and quality improvement organizations (QIOs)—through its protection efforts as part of the Comprehensive Error Rate Testing (CERT) program and Hospital Payment Monitoring Program (HPMP). The CERT program’s contractors review physician (i.e., professional) claims processed by MACs and carriers.

The primary goal of a contractor is to “pay it right”—that is, pay the correct amount to the right provider for covered and correctly coded services.1 During the 12-month reporting period ending Sept. 30, 2007, the CERT program sampled 129,875 claims from carriers, DMERCs, FIs, and MACs.

The CERT contractor randomly and electronically selects about 172 claims each month from each type of claims-processing contractor. Since some of these contractors were transitioning to MACs, the target Part B (i.e., professional) sample size for the May 2008 report was approximately 2,000 reviewable claims per MAC cluster. However, this might have varied if a MAC was not processing claims during the entire sampling period.

click table for large version

click table for large version

Document Requests

Physicians need to be mindful of CERT requests for documentation. When possible, every attempt is made to benefit the physician. Initial CERT requests are attempted by way of a letter. If the physician does not respond within 30 days, the CERT contractor attempts one to three more contacts with correspondence and phone calls. If documentation is received after 75 days, it is considered “late.” It then will be reviewed, unless the reporting period has expired.

However, this should not be considered a prudent approach, and timely responses are ideal. If the physician offers no response, and documentation is not received, it is counted as a “no documentation” error.

Physicians often worry about accusations of fraud. The purpose of the CERT program is not to assume or accuse physicians of fraud, although it may serve as a deterrent. It does not, and cannot, label a claim fraudulent.

One scenario of potential fraud the CERT program is able to identify occurs when a CERT documentation contractor is unable to locate a provider or supplier when requesting medical record documentation.2

 

Outcomes

Individual contractors are notified of improper payments. These include overpayments and underpayments. Unfortunately, contractors do not have to resolve CERT issues involving underpayments, although they are encouraged to do so by CMS.

The CERT program identified overpayments totaling $875,005 during the 12-month reporting period, but collected only $650,418 in overpayments after consideration of appeals that overturned a CERT decision or the provider discontinued business operations. (See Table 1, p. 18, for error rates and Table 2, p. 18, for highest rates of improper payment)

To improve billing compliance and prevent repetitive errors, contractors must implement provider education regarding erroneously paid claims. A contractor may determine the best education method to distribute information about Medicare rules and effectively answer coverage and coding questions.

Some contractors have designed Web-based training modules, Web pages with frequently-asked-questions sections, or local coverage analyses to address contractor-specific errors. Detailed CERT contractor information can be found at www.cms.hhs.gov/ mcd/indexes.asp?from2=indexes.asp&

Due to its successful outcomes, future CMS goals include the continuation of the CERT program. MACs will look more closely at service types based on identified error rates.

Apart from CERT requests, prepayment contractor reviews already exist for most of the services included in Table 2 (p. 18). Timely response is crucial to justify and receive appropriate reimbursement. TH

Carol Pohlig is a billing and coding expert with the University of Pennsylvania Medical Center, Philadelphia. She is on the faculty of SHM’s inpatient coding course.

References

1. Centers for Medicare and Medicaid Services. Improper Medicare fee-for-service payments report: May 2008. CMS Web site. Available at: www.cms.hhs.gov/apps/er_report/preview_er_report.asp?from=public&which=long&reportID=9. Accessed Dec. 20, 2008.

2. Beebe M, Dalton J, Espronceda M, Evans D, Glenn R. Current Procedural Terminology Professional Edition. Chicago: American Medical Association; 2008.

Protection of the Medicare program has reached new heights in recent years. One of the most important ways hospitalist groups can protect their Medicare funding is the discovery and recovery of improper contractor payments of Medicare claims.

The Centers for Medicare and Medicaid Services (CMS) reviews various types of contractors—Medicare administrative contractors (MACs),  carriers, durable medical equipment regional carriers (DMERCs), fiscal intermediaries (FIs), and quality improvement organizations (QIOs)—through its protection efforts as part of the Comprehensive Error Rate Testing (CERT) program and Hospital Payment Monitoring Program (HPMP). The CERT program’s contractors review physician (i.e., professional) claims processed by MACs and carriers.

The primary goal of a contractor is to “pay it right”—that is, pay the correct amount to the right provider for covered and correctly coded services.1 During the 12-month reporting period ending Sept. 30, 2007, the CERT program sampled 129,875 claims from carriers, DMERCs, FIs, and MACs.

The CERT contractor randomly and electronically selects about 172 claims each month from each type of claims-processing contractor. Since some of these contractors were transitioning to MACs, the target Part B (i.e., professional) sample size for the May 2008 report was approximately 2,000 reviewable claims per MAC cluster. However, this might have varied if a MAC was not processing claims during the entire sampling period.

click table for large version

click table for large version

Document Requests

Physicians need to be mindful of CERT requests for documentation. When possible, every attempt is made to benefit the physician. Initial CERT requests are attempted by way of a letter. If the physician does not respond within 30 days, the CERT contractor attempts one to three more contacts with correspondence and phone calls. If documentation is received after 75 days, it is considered “late.” It then will be reviewed, unless the reporting period has expired.

However, this should not be considered a prudent approach, and timely responses are ideal. If the physician offers no response, and documentation is not received, it is counted as a “no documentation” error.

Physicians often worry about accusations of fraud. The purpose of the CERT program is not to assume or accuse physicians of fraud, although it may serve as a deterrent. It does not, and cannot, label a claim fraudulent.

One scenario of potential fraud the CERT program is able to identify occurs when a CERT documentation contractor is unable to locate a provider or supplier when requesting medical record documentation.2

 

Outcomes

Individual contractors are notified of improper payments. These include overpayments and underpayments. Unfortunately, contractors do not have to resolve CERT issues involving underpayments, although they are encouraged to do so by CMS.

The CERT program identified overpayments totaling $875,005 during the 12-month reporting period, but collected only $650,418 in overpayments after consideration of appeals that overturned a CERT decision or the provider discontinued business operations. (See Table 1, p. 18, for error rates and Table 2, p. 18, for highest rates of improper payment)

To improve billing compliance and prevent repetitive errors, contractors must implement provider education regarding erroneously paid claims. A contractor may determine the best education method to distribute information about Medicare rules and effectively answer coverage and coding questions.

Some contractors have designed Web-based training modules, Web pages with frequently-asked-questions sections, or local coverage analyses to address contractor-specific errors. Detailed CERT contractor information can be found at www.cms.hhs.gov/ mcd/indexes.asp?from2=indexes.asp&

Due to its successful outcomes, future CMS goals include the continuation of the CERT program. MACs will look more closely at service types based on identified error rates.

Apart from CERT requests, prepayment contractor reviews already exist for most of the services included in Table 2 (p. 18). Timely response is crucial to justify and receive appropriate reimbursement. TH

Carol Pohlig is a billing and coding expert with the University of Pennsylvania Medical Center, Philadelphia. She is on the faculty of SHM’s inpatient coding course.

References

1. Centers for Medicare and Medicaid Services. Improper Medicare fee-for-service payments report: May 2008. CMS Web site. Available at: www.cms.hhs.gov/apps/er_report/preview_er_report.asp?from=public&which=long&reportID=9. Accessed Dec. 20, 2008.

2. Beebe M, Dalton J, Espronceda M, Evans D, Glenn R. Current Procedural Terminology Professional Edition. Chicago: American Medical Association; 2008.

Protection of the Medicare program has reached new heights in recent years. One of the most important ways hospitalist groups can protect their Medicare funding is the discovery and recovery of improper contractor payments of Medicare claims.

The Centers for Medicare and Medicaid Services (CMS) reviews various types of contractors—Medicare administrative contractors (MACs),  carriers, durable medical equipment regional carriers (DMERCs), fiscal intermediaries (FIs), and quality improvement organizations (QIOs)—through its protection efforts as part of the Comprehensive Error Rate Testing (CERT) program and Hospital Payment Monitoring Program (HPMP). The CERT program’s contractors review physician (i.e., professional) claims processed by MACs and carriers.

The primary goal of a contractor is to “pay it right”—that is, pay the correct amount to the right provider for covered and correctly coded services.1 During the 12-month reporting period ending Sept. 30, 2007, the CERT program sampled 129,875 claims from carriers, DMERCs, FIs, and MACs.

The CERT contractor randomly and electronically selects about 172 claims each month from each type of claims-processing contractor. Since some of these contractors were transitioning to MACs, the target Part B (i.e., professional) sample size for the May 2008 report was approximately 2,000 reviewable claims per MAC cluster. However, this might have varied if a MAC was not processing claims during the entire sampling period.

click table for large version

click table for large version

Document Requests

Physicians need to be mindful of CERT requests for documentation. When possible, every attempt is made to benefit the physician. Initial CERT requests are attempted by way of a letter. If the physician does not respond within 30 days, the CERT contractor attempts one to three more contacts with correspondence and phone calls. If documentation is received after 75 days, it is considered “late.” It then will be reviewed, unless the reporting period has expired.

However, this should not be considered a prudent approach, and timely responses are ideal. If the physician offers no response, and documentation is not received, it is counted as a “no documentation” error.

Physicians often worry about accusations of fraud. The purpose of the CERT program is not to assume or accuse physicians of fraud, although it may serve as a deterrent. It does not, and cannot, label a claim fraudulent.

One scenario of potential fraud the CERT program is able to identify occurs when a CERT documentation contractor is unable to locate a provider or supplier when requesting medical record documentation.2

 

Outcomes

Individual contractors are notified of improper payments. These include overpayments and underpayments. Unfortunately, contractors do not have to resolve CERT issues involving underpayments, although they are encouraged to do so by CMS.

The CERT program identified overpayments totaling $875,005 during the 12-month reporting period, but collected only $650,418 in overpayments after consideration of appeals that overturned a CERT decision or the provider discontinued business operations. (See Table 1, p. 18, for error rates and Table 2, p. 18, for highest rates of improper payment)

To improve billing compliance and prevent repetitive errors, contractors must implement provider education regarding erroneously paid claims. A contractor may determine the best education method to distribute information about Medicare rules and effectively answer coverage and coding questions.

Some contractors have designed Web-based training modules, Web pages with frequently-asked-questions sections, or local coverage analyses to address contractor-specific errors. Detailed CERT contractor information can be found at www.cms.hhs.gov/ mcd/indexes.asp?from2=indexes.asp&

Due to its successful outcomes, future CMS goals include the continuation of the CERT program. MACs will look more closely at service types based on identified error rates.

Apart from CERT requests, prepayment contractor reviews already exist for most of the services included in Table 2 (p. 18). Timely response is crucial to justify and receive appropriate reimbursement. TH

Carol Pohlig is a billing and coding expert with the University of Pennsylvania Medical Center, Philadelphia. She is on the faculty of SHM’s inpatient coding course.

References

1. Centers for Medicare and Medicaid Services. Improper Medicare fee-for-service payments report: May 2008. CMS Web site. Available at: www.cms.hhs.gov/apps/er_report/preview_er_report.asp?from=public&which=long&reportID=9. Accessed Dec. 20, 2008.

2. Beebe M, Dalton J, Espronceda M, Evans D, Glenn R. Current Procedural Terminology Professional Edition. Chicago: American Medical Association; 2008.

Sunil Kripalani, MD, MSc, chief of hospital medicine at Vanderbilt University in Nashville, Tenn., was working in the emergency department when a woman arrived with an asthma exacerbation. The woman, who spoke only Spanish, had been hospitalized just five days earlier for asthma, and hospital staff had given her discharge instructions through her husband. Speaking to the patient in Spanish, Dr. Kripalani soon learned something had been lost in translation: The patient had not taken any of the prescribed prednisone tablets, and instead was taking a burst of montelukast. She also was taking a long-acting bronchodilator every two hours instead of every 12, and she was incorrectly using her rescue inhaler.

As the principal investigator of a trial aiming to reduce post-discharge adverse events and emergency room visits, Dr. Kripalani knows well the issues that contributed to the patient’s re-hospitalization.1 Through research, he and his colleagues hope to prevent future cases.

“It’s very rewarding to identify problems in the care of hospitalized patients and then develop and evaluate interventions to solve those problems,” says Dr. Kripalani, a 2001 graduate of the Emory Mentored Clinical Research Scholars Program who also leads Vanderbilt University’s hospital medicine fellowship. “Sharing those solutions with colleagues so they can be applied to patient care at my institution and others brings the research full circle.”

As the field of hospital medicine grows, the number of hospitalists moving into research careers is expanding, says Peter Kaboli, MD, MS, associate professor in the Department of Internal Medicine at the University of Iowa and a 2001 graduate of the Veterans Administration Quality Scholars Fellowship program. Research training programs, or fellowships, put hospitalists on the path to new skills and position them for careers in academic medicine and other leadership positions, Dr. Kaboli says. Training programs also put fellows in contact with mentors who provide valuable guidance.

Although there are dozens of general internal medicine (GIM) fellowships available to hospitalists, few programs are specifically designed to train hospitalists in research. “Hospital medicine is still a relatively new field,” Dr. Kaboli explains. “The field still does not have many research training options that are separate from general internal medicine.”

Still, hospitalists have advanced training choices, and, depending on their interests, can pursue field-specific programs or follow a general internal medicine path.

 

Career Investment

Many hospitalists receive basic research training from GIM fellowships. Once they have a research foundation, they can take their experience in another direction.

“Some physicians use their clinical interest—hospital medicine—as the platform for their research,” Dr. Kaboli says, using his own resume as an example. “It’s a nice synergy—doing research in a clinical area of interest.”

Physicians interested in fellowships often start looking for opportunities before they complete their residency, or immediately after. The transition makes sense for some; they move from one academic setting to another. Others, however, consider fellowship programs after they have spent some time in practice and get what Dr. Kaboli calls “boots-on-the-ground experience.”

“I think this is an area where there is potential for growth,” Dr. Kaboli says of physicians returning to fellowship programs after years spent in practice. “It’s the equivalent of a businessperson going back to school to get an MBA. They say, ‘Now I understand what this job really means, and I want to do more.’ ”

The caveat is a pay cut. Physicians in fellowship programs generally are paid a stipend of about $50,000 a year, Kaboli says. By comparison, the average hospitalist makes about $193,000 per year, according to SHM’s 2007-2008 Bi-Annual Survey on the State of Hospital Medicine. For two years, fellows devote their lives to training, coursework, and research, and spend only about 25% of their time treating patients, he says.

Road to Research

Hospitalists can choose from a range of general internal medicine fellowships at universities, clinics, and medical centers across the country. Each program offers something different; the fit depends on the candidates’ interests, says Geri Barnes, SHM senior director of education and meetings. For instance, training programs offer advanced study in the areas of biostatistics, epidemiology, and research methodology, to name a few. GIM fellowships (see “To Be or Not to Be a Fellow,” May 2006, p. 26) encourage scholars to develop relationships with mentors to guide them through research projects, she explains. A program’s duration can span one to three years. Some programs give fellows the opportunity to earn an advanced degree in quality improvement, clinical research, public policy, health studies, public health, or clinical epidemiology.

A handful of institutions, including Johns Hopkins Hospital in Baltimore, offer GIM fellowships with a hospital medicine emphasis. The National Institutes of Health (NIH) funds the Johns Hopkins program with training grants, says Daniel J. Brotman, MD, director of the hospitalist program there. GIM leadership is taking a “big tent” approach, promoting the development of hospital medicine tracks within the full program, which is good for the fellowship and for the hospitalist program, Dr. Brotman says.

“Some of the challenges for hospitalists are that they are generally young and don’t have the skills to succeed in academic medicine,” Dr. Brotman says, “and the number of mentors in hospitalist medicine is few and far between. [The fellowship] allows scholars to tap into experienced research mentors who may not be hospitalists themselves but are interested in investigating research questions and promoting academic careers in hospitalist medicine.”

The GIM program at Johns Hopkins draws physicians trained in internal medicine as well as general medicine/pediatrics. Candidates are required to have completed an internal medicine or medicine/pediatrics residency and must provide strong letters of recommendation. Scholars receive training in statistical methods while obtaining a master’s degree in public health or health science at the Johns Hopkins Bloomberg School of Public Health. Fellows commit 80% of their time to research and research training, and 20% of their time to clinical duties; they are expected to form relationships with faculty, which ultimately leads to careers in academia or public health, Dr. Brotman explains.

 

Minimize Burnout

Physician burnout—so common in the current healthcare system—is an excellent reason to consider a research career. Five years ago, David Meltzer, MD, PhD, an associate professor in the Department of Medicine at the University of Chicago, wanted to increase the number of research-trained hospitalists, so he moved to create a hospitalist training program. Around the same time, the hospital approached Dr. Meltzer and others, asking them to expand the number of clinical physician positions.

“We were afraid the new physicians would burn out rather quickly if their jobs included only clinical work,” Dr. Meltzer says. “We designed positions that had less clinical work but more time for physicians to develop research skills to support sustainable academic careers.”

Hospital leaders agreed, and the university’s Hospitalist Scholars Training Program was born. The two-year curriculum trains hospitalists for a career in academic research, and combines inpatient clinical work, coursework, and mentored training related to an academic project. Scholars typically leave the program with a master’s degree in public policy or health studies.

“Most of our graduates are working in academic research,” Dr. Meltzer says. “The program has been a great source of new faculty for us.”

Short-term programs are available in select topics. For example, the University of Chicago offers a summer program in outcomes research training for hospitalists interested in careers in health research, Dr. Meltzer says. SHM and the Agency for Healthcare Research and Quality have provided funding to expand the program to include as many as six hospitalists from around the country.

Pioneer Program

Applicants from any medical or surgical specialty are eligible to apply for the Robert Wood Johnson (RWJ) Clinical Scholars Program, the nation’s oldest research training program for physicians in health services, research, and leadership.

“The mandate of Robert Wood Johnson is ‘health and healthcare for all Americans,’ ” says Desmond Runyan, MD, DrPH, national program director of the RWJ Clinical Scholars Program. “We give physicians the skills they need to be leaders, and then we push them out the door so they can go out and shape the future of healthcare in this country.”

Applicants must be U.S. citizens and, with the exception of surgeons, must complete their residency training before entering the clinical scholars program. The two-year program offers a master’s degree in graduate-level study and research, and scholars may be considered for a third year of support. Scholars have their choice of four training sites: the University of California at Los Angeles; Yale University in New Haven, Conn.; the University of Pennsylvania in Philadelphia; or the University of Michigan in Ann Arbor.

Programs vary, but each university has a curriculum to teach the basics of healthcare research. It also provides protected time for research; about 20% of time is spent on clinical activities, according to the program’s Web site. Graduates receive leadership, health services, and community-based research training.

The RWJ Foundation spends about $9 million per year on the program, which covers research support, salaries for scholars and program administrators, travel, and other expenses. About half of the program’s graduates go into academic positions; the other half go into public health or other leadership positions. One recent graduate opted for a position in quality control; three other graduates serve as staff in the U.S. House of Representatives and the U.S. Senate, he says. Other graduates work with foundations, state and federal health agencies, or with companies working in the healthcare industry.

“This program looks for people who don’t march to a standard drummer,” Dr. Runyon says. “We are looking for risk-takers who want to make a difference.”

 

VA Training

The Veterans Administration National Quality Scholars Fellowship Program (VAQS) welcomes physicians from all medical specialties, including pathology, OB/GYN, surgery, and dermatology. This year, the program will begin recruiting nurses.

The program is offered at six academic-affiliated VA medical centers: Iowa City, Iowa; Nashville, Tenn.; Birmingham, Ala.; Cleveland; San Francisco; and White River Junction, Vt. The Iowa City and Nashville programs have a track designed specifically for hospitalists. These tracks focus on clinical research and quality improvement work in the inpatient setting, and provide fellows with training for advancement in academic and private-sector hospitalist careers, says Dr. Kaboli, the Iowa City VAQS Fellowship director.

To qualify, fellowship applicants must have completed an Accreditation Council for Graduate Medical Education residency or fellowship (see “A Pregnant Pause: The necessary evolution of residency training,” January 2007, p. 35), be board-eligible or board-certified, and have an active, unrestricted U.S. license to practice. International graduates must meet visa and Educational Commission for Foreign Medical Graduates requirements.

The two-year VAQS focuses on quality improvement in healthcare, Dr. Kaboli says. The program offers master’s-level training in epidemiology and biostatistics, and trains fellows to design and conduct research and improvement projects. Fellows publish the results of their research in peer-reviewed journals. They also learn how to write grants to gain funding for future projects.

Mentoring is an important element of the VAQS program, Dr. Kaboli says, adding that the value a trainee receives from any fellowship depends on the level of mentoring available through the program. Fellows work with senior faculty members who provide guidance on all aspects of research, Dr. Kaboli says. This includes study design, research methodology, data collection and analyses, and writing.

New experiences and the opportunity to take part in research are among the benefits of completing the VAQS program, Dr. Kaboli says. Some physicians also find a great deal of career satisfaction through research.

“I love seeing patients,” Dr. Kaboli says, “but I also like the challenge of doing research to find new ways to improve patient care.” TH

Gina Gotsill is a freelance medical writer based in California.

Reference

1. Ranji SR, Rosenman DJ, Amin AN, Kripalani S. Hospital medicine fellowship: works in progress. Am J Med. 2006;119;72.e1-72.e7.

Sunil Kripalani, MD, MSc, chief of hospital medicine at Vanderbilt University in Nashville, Tenn., was working in the emergency department when a woman arrived with an asthma exacerbation. The woman, who spoke only Spanish, had been hospitalized just five days earlier for asthma, and hospital staff had given her discharge instructions through her husband. Speaking to the patient in Spanish, Dr. Kripalani soon learned something had been lost in translation: The patient had not taken any of the prescribed prednisone tablets, and instead was taking a burst of montelukast. She also was taking a long-acting bronchodilator every two hours instead of every 12, and she was incorrectly using her rescue inhaler.

As the principal investigator of a trial aiming to reduce post-discharge adverse events and emergency room visits, Dr. Kripalani knows well the issues that contributed to the patient’s re-hospitalization.1 Through research, he and his colleagues hope to prevent future cases.

“It’s very rewarding to identify problems in the care of hospitalized patients and then develop and evaluate interventions to solve those problems,” says Dr. Kripalani, a 2001 graduate of the Emory Mentored Clinical Research Scholars Program who also leads Vanderbilt University’s hospital medicine fellowship. “Sharing those solutions with colleagues so they can be applied to patient care at my institution and others brings the research full circle.”

As the field of hospital medicine grows, the number of hospitalists moving into research careers is expanding, says Peter Kaboli, MD, MS, associate professor in the Department of Internal Medicine at the University of Iowa and a 2001 graduate of the Veterans Administration Quality Scholars Fellowship program. Research training programs, or fellowships, put hospitalists on the path to new skills and position them for careers in academic medicine and other leadership positions, Dr. Kaboli says. Training programs also put fellows in contact with mentors who provide valuable guidance.

Although there are dozens of general internal medicine (GIM) fellowships available to hospitalists, few programs are specifically designed to train hospitalists in research. “Hospital medicine is still a relatively new field,” Dr. Kaboli explains. “The field still does not have many research training options that are separate from general internal medicine.”

Still, hospitalists have advanced training choices, and, depending on their interests, can pursue field-specific programs or follow a general internal medicine path.

 

Career Investment

Many hospitalists receive basic research training from GIM fellowships. Once they have a research foundation, they can take their experience in another direction.

“Some physicians use their clinical interest—hospital medicine—as the platform for their research,” Dr. Kaboli says, using his own resume as an example. “It’s a nice synergy—doing research in a clinical area of interest.”

Physicians interested in fellowships often start looking for opportunities before they complete their residency, or immediately after. The transition makes sense for some; they move from one academic setting to another. Others, however, consider fellowship programs after they have spent some time in practice and get what Dr. Kaboli calls “boots-on-the-ground experience.”

“I think this is an area where there is potential for growth,” Dr. Kaboli says of physicians returning to fellowship programs after years spent in practice. “It’s the equivalent of a businessperson going back to school to get an MBA. They say, ‘Now I understand what this job really means, and I want to do more.’ ”

The caveat is a pay cut. Physicians in fellowship programs generally are paid a stipend of about $50,000 a year, Kaboli says. By comparison, the average hospitalist makes about $193,000 per year, according to SHM’s 2007-2008 Bi-Annual Survey on the State of Hospital Medicine. For two years, fellows devote their lives to training, coursework, and research, and spend only about 25% of their time treating patients, he says.

Road to Research

Hospitalists can choose from a range of general internal medicine fellowships at universities, clinics, and medical centers across the country. Each program offers something different; the fit depends on the candidates’ interests, says Geri Barnes, SHM senior director of education and meetings. For instance, training programs offer advanced study in the areas of biostatistics, epidemiology, and research methodology, to name a few. GIM fellowships (see “To Be or Not to Be a Fellow,” May 2006, p. 26) encourage scholars to develop relationships with mentors to guide them through research projects, she explains. A program’s duration can span one to three years. Some programs give fellows the opportunity to earn an advanced degree in quality improvement, clinical research, public policy, health studies, public health, or clinical epidemiology.

A handful of institutions, including Johns Hopkins Hospital in Baltimore, offer GIM fellowships with a hospital medicine emphasis. The National Institutes of Health (NIH) funds the Johns Hopkins program with training grants, says Daniel J. Brotman, MD, director of the hospitalist program there. GIM leadership is taking a “big tent” approach, promoting the development of hospital medicine tracks within the full program, which is good for the fellowship and for the hospitalist program, Dr. Brotman says.

“Some of the challenges for hospitalists are that they are generally young and don’t have the skills to succeed in academic medicine,” Dr. Brotman says, “and the number of mentors in hospitalist medicine is few and far between. [The fellowship] allows scholars to tap into experienced research mentors who may not be hospitalists themselves but are interested in investigating research questions and promoting academic careers in hospitalist medicine.”

The GIM program at Johns Hopkins draws physicians trained in internal medicine as well as general medicine/pediatrics. Candidates are required to have completed an internal medicine or medicine/pediatrics residency and must provide strong letters of recommendation. Scholars receive training in statistical methods while obtaining a master’s degree in public health or health science at the Johns Hopkins Bloomberg School of Public Health. Fellows commit 80% of their time to research and research training, and 20% of their time to clinical duties; they are expected to form relationships with faculty, which ultimately leads to careers in academia or public health, Dr. Brotman explains.

 

Minimize Burnout

Physician burnout—so common in the current healthcare system—is an excellent reason to consider a research career. Five years ago, David Meltzer, MD, PhD, an associate professor in the Department of Medicine at the University of Chicago, wanted to increase the number of research-trained hospitalists, so he moved to create a hospitalist training program. Around the same time, the hospital approached Dr. Meltzer and others, asking them to expand the number of clinical physician positions.

“We were afraid the new physicians would burn out rather quickly if their jobs included only clinical work,” Dr. Meltzer says. “We designed positions that had less clinical work but more time for physicians to develop research skills to support sustainable academic careers.”

Hospital leaders agreed, and the university’s Hospitalist Scholars Training Program was born. The two-year curriculum trains hospitalists for a career in academic research, and combines inpatient clinical work, coursework, and mentored training related to an academic project. Scholars typically leave the program with a master’s degree in public policy or health studies.

“Most of our graduates are working in academic research,” Dr. Meltzer says. “The program has been a great source of new faculty for us.”

Short-term programs are available in select topics. For example, the University of Chicago offers a summer program in outcomes research training for hospitalists interested in careers in health research, Dr. Meltzer says. SHM and the Agency for Healthcare Research and Quality have provided funding to expand the program to include as many as six hospitalists from around the country.

Pioneer Program

Applicants from any medical or surgical specialty are eligible to apply for the Robert Wood Johnson (RWJ) Clinical Scholars Program, the nation’s oldest research training program for physicians in health services, research, and leadership.

“The mandate of Robert Wood Johnson is ‘health and healthcare for all Americans,’ ” says Desmond Runyan, MD, DrPH, national program director of the RWJ Clinical Scholars Program. “We give physicians the skills they need to be leaders, and then we push them out the door so they can go out and shape the future of healthcare in this country.”

Applicants must be U.S. citizens and, with the exception of surgeons, must complete their residency training before entering the clinical scholars program. The two-year program offers a master’s degree in graduate-level study and research, and scholars may be considered for a third year of support. Scholars have their choice of four training sites: the University of California at Los Angeles; Yale University in New Haven, Conn.; the University of Pennsylvania in Philadelphia; or the University of Michigan in Ann Arbor.

Programs vary, but each university has a curriculum to teach the basics of healthcare research. It also provides protected time for research; about 20% of time is spent on clinical activities, according to the program’s Web site. Graduates receive leadership, health services, and community-based research training.

The RWJ Foundation spends about $9 million per year on the program, which covers research support, salaries for scholars and program administrators, travel, and other expenses. About half of the program’s graduates go into academic positions; the other half go into public health or other leadership positions. One recent graduate opted for a position in quality control; three other graduates serve as staff in the U.S. House of Representatives and the U.S. Senate, he says. Other graduates work with foundations, state and federal health agencies, or with companies working in the healthcare industry.

“This program looks for people who don’t march to a standard drummer,” Dr. Runyon says. “We are looking for risk-takers who want to make a difference.”

