A 28‐year‐old man with sickle cell anemia was admitted with generalized pain. He noted an upper lip lesion 2 weeks prior to admission. He subsequently developed generalized pain in his legs, chest, and back typical of his pain crises. At admission he noted subjective fevers without chills for a week. Vital signs revealed a blood pressure of 135/80, a pulse of 81, a respiratory rate of 16, and an initial temperature of 37.7C. On examination he had scleral icterus and a large upper lip ulcer (Fig. 1). His hospital course was complicated by persistent fevers, a hepatic sequestration crisis, persistent hemolytic anemia requiring blood transfusion, and ultimately the identification of iris‐shaped targetoid lesions on the palms (Fig. 2).These lesions were believed to be consistent with erythema multiforme (EM) secondary to his recent HSV labialis, confirmed by a herpes culture. The patient recovered uneventfully after a 10‐day hospitalization. Erythema multiforme is an acute, self‐limited, but sometimes recurrent dermatologic condition considered to be a distinct hypersensitivity reaction.1 It is associated with certain infections such as herpes simplex 1 and 2, Mycoplasma pneumoniae and fungal infections, and a number of medications in the classes barbiturates, nonsteroidal anti‐inflammatory drugs, penicillins, hydantoins, phenothiazines, and sulfonamides.2 EM is diagnosed clinically by the characteristic rash on the hands and feet, with some cases involving the oral cavity. Treatment is typically focused on resolving the underlying infection or removing the offending drug. Dermatologic manifestations usually improve over 3‐5 weeks without residual sequelae.

Figure 1

Figure 2

A 28‐year‐old man with sickle cell anemia was admitted with generalized pain. He noted an upper lip lesion 2 weeks prior to admission. He subsequently developed generalized pain in his legs, chest, and back typical of his pain crises. At admission he noted subjective fevers without chills for a week. Vital signs revealed a blood pressure of 135/80, a pulse of 81, a respiratory rate of 16, and an initial temperature of 37.7C. On examination he had scleral icterus and a large upper lip ulcer (Fig. 1). His hospital course was complicated by persistent fevers, a hepatic sequestration crisis, persistent hemolytic anemia requiring blood transfusion, and ultimately the identification of iris‐shaped targetoid lesions on the palms (Fig. 2).These lesions were believed to be consistent with erythema multiforme (EM) secondary to his recent HSV labialis, confirmed by a herpes culture. The patient recovered uneventfully after a 10‐day hospitalization. Erythema multiforme is an acute, self‐limited, but sometimes recurrent dermatologic condition considered to be a distinct hypersensitivity reaction.1 It is associated with certain infections such as herpes simplex 1 and 2, Mycoplasma pneumoniae and fungal infections, and a number of medications in the classes barbiturates, nonsteroidal anti‐inflammatory drugs, penicillins, hydantoins, phenothiazines, and sulfonamides.2 EM is diagnosed clinically by the characteristic rash on the hands and feet, with some cases involving the oral cavity. Treatment is typically focused on resolving the underlying infection or removing the offending drug. Dermatologic manifestations usually improve over 3‐5 weeks without residual sequelae.

Figure 1

Figure 2

A 28‐year‐old man with sickle cell anemia was admitted with generalized pain. He noted an upper lip lesion 2 weeks prior to admission. He subsequently developed generalized pain in his legs, chest, and back typical of his pain crises. At admission he noted subjective fevers without chills for a week. Vital signs revealed a blood pressure of 135/80, a pulse of 81, a respiratory rate of 16, and an initial temperature of 37.7C. On examination he had scleral icterus and a large upper lip ulcer (Fig. 1). His hospital course was complicated by persistent fevers, a hepatic sequestration crisis, persistent hemolytic anemia requiring blood transfusion, and ultimately the identification of iris‐shaped targetoid lesions on the palms (Fig. 2).These lesions were believed to be consistent with erythema multiforme (EM) secondary to his recent HSV labialis, confirmed by a herpes culture. The patient recovered uneventfully after a 10‐day hospitalization. Erythema multiforme is an acute, self‐limited, but sometimes recurrent dermatologic condition considered to be a distinct hypersensitivity reaction.1 It is associated with certain infections such as herpes simplex 1 and 2, Mycoplasma pneumoniae and fungal infections, and a number of medications in the classes barbiturates, nonsteroidal anti‐inflammatory drugs, penicillins, hydantoins, phenothiazines, and sulfonamides.2 EM is diagnosed clinically by the characteristic rash on the hands and feet, with some cases involving the oral cavity. Treatment is typically focused on resolving the underlying infection or removing the offending drug. Dermatologic manifestations usually improve over 3‐5 weeks without residual sequelae.