 

VA Training

The Veterans Administration National Quality Scholars Fellowship Program (VAQS) welcomes physicians from all medical specialties, including pathology, OB/GYN, surgery, and dermatology. This year, the program will begin recruiting nurses.

The program is offered at six academic-affiliated VA medical centers: Iowa City, Iowa; Nashville, Tenn.; Birmingham, Ala.; Cleveland; San Francisco; and White River Junction, Vt. The Iowa City and Nashville programs have a track designed specifically for hospitalists. These tracks focus on clinical research and quality improvement work in the inpatient setting, and provide fellows with training for advancement in academic and private-sector hospitalist careers, says Dr. Kaboli, the Iowa City VAQS Fellowship director.

To qualify, fellowship applicants must have completed an Accreditation Council for Graduate Medical Education residency or fellowship (see “A Pregnant Pause: The necessary evolution of residency training,” January 2007, p. 35), be board-eligible or board-certified, and have an active, unrestricted U.S. license to practice. International graduates must meet visa and Educational Commission for Foreign Medical Graduates requirements.

The two-year VAQS focuses on quality improvement in healthcare, Dr. Kaboli says. The program offers master’s-level training in epidemiology and biostatistics, and trains fellows to design and conduct research and improvement projects. Fellows publish the results of their research in peer-reviewed journals. They also learn how to write grants to gain funding for future projects.

Mentoring is an important element of the VAQS program, Dr. Kaboli says, adding that the value a trainee receives from any fellowship depends on the level of mentoring available through the program. Fellows work with senior faculty members who provide guidance on all aspects of research, Dr. Kaboli says. This includes study design, research methodology, data collection and analyses, and writing.

New experiences and the opportunity to take part in research are among the benefits of completing the VAQS program, Dr. Kaboli says. Some physicians also find a great deal of career satisfaction through research.

“I love seeing patients,” Dr. Kaboli says, “but I also like the challenge of doing research to find new ways to improve patient care.” TH

Gina Gotsill is a freelance medical writer based in California.

Reference

1. Ranji SR, Rosenman DJ, Amin AN, Kripalani S. Hospital medicine fellowship: works in progress. Am J Med. 2006;119;72.e1-72.e7.

Sunil Kripalani, MD, MSc, chief of hospital medicine at Vanderbilt University in Nashville, Tenn., was working in the emergency department when a woman arrived with an asthma exacerbation. The woman, who spoke only Spanish, had been hospitalized just five days earlier for asthma, and hospital staff had given her discharge instructions through her husband. Speaking to the patient in Spanish, Dr. Kripalani soon learned something had been lost in translation: The patient had not taken any of the prescribed prednisone tablets, and instead was taking a burst of montelukast. She also was taking a long-acting bronchodilator every two hours instead of every 12, and she was incorrectly using her rescue inhaler.

As the principal investigator of a trial aiming to reduce post-discharge adverse events and emergency room visits, Dr. Kripalani knows well the issues that contributed to the patient’s re-hospitalization.1 Through research, he and his colleagues hope to prevent future cases.

“It’s very rewarding to identify problems in the care of hospitalized patients and then develop and evaluate interventions to solve those problems,” says Dr. Kripalani, a 2001 graduate of the Emory Mentored Clinical Research Scholars Program who also leads Vanderbilt University’s hospital medicine fellowship. “Sharing those solutions with colleagues so they can be applied to patient care at my institution and others brings the research full circle.”

As the field of hospital medicine grows, the number of hospitalists moving into research careers is expanding, says Peter Kaboli, MD, MS, associate professor in the Department of Internal Medicine at the University of Iowa and a 2001 graduate of the Veterans Administration Quality Scholars Fellowship program. Research training programs, or fellowships, put hospitalists on the path to new skills and position them for careers in academic medicine and other leadership positions, Dr. Kaboli says. Training programs also put fellows in contact with mentors who provide valuable guidance.

Although there are dozens of general internal medicine (GIM) fellowships available to hospitalists, few programs are specifically designed to train hospitalists in research. “Hospital medicine is still a relatively new field,” Dr. Kaboli explains. “The field still does not have many research training options that are separate from general internal medicine.”

Still, hospitalists have advanced training choices, and, depending on their interests, can pursue field-specific programs or follow a general internal medicine path.

 

Career Investment

Many hospitalists receive basic research training from GIM fellowships. Once they have a research foundation, they can take their experience in another direction.

“Some physicians use their clinical interest—hospital medicine—as the platform for their research,” Dr. Kaboli says, using his own resume as an example. “It’s a nice synergy—doing research in a clinical area of interest.”

Physicians interested in fellowships often start looking for opportunities before they complete their residency, or immediately after. The transition makes sense for some; they move from one academic setting to another. Others, however, consider fellowship programs after they have spent some time in practice and get what Dr. Kaboli calls “boots-on-the-ground experience.”

“I think this is an area where there is potential for growth,” Dr. Kaboli says of physicians returning to fellowship programs after years spent in practice. “It’s the equivalent of a businessperson going back to school to get an MBA. They say, ‘Now I understand what this job really means, and I want to do more.’ ”

The caveat is a pay cut. Physicians in fellowship programs generally are paid a stipend of about $50,000 a year, Kaboli says. By comparison, the average hospitalist makes about $193,000 per year, according to SHM’s 2007-2008 Bi-Annual Survey on the State of Hospital Medicine. For two years, fellows devote their lives to training, coursework, and research, and spend only about 25% of their time treating patients, he says.

Road to Research

Hospitalists can choose from a range of general internal medicine fellowships at universities, clinics, and medical centers across the country. Each program offers something different; the fit depends on the candidates’ interests, says Geri Barnes, SHM senior director of education and meetings. For instance, training programs offer advanced study in the areas of biostatistics, epidemiology, and research methodology, to name a few. GIM fellowships (see “To Be or Not to Be a Fellow,” May 2006, p. 26) encourage scholars to develop relationships with mentors to guide them through research projects, she explains. A program’s duration can span one to three years. Some programs give fellows the opportunity to earn an advanced degree in quality improvement, clinical research, public policy, health studies, public health, or clinical epidemiology.

A handful of institutions, including Johns Hopkins Hospital in Baltimore, offer GIM fellowships with a hospital medicine emphasis. The National Institutes of Health (NIH) funds the Johns Hopkins program with training grants, says Daniel J. Brotman, MD, director of the hospitalist program there. GIM leadership is taking a “big tent” approach, promoting the development of hospital medicine tracks within the full program, which is good for the fellowship and for the hospitalist program, Dr. Brotman says.

“Some of the challenges for hospitalists are that they are generally young and don’t have the skills to succeed in academic medicine,” Dr. Brotman says, “and the number of mentors in hospitalist medicine is few and far between. [The fellowship] allows scholars to tap into experienced research mentors who may not be hospitalists themselves but are interested in investigating research questions and promoting academic careers in hospitalist medicine.”

The GIM program at Johns Hopkins draws physicians trained in internal medicine as well as general medicine/pediatrics. Candidates are required to have completed an internal medicine or medicine/pediatrics residency and must provide strong letters of recommendation. Scholars receive training in statistical methods while obtaining a master’s degree in public health or health science at the Johns Hopkins Bloomberg School of Public Health. Fellows commit 80% of their time to research and research training, and 20% of their time to clinical duties; they are expected to form relationships with faculty, which ultimately leads to careers in academia or public health, Dr. Brotman explains.

 

Minimize Burnout

Physician burnout—so common in the current healthcare system—is an excellent reason to consider a research career. Five years ago, David Meltzer, MD, PhD, an associate professor in the Department of Medicine at the University of Chicago, wanted to increase the number of research-trained hospitalists, so he moved to create a hospitalist training program. Around the same time, the hospital approached Dr. Meltzer and others, asking them to expand the number of clinical physician positions.

“We were afraid the new physicians would burn out rather quickly if their jobs included only clinical work,” Dr. Meltzer says. “We designed positions that had less clinical work but more time for physicians to develop research skills to support sustainable academic careers.”

Hospital leaders agreed, and the university’s Hospitalist Scholars Training Program was born. The two-year curriculum trains hospitalists for a career in academic research, and combines inpatient clinical work, coursework, and mentored training related to an academic project. Scholars typically leave the program with a master’s degree in public policy or health studies.

“Most of our graduates are working in academic research,” Dr. Meltzer says. “The program has been a great source of new faculty for us.”

Short-term programs are available in select topics. For example, the University of Chicago offers a summer program in outcomes research training for hospitalists interested in careers in health research, Dr. Meltzer says. SHM and the Agency for Healthcare Research and Quality have provided funding to expand the program to include as many as six hospitalists from around the country.

Pioneer Program

Applicants from any medical or surgical specialty are eligible to apply for the Robert Wood Johnson (RWJ) Clinical Scholars Program, the nation’s oldest research training program for physicians in health services, research, and leadership.

“The mandate of Robert Wood Johnson is ‘health and healthcare for all Americans,’ ” says Desmond Runyan, MD, DrPH, national program director of the RWJ Clinical Scholars Program. “We give physicians the skills they need to be leaders, and then we push them out the door so they can go out and shape the future of healthcare in this country.”

Applicants must be U.S. citizens and, with the exception of surgeons, must complete their residency training before entering the clinical scholars program. The two-year program offers a master’s degree in graduate-level study and research, and scholars may be considered for a third year of support. Scholars have their choice of four training sites: the University of California at Los Angeles; Yale University in New Haven, Conn.; the University of Pennsylvania in Philadelphia; or the University of Michigan in Ann Arbor.

Programs vary, but each university has a curriculum to teach the basics of healthcare research. It also provides protected time for research; about 20% of time is spent on clinical activities, according to the program’s Web site. Graduates receive leadership, health services, and community-based research training.

The RWJ Foundation spends about $9 million per year on the program, which covers research support, salaries for scholars and program administrators, travel, and other expenses. About half of the program’s graduates go into academic positions; the other half go into public health or other leadership positions. One recent graduate opted for a position in quality control; three other graduates serve as staff in the U.S. House of Representatives and the U.S. Senate, he says. Other graduates work with foundations, state and federal health agencies, or with companies working in the healthcare industry.

“This program looks for people who don’t march to a standard drummer,” Dr. Runyon says. “We are looking for risk-takers who want to make a difference.”

 

VA Training

The Veterans Administration National Quality Scholars Fellowship Program (VAQS) welcomes physicians from all medical specialties, including pathology, OB/GYN, surgery, and dermatology. This year, the program will begin recruiting nurses.

The program is offered at six academic-affiliated VA medical centers: Iowa City, Iowa; Nashville, Tenn.; Birmingham, Ala.; Cleveland; San Francisco; and White River Junction, Vt. The Iowa City and Nashville programs have a track designed specifically for hospitalists. These tracks focus on clinical research and quality improvement work in the inpatient setting, and provide fellows with training for advancement in academic and private-sector hospitalist careers, says Dr. Kaboli, the Iowa City VAQS Fellowship director.

To qualify, fellowship applicants must have completed an Accreditation Council for Graduate Medical Education residency or fellowship (see “A Pregnant Pause: The necessary evolution of residency training,” January 2007, p. 35), be board-eligible or board-certified, and have an active, unrestricted U.S. license to practice. International graduates must meet visa and Educational Commission for Foreign Medical Graduates requirements.

The two-year VAQS focuses on quality improvement in healthcare, Dr. Kaboli says. The program offers master’s-level training in epidemiology and biostatistics, and trains fellows to design and conduct research and improvement projects. Fellows publish the results of their research in peer-reviewed journals. They also learn how to write grants to gain funding for future projects.

Mentoring is an important element of the VAQS program, Dr. Kaboli says, adding that the value a trainee receives from any fellowship depends on the level of mentoring available through the program. Fellows work with senior faculty members who provide guidance on all aspects of research, Dr. Kaboli says. This includes study design, research methodology, data collection and analyses, and writing.

New experiences and the opportunity to take part in research are among the benefits of completing the VAQS program, Dr. Kaboli says. Some physicians also find a great deal of career satisfaction through research.

“I love seeing patients,” Dr. Kaboli says, “but I also like the challenge of doing research to find new ways to improve patient care.” TH

Gina Gotsill is a freelance medical writer based in California.

Reference

1. Ranji SR, Rosenman DJ, Amin AN, Kripalani S. Hospital medicine fellowship: works in progress. Am J Med. 2006;119;72.e1-72.e7.

The Value of Medicare’s Nursing Home Ratings

Is it true that the government has gone public with ratings of nursing homes? If so, where can I find this information? Is this information useful?

H. Sawyer, Richmond, Va.

Dr. Hospitalist responds: Many healthcare providers are familiar with Medicare’s goal to improve the quality of inpatient care. Medicare reports this data at www.hospitalcompare.hhs.gov. The program has its critics, many of whom question whether checking off a list really represents an improved quality of care.

Analogous to its Web site with information about hospital care, Medicare recently unveiled a site with information about the quality of care that our nation’s nursing homes are delivering to Medicare beneficiaries. You can find this information at www.medicare.gov/nhcompare. Medi-care ranks nursing homes on a system that awards ratings from one to five stars, with five stars being the best. Medicare explains it created this rating system to “help consumers, their families, and caregivers compare nursing homes more easily and help identify areas about which you may want to ask questions.” Medicare utilized information from three sources of data to create this overall rating:

• Staffing;
• Quality measures; and
• Health inspections.

The site provides an individual rating for each piece of data and combines the info to determine a composite rating.

Pros and Cons

Medicare acknowledges the rating system has strengths and weaknesses. The staffing information is adjusted for acuity of illness in a given facility’s resident population. That said, the data is self-reported and gathered annually, so it reflects data from just two weeks out of the year. Medicare notes each facility is judged on 10 quality measures, but again, the data is self-reported, is not adjusted for severity, and represents just a few of the many aspects of care that may be important to residents and their families.

Medicare also notes the health inspections are comprehensive and require onsite visits by trained inspectors. Comparisons are best made between facilities in the same state.

Nursing Home Checklist

Aside from facility ratings, Medicare also provides the public with a “nursing home checklist” and encourages the public to take a printed copy of the checklist, along with other information provided on its Web site, when they visit a nursing home. Medicare encourages the public to “talk with the nursing home staff about the information.”

I found no surprising information on this checklist. It encourages the public to think about basic information, such as:

• Is the home Medicare- and Medicaid-certified?
• Is the facility close to family and friends, clean, free from unpleasant odors, and comfortable for its residents?
• Is there a physician present every day and available when necessary?
• Are licensed nurses available 24 hours a day; is an RN available eight hours per day, seven days per week.

The site says individuals should think about resident rooms and the areas outside the resident rooms. It also encourages the public to think about the food and activities available to residents.

Much like the program for evaluating hospital care, I believe Medicare has taken a reasonable first step in providing information to the public to evaluate the care being provided in our nation’s nursing homes. But you will not find information regarding nursing homes that do not accept Medicare. And this information is only about nursing homes, and does not include other types of residential facilities. TH

The Value of Medicare’s Nursing Home Ratings

Is it true that the government has gone public with ratings of nursing homes? If so, where can I find this information? Is this information useful?

H. Sawyer, Richmond, Va.

Dr. Hospitalist responds: Many healthcare providers are familiar with Medicare’s goal to improve the quality of inpatient care. Medicare reports this data at www.hospitalcompare.hhs.gov. The program has its critics, many of whom question whether checking off a list really represents an improved quality of care.

Analogous to its Web site with information about hospital care, Medicare recently unveiled a site with information about the quality of care that our nation’s nursing homes are delivering to Medicare beneficiaries. You can find this information at www.medicare.gov/nhcompare. Medi-care ranks nursing homes on a system that awards ratings from one to five stars, with five stars being the best. Medicare explains it created this rating system to “help consumers, their families, and caregivers compare nursing homes more easily and help identify areas about which you may want to ask questions.” Medicare utilized information from three sources of data to create this overall rating:

• Staffing;
• Quality measures; and
• Health inspections.

The site provides an individual rating for each piece of data and combines the info to determine a composite rating.

Pros and Cons

Medicare acknowledges the rating system has strengths and weaknesses. The staffing information is adjusted for acuity of illness in a given facility’s resident population. That said, the data is self-reported and gathered annually, so it reflects data from just two weeks out of the year. Medicare notes each facility is judged on 10 quality measures, but again, the data is self-reported, is not adjusted for severity, and represents just a few of the many aspects of care that may be important to residents and their families.

Medicare also notes the health inspections are comprehensive and require onsite visits by trained inspectors. Comparisons are best made between facilities in the same state.

Nursing Home Checklist

Aside from facility ratings, Medicare also provides the public with a “nursing home checklist” and encourages the public to take a printed copy of the checklist, along with other information provided on its Web site, when they visit a nursing home. Medicare encourages the public to “talk with the nursing home staff about the information.”

I found no surprising information on this checklist. It encourages the public to think about basic information, such as:

• Is the home Medicare- and Medicaid-certified?
• Is the facility close to family and friends, clean, free from unpleasant odors, and comfortable for its residents?
• Is there a physician present every day and available when necessary?
• Are licensed nurses available 24 hours a day; is an RN available eight hours per day, seven days per week.

The site says individuals should think about resident rooms and the areas outside the resident rooms. It also encourages the public to think about the food and activities available to residents.

Much like the program for evaluating hospital care, I believe Medicare has taken a reasonable first step in providing information to the public to evaluate the care being provided in our nation’s nursing homes. But you will not find information regarding nursing homes that do not accept Medicare. And this information is only about nursing homes, and does not include other types of residential facilities. TH

The Value of Medicare’s Nursing Home Ratings

Is it true that the government has gone public with ratings of nursing homes? If so, where can I find this information? Is this information useful?

H. Sawyer, Richmond, Va.

Dr. Hospitalist responds: Many healthcare providers are familiar with Medicare’s goal to improve the quality of inpatient care. Medicare reports this data at www.hospitalcompare.hhs.gov. The program has its critics, many of whom question whether checking off a list really represents an improved quality of care.

Analogous to its Web site with information about hospital care, Medicare recently unveiled a site with information about the quality of care that our nation’s nursing homes are delivering to Medicare beneficiaries. You can find this information at www.medicare.gov/nhcompare. Medi-care ranks nursing homes on a system that awards ratings from one to five stars, with five stars being the best. Medicare explains it created this rating system to “help consumers, their families, and caregivers compare nursing homes more easily and help identify areas about which you may want to ask questions.” Medicare utilized information from three sources of data to create this overall rating:

• Staffing;
• Quality measures; and
• Health inspections.

The site provides an individual rating for each piece of data and combines the info to determine a composite rating.

Pros and Cons

Medicare acknowledges the rating system has strengths and weaknesses. The staffing information is adjusted for acuity of illness in a given facility’s resident population. That said, the data is self-reported and gathered annually, so it reflects data from just two weeks out of the year. Medicare notes each facility is judged on 10 quality measures, but again, the data is self-reported, is not adjusted for severity, and represents just a few of the many aspects of care that may be important to residents and their families.

Medicare also notes the health inspections are comprehensive and require onsite visits by trained inspectors. Comparisons are best made between facilities in the same state.

Nursing Home Checklist

Aside from facility ratings, Medicare also provides the public with a “nursing home checklist” and encourages the public to take a printed copy of the checklist, along with other information provided on its Web site, when they visit a nursing home. Medicare encourages the public to “talk with the nursing home staff about the information.”

I found no surprising information on this checklist. It encourages the public to think about basic information, such as:

• Is the home Medicare- and Medicaid-certified?
• Is the facility close to family and friends, clean, free from unpleasant odors, and comfortable for its residents?
• Is there a physician present every day and available when necessary?
• Are licensed nurses available 24 hours a day; is an RN available eight hours per day, seven days per week.

The site says individuals should think about resident rooms and the areas outside the resident rooms. It also encourages the public to think about the food and activities available to residents.

Much like the program for evaluating hospital care, I believe Medicare has taken a reasonable first step in providing information to the public to evaluate the care being provided in our nation’s nursing homes. But you will not find information regarding nursing homes that do not accept Medicare. And this information is only about nursing homes, and does not include other types of residential facilities. TH

I always wear a sport coat and tie when I’m speaking, but I thought I knew the orthopedic psyche well enough to know they would be very casually dressed for their conference on a warm Saturday this past fall. I was stunned to see about 40 of the 60 orthopods in attendance wearing jackets and ties—a very dapper bunch. While I misjudged their fashion sense, I’m still confident I’ll fit in wearing a bow tie (borrowed, since I don’t own one) to a neurology conference or a Mickey Mouse tie to a pediatric conference.

I had been invited to speak at the Washington State Orthopedic Association last fall. (Maybe they spell it “orthopædics,” but that seems a little pretentious to me.) They wanted to hear about the latest trends in how orthopods and hospitalists collaborate in the care of patients, and how this interaction might evolve.

Attending or Consultants?

I told them that, in my experience, determining the best doctor to serve as attending for certain types of patients generates a wide range of sometimes passionately held opinions among hospitalists. In my consulting work with practices around the country, I’ve come across some hospitalists who are insistent that they should never serve as attending for patients whose primary reason for admission is:

• Hip fracture due to osteoporosis and fall from ground level;
• Nonoperative low-speed or low-impact trauma, such as pelvic fracture; and
• Limb infection with potential for compartment syndrome.

Interestingly, I’ve found that hospitalists almost universally admit patients with osteoporotic vertebral compression fractures, even if they strongly believe that they shouldn’t admit patients with pelvic fractures.

My own experience leads me to believe that hospitalists in most settings should plan to serve as attending for all of these patient types, if they aren’t already. For example, a hip fracture is essentially a marker for a sick and frail person with complex medical needs. While it is the marquee event of the hospital stay, surgical repair of the fracture is just one of many important things that need to happen before discharge. Most of these patients need attention for medical comorbidities—such as a urinary infection or decompensated heart failure—which often are the proximate cause of the fracture. The patient might need a discussion of medical directives, which usually is an area in which orthopods usually don’t excel (and I’m being kind to the orthopods).

Let me be clear: Reasonable people can conclude hospitalists should not serve as attending for the diagnoses listed above. SHM does not have a position on this, and I’m not speaking for all hospitalists. But don’t you think hospitalists opposed to admitting these types of patients will find themselves in a small and shrinking minority? It seems to me that the pressure to serve as attending for these patients is similar to surviving a riptide: You shouldn’t try to swim directly against the riptide toward shore, and instead should swim across it or even go with the flow.

Popular Term, No Universal Definition

I went on to talk with the orthopods about the concept of partnering with hospitalists to co-manage patients. Orthopods and hospital executives usually are enthusiastic supporters of the co-management idea, and hospitalists usually are supportive, though sometimes with a little less excitement than the others. In public, all three parties usually express confidence that co-management will be good for patient outcomes and have other benefits, such as improved efficiency. But in private, orthopods sometimes let on that their support of the idea is largely based on their belief that it relieves them of tedious paperwork and late-night phone calls.

 

A hospital CEO might not know the details of the co-management model, so the CEO’s public support of it often boils down to an analysis along the lines of “Isn’t co-management just a euphemism for hospitalists doing more of the scut work to keep the hospital’s money-making specialists—like orthopods—happy?” Even hospitalists themselves sometimes express public support for the idea, but privately are thinking, “These guys want me to do what?”

My view is that co-management is a broad term and can mean very different things from one institution to the next. The term “co-management” has a connotation of something new and progressive, and might help steer conversations about who does what in a more positive direction than the old vocabulary of who is dumping on whom—you know, the traditional role for the doctors in each specialty.

A terrific entry in “Debates in Hospital Medicine” that runs periodically in the Journal of Hospital Medicine offers two points of view. In the September/October 2008 issue of JHM, Christopher Whinney, MD, and Frank Michota, MD, of Cleveland Clinic took the stance in favor of co-management, and Eric Siegal, MD, SHM’s Public Policy Committee chair (and formerly in private and corporate hospitalist practice), raised concerns about co-management.1 The articles review what little—and in my view inconclusive—research exists on this topic but provide some thoughtful advice and opinions.

Issues to Address

As I have written in the past, I’m convinced hospitalists’ scope of practice will broaden and grow to include patients we don’t commonly admit today.2 But we will need to think carefully about how to mitigate the potential problems created by changes in how doctors divide responsibility for who does what. In the case of hospitalists serving as admitters and attending for hip fracture patients, I have concerns, such as:

• Will there be delays in going to the operating room or confusion regarding which orthopedist is responsible for the patient?
• Will the orthopedist be less available to talk with the patient and family post-op?
• How long before the orthopedist stops making post-op visits?
• Who decides about transfusion and manages post-op and discharge pain control, wound care, and rehab?
• Who gets the nighttime call regarding a laxative or sleeping pill?
• Who handles discharge paperwork?

Your list of concerns probably differs from mine, but you should take the time to write down the issues that concern you any time duties and responsibilities shift from one specialty to another. Keep that list handy the next time you talk with another specialty about co-management or other new ways of dividing the work to ensure good outcomes for patients, doctors (including hospitalists), and the healthcare system as a whole. TH

Dr. Nelson has been a practicing hospitalist since 1988 and is co-founder and past president of SHM. He is a principal in Nelson/Flores Associates, a national hospital practice management consulting firm. He is part of the faculty for SHM’s “Best Practices in Managing a Hospital Medicine Program” course. This column represents his views and is not intended to reflect an official SHM position.

References

1. Whinney C, Michota F, and Siegal EM. Surgical comanagement: a natural evolution of hospitalist practice. Just because you can, doesn’t mean that you should: A call for the rational application of hospitalist comanagement. J Hosp Med. 2008;3(5); 394-402.

2. Nelson J. Hip fractures to head bleeds: The hospitalist’s ever-changing scope of practice. The Hospitalist. 2006; 10(9);77.

I always wear a sport coat and tie when I’m speaking, but I thought I knew the orthopedic psyche well enough to know they would be very casually dressed for their conference on a warm Saturday this past fall. I was stunned to see about 40 of the 60 orthopods in attendance wearing jackets and ties—a very dapper bunch. While I misjudged their fashion sense, I’m still confident I’ll fit in wearing a bow tie (borrowed, since I don’t own one) to a neurology conference or a Mickey Mouse tie to a pediatric conference.

I had been invited to speak at the Washington State Orthopedic Association last fall. (Maybe they spell it “orthopædics,” but that seems a little pretentious to me.) They wanted to hear about the latest trends in how orthopods and hospitalists collaborate in the care of patients, and how this interaction might evolve.

Attending or Consultants?

I told them that, in my experience, determining the best doctor to serve as attending for certain types of patients generates a wide range of sometimes passionately held opinions among hospitalists. In my consulting work with practices around the country, I’ve come across some hospitalists who are insistent that they should never serve as attending for patients whose primary reason for admission is:

• Hip fracture due to osteoporosis and fall from ground level;
• Nonoperative low-speed or low-impact trauma, such as pelvic fracture; and
• Limb infection with potential for compartment syndrome.

Interestingly, I’ve found that hospitalists almost universally admit patients with osteoporotic vertebral compression fractures, even if they strongly believe that they shouldn’t admit patients with pelvic fractures.

My own experience leads me to believe that hospitalists in most settings should plan to serve as attending for all of these patient types, if they aren’t already. For example, a hip fracture is essentially a marker for a sick and frail person with complex medical needs. While it is the marquee event of the hospital stay, surgical repair of the fracture is just one of many important things that need to happen before discharge. Most of these patients need attention for medical comorbidities—such as a urinary infection or decompensated heart failure—which often are the proximate cause of the fracture. The patient might need a discussion of medical directives, which usually is an area in which orthopods usually don’t excel (and I’m being kind to the orthopods).

Let me be clear: Reasonable people can conclude hospitalists should not serve as attending for the diagnoses listed above. SHM does not have a position on this, and I’m not speaking for all hospitalists. But don’t you think hospitalists opposed to admitting these types of patients will find themselves in a small and shrinking minority? It seems to me that the pressure to serve as attending for these patients is similar to surviving a riptide: You shouldn’t try to swim directly against the riptide toward shore, and instead should swim across it or even go with the flow.

Popular Term, No Universal Definition

I went on to talk with the orthopods about the concept of partnering with hospitalists to co-manage patients. Orthopods and hospital executives usually are enthusiastic supporters of the co-management idea, and hospitalists usually are supportive, though sometimes with a little less excitement than the others. In public, all three parties usually express confidence that co-management will be good for patient outcomes and have other benefits, such as improved efficiency. But in private, orthopods sometimes let on that their support of the idea is largely based on their belief that it relieves them of tedious paperwork and late-night phone calls.

 

A hospital CEO might not know the details of the co-management model, so the CEO’s public support of it often boils down to an analysis along the lines of “Isn’t co-management just a euphemism for hospitalists doing more of the scut work to keep the hospital’s money-making specialists—like orthopods—happy?” Even hospitalists themselves sometimes express public support for the idea, but privately are thinking, “These guys want me to do what?”

My view is that co-management is a broad term and can mean very different things from one institution to the next. The term “co-management” has a connotation of something new and progressive, and might help steer conversations about who does what in a more positive direction than the old vocabulary of who is dumping on whom—you know, the traditional role for the doctors in each specialty.

A terrific entry in “Debates in Hospital Medicine” that runs periodically in the Journal of Hospital Medicine offers two points of view. In the September/October 2008 issue of JHM, Christopher Whinney, MD, and Frank Michota, MD, of Cleveland Clinic took the stance in favor of co-management, and Eric Siegal, MD, SHM’s Public Policy Committee chair (and formerly in private and corporate hospitalist practice), raised concerns about co-management.1 The articles review what little—and in my view inconclusive—research exists on this topic but provide some thoughtful advice and opinions.

Issues to Address

As I have written in the past, I’m convinced hospitalists’ scope of practice will broaden and grow to include patients we don’t commonly admit today.2 But we will need to think carefully about how to mitigate the potential problems created by changes in how doctors divide responsibility for who does what. In the case of hospitalists serving as admitters and attending for hip fracture patients, I have concerns, such as:

• Will there be delays in going to the operating room or confusion regarding which orthopedist is responsible for the patient?
• Will the orthopedist be less available to talk with the patient and family post-op?
• How long before the orthopedist stops making post-op visits?
• Who decides about transfusion and manages post-op and discharge pain control, wound care, and rehab?
• Who gets the nighttime call regarding a laxative or sleeping pill?
• Who handles discharge paperwork?

Your list of concerns probably differs from mine, but you should take the time to write down the issues that concern you any time duties and responsibilities shift from one specialty to another. Keep that list handy the next time you talk with another specialty about co-management or other new ways of dividing the work to ensure good outcomes for patients, doctors (including hospitalists), and the healthcare system as a whole. TH

Dr. Nelson has been a practicing hospitalist since 1988 and is co-founder and past president of SHM. He is a principal in Nelson/Flores Associates, a national hospital practice management consulting firm. He is part of the faculty for SHM’s “Best Practices in Managing a Hospital Medicine Program” course. This column represents his views and is not intended to reflect an official SHM position.

References

1. Whinney C, Michota F, and Siegal EM. Surgical comanagement: a natural evolution of hospitalist practice. Just because you can, doesn’t mean that you should: A call for the rational application of hospitalist comanagement. J Hosp Med. 2008;3(5); 394-402.

2. Nelson J. Hip fractures to head bleeds: The hospitalist’s ever-changing scope of practice. The Hospitalist. 2006; 10(9);77.

I always wear a sport coat and tie when I’m speaking, but I thought I knew the orthopedic psyche well enough to know they would be very casually dressed for their conference on a warm Saturday this past fall. I was stunned to see about 40 of the 60 orthopods in attendance wearing jackets and ties—a very dapper bunch. While I misjudged their fashion sense, I’m still confident I’ll fit in wearing a bow tie (borrowed, since I don’t own one) to a neurology conference or a Mickey Mouse tie to a pediatric conference.

I had been invited to speak at the Washington State Orthopedic Association last fall. (Maybe they spell it “orthopædics,” but that seems a little pretentious to me.) They wanted to hear about the latest trends in how orthopods and hospitalists collaborate in the care of patients, and how this interaction might evolve.

Attending or Consultants?

I told them that, in my experience, determining the best doctor to serve as attending for certain types of patients generates a wide range of sometimes passionately held opinions among hospitalists. In my consulting work with practices around the country, I’ve come across some hospitalists who are insistent that they should never serve as attending for patients whose primary reason for admission is:

• Hip fracture due to osteoporosis and fall from ground level;
• Nonoperative low-speed or low-impact trauma, such as pelvic fracture; and
• Limb infection with potential for compartment syndrome.

Interestingly, I’ve found that hospitalists almost universally admit patients with osteoporotic vertebral compression fractures, even if they strongly believe that they shouldn’t admit patients with pelvic fractures.

My own experience leads me to believe that hospitalists in most settings should plan to serve as attending for all of these patient types, if they aren’t already. For example, a hip fracture is essentially a marker for a sick and frail person with complex medical needs. While it is the marquee event of the hospital stay, surgical repair of the fracture is just one of many important things that need to happen before discharge. Most of these patients need attention for medical comorbidities—such as a urinary infection or decompensated heart failure—which often are the proximate cause of the fracture. The patient might need a discussion of medical directives, which usually is an area in which orthopods usually don’t excel (and I’m being kind to the orthopods).

Let me be clear: Reasonable people can conclude hospitalists should not serve as attending for the diagnoses listed above. SHM does not have a position on this, and I’m not speaking for all hospitalists. But don’t you think hospitalists opposed to admitting these types of patients will find themselves in a small and shrinking minority? It seems to me that the pressure to serve as attending for these patients is similar to surviving a riptide: You shouldn’t try to swim directly against the riptide toward shore, and instead should swim across it or even go with the flow.

Popular Term, No Universal Definition

I went on to talk with the orthopods about the concept of partnering with hospitalists to co-manage patients. Orthopods and hospital executives usually are enthusiastic supporters of the co-management idea, and hospitalists usually are supportive, though sometimes with a little less excitement than the others. In public, all three parties usually express confidence that co-management will be good for patient outcomes and have other benefits, such as improved efficiency. But in private, orthopods sometimes let on that their support of the idea is largely based on their belief that it relieves them of tedious paperwork and late-night phone calls.

 

A hospital CEO might not know the details of the co-management model, so the CEO’s public support of it often boils down to an analysis along the lines of “Isn’t co-management just a euphemism for hospitalists doing more of the scut work to keep the hospital’s money-making specialists—like orthopods—happy?” Even hospitalists themselves sometimes express public support for the idea, but privately are thinking, “These guys want me to do what?”

My view is that co-management is a broad term and can mean very different things from one institution to the next. The term “co-management” has a connotation of something new and progressive, and might help steer conversations about who does what in a more positive direction than the old vocabulary of who is dumping on whom—you know, the traditional role for the doctors in each specialty.

A terrific entry in “Debates in Hospital Medicine” that runs periodically in the Journal of Hospital Medicine offers two points of view. In the September/October 2008 issue of JHM, Christopher Whinney, MD, and Frank Michota, MD, of Cleveland Clinic took the stance in favor of co-management, and Eric Siegal, MD, SHM’s Public Policy Committee chair (and formerly in private and corporate hospitalist practice), raised concerns about co-management.1 The articles review what little—and in my view inconclusive—research exists on this topic but provide some thoughtful advice and opinions.

Issues to Address

As I have written in the past, I’m convinced hospitalists’ scope of practice will broaden and grow to include patients we don’t commonly admit today.2 But we will need to think carefully about how to mitigate the potential problems created by changes in how doctors divide responsibility for who does what. In the case of hospitalists serving as admitters and attending for hip fracture patients, I have concerns, such as:

• Will there be delays in going to the operating room or confusion regarding which orthopedist is responsible for the patient?
• Will the orthopedist be less available to talk with the patient and family post-op?
• How long before the orthopedist stops making post-op visits?
• Who decides about transfusion and manages post-op and discharge pain control, wound care, and rehab?
• Who gets the nighttime call regarding a laxative or sleeping pill?
• Who handles discharge paperwork?

Your list of concerns probably differs from mine, but you should take the time to write down the issues that concern you any time duties and responsibilities shift from one specialty to another. Keep that list handy the next time you talk with another specialty about co-management or other new ways of dividing the work to ensure good outcomes for patients, doctors (including hospitalists), and the healthcare system as a whole. TH

Dr. Nelson has been a practicing hospitalist since 1988 and is co-founder and past president of SHM. He is a principal in Nelson/Flores Associates, a national hospital practice management consulting firm. He is part of the faculty for SHM’s “Best Practices in Managing a Hospital Medicine Program” course. This column represents his views and is not intended to reflect an official SHM position.

References

1. Whinney C, Michota F, and Siegal EM. Surgical comanagement: a natural evolution of hospitalist practice. Just because you can, doesn’t mean that you should: A call for the rational application of hospitalist comanagement. J Hosp Med. 2008;3(5); 394-402.

2. Nelson J. Hip fractures to head bleeds: The hospitalist’s ever-changing scope of practice. The Hospitalist. 2006; 10(9);77.

Round One

“Plane down, mass casualties possible; initiate disaster plan.”

The page interrupted my evening out with friends a few Saturday nights ago. Looking up from my dinner, I noticed the restaurant television had cut away to a news story at Denver International Airport. Continental Flight 1404, en route to Houston, had crashed during takeoff, belly-flopping to a fiery rest a few hundred yards off the runway. The airport is about 10 miles from the nearest hospital—mine.

The situation ended considerably better than originally expected. Thirty-eight people were treated at several Denver hospitals, 11 of them at my hospital, with most patients discharged from the emergency department. No one died. The case remains under review, and little is known about the cause of the crash.

Round Two

“Give me a call. I need to talk to you urgently.”

That page arrived the following Monday morning. It was from a co-worker. There had been an unexpected bad outcome in a young male patient. The hospital’s quality and risk management group had found out about the case and called for a peer review. My colleague was scared; would he be publicly criticized? Punished? Fired?

The patient had been admitted with a chronic disease flare-up. He was on the mend after receiving an increased dose of medication. The night before he was scheduled to be discharged, he developed a new symptom, was evaluated by the cross-cover team, and a plan was set in motion. However, a critical lab result, which became available overnight, mistakenly was not called to the provider and went unnoticed by the primary team that triaged the patient to the end of the team’s rounds. By then, he was in extremis.

Getty Images

Planes and Patients

The proximity of these two events provoked comparisons.

By now, comparing healthcare to the aviation industry has become cliché. Both industries demand highly trained and skilled conductors; errors in both industries can result in death; both depend on technology; and both have turned to systems engineering to improve efficiencies and reduce mistakes. This is where the two industries diverge, and I think we get it wrong in medicine.

In aviation, there are very proscriptive algorithms that must be followed, and much of a pilot’s work is under constant scrutiny by air traffic controllers and data recorders. A deviation in protocol rarely goes unnoticed. Errors are systematically compiled, scrutinized, and compartmentalized, with the aim of further refining systems to reduce the likelihood of future errors. Although blame is often prescribed, it is in the context of improving the system. Thus, the aviation industry is awash with data to inform and fuel its systems engineering.

Meanwhile, in medicine our indelible sense of autonomy breeds variability, which is not only tolerated, but often goes unnoticed. Further, we employ a model of error analysis that focuses on affixing blame, as if somehow culpability will prevent future errors. Someone made an error, a bad outcome ensued, and the culprit must be identified and punished. This results in reprimand, remediation, or banishment from the medical staff. At times, this is an appropriate response, as some errors are so egregious or indicative of a chronic problem. More often, the punitive process misses the mark because it focuses on blame instead of prevention of the next error. Unlike the aviation industry, this leaves medicine bereft of data for improving our care systems.

 

“Blame and Punish” Doesn’t Work

There are two problems with the “blame and punish” approach. First, it is predicated on the belief that providers make errors because they are poorly trained, inept, or just plain careless. Sometimes this is the case.

However, the vast majority of peer reviews that I’ve participated in involved an error performed by extremely well trained, highly skilled clinicians with the highest level of integrity and vigilance. The real problem lies in the human condition.

Humans make mistakes. Always have, always will.

In college, I worked summers in a factory that applied coating to paper. This combined colossal machines spinning at breakneck speeds, huge rolls of paper, and hands—a recipe for handless employees. But accidents rarely happened. Over time, the mill engineers had designed systems so foolproof that the workers couldn’t chop their hands off, even if they wanted to. This level of safety was achieved, in principle, by learning how errors were made so that future errors could be prevented. It was not achieved by blaming handless employees. This paper-plant process recognizes the fallible nature of human beings; it’s the same recognition we need in medicine.

Whether we commit a systems error (e.g., the lab test results arrived after the patient was discharged), a cognitive error (e.g., I continue to believe this pulmonary embolism is pneumonia because my night-coverage partner signed it out as pneumonia), or simply a human error (e.g., the lab forgot to call a critical result to the ordering physician), we work in systems that often result in errors. And the only meaningful hope we have to reduce errors depends on our ability to identify them and build systems so safe that we couldn’t hurt a patient, even if we tried.

This leads to the second problem with the blame-and-punish mentality: It breeds concealment of errors, as providers become reticent to expose mistakes for fear of retribution. Thus, an important pipeline of information about system deficiencies dries up, and we are left to suffer the same cycle of errors.

Budging the quality and patient-safety needle will require a culture that freely and openly admits mistakes in order to analyze and prevent future mistakes. This is inherently difficult for most of us to do, and next to impossible when we fear reprimand. Then again, if we endeavor to fundamentally enhance the safety of hospital care, we must allow providers to openly discuss errors without fear of rebuke. Accomplishing this will require understanding, leadership and action—and it starts with each of us.

Anything short of this will just result in more bad pages. TH

Dr. Glasheen is associate professor of medicine at the University of Colorado Denver, where he serves as director of Hospital Medicine and the Hospitalist Training Program, and as associate program director of the Internal Medicine Residency Program.

Round One

“Plane down, mass casualties possible; initiate disaster plan.”

The page interrupted my evening out with friends a few Saturday nights ago. Looking up from my dinner, I noticed the restaurant television had cut away to a news story at Denver International Airport. Continental Flight 1404, en route to Houston, had crashed during takeoff, belly-flopping to a fiery rest a few hundred yards off the runway. The airport is about 10 miles from the nearest hospital—mine.

The situation ended considerably better than originally expected. Thirty-eight people were treated at several Denver hospitals, 11 of them at my hospital, with most patients discharged from the emergency department. No one died. The case remains under review, and little is known about the cause of the crash.

Round Two

“Give me a call. I need to talk to you urgently.”

That page arrived the following Monday morning. It was from a co-worker. There had been an unexpected bad outcome in a young male patient. The hospital’s quality and risk management group had found out about the case and called for a peer review. My colleague was scared; would he be publicly criticized? Punished? Fired?

The patient had been admitted with a chronic disease flare-up. He was on the mend after receiving an increased dose of medication. The night before he was scheduled to be discharged, he developed a new symptom, was evaluated by the cross-cover team, and a plan was set in motion. However, a critical lab result, which became available overnight, mistakenly was not called to the provider and went unnoticed by the primary team that triaged the patient to the end of the team’s rounds. By then, he was in extremis.

Getty Images

Planes and Patients

The proximity of these two events provoked comparisons.

By now, comparing healthcare to the aviation industry has become cliché. Both industries demand highly trained and skilled conductors; errors in both industries can result in death; both depend on technology; and both have turned to systems engineering to improve efficiencies and reduce mistakes. This is where the two industries diverge, and I think we get it wrong in medicine.

In aviation, there are very proscriptive algorithms that must be followed, and much of a pilot’s work is under constant scrutiny by air traffic controllers and data recorders. A deviation in protocol rarely goes unnoticed. Errors are systematically compiled, scrutinized, and compartmentalized, with the aim of further refining systems to reduce the likelihood of future errors. Although blame is often prescribed, it is in the context of improving the system. Thus, the aviation industry is awash with data to inform and fuel its systems engineering.

Meanwhile, in medicine our indelible sense of autonomy breeds variability, which is not only tolerated, but often goes unnoticed. Further, we employ a model of error analysis that focuses on affixing blame, as if somehow culpability will prevent future errors. Someone made an error, a bad outcome ensued, and the culprit must be identified and punished. This results in reprimand, remediation, or banishment from the medical staff. At times, this is an appropriate response, as some errors are so egregious or indicative of a chronic problem. More often, the punitive process misses the mark because it focuses on blame instead of prevention of the next error. Unlike the aviation industry, this leaves medicine bereft of data for improving our care systems.

 

“Blame and Punish” Doesn’t Work

There are two problems with the “blame and punish” approach. First, it is predicated on the belief that providers make errors because they are poorly trained, inept, or just plain careless. Sometimes this is the case.

However, the vast majority of peer reviews that I’ve participated in involved an error performed by extremely well trained, highly skilled clinicians with the highest level of integrity and vigilance. The real problem lies in the human condition.

Humans make mistakes. Always have, always will.

In college, I worked summers in a factory that applied coating to paper. This combined colossal machines spinning at breakneck speeds, huge rolls of paper, and hands—a recipe for handless employees. But accidents rarely happened. Over time, the mill engineers had designed systems so foolproof that the workers couldn’t chop their hands off, even if they wanted to. This level of safety was achieved, in principle, by learning how errors were made so that future errors could be prevented. It was not achieved by blaming handless employees. This paper-plant process recognizes the fallible nature of human beings; it’s the same recognition we need in medicine.

Whether we commit a systems error (e.g., the lab test results arrived after the patient was discharged), a cognitive error (e.g., I continue to believe this pulmonary embolism is pneumonia because my night-coverage partner signed it out as pneumonia), or simply a human error (e.g., the lab forgot to call a critical result to the ordering physician), we work in systems that often result in errors. And the only meaningful hope we have to reduce errors depends on our ability to identify them and build systems so safe that we couldn’t hurt a patient, even if we tried.

This leads to the second problem with the blame-and-punish mentality: It breeds concealment of errors, as providers become reticent to expose mistakes for fear of retribution. Thus, an important pipeline of information about system deficiencies dries up, and we are left to suffer the same cycle of errors.

Budging the quality and patient-safety needle will require a culture that freely and openly admits mistakes in order to analyze and prevent future mistakes. This is inherently difficult for most of us to do, and next to impossible when we fear reprimand. Then again, if we endeavor to fundamentally enhance the safety of hospital care, we must allow providers to openly discuss errors without fear of rebuke. Accomplishing this will require understanding, leadership and action—and it starts with each of us.

Anything short of this will just result in more bad pages. TH

Dr. Glasheen is associate professor of medicine at the University of Colorado Denver, where he serves as director of Hospital Medicine and the Hospitalist Training Program, and as associate program director of the Internal Medicine Residency Program.

Round One

“Plane down, mass casualties possible; initiate disaster plan.”

The page interrupted my evening out with friends a few Saturday nights ago. Looking up from my dinner, I noticed the restaurant television had cut away to a news story at Denver International Airport. Continental Flight 1404, en route to Houston, had crashed during takeoff, belly-flopping to a fiery rest a few hundred yards off the runway. The airport is about 10 miles from the nearest hospital—mine.

The situation ended considerably better than originally expected. Thirty-eight people were treated at several Denver hospitals, 11 of them at my hospital, with most patients discharged from the emergency department. No one died. The case remains under review, and little is known about the cause of the crash.

Round Two

“Give me a call. I need to talk to you urgently.”

That page arrived the following Monday morning. It was from a co-worker. There had been an unexpected bad outcome in a young male patient. The hospital’s quality and risk management group had found out about the case and called for a peer review. My colleague was scared; would he be publicly criticized? Punished? Fired?

The patient had been admitted with a chronic disease flare-up. He was on the mend after receiving an increased dose of medication. The night before he was scheduled to be discharged, he developed a new symptom, was evaluated by the cross-cover team, and a plan was set in motion. However, a critical lab result, which became available overnight, mistakenly was not called to the provider and went unnoticed by the primary team that triaged the patient to the end of the team’s rounds. By then, he was in extremis.

Getty Images

Planes and Patients

The proximity of these two events provoked comparisons.

By now, comparing healthcare to the aviation industry has become cliché. Both industries demand highly trained and skilled conductors; errors in both industries can result in death; both depend on technology; and both have turned to systems engineering to improve efficiencies and reduce mistakes. This is where the two industries diverge, and I think we get it wrong in medicine.

In aviation, there are very proscriptive algorithms that must be followed, and much of a pilot’s work is under constant scrutiny by air traffic controllers and data recorders. A deviation in protocol rarely goes unnoticed. Errors are systematically compiled, scrutinized, and compartmentalized, with the aim of further refining systems to reduce the likelihood of future errors. Although blame is often prescribed, it is in the context of improving the system. Thus, the aviation industry is awash with data to inform and fuel its systems engineering.

Meanwhile, in medicine our indelible sense of autonomy breeds variability, which is not only tolerated, but often goes unnoticed. Further, we employ a model of error analysis that focuses on affixing blame, as if somehow culpability will prevent future errors. Someone made an error, a bad outcome ensued, and the culprit must be identified and punished. This results in reprimand, remediation, or banishment from the medical staff. At times, this is an appropriate response, as some errors are so egregious or indicative of a chronic problem. More often, the punitive process misses the mark because it focuses on blame instead of prevention of the next error. Unlike the aviation industry, this leaves medicine bereft of data for improving our care systems.

 

“Blame and Punish” Doesn’t Work

There are two problems with the “blame and punish” approach. First, it is predicated on the belief that providers make errors because they are poorly trained, inept, or just plain careless. Sometimes this is the case.

However, the vast majority of peer reviews that I’ve participated in involved an error performed by extremely well trained, highly skilled clinicians with the highest level of integrity and vigilance. The real problem lies in the human condition.

Humans make mistakes. Always have, always will.

In college, I worked summers in a factory that applied coating to paper. This combined colossal machines spinning at breakneck speeds, huge rolls of paper, and hands—a recipe for handless employees. But accidents rarely happened. Over time, the mill engineers had designed systems so foolproof that the workers couldn’t chop their hands off, even if they wanted to. This level of safety was achieved, in principle, by learning how errors were made so that future errors could be prevented. It was not achieved by blaming handless employees. This paper-plant process recognizes the fallible nature of human beings; it’s the same recognition we need in medicine.

Whether we commit a systems error (e.g., the lab test results arrived after the patient was discharged), a cognitive error (e.g., I continue to believe this pulmonary embolism is pneumonia because my night-coverage partner signed it out as pneumonia), or simply a human error (e.g., the lab forgot to call a critical result to the ordering physician), we work in systems that often result in errors. And the only meaningful hope we have to reduce errors depends on our ability to identify them and build systems so safe that we couldn’t hurt a patient, even if we tried.

This leads to the second problem with the blame-and-punish mentality: It breeds concealment of errors, as providers become reticent to expose mistakes for fear of retribution. Thus, an important pipeline of information about system deficiencies dries up, and we are left to suffer the same cycle of errors.

Budging the quality and patient-safety needle will require a culture that freely and openly admits mistakes in order to analyze and prevent future mistakes. This is inherently difficult for most of us to do, and next to impossible when we fear reprimand. Then again, if we endeavor to fundamentally enhance the safety of hospital care, we must allow providers to openly discuss errors without fear of rebuke. Accomplishing this will require understanding, leadership and action—and it starts with each of us.

Anything short of this will just result in more bad pages. TH

Dr. Glasheen is associate professor of medicine at the University of Colorado Denver, where he serves as director of Hospital Medicine and the Hospitalist Training Program, and as associate program director of the Internal Medicine Residency Program.

Hospitals as major employers and community resources can do nothing but reflect the realities of our country’s recession, now in its second year. For hospitalists who are integral to a hospital’s performance and are, at the same time, dependent on the institution’s financial success, there is the shared concern often seen by passengers in a two-person airplane buffeted by storms and fierce winds.

Hospitals are hit by a variety of forces during recessions, including tightening credit, increased borrowing costs, reduced returns from investments, decreased philanthropic donations, and the unkindest cut of all: more patients with less ability to pay.

American hospitals, which employ more than 5 million people, have witnessed all these forces magnify the long-standing issue of under-reimbursements from Medicare and Medicaid, which generally don’t even cover the rising costs of labor and technology. In New Jersey, 47% of hospitals were in the red in 2007, and five of the state’s 79 acute-care hospitals closed in 2008.

According to recent data, more than 65% of surveyed hospitals saw decreases in elective procedures and an increase in nonpaying patients. The hit to hospitals’ investments has mirrored the 401(k) crisis. More than 550 hospitals watched their recent investment declines combine for a total loss of $832 million in the third quarter of 2008, compared with a $396 million aggregate gain in the same time period in 2007. All this bad news led Moody’s to change its 12- to 18-month outlook for both profit and nonprofit hospitals from stable to negative due to increasing bad debt, credit tightening, and loss of investments.

Hospitals are keenly affected by local employment, too. When local businesses have layoffs, former employees often lose their insurance coverage. When companies cut back on expenses to hold on to their workers, often that translates into no health insurance or very high deductibles. When patients lose their jobs or their insurance, they stop getting preventive care; they stop buying prescriptions. The end result is increased ED visits and admissions for decompensated heart failure, flu that turns into pneumonia, or out-of-control diabetes.

More admissions might mean more business for hospitals and hospitalists, but it certainly does not mean more money. It likely means more no-pays and increasing bad debt. It means turning a precarious, marginally balanced bottom line into losses and layoffs.

As if that weren’t bad enough, 44 of our 50 states are operating in the red and looking at trimming big-ticket items to stem the losses. For most states, the budget items under scrutiny include education, prisons, and healthcare. Medicaid payments—already inadequate—are shrinking further at a time when more people need a safety net.

Prove Thy Worth

These are tough times to be running a hospital, but aren’t hospitalists, so dependent on the viability of their hospitals, also on a slippery slope—and running downhill? Actually, these tough times might make hospitalists—and our value—all the more important to their hospitals, helping administrators weather the storm and be resources for their healthcare communities.

Hospitalists can deliver just what we need today—efficient and effective care with appropriate use of resources, better hospital throughput, attention to safety, and measurable efforts to improve performance.

In addition, as primary-care physicians (PCPs), surgeons, and subspecialists retrench to stay away from no-pays so they can find a better payor mix in order to survive, patients keep coming to hospitals, and hospitalists are positioned to pick up the slack and jump right in. Obviously, there is the chance PCPs and others in difficult times might actually come back to inpatient care as office and procedure revenues dwindle, but this is less likely to affect hospitalists when we seem to always have far more work than we have staff or time to manage.

 

Change Agents

Times of crisis create opportunities for real change. President Obama and many key legislators and thought leaders have signaled a genuine desire to change a system that rewards performance (value-based purchasing) and bundles hospital and physician payments, which will be tied to key outcomes and performance. SHM has been able to show Washington decision-makers that hospitalists can reduce preventable deep vein thrombosis (DVT) in hospitalized patients from 50 per year to three per year. We have shown that hospitalists, using SHM’s BOOST protocols, can improve the discharge process, identify high-risk patients, and reduce ED visits and readmissions. This is just the type of system improvement that leads to better care at a lower cost—the Holy Grail in hard times.

Couple all this with the Institute of Medicine’s call to further reduce residency hours, which only leads to a greater need for hospitalists in teaching institutions, and there is an increasing demand for hospitalists seemingly everywhere. And even in a recession, high demand with a small supply leads to the need to nurture and reward hospitalists, especially those who are experienced and can deliver efficient and effective inpatient care.

At a national level, we will see experimentation with demonstration projects to look at rewarding performance and bundling payments for inpatient care. Similarly, hospitalists should be emboldened to use the current crisis to experiment locally by using teams of hospitalists, nurses, pharmacists, and case managers to revise the way care is delivered. There are opportunities to responsibly involve nurse practitioners and physician assistants as integral parts of your hospitalist team.

While the rest of medicine might be forced to look out for themselves in tough times, hospitalists, by their very positioning, must focus on the survival and improvement of the system, of their hospital, and of the healthcare community. In hospital medicine, we recognize that the days of “Lone Ranger” physicians carving out their own destinies are long gone. In many ways, physicians are intricately intertwined. And that forces us to survive or fail together. That will be hospitalists’ salvation in these hard times: knowing there are better times ahead for us, our hospitals, and our patients. TH

Larry Wellikson is CEO of SHM.

Hospitals as major employers and community resources can do nothing but reflect the realities of our country’s recession, now in its second year. For hospitalists who are integral to a hospital’s performance and are, at the same time, dependent on the institution’s financial success, there is the shared concern often seen by passengers in a two-person airplane buffeted by storms and fierce winds.

Hospitals are hit by a variety of forces during recessions, including tightening credit, increased borrowing costs, reduced returns from investments, decreased philanthropic donations, and the unkindest cut of all: more patients with less ability to pay.

American hospitals, which employ more than 5 million people, have witnessed all these forces magnify the long-standing issue of under-reimbursements from Medicare and Medicaid, which generally don’t even cover the rising costs of labor and technology. In New Jersey, 47% of hospitals were in the red in 2007, and five of the state’s 79 acute-care hospitals closed in 2008.

According to recent data, more than 65% of surveyed hospitals saw decreases in elective procedures and an increase in nonpaying patients. The hit to hospitals’ investments has mirrored the 401(k) crisis. More than 550 hospitals watched their recent investment declines combine for a total loss of $832 million in the third quarter of 2008, compared with a $396 million aggregate gain in the same time period in 2007. All this bad news led Moody’s to change its 12- to 18-month outlook for both profit and nonprofit hospitals from stable to negative due to increasing bad debt, credit tightening, and loss of investments.

Hospitals are keenly affected by local employment, too. When local businesses have layoffs, former employees often lose their insurance coverage. When companies cut back on expenses to hold on to their workers, often that translates into no health insurance or very high deductibles. When patients lose their jobs or their insurance, they stop getting preventive care; they stop buying prescriptions. The end result is increased ED visits and admissions for decompensated heart failure, flu that turns into pneumonia, or out-of-control diabetes.

More admissions might mean more business for hospitals and hospitalists, but it certainly does not mean more money. It likely means more no-pays and increasing bad debt. It means turning a precarious, marginally balanced bottom line into losses and layoffs.

As if that weren’t bad enough, 44 of our 50 states are operating in the red and looking at trimming big-ticket items to stem the losses. For most states, the budget items under scrutiny include education, prisons, and healthcare. Medicaid payments—already inadequate—are shrinking further at a time when more people need a safety net.

Prove Thy Worth

These are tough times to be running a hospital, but aren’t hospitalists, so dependent on the viability of their hospitals, also on a slippery slope—and running downhill? Actually, these tough times might make hospitalists—and our value—all the more important to their hospitals, helping administrators weather the storm and be resources for their healthcare communities.