Figure 1

Figure 2

The cornerstones of American medical ethics include respect for patient autonomy and beneficence. Although informed consent is required for surgical procedures and transfusion of blood products, the overwhelming majority of medical treatments administered by physicians to hospitalized patients are given without discussing risks, benefits, and alternatives. Although patients may sign a general permission‐to‐treat form on admission to the hospital, informed consent for medical treatments is generally ad hoc, and there are no national standards or mandates. We hypothesized that given the choice, hospitalized patients would want to participate in informed decision making, especially for therapies associated with substantial risks and benefits.

METHODS

The Institutional Review Board of Bridgeport Hospital approved this study. Each day between June and August 2006, the hospital's admitting department provided investigators with a list that included names and locations of all patients admitted to the Department of Medicine inpatient service. All the patients were eligible for participation in the study. Patients were excluded if they were in a comatose state, were encephalopathic, or were judged to be severely demented. In addition, patients were assessed during the scripted intervention to ascertain whether they had the capacity to make informed decisions based on their ability: (a) to understand the presented information, (b) to consider the information in relation to their personal values, and (c) to communicate their wishes. If personnel doubted an individual's capacity in any of these 3 areas, they were not included in the study.

Study personnel read directly from the script (see Appendix) and recorded answers. Study personnel were permitted to reread questions but did not provide additional guidance beyond the questionnaire. Patients whose primary language was not English were interviewed through in‐house or 3‐way telephone (remote) translators.

Statistical analyses included the chi‐square test to examine responses across the 3 categories of answers (ie, always consent, qualified consent, waive consent) and simple comparisons of percentages. A P value < .05 was considered statistically significant.

RESULTS

A total of 634 patients were admitted to the medicine service during the study period June‐August 2006. Of these, 158 were judged to lack sufficient capacity by study personnel and were excluded from the study. Ninety‐five refused to participate, and 171 were discharged before the questionnaire could be administered. Two hundred and ten patients answered the questionnaire. They ranged in age from 18 to 96 years (mean age standard error, 63.3 1.1 years). One hundred and three (49%) were men, and 107 (51%) were women. A majority (67.5%) were white, 20% (42) were African American, and 11.9% (25) were Hispanic. Most (87.6%) had at least a high school education, and 35% had a college‐/graduate‐level education. Sixty‐seven percent had at least 2 comorbid conditions in addition to their principal reason for hospitalization. Their average acute physiology and chronic health care evaluation (APACHE II) score was 7.5 0.3 (median 7; range 0‐22).

Figure 1 shows the distribution of answers to each of the 4 questions.

Figure 1

DISCUSSION

The principal finding of this study is that most medical patients prefer to participate in making decisions about their medical care during acute hospitalization, even for relatively low‐risk treatments like potassium supplementation and administration of diuretics. Very few patients were prepared to waive consent and grant their physicians the absolute right to administer therapies such as thrombolysis, even if the risk of bleeding was estimated to be less than 5%. Whereas the elderly patients were less likely to prefer being asked to consent to treatments than were younger patients, most would want to be informed of even trivial therapies if time allowed.

In some situations older patients (65 years old) were more likely than younger patients (<65 years old) to allow their physicians to make unilateral decisions regarding their health care. This could be explained by those age 65 and older having grown up when physician paternalism was more prevalent in American medicine. In the 1970s physician paternalism waned, and respect for patient autonomy emerged as the dominant physicianpatient model. Patients who became adults after 1970 know only this relationship with their physician, and so it makes sense that they would be more inclined to prefer a participatory model.

These data complement and extend a series of studies we conducted with patients admitted to Bridgeport Hospital. Our data suggest that our patients wish to consent for end‐of‐life decisions,1, 2 invasive procedures,3 and, now, to be apprised of medical therapies administered during hospitalization. At the same time, we have found that consent practices at many centers are not consistent with these patient predilections.1, 2, 4 Our study suffered from having a small sample size obtained in one geographic location; so results should be generalized cautiously. Nonetheless, insofar as the expectations of patients for participation are not being met by the health care system in Connecticut (and we suspect elsewhere), clinicians, hospital administrators, and health care policy makers might consider whether more rigorous and explicit consent practices and policies are required. Another important limitation of the study was that patients included may not have entirely understood the implications of their answers (ie, how cumbersome to the system and bothersome to the patient seeking consent for every therapy could become). In fact, we cannot be certain that all patients truly understood the questions, some of which were complex. Nonetheless, these results support that considered in the abstract, most patients prefer to consent for medical therapies. Had the implications for safety and expediency been explained in detail, it is possible that patients would have waived the need to give consent for treatments with minimal risk. The questionnaire also presents an abbreviated list of risks and benefits for each intervention, and although it refers to the formal process of informed consent in its preamble, it uses terminology (ie, permission) that may not reflect the complexity of informed consent. Nonetheless, our goal was to examine the degree to which patients wished to participate in their medical decision making. Notwithstanding these weaknesses of the survey instrument, the data suggest patients want to be in the loop whenever possible.