Hospitalists can deliver just what we need today—efficient and effective care with appropriate use of resources, better hospital throughput, attention to safety, and measurable efforts to improve performance.

In addition, as primary-care physicians (PCPs), surgeons, and subspecialists retrench to stay away from no-pays so they can find a better payor mix in order to survive, patients keep coming to hospitals, and hospitalists are positioned to pick up the slack and jump right in. Obviously, there is the chance PCPs and others in difficult times might actually come back to inpatient care as office and procedure revenues dwindle, but this is less likely to affect hospitalists when we seem to always have far more work than we have staff or time to manage.

 

Change Agents

Times of crisis create opportunities for real change. President Obama and many key legislators and thought leaders have signaled a genuine desire to change a system that rewards performance (value-based purchasing) and bundles hospital and physician payments, which will be tied to key outcomes and performance. SHM has been able to show Washington decision-makers that hospitalists can reduce preventable deep vein thrombosis (DVT) in hospitalized patients from 50 per year to three per year. We have shown that hospitalists, using SHM’s BOOST protocols, can improve the discharge process, identify high-risk patients, and reduce ED visits and readmissions. This is just the type of system improvement that leads to better care at a lower cost—the Holy Grail in hard times.

Couple all this with the Institute of Medicine’s call to further reduce residency hours, which only leads to a greater need for hospitalists in teaching institutions, and there is an increasing demand for hospitalists seemingly everywhere. And even in a recession, high demand with a small supply leads to the need to nurture and reward hospitalists, especially those who are experienced and can deliver efficient and effective inpatient care.

At a national level, we will see experimentation with demonstration projects to look at rewarding performance and bundling payments for inpatient care. Similarly, hospitalists should be emboldened to use the current crisis to experiment locally by using teams of hospitalists, nurses, pharmacists, and case managers to revise the way care is delivered. There are opportunities to responsibly involve nurse practitioners and physician assistants as integral parts of your hospitalist team.

While the rest of medicine might be forced to look out for themselves in tough times, hospitalists, by their very positioning, must focus on the survival and improvement of the system, of their hospital, and of the healthcare community. In hospital medicine, we recognize that the days of “Lone Ranger” physicians carving out their own destinies are long gone. In many ways, physicians are intricately intertwined. And that forces us to survive or fail together. That will be hospitalists’ salvation in these hard times: knowing there are better times ahead for us, our hospitals, and our patients. TH

Larry Wellikson is CEO of SHM.

Hospitals as major employers and community resources can do nothing but reflect the realities of our country’s recession, now in its second year. For hospitalists who are integral to a hospital’s performance and are, at the same time, dependent on the institution’s financial success, there is the shared concern often seen by passengers in a two-person airplane buffeted by storms and fierce winds.

Hospitals are hit by a variety of forces during recessions, including tightening credit, increased borrowing costs, reduced returns from investments, decreased philanthropic donations, and the unkindest cut of all: more patients with less ability to pay.

American hospitals, which employ more than 5 million people, have witnessed all these forces magnify the long-standing issue of under-reimbursements from Medicare and Medicaid, which generally don’t even cover the rising costs of labor and technology. In New Jersey, 47% of hospitals were in the red in 2007, and five of the state’s 79 acute-care hospitals closed in 2008.

According to recent data, more than 65% of surveyed hospitals saw decreases in elective procedures and an increase in nonpaying patients. The hit to hospitals’ investments has mirrored the 401(k) crisis. More than 550 hospitals watched their recent investment declines combine for a total loss of $832 million in the third quarter of 2008, compared with a $396 million aggregate gain in the same time period in 2007. All this bad news led Moody’s to change its 12- to 18-month outlook for both profit and nonprofit hospitals from stable to negative due to increasing bad debt, credit tightening, and loss of investments.

Hospitals are keenly affected by local employment, too. When local businesses have layoffs, former employees often lose their insurance coverage. When companies cut back on expenses to hold on to their workers, often that translates into no health insurance or very high deductibles. When patients lose their jobs or their insurance, they stop getting preventive care; they stop buying prescriptions. The end result is increased ED visits and admissions for decompensated heart failure, flu that turns into pneumonia, or out-of-control diabetes.

More admissions might mean more business for hospitals and hospitalists, but it certainly does not mean more money. It likely means more no-pays and increasing bad debt. It means turning a precarious, marginally balanced bottom line into losses and layoffs.

As if that weren’t bad enough, 44 of our 50 states are operating in the red and looking at trimming big-ticket items to stem the losses. For most states, the budget items under scrutiny include education, prisons, and healthcare. Medicaid payments—already inadequate—are shrinking further at a time when more people need a safety net.

Prove Thy Worth

These are tough times to be running a hospital, but aren’t hospitalists, so dependent on the viability of their hospitals, also on a slippery slope—and running downhill? Actually, these tough times might make hospitalists—and our value—all the more important to their hospitals, helping administrators weather the storm and be resources for their healthcare communities.

Hospitalists can deliver just what we need today—efficient and effective care with appropriate use of resources, better hospital throughput, attention to safety, and measurable efforts to improve performance.

In addition, as primary-care physicians (PCPs), surgeons, and subspecialists retrench to stay away from no-pays so they can find a better payor mix in order to survive, patients keep coming to hospitals, and hospitalists are positioned to pick up the slack and jump right in. Obviously, there is the chance PCPs and others in difficult times might actually come back to inpatient care as office and procedure revenues dwindle, but this is less likely to affect hospitalists when we seem to always have far more work than we have staff or time to manage.

 

Change Agents

Times of crisis create opportunities for real change. President Obama and many key legislators and thought leaders have signaled a genuine desire to change a system that rewards performance (value-based purchasing) and bundles hospital and physician payments, which will be tied to key outcomes and performance. SHM has been able to show Washington decision-makers that hospitalists can reduce preventable deep vein thrombosis (DVT) in hospitalized patients from 50 per year to three per year. We have shown that hospitalists, using SHM’s BOOST protocols, can improve the discharge process, identify high-risk patients, and reduce ED visits and readmissions. This is just the type of system improvement that leads to better care at a lower cost—the Holy Grail in hard times.

Couple all this with the Institute of Medicine’s call to further reduce residency hours, which only leads to a greater need for hospitalists in teaching institutions, and there is an increasing demand for hospitalists seemingly everywhere. And even in a recession, high demand with a small supply leads to the need to nurture and reward hospitalists, especially those who are experienced and can deliver efficient and effective inpatient care.

At a national level, we will see experimentation with demonstration projects to look at rewarding performance and bundling payments for inpatient care. Similarly, hospitalists should be emboldened to use the current crisis to experiment locally by using teams of hospitalists, nurses, pharmacists, and case managers to revise the way care is delivered. There are opportunities to responsibly involve nurse practitioners and physician assistants as integral parts of your hospitalist team.

While the rest of medicine might be forced to look out for themselves in tough times, hospitalists, by their very positioning, must focus on the survival and improvement of the system, of their hospital, and of the healthcare community. In hospital medicine, we recognize that the days of “Lone Ranger” physicians carving out their own destinies are long gone. In many ways, physicians are intricately intertwined. And that forces us to survive or fail together. That will be hospitalists’ salvation in these hard times: knowing there are better times ahead for us, our hospitals, and our patients. TH

Larry Wellikson is CEO of SHM.

Dedication to hard work, a passion for improving health outcomes and medical curricula, a background in business administration, and a knack for team-building have catapulted Alpesh Amin, MD, MBA, FACP, to the forefront of change at the University of California at Irvine Health Affairs, comprised of the UC Irvine Medical Center and School of Medicine. Those skill sets and determination have landed Dr. Amin an HM first: appointment as interim chair of an academic Department of Medicine.

Dr. Amin’s new role—he supervises 11 divisions and more than 200 faculty—means he’s responsible for the department’s budget and administration. He also is charged with advancing the department’s clinical, teaching, and research missions, demonstrating that it’s possible for hospitalists to rise through the department ranks through an HM track. And that, says Scott Flanders, SHM’s president-elect and associate professor of medicine and director of the HM program at the University of Michigan Health System in Ann Arbor, “bodes well for the future of academic hospitalists at many institutions across the country.”

Traditionally, lofty hospital appointments have gone to academics with a background in biomedical and basic science research. But as academic and teaching hospitals focus more and more on quality issues and improved performance, hospitalists are positioned to advance into department leadership positions.

Dr. Amin’s appointment could signal the first of many opportunities for academic hospitalists, according to Joseph Ming-Wah Li, MD, assistant professor of medicine at Harvard Medical School and director of the HM program at Beth Israel Deaconess Medical Center in Boston. Dr. Li, who served with Dr. Amin on SHM’s Board of Directors, was not surprised when Alpesh was named the first hospitalist to chair a department of medicine. “He is a very gregarious person, he’s bright, and he’s logical in his thinking,” Dr. Li says.

Career Foundation

Dr. Amin credits his family with instilling in him strong values and dedication to his work. Born in Baroda, India, he emigrated to the U.S. before his first birthday; he graduated from Northgate High School in Walnut Creek, Calif., in 1985, and from UC San Diego with a degree in bioengineering in 1989. He obtained his MD in 1994 from Northwestern University’s Feinberg School of Medicine in Chicago.

During his internship and residency at UC Irvine, Dr. Amin pondered the possibilities of a subspecialty within internal medicine. He opted to follow his interests in medical education and healthcare outcomes and research. The HM field intrigued him, he says, “because there was an opportunity to improve on systems and patient-care delivery.” Numerous mentors along the way encouraged his interests in curriculum development and design, quality improvement, and developing delivery models for patient care.

 

Trendsetter

As a medical resident, Dr. Amin demonstrated a desire to become a leader and change agent. “He was truly an outstanding resident, and then he joined the faculty and did spectacularly in organizing the hospitalist program, which has become very successful,” recalls Nosratola D. Vaziri, MD, chief of the division of nephrology and hypertension at UC Irvine’s School of Medicine. Dr. Amin founded the UC Irvine hospitalist program in 1998. At the same time, he acquired his MBA in healthcare administration, thus rounding out an already impressive skill set. “The MBA has been a valuable tool,” says Dr. Amin, “because I learned—among other skills—leadership, strategic planning, developing business plans, and improving on operations.”

He has applied those techniques throughout his career, serving in various leadership roles at his institution, including medicine clerkship director, associate program director for the internal medicine residency program, vice chair for clinical affairs and quality assurance, and chief of the division of general internal medicine.

 

By developing and nurturing the UC Irvine hospitalist program, Dr. Amin has exhibited a deep commitment to the core missions of hospital medicine. “Our multidisciplinary program has nine different specialties managed under one program,” he notes. He has structured the program in such a way that members hold dual appointments in the HM program and their individual departments or divisions, thus creating a bridge between the HM program and other departments.

“We have an integrated group that is working together for the focus of advancement in the hospital setting, in terms of clinical care, teaching, team-building, quality and systems improvement. As a result, we’ve had great outcomes in terms of length of stay, quality, and core measures,” Dr. Amin says. “I’ve been fortunate to work with a team of hospitalist faculty who are spectacular and collectively deserve kudos for the success of our group.”

 

Dr. Amin has shared his passion for quality improvement and curriculum development with all of hospital medicine. As chair of SHM’s education committee, he pushed for the first education summit in 2001, securing support to form a core-curriculum task force. Four years later, Dr. Amin and a small group of industry leaders published “Core Competencies in Hospital Medicine” in the Journal of Hospital Medicine (www.hospitalmedicine.org/corecomp).

“Dr. Amin has really set the trend [for improved hospital performance], not only here for the hospitalist program, but nationwide,” says David N. Bailey, MD, dean and vice chancellor for UC Irvine Health Affairs.

Bucking Tradition

Hospitalists have been advancing into leadership positions in the private sector for many years. It’s been a slower ascent in the academic medical center setting.

“Until recently, it would not have been possible to ascend to the level of chair at most academic centers unless your background was in biomedical and basic science research,” says Robert Wachter, MD, professor and chief of the division of HM at the University of California San Francisco, a former SHM president and author of the blog Wachter’s World (www.wachtersworld .com). “Quality, patient safety, and systems improvement were not considered to be legitimate enough academic work to garner the necessary credibility. I think that’s changing.”

Jeffrey Wiese, MD, FACP, professor of medicine and associate dean for graduate medical education at Tulane University Health Sciences Center in New Orleans and an SHM board member, believes Dr. Amin’s interim appointment “speaks in broad strokes to the new skill set—that is, financial and organizational abilities—that are increasingly becoming valued by academic medicine.” Agendas of patient safety, quality, and delivery of efficient, cost-effective, and safe healthcare are gaining parity, Dr. Wiese says, with academic research agendas. “For one to supercede the other is not a good thing, but for the two to be in balance, I think, is a very good thing,” he says.

“Renaissance Physician”

Dr. Bailey appointed Dr. Amin to what he describes as a “long-term” interim post last June. To make his decision, Dr. Bailey consulted with 11 division chiefs, and Dr. Amin emerged as the leading candidate. “Alpesh does it all, from clinical research to leading a department to running an outstanding hospitalist service,” Dr. Bailey says. “He’s really a renaissance physician.”

The promotion coincides with another of Dr. Amin’s recent accomplishments: He received the Laureate Award for the California Southern Region 2 of the American College of Physicians.

Ever energetic, Dr. Amin is not resting on his laurels. “I’m looking forward to helping the department continue to be a flagship within the UC Irvine School of Medicine,” he says. “This is a challenging and positive opportunity to balance systems-based practice, the business of medicine, and the science of medicine.”

Dr. Amin thinks his appointment signifies the new opportunities open to the growing number of U.S. hospitalists—now more than 28,000 strong and growing every day. “This [appointment] shows that hospitalists can move in the direction of being both academic leaders and healthcare administrative leaders.” TH

 

Gretchen Henkel is a freelance medical writer based in California.

Dedication to hard work, a passion for improving health outcomes and medical curricula, a background in business administration, and a knack for team-building have catapulted Alpesh Amin, MD, MBA, FACP, to the forefront of change at the University of California at Irvine Health Affairs, comprised of the UC Irvine Medical Center and School of Medicine. Those skill sets and determination have landed Dr. Amin an HM first: appointment as interim chair of an academic Department of Medicine.

Dr. Amin’s new role—he supervises 11 divisions and more than 200 faculty—means he’s responsible for the department’s budget and administration. He also is charged with advancing the department’s clinical, teaching, and research missions, demonstrating that it’s possible for hospitalists to rise through the department ranks through an HM track. And that, says Scott Flanders, SHM’s president-elect and associate professor of medicine and director of the HM program at the University of Michigan Health System in Ann Arbor, “bodes well for the future of academic hospitalists at many institutions across the country.”

Traditionally, lofty hospital appointments have gone to academics with a background in biomedical and basic science research. But as academic and teaching hospitals focus more and more on quality issues and improved performance, hospitalists are positioned to advance into department leadership positions.

Dr. Amin’s appointment could signal the first of many opportunities for academic hospitalists, according to Joseph Ming-Wah Li, MD, assistant professor of medicine at Harvard Medical School and director of the HM program at Beth Israel Deaconess Medical Center in Boston. Dr. Li, who served with Dr. Amin on SHM’s Board of Directors, was not surprised when Alpesh was named the first hospitalist to chair a department of medicine. “He is a very gregarious person, he’s bright, and he’s logical in his thinking,” Dr. Li says.

Career Foundation

Dr. Amin credits his family with instilling in him strong values and dedication to his work. Born in Baroda, India, he emigrated to the U.S. before his first birthday; he graduated from Northgate High School in Walnut Creek, Calif., in 1985, and from UC San Diego with a degree in bioengineering in 1989. He obtained his MD in 1994 from Northwestern University’s Feinberg School of Medicine in Chicago.

During his internship and residency at UC Irvine, Dr. Amin pondered the possibilities of a subspecialty within internal medicine. He opted to follow his interests in medical education and healthcare outcomes and research. The HM field intrigued him, he says, “because there was an opportunity to improve on systems and patient-care delivery.” Numerous mentors along the way encouraged his interests in curriculum development and design, quality improvement, and developing delivery models for patient care.

 

Trendsetter

As a medical resident, Dr. Amin demonstrated a desire to become a leader and change agent. “He was truly an outstanding resident, and then he joined the faculty and did spectacularly in organizing the hospitalist program, which has become very successful,” recalls Nosratola D. Vaziri, MD, chief of the division of nephrology and hypertension at UC Irvine’s School of Medicine. Dr. Amin founded the UC Irvine hospitalist program in 1998. At the same time, he acquired his MBA in healthcare administration, thus rounding out an already impressive skill set. “The MBA has been a valuable tool,” says Dr. Amin, “because I learned—among other skills—leadership, strategic planning, developing business plans, and improving on operations.”

He has applied those techniques throughout his career, serving in various leadership roles at his institution, including medicine clerkship director, associate program director for the internal medicine residency program, vice chair for clinical affairs and quality assurance, and chief of the division of general internal medicine.

 

By developing and nurturing the UC Irvine hospitalist program, Dr. Amin has exhibited a deep commitment to the core missions of hospital medicine. “Our multidisciplinary program has nine different specialties managed under one program,” he notes. He has structured the program in such a way that members hold dual appointments in the HM program and their individual departments or divisions, thus creating a bridge between the HM program and other departments.

“We have an integrated group that is working together for the focus of advancement in the hospital setting, in terms of clinical care, teaching, team-building, quality and systems improvement. As a result, we’ve had great outcomes in terms of length of stay, quality, and core measures,” Dr. Amin says. “I’ve been fortunate to work with a team of hospitalist faculty who are spectacular and collectively deserve kudos for the success of our group.”

 

Dr. Amin has shared his passion for quality improvement and curriculum development with all of hospital medicine. As chair of SHM’s education committee, he pushed for the first education summit in 2001, securing support to form a core-curriculum task force. Four years later, Dr. Amin and a small group of industry leaders published “Core Competencies in Hospital Medicine” in the Journal of Hospital Medicine (www.hospitalmedicine.org/corecomp).

“Dr. Amin has really set the trend [for improved hospital performance], not only here for the hospitalist program, but nationwide,” says David N. Bailey, MD, dean and vice chancellor for UC Irvine Health Affairs.

Bucking Tradition

Hospitalists have been advancing into leadership positions in the private sector for many years. It’s been a slower ascent in the academic medical center setting.

“Until recently, it would not have been possible to ascend to the level of chair at most academic centers unless your background was in biomedical and basic science research,” says Robert Wachter, MD, professor and chief of the division of HM at the University of California San Francisco, a former SHM president and author of the blog Wachter’s World (www.wachtersworld .com). “Quality, patient safety, and systems improvement were not considered to be legitimate enough academic work to garner the necessary credibility. I think that’s changing.”

Jeffrey Wiese, MD, FACP, professor of medicine and associate dean for graduate medical education at Tulane University Health Sciences Center in New Orleans and an SHM board member, believes Dr. Amin’s interim appointment “speaks in broad strokes to the new skill set—that is, financial and organizational abilities—that are increasingly becoming valued by academic medicine.” Agendas of patient safety, quality, and delivery of efficient, cost-effective, and safe healthcare are gaining parity, Dr. Wiese says, with academic research agendas. “For one to supercede the other is not a good thing, but for the two to be in balance, I think, is a very good thing,” he says.

“Renaissance Physician”

Dr. Bailey appointed Dr. Amin to what he describes as a “long-term” interim post last June. To make his decision, Dr. Bailey consulted with 11 division chiefs, and Dr. Amin emerged as the leading candidate. “Alpesh does it all, from clinical research to leading a department to running an outstanding hospitalist service,” Dr. Bailey says. “He’s really a renaissance physician.”

The promotion coincides with another of Dr. Amin’s recent accomplishments: He received the Laureate Award for the California Southern Region 2 of the American College of Physicians.

Ever energetic, Dr. Amin is not resting on his laurels. “I’m looking forward to helping the department continue to be a flagship within the UC Irvine School of Medicine,” he says. “This is a challenging and positive opportunity to balance systems-based practice, the business of medicine, and the science of medicine.”

Dr. Amin thinks his appointment signifies the new opportunities open to the growing number of U.S. hospitalists—now more than 28,000 strong and growing every day. “This [appointment] shows that hospitalists can move in the direction of being both academic leaders and healthcare administrative leaders.” TH

 

Gretchen Henkel is a freelance medical writer based in California.

Dedication to hard work, a passion for improving health outcomes and medical curricula, a background in business administration, and a knack for team-building have catapulted Alpesh Amin, MD, MBA, FACP, to the forefront of change at the University of California at Irvine Health Affairs, comprised of the UC Irvine Medical Center and School of Medicine. Those skill sets and determination have landed Dr. Amin an HM first: appointment as interim chair of an academic Department of Medicine.

Dr. Amin’s new role—he supervises 11 divisions and more than 200 faculty—means he’s responsible for the department’s budget and administration. He also is charged with advancing the department’s clinical, teaching, and research missions, demonstrating that it’s possible for hospitalists to rise through the department ranks through an HM track. And that, says Scott Flanders, SHM’s president-elect and associate professor of medicine and director of the HM program at the University of Michigan Health System in Ann Arbor, “bodes well for the future of academic hospitalists at many institutions across the country.”

Traditionally, lofty hospital appointments have gone to academics with a background in biomedical and basic science research. But as academic and teaching hospitals focus more and more on quality issues and improved performance, hospitalists are positioned to advance into department leadership positions.

Dr. Amin’s appointment could signal the first of many opportunities for academic hospitalists, according to Joseph Ming-Wah Li, MD, assistant professor of medicine at Harvard Medical School and director of the HM program at Beth Israel Deaconess Medical Center in Boston. Dr. Li, who served with Dr. Amin on SHM’s Board of Directors, was not surprised when Alpesh was named the first hospitalist to chair a department of medicine. “He is a very gregarious person, he’s bright, and he’s logical in his thinking,” Dr. Li says.

Career Foundation

Dr. Amin credits his family with instilling in him strong values and dedication to his work. Born in Baroda, India, he emigrated to the U.S. before his first birthday; he graduated from Northgate High School in Walnut Creek, Calif., in 1985, and from UC San Diego with a degree in bioengineering in 1989. He obtained his MD in 1994 from Northwestern University’s Feinberg School of Medicine in Chicago.

During his internship and residency at UC Irvine, Dr. Amin pondered the possibilities of a subspecialty within internal medicine. He opted to follow his interests in medical education and healthcare outcomes and research. The HM field intrigued him, he says, “because there was an opportunity to improve on systems and patient-care delivery.” Numerous mentors along the way encouraged his interests in curriculum development and design, quality improvement, and developing delivery models for patient care.

 

Trendsetter

As a medical resident, Dr. Amin demonstrated a desire to become a leader and change agent. “He was truly an outstanding resident, and then he joined the faculty and did spectacularly in organizing the hospitalist program, which has become very successful,” recalls Nosratola D. Vaziri, MD, chief of the division of nephrology and hypertension at UC Irvine’s School of Medicine. Dr. Amin founded the UC Irvine hospitalist program in 1998. At the same time, he acquired his MBA in healthcare administration, thus rounding out an already impressive skill set. “The MBA has been a valuable tool,” says Dr. Amin, “because I learned—among other skills—leadership, strategic planning, developing business plans, and improving on operations.”

He has applied those techniques throughout his career, serving in various leadership roles at his institution, including medicine clerkship director, associate program director for the internal medicine residency program, vice chair for clinical affairs and quality assurance, and chief of the division of general internal medicine.

 

By developing and nurturing the UC Irvine hospitalist program, Dr. Amin has exhibited a deep commitment to the core missions of hospital medicine. “Our multidisciplinary program has nine different specialties managed under one program,” he notes. He has structured the program in such a way that members hold dual appointments in the HM program and their individual departments or divisions, thus creating a bridge between the HM program and other departments.

“We have an integrated group that is working together for the focus of advancement in the hospital setting, in terms of clinical care, teaching, team-building, quality and systems improvement. As a result, we’ve had great outcomes in terms of length of stay, quality, and core measures,” Dr. Amin says. “I’ve been fortunate to work with a team of hospitalist faculty who are spectacular and collectively deserve kudos for the success of our group.”

 

Dr. Amin has shared his passion for quality improvement and curriculum development with all of hospital medicine. As chair of SHM’s education committee, he pushed for the first education summit in 2001, securing support to form a core-curriculum task force. Four years later, Dr. Amin and a small group of industry leaders published “Core Competencies in Hospital Medicine” in the Journal of Hospital Medicine (www.hospitalmedicine.org/corecomp).

“Dr. Amin has really set the trend [for improved hospital performance], not only here for the hospitalist program, but nationwide,” says David N. Bailey, MD, dean and vice chancellor for UC Irvine Health Affairs.

Bucking Tradition

Hospitalists have been advancing into leadership positions in the private sector for many years. It’s been a slower ascent in the academic medical center setting.

“Until recently, it would not have been possible to ascend to the level of chair at most academic centers unless your background was in biomedical and basic science research,” says Robert Wachter, MD, professor and chief of the division of HM at the University of California San Francisco, a former SHM president and author of the blog Wachter’s World (www.wachtersworld .com). “Quality, patient safety, and systems improvement were not considered to be legitimate enough academic work to garner the necessary credibility. I think that’s changing.”

Jeffrey Wiese, MD, FACP, professor of medicine and associate dean for graduate medical education at Tulane University Health Sciences Center in New Orleans and an SHM board member, believes Dr. Amin’s interim appointment “speaks in broad strokes to the new skill set—that is, financial and organizational abilities—that are increasingly becoming valued by academic medicine.” Agendas of patient safety, quality, and delivery of efficient, cost-effective, and safe healthcare are gaining parity, Dr. Wiese says, with academic research agendas. “For one to supercede the other is not a good thing, but for the two to be in balance, I think, is a very good thing,” he says.

“Renaissance Physician”

Dr. Bailey appointed Dr. Amin to what he describes as a “long-term” interim post last June. To make his decision, Dr. Bailey consulted with 11 division chiefs, and Dr. Amin emerged as the leading candidate. “Alpesh does it all, from clinical research to leading a department to running an outstanding hospitalist service,” Dr. Bailey says. “He’s really a renaissance physician.”

The promotion coincides with another of Dr. Amin’s recent accomplishments: He received the Laureate Award for the California Southern Region 2 of the American College of Physicians.

Ever energetic, Dr. Amin is not resting on his laurels. “I’m looking forward to helping the department continue to be a flagship within the UC Irvine School of Medicine,” he says. “This is a challenging and positive opportunity to balance systems-based practice, the business of medicine, and the science of medicine.”

Dr. Amin thinks his appointment signifies the new opportunities open to the growing number of U.S. hospitalists—now more than 28,000 strong and growing every day. “This [appointment] shows that hospitalists can move in the direction of being both academic leaders and healthcare administrative leaders.” TH

 

Gretchen Henkel is a freelance medical writer based in California.

Case

An 84-year-old woman presents with watery diarrhea. She recently received a fluoroquinolone antibiotic during a hospitalization for pneumonia. Her temperature is 101 degrees, her heart rate is 110 beats per minute, and her respiratory rate is 22 breaths per minute. Her abdominal exam is significant for mild distention, hyperactive bowel sounds, and diffuse, mild tenderness without rebound or guarding. Her white blood cell count is 18,200 cells/mm3. You suspect C. difficile infection. Should you treat empirically with antibiotics and, if so, which antibiotic should you prescribe?

Overview

C. difficile is an anaerobic gram-positive bacillus that produces spores and toxins. In 1978, C. difficile was identified as the causative agent for antibiotic-associated diarrhea.1 The portal of entry is via the fecal-oral route.

Some patients carry C. difficile in their intestinal flora and show no signs of infection. Patients who develop symptoms commonly present with profuse, watery diarrhea. Nausea, vomiting, and abdominal pain also can be seen. Severe cases of C. difficile-associated diarrhea (CDAD) can present with significant abdominal pain and multisystem organ failure, with toxic megacolon resulting from toxin production and ileus.2 In severe cases due to ileus, diarrhea may be absent. Risk of mortality in severe cases is high, with some reviews citing death rates of 57% in patients requiring total colectomy.3 Risk factors for developing CDAD include the prior or current use of antibiotics, advanced age, hospitalization, and prior gastrointestinal surgery or procedures.4

The initial CDAD treatment involves removal of the agent that incited the infection. In most cases, this means discontinuation of an antimicrobial agent. Removal of the inciting agent allows restoration of the normal bowel flora. In mild CDAD cases, this may be sufficient therapy. However, most CDAD cases require treatment. Although many antimicrobial and probiotic agents have been used in CDAD treatment, metronidazole and vancomycin are the most commonly prescribed agents. There is an ongoing debate as to which should be considered the first-line agent.

Review of the Data

Metronidazole and vancomycin have the longest histories of use and are the most studied agents in CDAD. Metronidazole is prescribed 250 mg four times daily (or 500 mg twice daily) for 14 days. It is reasonably tolerated, although it can cause a metallic taste in the mouth. Vancomycin is given 125 mg four times daily (or 500 mg three times daily) for 10 to 14 days. Unlike metronidazole, which can be given by mouth or intravenously, only oral vancomycin is effective in CDAD.

 

Historically, metronidazole has been prescribed more frequently as the first-line agent in CDAD. Proponents of the drug tout its low cost and the importance of minimizing the development of vancomycin-resistant enteric pathogens. There are two small, prospective, randomized studies comparing the efficacy of the agents against one another in the treatment of C. difficile infection, with similar efficacy demonstrated in both studies. In the early 1980s, Teasley and colleagues randomized 94 patients with C. difficile infection to either metronidazole or vancomycin.5 All the patients receiving vancomycin resolved their disease; 95% of patients receiving metronidazole were cured. The differences were not statistically significant.

In the mid-1990s, Wenisch and colleagues randomized patients with C. difficile infection to receive vancomycin, metronidazole, fusidic acid, or teicoplanin therapy.6 Ninety-four percent of patients in both the vancomycin and metronidazole groups were cured.

However, since 2000, investigators have reported higher failure rates with metronidazole therapy in C. difficile infections. For example, in 2005, Pepin and colleagues reviewed cases of C. difficile infections at a hospital in Quebec.7 They determined the number of patients with C. difficile infection initially treated with metronidazole who required additional therapy had markedly increased. Between 1991 and 2002, 9.6% of patients who initially were treated with metronidazole required a switch to vancomycin (or the addition of vancomycin) because of a disappointing response. This figure doubled to 25.7% in 2003-2004. The 60-day probability of recurrence also increased in the 2003-2004 test group (47.2%), compared with the 1991-2002 group (20.8%). Both results were statistically significant. Such data contributed to the debate regarding whether metronidazole or vancomycin is the superior agent in the treatment of C. difficile infections.

In 2007, Zar and colleagues studied the efficacy of metronidazole and vancomycin in the treatment of CDAD patients, but the study stratified patients according to disease severity.8 This allowed the authors to investigate whether one agent was superior in treating mild or severe CDAD. They determined disease severity by assigning points to individual patient characteristics. Patients with two or more points were deemed to have “severe” CDAD.

The investigators assigned one point for each of the following patient characteristics: temperature >38.3 degrees Celsius, age >60 years, albumin level <2.5 mg/dL, and white blood cell count >15,000 cells/mm3 within 48 hours of enrolling in the study. Any patient with endoscopic evidence of pseudomembrane formation or admission to the intensive-care unit (ICU) for CDAD treatment was considered to have severe disease.

Medical-on-Line/Alamy

This was a prospective, randomized controlled trial of 150 patients. Patients were randomly prescribed 500 mg metronidazole by mouth three times daily or 125 mg of vancomycin by mouth four times daily. Patients with mild CDAD had similar cure rates: 90% metronidazole versus 98% vancomycin (P=0.36). However, patients with severe CDAD fared statistically better when treated with oral vancomycin. Ninety-seven percent of severe CDAD patients treated with oral vancomycin had a clinical cure, while only 76% of those treated with metronidazole were cured (P=0.02). Recurrence of the disease was similar in each treatment group.

Based on this study, metronidazole and vancomycin appear equally effective in the treatment of mild CDAD, but vancomycin is the superior agent in the treatment of patients with severe CDAD.

Back to the Case

Our patient had several risk factors predisposing her to developing CDAD. She was of advanced age and took a fluoroquinolone antibiotic during a recent hospitalization. She also presented with signs consistent with a severe case of CDAD. She had a fever, a white blood cell count >15,000 cells/mm3, and was older than 60. Thus, she should be treated with supportive care, placed on contact precautions, and administered oral vancomycin 125 mg by mouth every six hours for 10 days as empiric therapy for CDAD. Stool cultures should be sent to confirm the presence of the C. difficile toxin.

 

click for larger table

Bottom Line

The appropriate antibiotic choice to treat CDAD in any patient depends upon the clinical severity of the disease. Treat patients with mild CDAD with metronidazole; prescribe oral vancomycin for patients with severe CDAD. TH

Dr. Mattison, instructor of medicine at Harvard Medical School, is a hospitalist and co-director of the Inpatient Geriatrics Unit at Beth Israel Deaconess Medical Center (BIDMC) in Boston. Dr. Li, assistant professor of medicine at Harvard Medical School, is director of hospital medicine and associate chief of BIDMC’s Division of General Medicine and Primary Care.

References

1.Bartlett JG, Moon N, Chang TW, Taylor N, Onderdonk AB. Role of C. difficile in antibiotic-associated pseudomembranous colitis. Gastroenterology. 1978;75(5):778-782.

2.Poutanen SM, Simor AE. C. difficile-associated diarrhea in adults. CMAJ. 2004;171(1):51-58.

3.Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant C. difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235(3):363-372.

4.Bartlett JG. Narrative review: the new epidemic of C. difficile-associated enteric disease. Ann Intern Med. 2006;145(10):758-764.

5.Teasley DG, Gerding DN, Olson MM, et al. Prospective randomized trial of metronidazole versus vancomycin for C. difficile-associated diarrhea and colitis. Lancet. 1983;2:1043-1046.

6.Wenisch C, Parschalk B, Hasenhündl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of C. difficile-associated diarrhea. Clin Infect Dis. 1996;22:813-818.

7.Pepin J, Alary M, Valiquette L, et al. Increasing risk of relapse after treatment of C. difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-1597.

8.Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of C. difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302-307.

Case

An 84-year-old woman presents with watery diarrhea. She recently received a fluoroquinolone antibiotic during a hospitalization for pneumonia. Her temperature is 101 degrees, her heart rate is 110 beats per minute, and her respiratory rate is 22 breaths per minute. Her abdominal exam is significant for mild distention, hyperactive bowel sounds, and diffuse, mild tenderness without rebound or guarding. Her white blood cell count is 18,200 cells/mm3. You suspect C. difficile infection. Should you treat empirically with antibiotics and, if so, which antibiotic should you prescribe?

Overview

C. difficile is an anaerobic gram-positive bacillus that produces spores and toxins. In 1978, C. difficile was identified as the causative agent for antibiotic-associated diarrhea.1 The portal of entry is via the fecal-oral route.

Some patients carry C. difficile in their intestinal flora and show no signs of infection. Patients who develop symptoms commonly present with profuse, watery diarrhea. Nausea, vomiting, and abdominal pain also can be seen. Severe cases of C. difficile-associated diarrhea (CDAD) can present with significant abdominal pain and multisystem organ failure, with toxic megacolon resulting from toxin production and ileus.2 In severe cases due to ileus, diarrhea may be absent. Risk of mortality in severe cases is high, with some reviews citing death rates of 57% in patients requiring total colectomy.3 Risk factors for developing CDAD include the prior or current use of antibiotics, advanced age, hospitalization, and prior gastrointestinal surgery or procedures.4

The initial CDAD treatment involves removal of the agent that incited the infection. In most cases, this means discontinuation of an antimicrobial agent. Removal of the inciting agent allows restoration of the normal bowel flora. In mild CDAD cases, this may be sufficient therapy. However, most CDAD cases require treatment. Although many antimicrobial and probiotic agents have been used in CDAD treatment, metronidazole and vancomycin are the most commonly prescribed agents. There is an ongoing debate as to which should be considered the first-line agent.

Review of the Data

Metronidazole and vancomycin have the longest histories of use and are the most studied agents in CDAD. Metronidazole is prescribed 250 mg four times daily (or 500 mg twice daily) for 14 days. It is reasonably tolerated, although it can cause a metallic taste in the mouth. Vancomycin is given 125 mg four times daily (or 500 mg three times daily) for 10 to 14 days. Unlike metronidazole, which can be given by mouth or intravenously, only oral vancomycin is effective in CDAD.

 

Historically, metronidazole has been prescribed more frequently as the first-line agent in CDAD. Proponents of the drug tout its low cost and the importance of minimizing the development of vancomycin-resistant enteric pathogens. There are two small, prospective, randomized studies comparing the efficacy of the agents against one another in the treatment of C. difficile infection, with similar efficacy demonstrated in both studies. In the early 1980s, Teasley and colleagues randomized 94 patients with C. difficile infection to either metronidazole or vancomycin.5 All the patients receiving vancomycin resolved their disease; 95% of patients receiving metronidazole were cured. The differences were not statistically significant.

In the mid-1990s, Wenisch and colleagues randomized patients with C. difficile infection to receive vancomycin, metronidazole, fusidic acid, or teicoplanin therapy.6 Ninety-four percent of patients in both the vancomycin and metronidazole groups were cured.

However, since 2000, investigators have reported higher failure rates with metronidazole therapy in C. difficile infections. For example, in 2005, Pepin and colleagues reviewed cases of C. difficile infections at a hospital in Quebec.7 They determined the number of patients with C. difficile infection initially treated with metronidazole who required additional therapy had markedly increased. Between 1991 and 2002, 9.6% of patients who initially were treated with metronidazole required a switch to vancomycin (or the addition of vancomycin) because of a disappointing response. This figure doubled to 25.7% in 2003-2004. The 60-day probability of recurrence also increased in the 2003-2004 test group (47.2%), compared with the 1991-2002 group (20.8%). Both results were statistically significant. Such data contributed to the debate regarding whether metronidazole or vancomycin is the superior agent in the treatment of C. difficile infections.

In 2007, Zar and colleagues studied the efficacy of metronidazole and vancomycin in the treatment of CDAD patients, but the study stratified patients according to disease severity.8 This allowed the authors to investigate whether one agent was superior in treating mild or severe CDAD. They determined disease severity by assigning points to individual patient characteristics. Patients with two or more points were deemed to have “severe” CDAD.

The investigators assigned one point for each of the following patient characteristics: temperature >38.3 degrees Celsius, age >60 years, albumin level <2.5 mg/dL, and white blood cell count >15,000 cells/mm3 within 48 hours of enrolling in the study. Any patient with endoscopic evidence of pseudomembrane formation or admission to the intensive-care unit (ICU) for CDAD treatment was considered to have severe disease.

Medical-on-Line/Alamy

This was a prospective, randomized controlled trial of 150 patients. Patients were randomly prescribed 500 mg metronidazole by mouth three times daily or 125 mg of vancomycin by mouth four times daily. Patients with mild CDAD had similar cure rates: 90% metronidazole versus 98% vancomycin (P=0.36). However, patients with severe CDAD fared statistically better when treated with oral vancomycin. Ninety-seven percent of severe CDAD patients treated with oral vancomycin had a clinical cure, while only 76% of those treated with metronidazole were cured (P=0.02). Recurrence of the disease was similar in each treatment group.

Based on this study, metronidazole and vancomycin appear equally effective in the treatment of mild CDAD, but vancomycin is the superior agent in the treatment of patients with severe CDAD.

Back to the Case

Our patient had several risk factors predisposing her to developing CDAD. She was of advanced age and took a fluoroquinolone antibiotic during a recent hospitalization. She also presented with signs consistent with a severe case of CDAD. She had a fever, a white blood cell count >15,000 cells/mm3, and was older than 60. Thus, she should be treated with supportive care, placed on contact precautions, and administered oral vancomycin 125 mg by mouth every six hours for 10 days as empiric therapy for CDAD. Stool cultures should be sent to confirm the presence of the C. difficile toxin.

 

click for larger table

Bottom Line

The appropriate antibiotic choice to treat CDAD in any patient depends upon the clinical severity of the disease. Treat patients with mild CDAD with metronidazole; prescribe oral vancomycin for patients with severe CDAD. TH

Dr. Mattison, instructor of medicine at Harvard Medical School, is a hospitalist and co-director of the Inpatient Geriatrics Unit at Beth Israel Deaconess Medical Center (BIDMC) in Boston. Dr. Li, assistant professor of medicine at Harvard Medical School, is director of hospital medicine and associate chief of BIDMC’s Division of General Medicine and Primary Care.

References

1.Bartlett JG, Moon N, Chang TW, Taylor N, Onderdonk AB. Role of C. difficile in antibiotic-associated pseudomembranous colitis. Gastroenterology. 1978;75(5):778-782.

2.Poutanen SM, Simor AE. C. difficile-associated diarrhea in adults. CMAJ. 2004;171(1):51-58.

3.Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant C. difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235(3):363-372.

4.Bartlett JG. Narrative review: the new epidemic of C. difficile-associated enteric disease. Ann Intern Med. 2006;145(10):758-764.

5.Teasley DG, Gerding DN, Olson MM, et al. Prospective randomized trial of metronidazole versus vancomycin for C. difficile-associated diarrhea and colitis. Lancet. 1983;2:1043-1046.

6.Wenisch C, Parschalk B, Hasenhündl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of C. difficile-associated diarrhea. Clin Infect Dis. 1996;22:813-818.

7.Pepin J, Alary M, Valiquette L, et al. Increasing risk of relapse after treatment of C. difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-1597.

8.Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of C. difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302-307.

Case

An 84-year-old woman presents with watery diarrhea. She recently received a fluoroquinolone antibiotic during a hospitalization for pneumonia. Her temperature is 101 degrees, her heart rate is 110 beats per minute, and her respiratory rate is 22 breaths per minute. Her abdominal exam is significant for mild distention, hyperactive bowel sounds, and diffuse, mild tenderness without rebound or guarding. Her white blood cell count is 18,200 cells/mm3. You suspect C. difficile infection. Should you treat empirically with antibiotics and, if so, which antibiotic should you prescribe?

Overview

C. difficile is an anaerobic gram-positive bacillus that produces spores and toxins. In 1978, C. difficile was identified as the causative agent for antibiotic-associated diarrhea.1 The portal of entry is via the fecal-oral route.

Some patients carry C. difficile in their intestinal flora and show no signs of infection. Patients who develop symptoms commonly present with profuse, watery diarrhea. Nausea, vomiting, and abdominal pain also can be seen. Severe cases of C. difficile-associated diarrhea (CDAD) can present with significant abdominal pain and multisystem organ failure, with toxic megacolon resulting from toxin production and ileus.2 In severe cases due to ileus, diarrhea may be absent. Risk of mortality in severe cases is high, with some reviews citing death rates of 57% in patients requiring total colectomy.3 Risk factors for developing CDAD include the prior or current use of antibiotics, advanced age, hospitalization, and prior gastrointestinal surgery or procedures.4

The initial CDAD treatment involves removal of the agent that incited the infection. In most cases, this means discontinuation of an antimicrobial agent. Removal of the inciting agent allows restoration of the normal bowel flora. In mild CDAD cases, this may be sufficient therapy. However, most CDAD cases require treatment. Although many antimicrobial and probiotic agents have been used in CDAD treatment, metronidazole and vancomycin are the most commonly prescribed agents. There is an ongoing debate as to which should be considered the first-line agent.

Review of the Data

Metronidazole and vancomycin have the longest histories of use and are the most studied agents in CDAD. Metronidazole is prescribed 250 mg four times daily (or 500 mg twice daily) for 14 days. It is reasonably tolerated, although it can cause a metallic taste in the mouth. Vancomycin is given 125 mg four times daily (or 500 mg three times daily) for 10 to 14 days. Unlike metronidazole, which can be given by mouth or intravenously, only oral vancomycin is effective in CDAD.

 

Historically, metronidazole has been prescribed more frequently as the first-line agent in CDAD. Proponents of the drug tout its low cost and the importance of minimizing the development of vancomycin-resistant enteric pathogens. There are two small, prospective, randomized studies comparing the efficacy of the agents against one another in the treatment of C. difficile infection, with similar efficacy demonstrated in both studies. In the early 1980s, Teasley and colleagues randomized 94 patients with C. difficile infection to either metronidazole or vancomycin.5 All the patients receiving vancomycin resolved their disease; 95% of patients receiving metronidazole were cured. The differences were not statistically significant.

In the mid-1990s, Wenisch and colleagues randomized patients with C. difficile infection to receive vancomycin, metronidazole, fusidic acid, or teicoplanin therapy.6 Ninety-four percent of patients in both the vancomycin and metronidazole groups were cured.

However, since 2000, investigators have reported higher failure rates with metronidazole therapy in C. difficile infections. For example, in 2005, Pepin and colleagues reviewed cases of C. difficile infections at a hospital in Quebec.7 They determined the number of patients with C. difficile infection initially treated with metronidazole who required additional therapy had markedly increased. Between 1991 and 2002, 9.6% of patients who initially were treated with metronidazole required a switch to vancomycin (or the addition of vancomycin) because of a disappointing response. This figure doubled to 25.7% in 2003-2004. The 60-day probability of recurrence also increased in the 2003-2004 test group (47.2%), compared with the 1991-2002 group (20.8%). Both results were statistically significant. Such data contributed to the debate regarding whether metronidazole or vancomycin is the superior agent in the treatment of C. difficile infections.

In 2007, Zar and colleagues studied the efficacy of metronidazole and vancomycin in the treatment of CDAD patients, but the study stratified patients according to disease severity.8 This allowed the authors to investigate whether one agent was superior in treating mild or severe CDAD. They determined disease severity by assigning points to individual patient characteristics. Patients with two or more points were deemed to have “severe” CDAD.

The investigators assigned one point for each of the following patient characteristics: temperature >38.3 degrees Celsius, age >60 years, albumin level <2.5 mg/dL, and white blood cell count >15,000 cells/mm3 within 48 hours of enrolling in the study. Any patient with endoscopic evidence of pseudomembrane formation or admission to the intensive-care unit (ICU) for CDAD treatment was considered to have severe disease.

Medical-on-Line/Alamy

This was a prospective, randomized controlled trial of 150 patients. Patients were randomly prescribed 500 mg metronidazole by mouth three times daily or 125 mg of vancomycin by mouth four times daily. Patients with mild CDAD had similar cure rates: 90% metronidazole versus 98% vancomycin (P=0.36). However, patients with severe CDAD fared statistically better when treated with oral vancomycin. Ninety-seven percent of severe CDAD patients treated with oral vancomycin had a clinical cure, while only 76% of those treated with metronidazole were cured (P=0.02). Recurrence of the disease was similar in each treatment group.

Based on this study, metronidazole and vancomycin appear equally effective in the treatment of mild CDAD, but vancomycin is the superior agent in the treatment of patients with severe CDAD.

Back to the Case

Our patient had several risk factors predisposing her to developing CDAD. She was of advanced age and took a fluoroquinolone antibiotic during a recent hospitalization. She also presented with signs consistent with a severe case of CDAD. She had a fever, a white blood cell count >15,000 cells/mm3, and was older than 60. Thus, she should be treated with supportive care, placed on contact precautions, and administered oral vancomycin 125 mg by mouth every six hours for 10 days as empiric therapy for CDAD. Stool cultures should be sent to confirm the presence of the C. difficile toxin.

 

click for larger table

Bottom Line

The appropriate antibiotic choice to treat CDAD in any patient depends upon the clinical severity of the disease. Treat patients with mild CDAD with metronidazole; prescribe oral vancomycin for patients with severe CDAD. TH

Dr. Mattison, instructor of medicine at Harvard Medical School, is a hospitalist and co-director of the Inpatient Geriatrics Unit at Beth Israel Deaconess Medical Center (BIDMC) in Boston. Dr. Li, assistant professor of medicine at Harvard Medical School, is director of hospital medicine and associate chief of BIDMC’s Division of General Medicine and Primary Care.

References

1.Bartlett JG, Moon N, Chang TW, Taylor N, Onderdonk AB. Role of C. difficile in antibiotic-associated pseudomembranous colitis. Gastroenterology. 1978;75(5):778-782.

2.Poutanen SM, Simor AE. C. difficile-associated diarrhea in adults. CMAJ. 2004;171(1):51-58.

3.Dallal RM, Harbrecht BG, Boujoukas AJ, et al. Fulminant C. difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002;235(3):363-372.

4.Bartlett JG. Narrative review: the new epidemic of C. difficile-associated enteric disease. Ann Intern Med. 2006;145(10):758-764.

5.Teasley DG, Gerding DN, Olson MM, et al. Prospective randomized trial of metronidazole versus vancomycin for C. difficile-associated diarrhea and colitis. Lancet. 1983;2:1043-1046.

6.Wenisch C, Parschalk B, Hasenhündl M, Hirschl AM, Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of C. difficile-associated diarrhea. Clin Infect Dis. 1996;22:813-818.

7.Pepin J, Alary M, Valiquette L, et al. Increasing risk of relapse after treatment of C. difficile colitis in Quebec, Canada. Clin Infect Dis. 2005;40:1591-1597.

8.Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and metronidazole for the treatment of C. difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302-307.

A 37-year-old African American man presents to the emergency department with chest pain and dyspnea, which began suddenly 30 minutes ago. The pain is severe, pressure-like, nonradiating, and pleuritic.

His heart rate is 88 beats per minute, blood pressure 135/72 mm Hg, respiratory rate 12 per minute, and oral temperature 38.5°C (101.3°F). His oxygen saturation by pulse oximetry is 99% while breathing room air. He is given sublingual nitroglycerin, but this does not alleviate his pain.

On physical examination, he is a physically fit man in obvious distress. His jugular veins are not distended, and no lymph nodes are palpable in his neck. The heart sounds are muffled without murmurs, but a faint pericardial friction rub is heard that persists even when he holds his breath. His lungs are clear to auscultation, his abdomen is normal, and his lower extremities are warm, with normal pulses and no edema. Of note, neither a Kussmaul sign nor a paradoxical pulse is present. An electrocardiogram is ordered (Figure 1).

While blood samples are being drawn, we learn more about his history. He has hypertension, for which he takes amlodipine (Norvasc), and gastroesophageal reflux under control with esomeprazole (Nexium). He says he does not have hyperlipidemia, diabetes, or coronary artery disease and his surgical history is unremarkable. He says he does not smoke, rarely drinks, and does not use any drugs. No one in his family has had premature coronary artery disease.

He says he has had similar symptoms in the past few months, which resulted in two emergency room visits. Electrocardiograms at those times were unremarkable, and a stress test was negative for ischemia.

A computed tomographic (CT) scan of the chest was also obtained during one of those visits. The scan was negative for a pulmonary embolus but incidentally showed liver hemangiomas.

He goes on to add that his chest pain has recently increased in frequency, and it has occurred daily for the past 5 days. The pain is not related to exertion, occurs throughout the day, and is associated with significant shortness of breath. It worsens when he is taking a deep breath and improves when he leans forward. Although he is febrile, he says he has had no fevers or chills in the past. He gives no history of weight loss, cough, orthopnea, or paroxysmal nocturnal dyspnea, but has been experiencing malaise, weakness, and myalgia for the past month. His review of systems is otherwise negative.

The patient’s initial laboratory results are shown in Table 1.

 

WHAT IS THE CAUSE OF HIS CHEST PAIN?

1. Which is the most likely cause of this patient’s chest pain?

• Acute myocardial infarction
• Acute pericarditis
• Myocarditis
• Pulmonary embolism
• Aortic dissection
• Pneumonia

Acute myocardial infarction. This is a young man with chest pain, ST-segment elevation, and elevated cardiac enzymes. Acute myocardial infarction should always be included in the differential diagnosis of such a patient, as recognizing it early and making an effort to rapidly restore blood flow to the myocardium can greatly improve the clinical outcome. However, particular features in his electrocardiogram and the duration and nature of his chest pain suggest another diagnosis.

Acute pericarditis causes pleuritic chest pain with diffuse ST-segment elevation, and its electrocardiographic changes may be difficult to distinguish from those of ischemia. The features in our patient’s electrocardiogram that point to pericarditis are¹:

• ST-segment elevation that is concave upward, occurring in all leads except aVR
• T waves concordant with ST-segment deviation
• PR-segment depression, sparing V₁ and aVR
• PR-segment elevation and ST depression in aVR.

Pleuritic chest pain is the most common symptom in acute pericarditis. A prodrome of fever, myalgia, and malaise is also common, especially in younger patients.² On physical examination, a pericardial friction rub is pathognomonic.

Our patient has most if not all of the classic features of acute pericarditis. Elevated cardiac enzymes, which this patient has, are not a classic feature of pericarditis and are generally considered a marker of cardiac ischemia. However, because the myocardium is adjacent to the pericardium, the acute inflammatory process of acute pericarditis may also result in myocardial injury, resulting in release of creatine kinase-MB.³

An increase in cardiac troponin is also frequently observed in acute pericarditis, reflecting biochemical evidence of inflammatory myocardial cell damage.⁴ Furthermore, cardiac troponin can be elevated in several other medical conditions,⁵ such as ischemic heart disease, congestive heart failure, myocarditis, pulmonary embolism, severe pulmonary hypertension, significant left ventricular hypertrophy, renal failure, sepsis, critical illness, and subarachnoid hemorrhage. Therefore, cardiac enzymes are not good markers to distinguish between acute myocardial infarction and acute pericarditis. However, echocardiography is an effective way to help differentiate pericarditis from myocardial ischemia in the setting of elevated troponins and electrocardiographic changes, by determining if wall-motion abnormalities are present or absent.

Hence, the diagnosis of acute pericarditis should take into account the combination of the clinical picture, electrocardiographic findings, and laboratory values. Overreliance on any of these in isolation can lead to misdiagnosis.

Pulmonary embolism is another common cause of acute-onset pleuritic chest pain and dyspnea. Electrocardiographic changes can include ST-segment elevation, and cardiac enzymes can be elevated, although this is uncommon.

Myocarditis is commonly due to infections, collagen vascular diseases, or medications. Hallmarks of this disease are elevated cardiac enzymes and myocardial damage that results in reduction in heart function.

Aortic dissection typically causes a sharp, tearing chest pain that radiates to the back. This diagnosis is unlikely in this patient.

Pneumonia. Although our patient did not have a cough and no crackles were heard on lung examination to suggest pneumonia, his fever, pleuritic chest pain, and leukocytosis with a left shift warrant a workup for it. A parapneumonic effusion could manifest with fevers and pleuritic chest pain. However, the acuity of the symptoms and the characteristic electrocardiographic changes and elevated cardiac enzymes are better explained by the other diagnoses, notably acute pericarditis.

 

ACUTE PERICARDITIS: WHAT IS THE CAUSE?

2. Which is the most common cause of acute pericarditis?

• Idiopathic
• Neoplasm
• Autoimmune
• Tuberculosis

Most (approximately 80%) of cases of acute pericarditis are idiopathic.^6,7 In a study in 100 patients with acute pericarditis,⁶ a specific cause was identified in only 22. The most common identified cause was neoplasm, which was present in seven patients: four with lung cancer and one each with breast carcinoma, cystic duct adenocarcinoma, and cardiac angiosarcoma.

A more recent study in 453 patients revealed similar results: 377 (83.2%) of the cases were idiopathic, 23 (5.1%) were neoplastic, 17 (3.8%) were due to tuberculosis, 33 (7.3%) were autoimmune, and 3 (0.7%) were purulent. Of note, viral causes are categorized as idiopathic, since the diagnostic workup is usually unsuccessful and treatment is empiric⁶; therefore, most of the so-called idiopathic cases are likely viral. Table 2 summarizes the most common specific causes of acute pericarditis.

CASE CONTINUES: PERICARDIAL EFFUSION

The patient is admitted to the hospital for additional workup. His fever, myalgia, and chest pain persist, though the pain is less intense than before.

A chest roentgenogram and transthoracic echocardiogram are ordered and blood cultures are drawn.

The roentgenogram shows marked cardiomegaly, bilateral small pleural effusions, and minimal atelectatic changes in the lungs.

Echocardiography reveals a normal ejection fraction (60%) and a moderate-sized pericardial effusion without evidence of tamponade.

3. Which is the most common cause of pericardial effusion?

• Idiopathic
• Infection
• Malignancy
• Collagen vascular disease

Pericardial effusion is relatively common after acute pericarditis but also has many other possible causes. In a study of 204 patients with pericardial effusion,⁸ 48% of cases were labeled as idiopathic. Of the remaining 52%, the most common specific diagnoses were infection (16%) and cancer (15%). Collagen vascular disease accounted for 8% of the cases and included systemic lupus erythematosus, rheumatoid arthritis, and scleroderma.

Although small pericardial effusions are common in pericarditis, larger pericardial effusions or failure to respond to therapy necessitates additional workup.²

In our patient, an extensive workup is initiated to look for bacterial, viral, fungal, and autoimmune causes of pericardial effusion, but the results of the workup are negative.

 

TREATING ACUTE PERICARDITIS

4. Which is the most appropriate treatment for acute pericarditis?

• Steroids
• A nonsteroidal anti-inflammatory drug (NSAID) or aspirin
• Opioids
• Colchicine
• Colchicine plus an NSAID or aspirin

An NSAID or aspirin is the basis of treatment for acute pericarditis and is very effective in relieving symptoms. Aspirin 2–4 g daily, indomethacin (Indocin) 75–225 mg daily, or ibuprofen (Motrin) 1,600–3,200 mg daily are prescribed most often; ibuprofen is preferred because it has a lower incidence of adverse effects than the others.⁹

Colchicine is recommended in addition to aspirin or NSAIDs for the treatment of acute pericarditis. Although in the past colchicine was reserved for recurrent pericarditis, the Colchicine for Acute Pericarditis (COPE) trial¹⁰ found it to be beneficial for first episodes of pericarditis as well.¹⁰ In this study, patients were randomized to receive conventional treatment with aspirin 800 mg every 6 or 8 hours or aspirin at the same dose combined with colchicine 0.5 to 1.0 mg daily. Colchicine showed significant benefit over conventional therapy, resulting in reduced rates of recurrence.

CASE CONTINUES: HEPATIC LESIONS ON MRI

Although aspirin and colchicine were started at the time of admission, our patient’s symptoms fail to improve. A suspicion remains that a neoplastic disorder could be the underlying cause of the presentation and could explain his chronic malaise, pericardial disease, and fever. In view of the liver hemangiomas reported previously on CT, we decide to evaluate the liver further with magnetic resonance imaging (MRI).

To our surprise, the MRI reveals innumerable hepatic lesions, some of which show radiographic features consistent with hemangiomas, while the remainder are atypical and appear to warrant a biopsy (Figure 2). An oncology consultation is obtained and the need for biopsy is confirmed.

Since our patient’s symptoms have improved significantly during the past few days and his fever has resolved, biopsy is scheduled on an outpatient basis. Biopsy with ultrasonographic guidance is performed a week later and yields a pathologic diagnosis of hemangioma. The improvement, however, is short-lived, and his pain and dyspnea recur after 2 months. A follow-up echocardiogram is ordered.

A remarkable echocardiographic finding

To our astonishment, the echocardiogram reveals a mass in the right atrial free wall and right ventricle that appears to be invading the myocardial tissue (Figure 3).

The original echocardiogram that was performed a little over 2-1/2 months ago is re-reviewed. It very subtly suggests a complexity to the pericardial effusion in the area of the current mass, apparent only when the two studies are directly compared. Clearly, there has been interval development of a mass easily detectable by echocardiography. Although a small mass may have been obscured by the pericardial effusion in the original echocardiogram, the development of a mass of this size in such a short time suggests a rapidly growing tumor.

Cardiac MRI is performed, which confirms the finding and characterizes the mass as measuring 5.1 by 4.8 cm within the pericardial space adjacent to the right atrium and atrioventricular groove and adherent to the right atrium. There are small excrescences of soft tissue through the midportion of the right atrial wall, suggesting tissue invasion (Figure  4).

CARDIAC TUMORS

5. Which is the most common primary cardiac tumor?

• Myxoma
• Papillary fibroelastoma
• Sarcoma
• Lymphoma

Primary cardiac tumors are rare, with an incidence on autopsy series ranging between 0.0017% and 0.33%,^11,12 making them far less common than metastases to the heart.

Myxomas are benign cardiac tumors and are the most common primary cardiac neoplasm. Approximately 80% of myxomas originate in the left atrium, typically presenting with one or more of the triad of intracardiac obstruction, systemic embolization, and constitutional symptoms.¹⁴

Cardiac papillary fibroelastomas, the second most common cardiac tumors, are benign and predominantly affect the cardiac valves.¹⁵

Only one-fourth of all cardiac tumors are malignant. Nearly all of these malignant tumors are sarcomas, with angiosarcoma being the most common morphologic type, accounting for 30% of primary cardiac sarcomas.¹³

Primary cardiac lymphomas are extremely rare and account for only 1.3% of all primary cardiac tumors.¹⁶

 

A DIAGNOSIS IS MADE

Fluorodeoxyglucose (FDG) positron-emission tomography is done, and shows a hypermetabolic right-sided pericardial tumor in addition to several suspicious hepatic lesions with heterogeneously increased FDG uptake. Biopsy with ultrasonographic guidance is performed again and reveals tissue consistent with hemangioma in addition to other areas with features strongly suggestive of a low-grade angiosarcoma (Figure 5). Pathology findings are unable to differentiate primary cardiac angiosarcoma from a metastatic cardiac tumor; however, given the multiple liver lesions and the presence of a solitary cardiac mass, this is most likely a primary cardiac tumor with metastasis to the liver.

CARDIAC ANGIOSARCOMA

Cardiac angiosarcoma, the most common malignant primary cardiac tumor, has a predilection for the right atrium.¹³ These tumors tend to occur between the third and fifth decade of life and are three times more common in men than in women. Cardiac sarcomas proliferate rapidly and commonly extend into the pericardial space, causing pericardial effusion in up to one-fourth of patients.

Surgical resection is the treatment of choice, but due to the location and extent of involvement, complete resection is often difficult. Also, distant metastases are present at the time of diagnosis in 80% of cases, precluding a surgical cure.¹⁷ Adjuvant chemotherapy, radiotherapy, and even heart transplantation do not substantially improve the survival of these patients.^18–20 Because no effective treatment is available, the prognosis is dismal, with a median survival of 6 to 12 months.

Our patient is discharged home to follow up with an oncologist and initiate chemotherapy.

Acknowledgment: We thank Lisa M. Yerian, MD, for interpreting the biopsy specimens described in this article.

A 37-year-old African American man presents to the emergency department with chest pain and dyspnea, which began suddenly 30 minutes ago. The pain is severe, pressure-like, nonradiating, and pleuritic.

His heart rate is 88 beats per minute, blood pressure 135/72 mm Hg, respiratory rate 12 per minute, and oral temperature 38.5°C (101.3°F). His oxygen saturation by pulse oximetry is 99% while breathing room air. He is given sublingual nitroglycerin, but this does not alleviate his pain.

On physical examination, he is a physically fit man in obvious distress. His jugular veins are not distended, and no lymph nodes are palpable in his neck. The heart sounds are muffled without murmurs, but a faint pericardial friction rub is heard that persists even when he holds his breath. His lungs are clear to auscultation, his abdomen is normal, and his lower extremities are warm, with normal pulses and no edema. Of note, neither a Kussmaul sign nor a paradoxical pulse is present. An electrocardiogram is ordered (Figure 1).

While blood samples are being drawn, we learn more about his history. He has hypertension, for which he takes amlodipine (Norvasc), and gastroesophageal reflux under control with esomeprazole (Nexium). He says he does not have hyperlipidemia, diabetes, or coronary artery disease and his surgical history is unremarkable. He says he does not smoke, rarely drinks, and does not use any drugs. No one in his family has had premature coronary artery disease.

He says he has had similar symptoms in the past few months, which resulted in two emergency room visits. Electrocardiograms at those times were unremarkable, and a stress test was negative for ischemia.

A computed tomographic (CT) scan of the chest was also obtained during one of those visits. The scan was negative for a pulmonary embolus but incidentally showed liver hemangiomas.

He goes on to add that his chest pain has recently increased in frequency, and it has occurred daily for the past 5 days. The pain is not related to exertion, occurs throughout the day, and is associated with significant shortness of breath. It worsens when he is taking a deep breath and improves when he leans forward. Although he is febrile, he says he has had no fevers or chills in the past. He gives no history of weight loss, cough, orthopnea, or paroxysmal nocturnal dyspnea, but has been experiencing malaise, weakness, and myalgia for the past month. His review of systems is otherwise negative.

The patient’s initial laboratory results are shown in Table 1.

 

WHAT IS THE CAUSE OF HIS CHEST PAIN?

1. Which is the most likely cause of this patient’s chest pain?

• Acute myocardial infarction
• Acute pericarditis
• Myocarditis
• Pulmonary embolism
• Aortic dissection
• Pneumonia

Acute myocardial infarction. This is a young man with chest pain, ST-segment elevation, and elevated cardiac enzymes. Acute myocardial infarction should always be included in the differential diagnosis of such a patient, as recognizing it early and making an effort to rapidly restore blood flow to the myocardium can greatly improve the clinical outcome. However, particular features in his electrocardiogram and the duration and nature of his chest pain suggest another diagnosis.

Acute pericarditis causes pleuritic chest pain with diffuse ST-segment elevation, and its electrocardiographic changes may be difficult to distinguish from those of ischemia. The features in our patient’s electrocardiogram that point to pericarditis are¹:

• ST-segment elevation that is concave upward, occurring in all leads except aVR
• T waves concordant with ST-segment deviation
• PR-segment depression, sparing V₁ and aVR
• PR-segment elevation and ST depression in aVR.

Pleuritic chest pain is the most common symptom in acute pericarditis. A prodrome of fever, myalgia, and malaise is also common, especially in younger patients.² On physical examination, a pericardial friction rub is pathognomonic.

Our patient has most if not all of the classic features of acute pericarditis. Elevated cardiac enzymes, which this patient has, are not a classic feature of pericarditis and are generally considered a marker of cardiac ischemia. However, because the myocardium is adjacent to the pericardium, the acute inflammatory process of acute pericarditis may also result in myocardial injury, resulting in release of creatine kinase-MB.³

An increase in cardiac troponin is also frequently observed in acute pericarditis, reflecting biochemical evidence of inflammatory myocardial cell damage.⁴ Furthermore, cardiac troponin can be elevated in several other medical conditions,⁵ such as ischemic heart disease, congestive heart failure, myocarditis, pulmonary embolism, severe pulmonary hypertension, significant left ventricular hypertrophy, renal failure, sepsis, critical illness, and subarachnoid hemorrhage. Therefore, cardiac enzymes are not good markers to distinguish between acute myocardial infarction and acute pericarditis. However, echocardiography is an effective way to help differentiate pericarditis from myocardial ischemia in the setting of elevated troponins and electrocardiographic changes, by determining if wall-motion abnormalities are present or absent.

Hence, the diagnosis of acute pericarditis should take into account the combination of the clinical picture, electrocardiographic findings, and laboratory values. Overreliance on any of these in isolation can lead to misdiagnosis.

Pulmonary embolism is another common cause of acute-onset pleuritic chest pain and dyspnea. Electrocardiographic changes can include ST-segment elevation, and cardiac enzymes can be elevated, although this is uncommon.

Myocarditis is commonly due to infections, collagen vascular diseases, or medications. Hallmarks of this disease are elevated cardiac enzymes and myocardial damage that results in reduction in heart function.

Aortic dissection typically causes a sharp, tearing chest pain that radiates to the back. This diagnosis is unlikely in this patient.

Pneumonia. Although our patient did not have a cough and no crackles were heard on lung examination to suggest pneumonia, his fever, pleuritic chest pain, and leukocytosis with a left shift warrant a workup for it. A parapneumonic effusion could manifest with fevers and pleuritic chest pain. However, the acuity of the symptoms and the characteristic electrocardiographic changes and elevated cardiac enzymes are better explained by the other diagnoses, notably acute pericarditis.

 

ACUTE PERICARDITIS: WHAT IS THE CAUSE?

2. Which is the most common cause of acute pericarditis?

• Idiopathic
• Neoplasm
• Autoimmune
• Tuberculosis

Most (approximately 80%) of cases of acute pericarditis are idiopathic.^6,7 In a study in 100 patients with acute pericarditis,⁶ a specific cause was identified in only 22. The most common identified cause was neoplasm, which was present in seven patients: four with lung cancer and one each with breast carcinoma, cystic duct adenocarcinoma, and cardiac angiosarcoma.

A more recent study in 453 patients revealed similar results: 377 (83.2%) of the cases were idiopathic, 23 (5.1%) were neoplastic, 17 (3.8%) were due to tuberculosis, 33 (7.3%) were autoimmune, and 3 (0.7%) were purulent. Of note, viral causes are categorized as idiopathic, since the diagnostic workup is usually unsuccessful and treatment is empiric⁶; therefore, most of the so-called idiopathic cases are likely viral. Table 2 summarizes the most common specific causes of acute pericarditis.

CASE CONTINUES: PERICARDIAL EFFUSION

The patient is admitted to the hospital for additional workup. His fever, myalgia, and chest pain persist, though the pain is less intense than before.

A chest roentgenogram and transthoracic echocardiogram are ordered and blood cultures are drawn.

The roentgenogram shows marked cardiomegaly, bilateral small pleural effusions, and minimal atelectatic changes in the lungs.

Echocardiography reveals a normal ejection fraction (60%) and a moderate-sized pericardial effusion without evidence of tamponade.

3. Which is the most common cause of pericardial effusion?

• Idiopathic
• Infection
• Malignancy
• Collagen vascular disease

Pericardial effusion is relatively common after acute pericarditis but also has many other possible causes. In a study of 204 patients with pericardial effusion,⁸ 48% of cases were labeled as idiopathic. Of the remaining 52%, the most common specific diagnoses were infection (16%) and cancer (15%). Collagen vascular disease accounted for 8% of the cases and included systemic lupus erythematosus, rheumatoid arthritis, and scleroderma.

Although small pericardial effusions are common in pericarditis, larger pericardial effusions or failure to respond to therapy necessitates additional workup.²

In our patient, an extensive workup is initiated to look for bacterial, viral, fungal, and autoimmune causes of pericardial effusion, but the results of the workup are negative.

 

TREATING ACUTE PERICARDITIS

4. Which is the most appropriate treatment for acute pericarditis?

• Steroids
• A nonsteroidal anti-inflammatory drug (NSAID) or aspirin
• Opioids
• Colchicine
• Colchicine plus an NSAID or aspirin

An NSAID or aspirin is the basis of treatment for acute pericarditis and is very effective in relieving symptoms. Aspirin 2–4 g daily, indomethacin (Indocin) 75–225 mg daily, or ibuprofen (Motrin) 1,600–3,200 mg daily are prescribed most often; ibuprofen is preferred because it has a lower incidence of adverse effects than the others.⁹

Colchicine is recommended in addition to aspirin or NSAIDs for the treatment of acute pericarditis. Although in the past colchicine was reserved for recurrent pericarditis, the Colchicine for Acute Pericarditis (COPE) trial¹⁰ found it to be beneficial for first episodes of pericarditis as well.¹⁰ In this study, patients were randomized to receive conventional treatment with aspirin 800 mg every 6 or 8 hours or aspirin at the same dose combined with colchicine 0.5 to 1.0 mg daily. Colchicine showed significant benefit over conventional therapy, resulting in reduced rates of recurrence.

CASE CONTINUES: HEPATIC LESIONS ON MRI

Although aspirin and colchicine were started at the time of admission, our patient’s symptoms fail to improve. A suspicion remains that a neoplastic disorder could be the underlying cause of the presentation and could explain his chronic malaise, pericardial disease, and fever. In view of the liver hemangiomas reported previously on CT, we decide to evaluate the liver further with magnetic resonance imaging (MRI).

To our surprise, the MRI reveals innumerable hepatic lesions, some of which show radiographic features consistent with hemangiomas, while the remainder are atypical and appear to warrant a biopsy (Figure 2). An oncology consultation is obtained and the need for biopsy is confirmed.

Since our patient’s symptoms have improved significantly during the past few days and his fever has resolved, biopsy is scheduled on an outpatient basis. Biopsy with ultrasonographic guidance is performed a week later and yields a pathologic diagnosis of hemangioma. The improvement, however, is short-lived, and his pain and dyspnea recur after 2 months. A follow-up echocardiogram is ordered.

A remarkable echocardiographic finding

To our astonishment, the echocardiogram reveals a mass in the right atrial free wall and right ventricle that appears to be invading the myocardial tissue (Figure 3).

The original echocardiogram that was performed a little over 2-1/2 months ago is re-reviewed. It very subtly suggests a complexity to the pericardial effusion in the area of the current mass, apparent only when the two studies are directly compared. Clearly, there has been interval development of a mass easily detectable by echocardiography. Although a small mass may have been obscured by the pericardial effusion in the original echocardiogram, the development of a mass of this size in such a short time suggests a rapidly growing tumor.

Cardiac MRI is performed, which confirms the finding and characterizes the mass as measuring 5.1 by 4.8 cm within the pericardial space adjacent to the right atrium and atrioventricular groove and adherent to the right atrium. There are small excrescences of soft tissue through the midportion of the right atrial wall, suggesting tissue invasion (Figure  4).

CARDIAC TUMORS

5. Which is the most common primary cardiac tumor?

• Myxoma
• Papillary fibroelastoma
• Sarcoma
• Lymphoma

Primary cardiac tumors are rare, with an incidence on autopsy series ranging between 0.0017% and 0.33%,^11,12 making them far less common than metastases to the heart.

Myxomas are benign cardiac tumors and are the most common primary cardiac neoplasm. Approximately 80% of myxomas originate in the left atrium, typically presenting with one or more of the triad of intracardiac obstruction, systemic embolization, and constitutional symptoms.¹⁴

Cardiac papillary fibroelastomas, the second most common cardiac tumors, are benign and predominantly affect the cardiac valves.¹⁵

Only one-fourth of all cardiac tumors are malignant. Nearly all of these malignant tumors are sarcomas, with angiosarcoma being the most common morphologic type, accounting for 30% of primary cardiac sarcomas.¹³

Primary cardiac lymphomas are extremely rare and account for only 1.3% of all primary cardiac tumors.¹⁶

 

A DIAGNOSIS IS MADE

Fluorodeoxyglucose (FDG) positron-emission tomography is done, and shows a hypermetabolic right-sided pericardial tumor in addition to several suspicious hepatic lesions with heterogeneously increased FDG uptake. Biopsy with ultrasonographic guidance is performed again and reveals tissue consistent with hemangioma in addition to other areas with features strongly suggestive of a low-grade angiosarcoma (Figure 5). Pathology findings are unable to differentiate primary cardiac angiosarcoma from a metastatic cardiac tumor; however, given the multiple liver lesions and the presence of a solitary cardiac mass, this is most likely a primary cardiac tumor with metastasis to the liver.

CARDIAC ANGIOSARCOMA

Cardiac angiosarcoma, the most common malignant primary cardiac tumor, has a predilection for the right atrium.¹³ These tumors tend to occur between the third and fifth decade of life and are three times more common in men than in women. Cardiac sarcomas proliferate rapidly and commonly extend into the pericardial space, causing pericardial effusion in up to one-fourth of patients.

Surgical resection is the treatment of choice, but due to the location and extent of involvement, complete resection is often difficult. Also, distant metastases are present at the time of diagnosis in 80% of cases, precluding a surgical cure.¹⁷ Adjuvant chemotherapy, radiotherapy, and even heart transplantation do not substantially improve the survival of these patients.^18–20 Because no effective treatment is available, the prognosis is dismal, with a median survival of 6 to 12 months.

Our patient is discharged home to follow up with an oncologist and initiate chemotherapy.

Acknowledgment: We thank Lisa M. Yerian, MD, for interpreting the biopsy specimens described in this article.

A 37-year-old African American man presents to the emergency department with chest pain and dyspnea, which began suddenly 30 minutes ago. The pain is severe, pressure-like, nonradiating, and pleuritic.

His heart rate is 88 beats per minute, blood pressure 135/72 mm Hg, respiratory rate 12 per minute, and oral temperature 38.5°C (101.3°F). His oxygen saturation by pulse oximetry is 99% while breathing room air. He is given sublingual nitroglycerin, but this does not alleviate his pain.

On physical examination, he is a physically fit man in obvious distress. His jugular veins are not distended, and no lymph nodes are palpable in his neck. The heart sounds are muffled without murmurs, but a faint pericardial friction rub is heard that persists even when he holds his breath. His lungs are clear to auscultation, his abdomen is normal, and his lower extremities are warm, with normal pulses and no edema. Of note, neither a Kussmaul sign nor a paradoxical pulse is present. An electrocardiogram is ordered (Figure 1).

While blood samples are being drawn, we learn more about his history. He has hypertension, for which he takes amlodipine (Norvasc), and gastroesophageal reflux under control with esomeprazole (Nexium). He says he does not have hyperlipidemia, diabetes, or coronary artery disease and his surgical history is unremarkable. He says he does not smoke, rarely drinks, and does not use any drugs. No one in his family has had premature coronary artery disease.

He says he has had similar symptoms in the past few months, which resulted in two emergency room visits. Electrocardiograms at those times were unremarkable, and a stress test was negative for ischemia.

A computed tomographic (CT) scan of the chest was also obtained during one of those visits. The scan was negative for a pulmonary embolus but incidentally showed liver hemangiomas.

He goes on to add that his chest pain has recently increased in frequency, and it has occurred daily for the past 5 days. The pain is not related to exertion, occurs throughout the day, and is associated with significant shortness of breath. It worsens when he is taking a deep breath and improves when he leans forward. Although he is febrile, he says he has had no fevers or chills in the past. He gives no history of weight loss, cough, orthopnea, or paroxysmal nocturnal dyspnea, but has been experiencing malaise, weakness, and myalgia for the past month. His review of systems is otherwise negative.

The patient’s initial laboratory results are shown in Table 1.

 

WHAT IS THE CAUSE OF HIS CHEST PAIN?

1. Which is the most likely cause of this patient’s chest pain?

• Acute myocardial infarction
• Acute pericarditis
• Myocarditis
• Pulmonary embolism
• Aortic dissection
• Pneumonia

Acute myocardial infarction. This is a young man with chest pain, ST-segment elevation, and elevated cardiac enzymes. Acute myocardial infarction should always be included in the differential diagnosis of such a patient, as recognizing it early and making an effort to rapidly restore blood flow to the myocardium can greatly improve the clinical outcome. However, particular features in his electrocardiogram and the duration and nature of his chest pain suggest another diagnosis.

Acute pericarditis causes pleuritic chest pain with diffuse ST-segment elevation, and its electrocardiographic changes may be difficult to distinguish from those of ischemia. The features in our patient’s electrocardiogram that point to pericarditis are¹:

• ST-segment elevation that is concave upward, occurring in all leads except aVR
• T waves concordant with ST-segment deviation
• PR-segment depression, sparing V₁ and aVR
• PR-segment elevation and ST depression in aVR.

Pleuritic chest pain is the most common symptom in acute pericarditis. A prodrome of fever, myalgia, and malaise is also common, especially in younger patients.² On physical examination, a pericardial friction rub is pathognomonic.

Our patient has most if not all of the classic features of acute pericarditis. Elevated cardiac enzymes, which this patient has, are not a classic feature of pericarditis and are generally considered a marker of cardiac ischemia. However, because the myocardium is adjacent to the pericardium, the acute inflammatory process of acute pericarditis may also result in myocardial injury, resulting in release of creatine kinase-MB.³

An increase in cardiac troponin is also frequently observed in acute pericarditis, reflecting biochemical evidence of inflammatory myocardial cell damage.⁴ Furthermore, cardiac troponin can be elevated in several other medical conditions,⁵ such as ischemic heart disease, congestive heart failure, myocarditis, pulmonary embolism, severe pulmonary hypertension, significant left ventricular hypertrophy, renal failure, sepsis, critical illness, and subarachnoid hemorrhage. Therefore, cardiac enzymes are not good markers to distinguish between acute myocardial infarction and acute pericarditis. However, echocardiography is an effective way to help differentiate pericarditis from myocardial ischemia in the setting of elevated troponins and electrocardiographic changes, by determining if wall-motion abnormalities are present or absent.

Hence, the diagnosis of acute pericarditis should take into account the combination of the clinical picture, electrocardiographic findings, and laboratory values. Overreliance on any of these in isolation can lead to misdiagnosis.

Pulmonary embolism is another common cause of acute-onset pleuritic chest pain and dyspnea. Electrocardiographic changes can include ST-segment elevation, and cardiac enzymes can be elevated, although this is uncommon.

Myocarditis is commonly due to infections, collagen vascular diseases, or medications. Hallmarks of this disease are elevated cardiac enzymes and myocardial damage that results in reduction in heart function.

Aortic dissection typically causes a sharp, tearing chest pain that radiates to the back. This diagnosis is unlikely in this patient.

Pneumonia. Although our patient did not have a cough and no crackles were heard on lung examination to suggest pneumonia, his fever, pleuritic chest pain, and leukocytosis with a left shift warrant a workup for it. A parapneumonic effusion could manifest with fevers and pleuritic chest pain. However, the acuity of the symptoms and the characteristic electrocardiographic changes and elevated cardiac enzymes are better explained by the other diagnoses, notably acute pericarditis.

 

ACUTE PERICARDITIS: WHAT IS THE CAUSE?

2. Which is the most common cause of acute pericarditis?

• Idiopathic
• Neoplasm
• Autoimmune
• Tuberculosis

Most (approximately 80%) of cases of acute pericarditis are idiopathic.^6,7 In a study in 100 patients with acute pericarditis,⁶ a specific cause was identified in only 22. The most common identified cause was neoplasm, which was present in seven patients: four with lung cancer and one each with breast carcinoma, cystic duct adenocarcinoma, and cardiac angiosarcoma.

A more recent study in 453 patients revealed similar results: 377 (83.2%) of the cases were idiopathic, 23 (5.1%) were neoplastic, 17 (3.8%) were due to tuberculosis, 33 (7.3%) were autoimmune, and 3 (0.7%) were purulent. Of note, viral causes are categorized as idiopathic, since the diagnostic workup is usually unsuccessful and treatment is empiric⁶; therefore, most of the so-called idiopathic cases are likely viral. Table 2 summarizes the most common specific causes of acute pericarditis.

CASE CONTINUES: PERICARDIAL EFFUSION

The patient is admitted to the hospital for additional workup. His fever, myalgia, and chest pain persist, though the pain is less intense than before.

A chest roentgenogram and transthoracic echocardiogram are ordered and blood cultures are drawn.

The roentgenogram shows marked cardiomegaly, bilateral small pleural effusions, and minimal atelectatic changes in the lungs.

Echocardiography reveals a normal ejection fraction (60%) and a moderate-sized pericardial effusion without evidence of tamponade.

3. Which is the most common cause of pericardial effusion?

• Idiopathic
• Infection
• Malignancy
• Collagen vascular disease

Pericardial effusion is relatively common after acute pericarditis but also has many other possible causes. In a study of 204 patients with pericardial effusion,⁸ 48% of cases were labeled as idiopathic. Of the remaining 52%, the most common specific diagnoses were infection (16%) and cancer (15%). Collagen vascular disease accounted for 8% of the cases and included systemic lupus erythematosus, rheumatoid arthritis, and scleroderma.

Although small pericardial effusions are common in pericarditis, larger pericardial effusions or failure to respond to therapy necessitates additional workup.²

In our patient, an extensive workup is initiated to look for bacterial, viral, fungal, and autoimmune causes of pericardial effusion, but the results of the workup are negative.

 

TREATING ACUTE PERICARDITIS

4. Which is the most appropriate treatment for acute pericarditis?

• Steroids
• A nonsteroidal anti-inflammatory drug (NSAID) or aspirin
• Opioids
• Colchicine
• Colchicine plus an NSAID or aspirin

An NSAID or aspirin is the basis of treatment for acute pericarditis and is very effective in relieving symptoms. Aspirin 2–4 g daily, indomethacin (Indocin) 75–225 mg daily, or ibuprofen (Motrin) 1,600–3,200 mg daily are prescribed most often; ibuprofen is preferred because it has a lower incidence of adverse effects than the others.⁹

Colchicine is recommended in addition to aspirin or NSAIDs for the treatment of acute pericarditis. Although in the past colchicine was reserved for recurrent pericarditis, the Colchicine for Acute Pericarditis (COPE) trial¹⁰ found it to be beneficial for first episodes of pericarditis as well.¹⁰ In this study, patients were randomized to receive conventional treatment with aspirin 800 mg every 6 or 8 hours or aspirin at the same dose combined with colchicine 0.5 to 1.0 mg daily. Colchicine showed significant benefit over conventional therapy, resulting in reduced rates of recurrence.

CASE CONTINUES: HEPATIC LESIONS ON MRI

Although aspirin and colchicine were started at the time of admission, our patient’s symptoms fail to improve. A suspicion remains that a neoplastic disorder could be the underlying cause of the presentation and could explain his chronic malaise, pericardial disease, and fever. In view of the liver hemangiomas reported previously on CT, we decide to evaluate the liver further with magnetic resonance imaging (MRI).

To our surprise, the MRI reveals innumerable hepatic lesions, some of which show radiographic features consistent with hemangiomas, while the remainder are atypical and appear to warrant a biopsy (Figure 2). An oncology consultation is obtained and the need for biopsy is confirmed.

Since our patient’s symptoms have improved significantly during the past few days and his fever has resolved, biopsy is scheduled on an outpatient basis. Biopsy with ultrasonographic guidance is performed a week later and yields a pathologic diagnosis of hemangioma. The improvement, however, is short-lived, and his pain and dyspnea recur after 2 months. A follow-up echocardiogram is ordered.

A remarkable echocardiographic finding

To our astonishment, the echocardiogram reveals a mass in the right atrial free wall and right ventricle that appears to be invading the myocardial tissue (Figure 3).

The original echocardiogram that was performed a little over 2-1/2 months ago is re-reviewed. It very subtly suggests a complexity to the pericardial effusion in the area of the current mass, apparent only when the two studies are directly compared. Clearly, there has been interval development of a mass easily detectable by echocardiography. Although a small mass may have been obscured by the pericardial effusion in the original echocardiogram, the development of a mass of this size in such a short time suggests a rapidly growing tumor.

Cardiac MRI is performed, which confirms the finding and characterizes the mass as measuring 5.1 by 4.8 cm within the pericardial space adjacent to the right atrium and atrioventricular groove and adherent to the right atrium. There are small excrescences of soft tissue through the midportion of the right atrial wall, suggesting tissue invasion (Figure  4).

CARDIAC TUMORS

5. Which is the most common primary cardiac tumor?

• Myxoma
• Papillary fibroelastoma
• Sarcoma
• Lymphoma

Primary cardiac tumors are rare, with an incidence on autopsy series ranging between 0.0017% and 0.33%,^11,12 making them far less common than metastases to the heart.

Myxomas are benign cardiac tumors and are the most common primary cardiac neoplasm. Approximately 80% of myxomas originate in the left atrium, typically presenting with one or more of the triad of intracardiac obstruction, systemic embolization, and constitutional symptoms.¹⁴

Cardiac papillary fibroelastomas, the second most common cardiac tumors, are benign and predominantly affect the cardiac valves.¹⁵

Only one-fourth of all cardiac tumors are malignant. Nearly all of these malignant tumors are sarcomas, with angiosarcoma being the most common morphologic type, accounting for 30% of primary cardiac sarcomas.¹³

Primary cardiac lymphomas are extremely rare and account for only 1.3% of all primary cardiac tumors.¹⁶

 

A DIAGNOSIS IS MADE

Fluorodeoxyglucose (FDG) positron-emission tomography is done, and shows a hypermetabolic right-sided pericardial tumor in addition to several suspicious hepatic lesions with heterogeneously increased FDG uptake. Biopsy with ultrasonographic guidance is performed again and reveals tissue consistent with hemangioma in addition to other areas with features strongly suggestive of a low-grade angiosarcoma (Figure 5). Pathology findings are unable to differentiate primary cardiac angiosarcoma from a metastatic cardiac tumor; however, given the multiple liver lesions and the presence of a solitary cardiac mass, this is most likely a primary cardiac tumor with metastasis to the liver.

CARDIAC ANGIOSARCOMA

Cardiac angiosarcoma, the most common malignant primary cardiac tumor, has a predilection for the right atrium.¹³ These tumors tend to occur between the third and fifth decade of life and are three times more common in men than in women. Cardiac sarcomas proliferate rapidly and commonly extend into the pericardial space, causing pericardial effusion in up to one-fourth of patients.

Surgical resection is the treatment of choice, but due to the location and extent of involvement, complete resection is often difficult. Also, distant metastases are present at the time of diagnosis in 80% of cases, precluding a surgical cure.¹⁷ Adjuvant chemotherapy, radiotherapy, and even heart transplantation do not substantially improve the survival of these patients.^18–20 Because no effective treatment is available, the prognosis is dismal, with a median survival of 6 to 12 months.

Our patient is discharged home to follow up with an oncologist and initiate chemotherapy.

Acknowledgment: We thank Lisa M. Yerian, MD, for interpreting the biopsy specimens described in this article.

A 43-year-old woman presents to the emergency department with substernal chest pressure of moderate intensity that started approximately 6 hours ago. The pressure radiates to both arms and is accompanied by nausea. She says she has had no emesis, diaphoresis, fevers, chills, shortness of breath, abdominal pain, melena, dysuria, weight loss, headaches, change in vision, seizures, joint pain, or skin rashes. She also says she has had no prior similar episodes and has no history of myocardial infarction (MI) or stroke.

The patient has a history of gastroesophageal reflux disease and uterine fibroids. She has had three pregnancies, one ending in spontaneous abortion at 12 weeks and two ending with healthy children delivered by cesarean section. She does not take any daily medications. She has smoked one pack per day over the last 25 years. She denies using alcohol or illicit drugs.

The patient’s mother had idiopathic deep vein thrombosis (DVT) at age 46, her father had an MI at age 65, and her sister had an MI at age 43.

On examination, she is in mild distress but is alert and oriented. Her temperature is 99.0°F (37.2°C), blood pressure 98/66 mm Hg, heart rate 65 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 99% on room air. Her body mass index is 19.5 (normal range 18.5–24.9). Her skin appears normal. Her head and neck show no obvious abnormalities, lymphadenopathy, thyromegaly, or bruits. Her heart, lungs, and abdomen are normal, as are her strength, sensation, reflexes, and gait.

Laboratory values at the time of admission:

• White blood cell count 12.58 × 10⁹/L (reference range 4.0–11.0)
• Hemoglobin 15.4 g/dL (12.0–16.0)
• Platelet count 122 × 10⁹/L (150–400)
• International normalized ratio (INR) 1.1 (0.9–1.1)
• Activated partial thromboplastin time 29.1 seconds (24.6–34).

A heart attack, and then a stroke

An initial electrocardiogram shows normal sinus rhythm, left anterior hemiblock, and nonspecific T-wave abnormalities. Cardiac enzymes are measured at intervals: her troponin T level is less than 0.01 ng/mL at the time of admission but rises to 0.75 ng/mL 3 hours later (normal range 0.0–0.1 ng/mL). Similarly, her creatine kinase-MB level is 3.3 ng/mL at admission but rises to 71.9 ng/mL 3 hours later (normal range 0.0–8.0 ng/mL).

The patient is diagnosed with non-ST-elevation MI. An intravenous heparin drip is started, and she is sent for urgent cardiac catheterization, which shows a total occlusion in a lateral obtuse marginal branch of the left circumflex artery due to a thrombus in the vessel. Otherwise, her coronary arteries are angiographically free of disease. The heparin drip is continued, and treatment is started with abciximab (ReoPro) and tissue plasminogen activator (Alteplase). She is sent to the cardiac intensive care unit for recovery, where she is placed on continuous cardiac monitoring, with no evidence of arrhythmia.

One day later, the left side of her face is drooping, her left arm is weak, and her speech is slurred. Magnetic resonance imaging of the brain shows an acute ischemic infarct in the right temporoparietal area and multiple areas of subacute to chronic ischemia. Magnetic resonance angiography of the brain indicates patent vessels. Both transthoracic and transesophageal echocardiography are performed and indicate normal left ventricular size, ejection fraction of 55%, valves without thrombus or vegetations, aorta with mild atheroma, and no patent foramen ovale by Doppler flow or agitated saline contrast study. Carotid artery Doppler ultrasonography shows 40% to 59% stenosis bilaterally.

 

ARTERIAL THROMBOSIS

1. Which of the following is a risk factor for arterial thrombosis?

• Atherosclerosis
• Protein C deficiency
• Use of oral contraceptive pills
• The factor V Leiden mutation

Protein C deficiency, the use of oral contraceptives, and the factor V Leiden mutation are typically associated with venous thrombosis¹; they have been documented as a cause of arterial thrombosis only in some case reports. In contrast, atherosclerosis is a well-established risk factor for arterial thrombosis.

Arterial occlusion can be due to thrombosis, embolism, or trauma

The causes of arterial occlusion can be categorized as thrombotic, embolic, or traumatic (Table 1).

Atherosclerosis is a risk factor for thrombosis and can be a source of emboli. Atherosclerotic plaque rupture may release inflammatory mediators, which also predispose to thrombosis.² This patient’s coronary arteries are essentially free of atherosclerotic disease per angiography. However, studies of intravascular ultrasonography have shown that coronary angiography may not detect all atherosclerotic plaques, as angiography can show only the lumen of the artery and not the plaque itself.³ For that reason, atherosclerosis has not been ruled out completely, and further workup is needed to evaluate other possible causes of her thrombotic events.

Embolism is the most likely cause of her stroke, however. Cases of arterial embolism can be classified on the basis of the origin of the thrombus, ie, the heart, an artery, or the venous system via a patent foramen ovale (paradoxical embolism). This patient’s echocardiogram reveals mild aortic atheroma, which can be a source of emboli, especially soon after intervention.

Case continues: Acute and recurrent DVT

While recovering from her MI and stroke, the patient develops edema and pain in both legs. Doppler ultrasonography is performed, which reveals acute DVT in the right gastrocnemius and posterior tibial veins and left soleal vein, despite her continued heparin therapy.

Her platelet count is 189 × 10⁹/L, so heparin-induced thrombocytopenia is not suspected; the new DVT is thought to be due to her hospitalization. Several days later, oral warfarin (Coumadin) is started and titrated to an INR of 2.0 to 3.0, the heparin is phased out, and the patient is sent home.

In the first few months after discharge, the patient presents to the emergency department three times with severe leg pain, and each time she is found to have extensive DVT in various leg veins even though she is complying with her warfarin therapy. At each visit, her INR is in the range of 2.5 to 3.1.

Comment. Her recurrent DVT warrants further evaluation for risk factors for venous thrombosis, which can be divided into hereditary and acquired factors.

Hereditary risk factors include the factor V Leiden mutation, the prothrombin gene mutation, hyperhomocysteinemia, dysfibrinogenemia, and deficiencies of protein C, protein S, and antithrombin.

Acquired risk factors include the antiphospholipid antibody syndrome, cancer, immobilization, surgery, congestive heart failure, pregnancy, use of hormonal contraceptives, hormone replacement therapy, nephrotic syndrome, trauma, and infection.^1,4

TESTING FOR HYPERCOAGULABLE STATES

2. In view of our patient’s recurrent thrombotic episodes, should she be tested for hypercoagulable states?

• Yes
• No

Testing for hypercoagulable conditions is warranted if it will affect the patient’s management or outcome. Some authorities recommend testing patients who are clinically characterized as “strongly” thrombophilic,⁵ ie, those who present with DVT and are younger than age 50, have recurrent thrombotic episodes, have a first-degree relative with documented thromboembolism before age 50, or have thrombotic episodes despite warfarin therapy.

This patient should be tested for hypercoagulable conditions because her initial DVT occurred before age 50 (at age 43), she has had recurrent, apparently idiopathic thrombotic episodes, she has a family history of thromboembolism, and she had clots while on therapeutic warfarin therapy, all of which suggest a hypercoagulable state. Furthermore, the confirmation of her diagnosis may affect her medical management, as it may determine if further testing and therapies are needed.

Case continues: Tests are negative

Laboratory tests for hypercoagulable conditions are performed and are negative for the factor V Leiden mutation, the prothrombin gene mutation, antithrombin deficiency, and protein C and S deficiencies. A screen for antiphospholipid antibodies is indeterminate.

TREATMENT AFFECTS TEST RESULTS

3. If a patient is on warfarin therapy, which test results may be affected?

• Antithrombin levels
• Protein C and S levels
• Factor V Leiden mutation

Warfarin decreases the levels of proteins C and S; therefore, the levels of these substances cannot be accurately interpreted in a patient taking warfarin.

All anticoagulants prolong the clotting time and may affect the results of assays based on the clotting time, such as the prothrombin time, the partial thromboplastin time, the dilute Russell’s viper venom time (DRVVT), the hexagonal phase phospholipid neutralization assay, the thrombin time, and clottable protein C and protein S. Heparin reduces the level of antithrombin; however, laboratories now have heparin-binding agents that reduce the effect of heparin in clotting studies.

Acute thrombotic states lower the levels of antithrombin and proteins C and S.

Assays not based on the clotting time (immunogenic or genetic tests such as those for anticardiolipin antibodies and the factor V Leiden and prothrombin gene mutations) are not affected by anticoagulant use.⁵

However, the presence or absence of a hypercoagulable state should not affect the treatment of acute DVT, and a full 6- to 12-month course of anticoagulation should be completed.^6,7 If possible, lupus anticoagulant testing should be repeated 2 weeks after anticoagulation is stopped.⁸

This patient needs lifelong anticoagulation because of her repeated thrombotic episodes. Stopping the medication for 2 weeks for testing would increase the risk of rethrombosis in this patient, and most experts would not advise it.

In summary, testing for hypercoagulable conditions is not recommended during an acute thrombotic episode and is preferably performed while the patient is not on anticoagulation therapy. If the patient is already on anticoagulation, the results of tests for hypercoagulable conditions should be interpreted with caution.

Case continues: Another stroke

During the subsequent year, the patient’s primary care physician monitors her warfarin use and sends her for age-appropriate cancer screening, including a breast examination, Papanicolaou smear, and mammography. Also, given her history of smoking, a chest radiograph is ordered. All of these studies are normal. In addition, evaluations for hematologic disorders such as myelodysplastic syndrome, polycythemia vera, and Waldenström macroglobulinema reveal normal complete blood counts and normal results on serum and urine protein electrophoresis.

Later that year, she returns to the emergency department with complete aphasia and total right-sided paralysis. Magnetic resonance imaging shows an acute infarct in the left frontal operculum, a subacute infarct in the right cerebellum, and multiple chronic cortical and subcortical infarcts throughout the brain. Ultrasonography shows an extensive new DVT in her right leg. Her INR at this time is 3.1.

 

WHAT CONDITIONS CAUSE BOTH ARTERIAL AND VENOUS THROMBOSIS?

4. Given that the patient has evidence of both recurrent arterial and venous thromboses, which of the following conditions is likely?

• Antiphospholipid antibody syndrome
• Heparin-induced thrombocytopenia
• Malignancy
• All of the above

Conditions associated with both arterial and venous thrombosis include antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, malignancy, paradoxical embolism, hyperhomocysteinemia, myeloproliferative disorders, myelodysplastic disorder, paraproteinemia, vasculitis, and paroxysmal nocturnal hemoglobinuria.^1,4

The hypercoagulability associated with malignancy is also known as Trousseau syndrome. This term was originally used to describe migratory thrombophlebitis as a forewarning for occult visceral malignancy, and has grown over the years to describe malignancy-induced hypercoagulability.⁹

At present, the exact mechanism that causes Trousseau syndrome is unknown. Some hypotheses implicate mucin (produced by the cancer),¹⁰ tissue factor,¹¹ tumor-associated cysteine proteinase,¹² tumor hypoxia,¹³ and oncogene activation as plausible triggers for this syndrome.

As stated above, the patient has a normal platelet count and negative results on cancer screening tests. Tests for antiphospholipid antibodies and lupus anticoagulant are repeated. Tests for the specific antiphospholipid antibodies against beta-2 glycoprotein I and cardiolipin are negative (Table 2). However, the test for lupus anticoagulant is positive by the criteria of the International Society on Thrombosis and Haemostasis: the patient has a prolonged clotting time screening test (hexagonal phase screen, DRVVT screen), positive mixing study (DRVVT 1:1 mix and circulating anticoagulant), positive phospholipid dependence (hexagonal phase screen, confirm, and delta; DRVVT confirm ratio; and platelet neutralization procedure), and no evidence of other factor-specific inhibitors (Table 3).¹⁴

DOES SHE HAVE ANTIPHOSPHOLIPID ANTIBODY SYNDROME?

5. The patient is positive for lupus anticoagulant. Does she have antiphospholipid antibody syndrome?

• Yes
• No
• Repeat testing is needed to meet the diagnostic criteria

The Sapporo criteria¹⁵ indicate that antiphospholipid antibody syndrome is present if at least one clinical criterion and one laboratory criterion are met. The clinical criteria are one or more episodes of arterial or venous thrombosis or pregnancy-related morbidity, ie:

• Unexplained intrauterine fetal death at 10 weeks gestation or later with no apparent fetal abnormality
• Premature births of a morphologically normal fetus at less than 34 weeks of gestation due to preeclampsia, eclampsia, or placental insufficiency
• Three or more spontaneous abortions at 10 weeks of gestation or earlier, with no known paternal chromosomal abnormalities or maternal hormonal abnormalities and normal maternal anatomy.

The laboratory criteria are:

• Lupus anticoagulant present
• Anticardiolipin antibody (IgG or IgM) titer greater than 40 IgG antiphospholipid units (GPL) or IgM antiphospholipid units (MPL) or higher than the 99th percentile of the testing laboratory normal reference range
• Anti-beta-2 glycoprotein-I antibody (IgG or IgM) titer greater than 20 GPL or MPL or higher than the 99th percentile of the testing laboratory normal reference range.

The patient likely has antiphospholipid antibody syndrome because her lupus anticoagulant screen is positive and she meets the clinical criteria of thrombosis, and she should continue to be treated accordingly. However, to officially meet the revised Sapporo criteria, she would need to have laboratory tests that are positive on two or more occasions at least 12 weeks apart.

Case continues: Lung cancer is found

The patient reports that she has lost 10 pounds in 4 months. Since age-appropriate cancer testing was previously performed, a more extensive evaluation for weight loss is undertaken, with computed tomography of the chest, abdomen, and pelvis. These tests reveal a nodule in the right upper lobe of the lung, scarring in the right middle and left lower lung lobes, and hilar lymphadenopathy. Bronchoscopy with transbronchial biopsy confirms that she has adenocarcinoma of the lung.

6. What is suggested as a sufficient workup for malignancy in patients with idiopathic venous thromboembolism?

• Computed tomography of the chest, abdomen, and pelvis for every patient with idiopathic venous thromboembolism
• Positron emission tomography and tumor marker levels
• A comprehensive history and physical examination, routine laboratory tests, chest radiography, age- and sex-specific cancer screening, and patient-specific testing as indicated clinically

To date, there is no evidence to support a cancer evaluation beyond a comprehensive medical history and physical examination, routine laboratory testing, chest radiography, and age- and sex-specific cancer screening unless it is dictated by the patient’s clinical presentation. A study by Cornuz et al¹⁶ suggested that this approach is appropriate for detecting cancer in patients with idiopathic venous thromboembolism.

A 2004 study¹⁷ attempted to answer the question of what to do about patients who have idiopathic venous thromboembolism but no other signs or symptoms that raise any clinical suspicion of cancer. This study randomized patients with idiopathic venous thromboembolism to undergo either routine medical management or an extensive malignancy evaluation. The evaluation included ultrasonography of the abdomen and pelvis, computed tomography of the abdomen and pelvis, gastroscopy or a double-contrast barium swallow study, colonoscopy or sigmoidoscopy followed by a barium enema, stool occult blood testing, and sputum cytology. Women were also tested for the tumor markers carcinoembryonic antigen, alpha-fetoprotein, and CA-125, and they underwent mammography and Papanicolaou testing; men were tested for prostate-specific antigen and underwent ultrasonography of the prostate. The results of the study did not reveal a statistically significant survival benefit in the group that underwent extensive cancer evaluation.

These studies indicate that the decision to test for cancer should be guided by clinical suspicion. Our patient lost 10 pounds in 4 months, smokes, and has had recurrent venous thromboembolism, so testing was appropriate.

After her diagnosis with adenocarcinoma of the lung, the patient has yet another DVT despite an INR of 3.1 and treatment with warfarin and aspirin.

 

LOW-MOLECULAR-WEIGHT HEPARIN FOR PATIENTS WITH CANCER?

7. True or false? Low-molecular-weight heparin is more effective than warfarin in preventing DVT in cancer patients without increasing the bleeding risk.

• True
• False

This statement is true. The American College of Chest Physicians (ACCP) recommends immediate treatment of DVT with low-molecular-weight heparin for 6 to 12 months after a thrombotic event in a patient with malignancy.^6,18

Two major studies provide evidence for these recommendations: the Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer (CLOT)¹⁹ and the Trial of the Effect of Low-Molecular-Weight Heparin Versus Warfarin on Mortality in the Long-Term Treatment of Proximal Deep Vein Thrombosis (LITE)²⁰ studies.

The CLOT¹⁹ study showed that dalteparin (Fragmin) 200 IU/kg subcutaneously once daily for l month and then 150 IU/kg once daily was more effective than oral warfarin titrated to an INR of 2.5 and did not increase the risk of bleeding.

The LITE trial²⁰ showed the efficacy of tinzaparin (Innohep) 175 IU/kg subcutaneously daily, which can be used as an alternative.

Enoxaparin sodium (Lovenox) 1.5 mg/kg once daily has also been used. However, if low-molecular-weight heparin is not available, warfarin titrated to an INR of 2 to 3 is also acceptable.¹⁸

The ACCP consensus panel recommends giving anticoagulation for an initial 6 to 12 months and continuing it as long as there is evidence of active malignancy.⁶ The American Society for Clinical Oncology also recommends placement of an inferior vena cava filter for patients who have contraindications to anticoagulation or for whom low-molecular-weight heparin fails.¹⁸

Case continues: Summing up

In conclusion, our patient had an underlying malignancy, causing Trousseau syndrome. Before her cancer was diagnosed, she also had test results that suggested antiphospholipid antibody syndrome. Both of these conditions likely contributed to her hypercoagulable state, increasing her propensity for clotting and causing her recurrent thrombosis. The patient is currently on low-molecular-weight heparin and is undergoing palliative chemotherapy for metastatic adenocarcinoma of the lung. To this date, she has not had any new thrombotic events.

TAKE-HOME POINTS

• Risk factors for arterial occlusion can be divided into thrombotic, embolic, and traumatic categories.
• Risk factors for venous thrombosis can be divided into hereditary and acquired categories.
• Evaluation for hypercoagulable conditions is recommended if it will affect patient management or outcome. Patients to be considered for testing include those with idiopathic DVT and who are under age 50, those with a history of recurrent thrombosis, and those with a first-degree relative with documented venous thromboembolism before age 50.
• Evaluation for hypercoagulable conditions should ideally be performed either before starting anticoagulation therapy or 2 weeks after completing it.
• Potential causes of both arterial and venous thrombosis include antiphospholipid antibody syndrome, cancer, hyperhomocysteinemia, heparin-induced thrombocytopenia, paradoxical emboli, myeloproliferative disorders, myelodysplastic syndrome, paraproteinemia, vasculitis, and paroxysmal nocturnal hemoglobinuria.
• Current evidence does not support an extensive cancer evaluation in patients with idiopathic venous thromboembolism, unless dictated by the patient’s clinical condition.
• In patients with venous thromboembolism and active malignancy, anticoagulation is recommended for at least 6 to 12 months and as long as there is evidence of active malignancy.

A 43-year-old woman presents to the emergency department with substernal chest pressure of moderate intensity that started approximately 6 hours ago. The pressure radiates to both arms and is accompanied by nausea. She says she has had no emesis, diaphoresis, fevers, chills, shortness of breath, abdominal pain, melena, dysuria, weight loss, headaches, change in vision, seizures, joint pain, or skin rashes. She also says she has had no prior similar episodes and has no history of myocardial infarction (MI) or stroke.

The patient has a history of gastroesophageal reflux disease and uterine fibroids. She has had three pregnancies, one ending in spontaneous abortion at 12 weeks and two ending with healthy children delivered by cesarean section. She does not take any daily medications. She has smoked one pack per day over the last 25 years. She denies using alcohol or illicit drugs.

The patient’s mother had idiopathic deep vein thrombosis (DVT) at age 46, her father had an MI at age 65, and her sister had an MI at age 43.

On examination, she is in mild distress but is alert and oriented. Her temperature is 99.0°F (37.2°C), blood pressure 98/66 mm Hg, heart rate 65 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 99% on room air. Her body mass index is 19.5 (normal range 18.5–24.9). Her skin appears normal. Her head and neck show no obvious abnormalities, lymphadenopathy, thyromegaly, or bruits. Her heart, lungs, and abdomen are normal, as are her strength, sensation, reflexes, and gait.

Laboratory values at the time of admission:

• White blood cell count 12.58 × 10⁹/L (reference range 4.0–11.0)
• Hemoglobin 15.4 g/dL (12.0–16.0)
• Platelet count 122 × 10⁹/L (150–400)
• International normalized ratio (INR) 1.1 (0.9–1.1)
• Activated partial thromboplastin time 29.1 seconds (24.6–34).

A heart attack, and then a stroke

An initial electrocardiogram shows normal sinus rhythm, left anterior hemiblock, and nonspecific T-wave abnormalities. Cardiac enzymes are measured at intervals: her troponin T level is less than 0.01 ng/mL at the time of admission but rises to 0.75 ng/mL 3 hours later (normal range 0.0–0.1 ng/mL). Similarly, her creatine kinase-MB level is 3.3 ng/mL at admission but rises to 71.9 ng/mL 3 hours later (normal range 0.0–8.0 ng/mL).

The patient is diagnosed with non-ST-elevation MI. An intravenous heparin drip is started, and she is sent for urgent cardiac catheterization, which shows a total occlusion in a lateral obtuse marginal branch of the left circumflex artery due to a thrombus in the vessel. Otherwise, her coronary arteries are angiographically free of disease. The heparin drip is continued, and treatment is started with abciximab (ReoPro) and tissue plasminogen activator (Alteplase). She is sent to the cardiac intensive care unit for recovery, where she is placed on continuous cardiac monitoring, with no evidence of arrhythmia.

One day later, the left side of her face is drooping, her left arm is weak, and her speech is slurred. Magnetic resonance imaging of the brain shows an acute ischemic infarct in the right temporoparietal area and multiple areas of subacute to chronic ischemia. Magnetic resonance angiography of the brain indicates patent vessels. Both transthoracic and transesophageal echocardiography are performed and indicate normal left ventricular size, ejection fraction of 55%, valves without thrombus or vegetations, aorta with mild atheroma, and no patent foramen ovale by Doppler flow or agitated saline contrast study. Carotid artery Doppler ultrasonography shows 40% to 59% stenosis bilaterally.

 

ARTERIAL THROMBOSIS

1. Which of the following is a risk factor for arterial thrombosis?

• Atherosclerosis
• Protein C deficiency
• Use of oral contraceptive pills
• The factor V Leiden mutation

Protein C deficiency, the use of oral contraceptives, and the factor V Leiden mutation are typically associated with venous thrombosis¹; they have been documented as a cause of arterial thrombosis only in some case reports. In contrast, atherosclerosis is a well-established risk factor for arterial thrombosis.

Arterial occlusion can be due to thrombosis, embolism, or trauma

The causes of arterial occlusion can be categorized as thrombotic, embolic, or traumatic (Table 1).

Atherosclerosis is a risk factor for thrombosis and can be a source of emboli. Atherosclerotic plaque rupture may release inflammatory mediators, which also predispose to thrombosis.² This patient’s coronary arteries are essentially free of atherosclerotic disease per angiography. However, studies of intravascular ultrasonography have shown that coronary angiography may not detect all atherosclerotic plaques, as angiography can show only the lumen of the artery and not the plaque itself.³ For that reason, atherosclerosis has not been ruled out completely, and further workup is needed to evaluate other possible causes of her thrombotic events.

Embolism is the most likely cause of her stroke, however. Cases of arterial embolism can be classified on the basis of the origin of the thrombus, ie, the heart, an artery, or the venous system via a patent foramen ovale (paradoxical embolism). This patient’s echocardiogram reveals mild aortic atheroma, which can be a source of emboli, especially soon after intervention.

Case continues: Acute and recurrent DVT

While recovering from her MI and stroke, the patient develops edema and pain in both legs. Doppler ultrasonography is performed, which reveals acute DVT in the right gastrocnemius and posterior tibial veins and left soleal vein, despite her continued heparin therapy.

Her platelet count is 189 × 10⁹/L, so heparin-induced thrombocytopenia is not suspected; the new DVT is thought to be due to her hospitalization. Several days later, oral warfarin (Coumadin) is started and titrated to an INR of 2.0 to 3.0, the heparin is phased out, and the patient is sent home.

In the first few months after discharge, the patient presents to the emergency department three times with severe leg pain, and each time she is found to have extensive DVT in various leg veins even though she is complying with her warfarin therapy. At each visit, her INR is in the range of 2.5 to 3.1.

Comment. Her recurrent DVT warrants further evaluation for risk factors for venous thrombosis, which can be divided into hereditary and acquired factors.

Hereditary risk factors include the factor V Leiden mutation, the prothrombin gene mutation, hyperhomocysteinemia, dysfibrinogenemia, and deficiencies of protein C, protein S, and antithrombin.

Acquired risk factors include the antiphospholipid antibody syndrome, cancer, immobilization, surgery, congestive heart failure, pregnancy, use of hormonal contraceptives, hormone replacement therapy, nephrotic syndrome, trauma, and infection.^1,4

TESTING FOR HYPERCOAGULABLE STATES

2. In view of our patient’s recurrent thrombotic episodes, should she be tested for hypercoagulable states?

• Yes
• No

Testing for hypercoagulable conditions is warranted if it will affect the patient’s management or outcome. Some authorities recommend testing patients who are clinically characterized as “strongly” thrombophilic,⁵ ie, those who present with DVT and are younger than age 50, have recurrent thrombotic episodes, have a first-degree relative with documented thromboembolism before age 50, or have thrombotic episodes despite warfarin therapy.

This patient should be tested for hypercoagulable conditions because her initial DVT occurred before age 50 (at age 43), she has had recurrent, apparently idiopathic thrombotic episodes, she has a family history of thromboembolism, and she had clots while on therapeutic warfarin therapy, all of which suggest a hypercoagulable state. Furthermore, the confirmation of her diagnosis may affect her medical management, as it may determine if further testing and therapies are needed.

Case continues: Tests are negative

Laboratory tests for hypercoagulable conditions are performed and are negative for the factor V Leiden mutation, the prothrombin gene mutation, antithrombin deficiency, and protein C and S deficiencies. A screen for antiphospholipid antibodies is indeterminate.

TREATMENT AFFECTS TEST RESULTS

3. If a patient is on warfarin therapy, which test results may be affected?

• Antithrombin levels
• Protein C and S levels
• Factor V Leiden mutation

Warfarin decreases the levels of proteins C and S; therefore, the levels of these substances cannot be accurately interpreted in a patient taking warfarin.

All anticoagulants prolong the clotting time and may affect the results of assays based on the clotting time, such as the prothrombin time, the partial thromboplastin time, the dilute Russell’s viper venom time (DRVVT), the hexagonal phase phospholipid neutralization assay, the thrombin time, and clottable protein C and protein S. Heparin reduces the level of antithrombin; however, laboratories now have heparin-binding agents that reduce the effect of heparin in clotting studies.

Acute thrombotic states lower the levels of antithrombin and proteins C and S.

Assays not based on the clotting time (immunogenic or genetic tests such as those for anticardiolipin antibodies and the factor V Leiden and prothrombin gene mutations) are not affected by anticoagulant use.⁵

However, the presence or absence of a hypercoagulable state should not affect the treatment of acute DVT, and a full 6- to 12-month course of anticoagulation should be completed.^6,7 If possible, lupus anticoagulant testing should be repeated 2 weeks after anticoagulation is stopped.⁸

This patient needs lifelong anticoagulation because of her repeated thrombotic episodes. Stopping the medication for 2 weeks for testing would increase the risk of rethrombosis in this patient, and most experts would not advise it.

In summary, testing for hypercoagulable conditions is not recommended during an acute thrombotic episode and is preferably performed while the patient is not on anticoagulation therapy. If the patient is already on anticoagulation, the results of tests for hypercoagulable conditions should be interpreted with caution.

Case continues: Another stroke

During the subsequent year, the patient’s primary care physician monitors her warfarin use and sends her for age-appropriate cancer screening, including a breast examination, Papanicolaou smear, and mammography. Also, given her history of smoking, a chest radiograph is ordered. All of these studies are normal. In addition, evaluations for hematologic disorders such as myelodysplastic syndrome, polycythemia vera, and Waldenström macroglobulinema reveal normal complete blood counts and normal results on serum and urine protein electrophoresis.

Later that year, she returns to the emergency department with complete aphasia and total right-sided paralysis. Magnetic resonance imaging shows an acute infarct in the left frontal operculum, a subacute infarct in the right cerebellum, and multiple chronic cortical and subcortical infarcts throughout the brain. Ultrasonography shows an extensive new DVT in her right leg. Her INR at this time is 3.1.

 

WHAT CONDITIONS CAUSE BOTH ARTERIAL AND VENOUS THROMBOSIS?

4. Given that the patient has evidence of both recurrent arterial and venous thromboses, which of the following conditions is likely?

• Antiphospholipid antibody syndrome
• Heparin-induced thrombocytopenia
• Malignancy
• All of the above

Conditions associated with both arterial and venous thrombosis include antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, malignancy, paradoxical embolism, hyperhomocysteinemia, myeloproliferative disorders, myelodysplastic disorder, paraproteinemia, vasculitis, and paroxysmal nocturnal hemoglobinuria.^1,4

The hypercoagulability associated with malignancy is also known as Trousseau syndrome. This term was originally used to describe migratory thrombophlebitis as a forewarning for occult visceral malignancy, and has grown over the years to describe malignancy-induced hypercoagulability.⁹

At present, the exact mechanism that causes Trousseau syndrome is unknown. Some hypotheses implicate mucin (produced by the cancer),¹⁰ tissue factor,¹¹ tumor-associated cysteine proteinase,¹² tumor hypoxia,¹³ and oncogene activation as plausible triggers for this syndrome.

As stated above, the patient has a normal platelet count and negative results on cancer screening tests. Tests for antiphospholipid antibodies and lupus anticoagulant are repeated. Tests for the specific antiphospholipid antibodies against beta-2 glycoprotein I and cardiolipin are negative (Table 2). However, the test for lupus anticoagulant is positive by the criteria of the International Society on Thrombosis and Haemostasis: the patient has a prolonged clotting time screening test (hexagonal phase screen, DRVVT screen), positive mixing study (DRVVT 1:1 mix and circulating anticoagulant), positive phospholipid dependence (hexagonal phase screen, confirm, and delta; DRVVT confirm ratio; and platelet neutralization procedure), and no evidence of other factor-specific inhibitors (Table 3).¹⁴

DOES SHE HAVE ANTIPHOSPHOLIPID ANTIBODY SYNDROME?

5. The patient is positive for lupus anticoagulant. Does she have antiphospholipid antibody syndrome?

• Yes
• No
• Repeat testing is needed to meet the diagnostic criteria

The Sapporo criteria¹⁵ indicate that antiphospholipid antibody syndrome is present if at least one clinical criterion and one laboratory criterion are met. The clinical criteria are one or more episodes of arterial or venous thrombosis or pregnancy-related morbidity, ie:

• Unexplained intrauterine fetal death at 10 weeks gestation or later with no apparent fetal abnormality
• Premature births of a morphologically normal fetus at less than 34 weeks of gestation due to preeclampsia, eclampsia, or placental insufficiency
• Three or more spontaneous abortions at 10 weeks of gestation or earlier, with no known paternal chromosomal abnormalities or maternal hormonal abnormalities and normal maternal anatomy.

The laboratory criteria are:

• Lupus anticoagulant present
• Anticardiolipin antibody (IgG or IgM) titer greater than 40 IgG antiphospholipid units (GPL) or IgM antiphospholipid units (MPL) or higher than the 99th percentile of the testing laboratory normal reference range
• Anti-beta-2 glycoprotein-I antibody (IgG or IgM) titer greater than 20 GPL or MPL or higher than the 99th percentile of the testing laboratory normal reference range.

The patient likely has antiphospholipid antibody syndrome because her lupus anticoagulant screen is positive and she meets the clinical criteria of thrombosis, and she should continue to be treated accordingly. However, to officially meet the revised Sapporo criteria, she would need to have laboratory tests that are positive on two or more occasions at least 12 weeks apart.

Case continues: Lung cancer is found

The patient reports that she has lost 10 pounds in 4 months. Since age-appropriate cancer testing was previously performed, a more extensive evaluation for weight loss is undertaken, with computed tomography of the chest, abdomen, and pelvis. These tests reveal a nodule in the right upper lobe of the lung, scarring in the right middle and left lower lung lobes, and hilar lymphadenopathy. Bronchoscopy with transbronchial biopsy confirms that she has adenocarcinoma of the lung.

6. What is suggested as a sufficient workup for malignancy in patients with idiopathic venous thromboembolism?

• Computed tomography of the chest, abdomen, and pelvis for every patient with idiopathic venous thromboembolism
• Positron emission tomography and tumor marker levels
• A comprehensive history and physical examination, routine laboratory tests, chest radiography, age- and sex-specific cancer screening, and patient-specific testing as indicated clinically

To date, there is no evidence to support a cancer evaluation beyond a comprehensive medical history and physical examination, routine laboratory testing, chest radiography, and age- and sex-specific cancer screening unless it is dictated by the patient’s clinical presentation. A study by Cornuz et al¹⁶ suggested that this approach is appropriate for detecting cancer in patients with idiopathic venous thromboembolism.

A 2004 study¹⁷ attempted to answer the question of what to do about patients who have idiopathic venous thromboembolism but no other signs or symptoms that raise any clinical suspicion of cancer. This study randomized patients with idiopathic venous thromboembolism to undergo either routine medical management or an extensive malignancy evaluation. The evaluation included ultrasonography of the abdomen and pelvis, computed tomography of the abdomen and pelvis, gastroscopy or a double-contrast barium swallow study, colonoscopy or sigmoidoscopy followed by a barium enema, stool occult blood testing, and sputum cytology. Women were also tested for the tumor markers carcinoembryonic antigen, alpha-fetoprotein, and CA-125, and they underwent mammography and Papanicolaou testing; men were tested for prostate-specific antigen and underwent ultrasonography of the prostate. The results of the study did not reveal a statistically significant survival benefit in the group that underwent extensive cancer evaluation.

These studies indicate that the decision to test for cancer should be guided by clinical suspicion. Our patient lost 10 pounds in 4 months, smokes, and has had recurrent venous thromboembolism, so testing was appropriate.

After her diagnosis with adenocarcinoma of the lung, the patient has yet another DVT despite an INR of 3.1 and treatment with warfarin and aspirin.

 

LOW-MOLECULAR-WEIGHT HEPARIN FOR PATIENTS WITH CANCER?

7. True or false? Low-molecular-weight heparin is more effective than warfarin in preventing DVT in cancer patients without increasing the bleeding risk.

• True
• False

This statement is true. The American College of Chest Physicians (ACCP) recommends immediate treatment of DVT with low-molecular-weight heparin for 6 to 12 months after a thrombotic event in a patient with malignancy.^6,18

Two major studies provide evidence for these recommendations: the Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer (CLOT)¹⁹ and the Trial of the Effect of Low-Molecular-Weight Heparin Versus Warfarin on Mortality in the Long-Term Treatment of Proximal Deep Vein Thrombosis (LITE)²⁰ studies.

The CLOT¹⁹ study showed that dalteparin (Fragmin) 200 IU/kg subcutaneously once daily for l month and then 150 IU/kg once daily was more effective than oral warfarin titrated to an INR of 2.5 and did not increase the risk of bleeding.

The LITE trial²⁰ showed the efficacy of tinzaparin (Innohep) 175 IU/kg subcutaneously daily, which can be used as an alternative.

Enoxaparin sodium (Lovenox) 1.5 mg/kg once daily has also been used. However, if low-molecular-weight heparin is not available, warfarin titrated to an INR of 2 to 3 is also acceptable.¹⁸

The ACCP consensus panel recommends giving anticoagulation for an initial 6 to 12 months and continuing it as long as there is evidence of active malignancy.⁶ The American Society for Clinical Oncology also recommends placement of an inferior vena cava filter for patients who have contraindications to anticoagulation or for whom low-molecular-weight heparin fails.¹⁸

Case continues: Summing up

In conclusion, our patient had an underlying malignancy, causing Trousseau syndrome. Before her cancer was diagnosed, she also had test results that suggested antiphospholipid antibody syndrome. Both of these conditions likely contributed to her hypercoagulable state, increasing her propensity for clotting and causing her recurrent thrombosis. The patient is currently on low-molecular-weight heparin and is undergoing palliative chemotherapy for metastatic adenocarcinoma of the lung. To this date, she has not had any new thrombotic events.

TAKE-HOME POINTS

• Risk factors for arterial occlusion can be divided into thrombotic, embolic, and traumatic categories.
• Risk factors for venous thrombosis can be divided into hereditary and acquired categories.
• Evaluation for hypercoagulable conditions is recommended if it will affect patient management or outcome. Patients to be considered for testing include those with idiopathic DVT and who are under age 50, those with a history of recurrent thrombosis, and those with a first-degree relative with documented venous thromboembolism before age 50.
• Evaluation for hypercoagulable conditions should ideally be performed either before starting anticoagulation therapy or 2 weeks after completing it.
• Potential causes of both arterial and venous thrombosis include antiphospholipid antibody syndrome, cancer, hyperhomocysteinemia, heparin-induced thrombocytopenia, paradoxical emboli, myeloproliferative disorders, myelodysplastic syndrome, paraproteinemia, vasculitis, and paroxysmal nocturnal hemoglobinuria.
• Current evidence does not support an extensive cancer evaluation in patients with idiopathic venous thromboembolism, unless dictated by the patient’s clinical condition.
• In patients with venous thromboembolism and active malignancy, anticoagulation is recommended for at least 6 to 12 months and as long as there is evidence of active malignancy.

A 43-year-old woman presents to the emergency department with substernal chest pressure of moderate intensity that started approximately 6 hours ago. The pressure radiates to both arms and is accompanied by nausea. She says she has had no emesis, diaphoresis, fevers, chills, shortness of breath, abdominal pain, melena, dysuria, weight loss, headaches, change in vision, seizures, joint pain, or skin rashes. She also says she has had no prior similar episodes and has no history of myocardial infarction (MI) or stroke.

The patient has a history of gastroesophageal reflux disease and uterine fibroids. She has had three pregnancies, one ending in spontaneous abortion at 12 weeks and two ending with healthy children delivered by cesarean section. She does not take any daily medications. She has smoked one pack per day over the last 25 years. She denies using alcohol or illicit drugs.

The patient’s mother had idiopathic deep vein thrombosis (DVT) at age 46, her father had an MI at age 65, and her sister had an MI at age 43.

On examination, she is in mild distress but is alert and oriented. Her temperature is 99.0°F (37.2°C), blood pressure 98/66 mm Hg, heart rate 65 beats per minute, respiratory rate 18 breaths per minute, and oxygen saturation 99% on room air. Her body mass index is 19.5 (normal range 18.5–24.9). Her skin appears normal. Her head and neck show no obvious abnormalities, lymphadenopathy, thyromegaly, or bruits. Her heart, lungs, and abdomen are normal, as are her strength, sensation, reflexes, and gait.

Laboratory values at the time of admission:

• White blood cell count 12.58 × 10⁹/L (reference range 4.0–11.0)
• Hemoglobin 15.4 g/dL (12.0–16.0)
• Platelet count 122 × 10⁹/L (150–400)
• International normalized ratio (INR) 1.1 (0.9–1.1)
• Activated partial thromboplastin time 29.1 seconds (24.6–34).

A heart attack, and then a stroke

An initial electrocardiogram shows normal sinus rhythm, left anterior hemiblock, and nonspecific T-wave abnormalities. Cardiac enzymes are measured at intervals: her troponin T level is less than 0.01 ng/mL at the time of admission but rises to 0.75 ng/mL 3 hours later (normal range 0.0–0.1 ng/mL). Similarly, her creatine kinase-MB level is 3.3 ng/mL at admission but rises to 71.9 ng/mL 3 hours later (normal range 0.0–8.0 ng/mL).

The patient is diagnosed with non-ST-elevation MI. An intravenous heparin drip is started, and she is sent for urgent cardiac catheterization, which shows a total occlusion in a lateral obtuse marginal branch of the left circumflex artery due to a thrombus in the vessel. Otherwise, her coronary arteries are angiographically free of disease. The heparin drip is continued, and treatment is started with abciximab (ReoPro) and tissue plasminogen activator (Alteplase). She is sent to the cardiac intensive care unit for recovery, where she is placed on continuous cardiac monitoring, with no evidence of arrhythmia.

One day later, the left side of her face is drooping, her left arm is weak, and her speech is slurred. Magnetic resonance imaging of the brain shows an acute ischemic infarct in the right temporoparietal area and multiple areas of subacute to chronic ischemia. Magnetic resonance angiography of the brain indicates patent vessels. Both transthoracic and transesophageal echocardiography are performed and indicate normal left ventricular size, ejection fraction of 55%, valves without thrombus or vegetations, aorta with mild atheroma, and no patent foramen ovale by Doppler flow or agitated saline contrast study. Carotid artery Doppler ultrasonography shows 40% to 59% stenosis bilaterally.

 

ARTERIAL THROMBOSIS

1. Which of the following is a risk factor for arterial thrombosis?

• Atherosclerosis
• Protein C deficiency
• Use of oral contraceptive pills
• The factor V Leiden mutation

Protein C deficiency, the use of oral contraceptives, and the factor V Leiden mutation are typically associated with venous thrombosis¹; they have been documented as a cause of arterial thrombosis only in some case reports. In contrast, atherosclerosis is a well-established risk factor for arterial thrombosis.

Arterial occlusion can be due to thrombosis, embolism, or trauma

The causes of arterial occlusion can be categorized as thrombotic, embolic, or traumatic (Table 1).

Atherosclerosis is a risk factor for thrombosis and can be a source of emboli. Atherosclerotic plaque rupture may release inflammatory mediators, which also predispose to thrombosis.² This patient’s coronary arteries are essentially free of atherosclerotic disease per angiography. However, studies of intravascular ultrasonography have shown that coronary angiography may not detect all atherosclerotic plaques, as angiography can show only the lumen of the artery and not the plaque itself.³ For that reason, atherosclerosis has not been ruled out completely, and further workup is needed to evaluate other possible causes of her thrombotic events.

Embolism is the most likely cause of her stroke, however. Cases of arterial embolism can be classified on the basis of the origin of the thrombus, ie, the heart, an artery, or the venous system via a patent foramen ovale (paradoxical embolism). This patient’s echocardiogram reveals mild aortic atheroma, which can be a source of emboli, especially soon after intervention.

Case continues: Acute and recurrent DVT

While recovering from her MI and stroke, the patient develops edema and pain in both legs. Doppler ultrasonography is performed, which reveals acute DVT in the right gastrocnemius and posterior tibial veins and left soleal vein, despite her continued heparin therapy.

Her platelet count is 189 × 10⁹/L, so heparin-induced thrombocytopenia is not suspected; the new DVT is thought to be due to her hospitalization. Several days later, oral warfarin (Coumadin) is started and titrated to an INR of 2.0 to 3.0, the heparin is phased out, and the patient is sent home.

In the first few months after discharge, the patient presents to the emergency department three times with severe leg pain, and each time she is found to have extensive DVT in various leg veins even though she is complying with her warfarin therapy. At each visit, her INR is in the range of 2.5 to 3.1.

Comment. Her recurrent DVT warrants further evaluation for risk factors for venous thrombosis, which can be divided into hereditary and acquired factors.

Hereditary risk factors include the factor V Leiden mutation, the prothrombin gene mutation, hyperhomocysteinemia, dysfibrinogenemia, and deficiencies of protein C, protein S, and antithrombin.

Acquired risk factors include the antiphospholipid antibody syndrome, cancer, immobilization, surgery, congestive heart failure, pregnancy, use of hormonal contraceptives, hormone replacement therapy, nephrotic syndrome, trauma, and infection.^1,4

TESTING FOR HYPERCOAGULABLE STATES

2. In view of our patient’s recurrent thrombotic episodes, should she be tested for hypercoagulable states?

• Yes
• No

Testing for hypercoagulable conditions is warranted if it will affect the patient’s management or outcome. Some authorities recommend testing patients who are clinically characterized as “strongly” thrombophilic,⁵ ie, those who present with DVT and are younger than age 50, have recurrent thrombotic episodes, have a first-degree relative with documented thromboembolism before age 50, or have thrombotic episodes despite warfarin therapy.

This patient should be tested for hypercoagulable conditions because her initial DVT occurred before age 50 (at age 43), she has had recurrent, apparently idiopathic thrombotic episodes, she has a family history of thromboembolism, and she had clots while on therapeutic warfarin therapy, all of which suggest a hypercoagulable state. Furthermore, the confirmation of her diagnosis may affect her medical management, as it may determine if further testing and therapies are needed.

Case continues: Tests are negative

Laboratory tests for hypercoagulable conditions are performed and are negative for the factor V Leiden mutation, the prothrombin gene mutation, antithrombin deficiency, and protein C and S deficiencies. A screen for antiphospholipid antibodies is indeterminate.

TREATMENT AFFECTS TEST RESULTS

3. If a patient is on warfarin therapy, which test results may be affected?

• Antithrombin levels
• Protein C and S levels
• Factor V Leiden mutation

Warfarin decreases the levels of proteins C and S; therefore, the levels of these substances cannot be accurately interpreted in a patient taking warfarin.

All anticoagulants prolong the clotting time and may affect the results of assays based on the clotting time, such as the prothrombin time, the partial thromboplastin time, the dilute Russell’s viper venom time (DRVVT), the hexagonal phase phospholipid neutralization assay, the thrombin time, and clottable protein C and protein S. Heparin reduces the level of antithrombin; however, laboratories now have heparin-binding agents that reduce the effect of heparin in clotting studies.

Acute thrombotic states lower the levels of antithrombin and proteins C and S.

Assays not based on the clotting time (immunogenic or genetic tests such as those for anticardiolipin antibodies and the factor V Leiden and prothrombin gene mutations) are not affected by anticoagulant use.⁵

However, the presence or absence of a hypercoagulable state should not affect the treatment of acute DVT, and a full 6- to 12-month course of anticoagulation should be completed.^6,7 If possible, lupus anticoagulant testing should be repeated 2 weeks after anticoagulation is stopped.⁸

This patient needs lifelong anticoagulation because of her repeated thrombotic episodes. Stopping the medication for 2 weeks for testing would increase the risk of rethrombosis in this patient, and most experts would not advise it.

In summary, testing for hypercoagulable conditions is not recommended during an acute thrombotic episode and is preferably performed while the patient is not on anticoagulation therapy. If the patient is already on anticoagulation, the results of tests for hypercoagulable conditions should be interpreted with caution.

Case continues: Another stroke

During the subsequent year, the patient’s primary care physician monitors her warfarin use and sends her for age-appropriate cancer screening, including a breast examination, Papanicolaou smear, and mammography. Also, given her history of smoking, a chest radiograph is ordered. All of these studies are normal. In addition, evaluations for hematologic disorders such as myelodysplastic syndrome, polycythemia vera, and Waldenström macroglobulinema reveal normal complete blood counts and normal results on serum and urine protein electrophoresis.

Later that year, she returns to the emergency department with complete aphasia and total right-sided paralysis. Magnetic resonance imaging shows an acute infarct in the left frontal operculum, a subacute infarct in the right cerebellum, and multiple chronic cortical and subcortical infarcts throughout the brain. Ultrasonography shows an extensive new DVT in her right leg. Her INR at this time is 3.1.

 

WHAT CONDITIONS CAUSE BOTH ARTERIAL AND VENOUS THROMBOSIS?

4. Given that the patient has evidence of both recurrent arterial and venous thromboses, which of the following conditions is likely?

• Antiphospholipid antibody syndrome
• Heparin-induced thrombocytopenia
• Malignancy
• All of the above

Conditions associated with both arterial and venous thrombosis include antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, malignancy, paradoxical embolism, hyperhomocysteinemia, myeloproliferative disorders, myelodysplastic disorder, paraproteinemia, vasculitis, and paroxysmal nocturnal hemoglobinuria.^1,4

The hypercoagulability associated with malignancy is also known as Trousseau syndrome. This term was originally used to describe migratory thrombophlebitis as a forewarning for occult visceral malignancy, and has grown over the years to describe malignancy-induced hypercoagulability.⁹

At present, the exact mechanism that causes Trousseau syndrome is unknown. Some hypotheses implicate mucin (produced by the cancer),¹⁰ tissue factor,¹¹ tumor-associated cysteine proteinase,¹² tumor hypoxia,¹³ and oncogene activation as plausible triggers for this syndrome.

As stated above, the patient has a normal platelet count and negative results on cancer screening tests. Tests for antiphospholipid antibodies and lupus anticoagulant are repeated. Tests for the specific antiphospholipid antibodies against beta-2 glycoprotein I and cardiolipin are negative (Table 2). However, the test for lupus anticoagulant is positive by the criteria of the International Society on Thrombosis and Haemostasis: the patient has a prolonged clotting time screening test (hexagonal phase screen, DRVVT screen), positive mixing study (DRVVT 1:1 mix and circulating anticoagulant), positive phospholipid dependence (hexagonal phase screen, confirm, and delta; DRVVT confirm ratio; and platelet neutralization procedure), and no evidence of other factor-specific inhibitors (Table 3).¹⁴

DOES SHE HAVE ANTIPHOSPHOLIPID ANTIBODY SYNDROME?

5. The patient is positive for lupus anticoagulant. Does she have antiphospholipid antibody syndrome?

• Yes
• No
• Repeat testing is needed to meet the diagnostic criteria

The Sapporo criteria¹⁵ indicate that antiphospholipid antibody syndrome is present if at least one clinical criterion and one laboratory criterion are met. The clinical criteria are one or more episodes of arterial or venous thrombosis or pregnancy-related morbidity, ie:

• Unexplained intrauterine fetal death at 10 weeks gestation or later with no apparent fetal abnormality
• Premature births of a morphologically normal fetus at less than 34 weeks of gestation due to preeclampsia, eclampsia, or placental insufficiency
• Three or more spontaneous abortions at 10 weeks of gestation or earlier, with no known paternal chromosomal abnormalities or maternal hormonal abnormalities and normal maternal anatomy.

The laboratory criteria are:

• Lupus anticoagulant present
• Anticardiolipin antibody (IgG or IgM) titer greater than 40 IgG antiphospholipid units (GPL) or IgM antiphospholipid units (MPL) or higher than the 99th percentile of the testing laboratory normal reference range
• Anti-beta-2 glycoprotein-I antibody (IgG or IgM) titer greater than 20 GPL or MPL or higher than the 99th percentile of the testing laboratory normal reference range.

The patient likely has antiphospholipid antibody syndrome because her lupus anticoagulant screen is positive and she meets the clinical criteria of thrombosis, and she should continue to be treated accordingly. However, to officially meet the revised Sapporo criteria, she would need to have laboratory tests that are positive on two or more occasions at least 12 weeks apart.

Case continues: Lung cancer is found

The patient reports that she has lost 10 pounds in 4 months. Since age-appropriate cancer testing was previously performed, a more extensive evaluation for weight loss is undertaken, with computed tomography of the chest, abdomen, and pelvis. These tests reveal a nodule in the right upper lobe of the lung, scarring in the right middle and left lower lung lobes, and hilar lymphadenopathy. Bronchoscopy with transbronchial biopsy confirms that she has adenocarcinoma of the lung.

6. What is suggested as a sufficient workup for malignancy in patients with idiopathic venous thromboembolism?

• Computed tomography of the chest, abdomen, and pelvis for every patient with idiopathic venous thromboembolism
• Positron emission tomography and tumor marker levels
• A comprehensive history and physical examination, routine laboratory tests, chest radiography, age- and sex-specific cancer screening, and patient-specific testing as indicated clinically

To date, there is no evidence to support a cancer evaluation beyond a comprehensive medical history and physical examination, routine laboratory testing, chest radiography, and age- and sex-specific cancer screening unless it is dictated by the patient’s clinical presentation. A study by Cornuz et al¹⁶ suggested that this approach is appropriate for detecting cancer in patients with idiopathic venous thromboembolism.

A 2004 study¹⁷ attempted to answer the question of what to do about patients who have idiopathic venous thromboembolism but no other signs or symptoms that raise any clinical suspicion of cancer. This study randomized patients with idiopathic venous thromboembolism to undergo either routine medical management or an extensive malignancy evaluation. The evaluation included ultrasonography of the abdomen and pelvis, computed tomography of the abdomen and pelvis, gastroscopy or a double-contrast barium swallow study, colonoscopy or sigmoidoscopy followed by a barium enema, stool occult blood testing, and sputum cytology. Women were also tested for the tumor markers carcinoembryonic antigen, alpha-fetoprotein, and CA-125, and they underwent mammography and Papanicolaou testing; men were tested for prostate-specific antigen and underwent ultrasonography of the prostate. The results of the study did not reveal a statistically significant survival benefit in the group that underwent extensive cancer evaluation.

These studies indicate that the decision to test for cancer should be guided by clinical suspicion. Our patient lost 10 pounds in 4 months, smokes, and has had recurrent venous thromboembolism, so testing was appropriate.

After her diagnosis with adenocarcinoma of the lung, the patient has yet another DVT despite an INR of 3.1 and treatment with warfarin and aspirin.

 

LOW-MOLECULAR-WEIGHT HEPARIN FOR PATIENTS WITH CANCER?

7. True or false? Low-molecular-weight heparin is more effective than warfarin in preventing DVT in cancer patients without increasing the bleeding risk.

• True
• False

This statement is true. The American College of Chest Physicians (ACCP) recommends immediate treatment of DVT with low-molecular-weight heparin for 6 to 12 months after a thrombotic event in a patient with malignancy.^6,18

Two major studies provide evidence for these recommendations: the Comparison of Low-Molecular-Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients With Cancer (CLOT)¹⁹ and the Trial of the Effect of Low-Molecular-Weight Heparin Versus Warfarin on Mortality in the Long-Term Treatment of Proximal Deep Vein Thrombosis (LITE)²⁰ studies.

The CLOT¹⁹ study showed that dalteparin (Fragmin) 200 IU/kg subcutaneously once daily for l month and then 150 IU/kg once daily was more effective than oral warfarin titrated to an INR of 2.5 and did not increase the risk of bleeding.

The LITE trial²⁰ showed the efficacy of tinzaparin (Innohep) 175 IU/kg subcutaneously daily, which can be used as an alternative.

Enoxaparin sodium (Lovenox) 1.5 mg/kg once daily has also been used. However, if low-molecular-weight heparin is not available, warfarin titrated to an INR of 2 to 3 is also acceptable.¹⁸

The ACCP consensus panel recommends giving anticoagulation for an initial 6 to 12 months and continuing it as long as there is evidence of active malignancy.⁶ The American Society for Clinical Oncology also recommends placement of an inferior vena cava filter for patients who have contraindications to anticoagulation or for whom low-molecular-weight heparin fails.¹⁸

Case continues: Summing up

In conclusion, our patient had an underlying malignancy, causing Trousseau syndrome. Before her cancer was diagnosed, she also had test results that suggested antiphospholipid antibody syndrome. Both of these conditions likely contributed to her hypercoagulable state, increasing her propensity for clotting and causing her recurrent thrombosis. The patient is currently on low-molecular-weight heparin and is undergoing palliative chemotherapy for metastatic adenocarcinoma of the lung. To this date, she has not had any new thrombotic events.

TAKE-HOME POINTS

• Risk factors for arterial occlusion can be divided into thrombotic, embolic, and traumatic categories.
• Risk factors for venous thrombosis can be divided into hereditary and acquired categories.
• Evaluation for hypercoagulable conditions is recommended if it will affect patient management or outcome. Patients to be considered for testing include those with idiopathic DVT and who are under age 50, those with a history of recurrent thrombosis, and those with a first-degree relative with documented venous thromboembolism before age 50.
• Evaluation for hypercoagulable conditions should ideally be performed either before starting anticoagulation therapy or 2 weeks after completing it.
• Potential causes of both arterial and venous thrombosis include antiphospholipid antibody syndrome, cancer, hyperhomocysteinemia, heparin-induced thrombocytopenia, paradoxical emboli, myeloproliferative disorders, myelodysplastic syndrome, paraproteinemia, vasculitis, and paroxysmal nocturnal hemoglobinuria.
• Current evidence does not support an extensive cancer evaluation in patients with idiopathic venous thromboembolism, unless dictated by the patient’s clinical condition.
• In patients with venous thromboembolism and active malignancy, anticoagulation is recommended for at least 6 to 12 months and as long as there is evidence of active malignancy.