There are no national standards of consent for medical treatments. The Veterans' Administration, which has led the way in many areas of patients' rights, has a policy:

Compliance with this standard (ie, consent for every new medication) is not routine in most acute care hospitals. Although some clinicians obtain formal consent for high‐risk therapies (perhaps out of respect for autonomy, perhaps to reduce medical‐legal liability), there are no explicit decision rules to guide clinicians regarding for which treatments they should obtain formal consent. Accordingly, some might obtain formal consent for thrombolysis for massive pulmonary embolus, and others might not. It is not clear that the consent‐to‐treat form signed during hospital admission would legally cover all medical therapies during hospitalization. The legal standard for informed consent is what any reasonable patient would want to consent for. Our data suggest that most reasonable patients wish to at least assent and perhaps consent for much of what they receive during hospitalization. Although we have been unable to find case law predicated entirely on failure to obtain consent prior to administration of a therapy that caused a complication, it is plausible that the reasonable patient standard could be used in this manner. Regardless, it is impractical to require consent for the thousands of medical therapies administered each day in hospitals. Requiring consent for all therapies, if respected rigidly, would threaten the safety and efficiency of American hospitals. Naturally, a balance betweem respect for autonomy, that is, informed consent for the riskiest therapies, and efficiency is necessary. Explicit guidelines issued by accrediting agencies or the federal government would be helpful. The rules for consent (and/or assent) should be more explicit and less arbitrary, that is, determined independently by each clinician.

In conclusion, these data demonstrate that when considered in the abstract, that is, without explaining the logistical hurdles that it would create, inpatients wish to participate in decision making for both low‐ and high‐risk treatments. Clinicians are faced with demands and obligations that preclude full consent for the myriad low‐risk treatments administered daily to hospitalized patients. Some treatments are likely to be covered implicitly under the general consent‐to‐treat process and paperwork. Nonetheless, clinicians should consider explaining the principal risks and benefits of moderate‐risk treatments in order to secure informed assent. Full informed consent may be most appropriate for very high‐risk therapies. Patients expect and deserve frequent communication with caregivers that balances their safety with their right to self‐determination.

The cornerstones of American medical ethics include respect for patient autonomy and beneficence. Although informed consent is required for surgical procedures and transfusion of blood products, the overwhelming majority of medical treatments administered by physicians to hospitalized patients are given without discussing risks, benefits, and alternatives. Although patients may sign a general permission‐to‐treat form on admission to the hospital, informed consent for medical treatments is generally ad hoc, and there are no national standards or mandates. We hypothesized that given the choice, hospitalized patients would want to participate in informed decision making, especially for therapies associated with substantial risks and benefits.

METHODS

The Institutional Review Board of Bridgeport Hospital approved this study. Each day between June and August 2006, the hospital's admitting department provided investigators with a list that included names and locations of all patients admitted to the Department of Medicine inpatient service. All the patients were eligible for participation in the study. Patients were excluded if they were in a comatose state, were encephalopathic, or were judged to be severely demented. In addition, patients were assessed during the scripted intervention to ascertain whether they had the capacity to make informed decisions based on their ability: (a) to understand the presented information, (b) to consider the information in relation to their personal values, and (c) to communicate their wishes. If personnel doubted an individual's capacity in any of these 3 areas, they were not included in the study.

Study personnel read directly from the script (see Appendix) and recorded answers. Study personnel were permitted to reread questions but did not provide additional guidance beyond the questionnaire. Patients whose primary language was not English were interviewed through in‐house or 3‐way telephone (remote) translators.

Statistical analyses included the chi‐square test to examine responses across the 3 categories of answers (ie, always consent, qualified consent, waive consent) and simple comparisons of percentages. A P value < .05 was considered statistically significant.

RESULTS

A total of 634 patients were admitted to the medicine service during the study period June‐August 2006. Of these, 158 were judged to lack sufficient capacity by study personnel and were excluded from the study. Ninety‐five refused to participate, and 171 were discharged before the questionnaire could be administered. Two hundred and ten patients answered the questionnaire. They ranged in age from 18 to 96 years (mean age standard error, 63.3 1.1 years). One hundred and three (49%) were men, and 107 (51%) were women. A majority (67.5%) were white, 20% (42) were African American, and 11.9% (25) were Hispanic. Most (87.6%) had at least a high school education, and 35% had a college‐/graduate‐level education. Sixty‐seven percent had at least 2 comorbid conditions in addition to their principal reason for hospitalization. Their average acute physiology and chronic health care evaluation (APACHE II) score was 7.5 0.3 (median 7; range 0‐22).

Figure 1 shows the distribution of answers to each of the 4 questions.

Figure 1

DISCUSSION

The principal finding of this study is that most medical patients prefer to participate in making decisions about their medical care during acute hospitalization, even for relatively low‐risk treatments like potassium supplementation and administration of diuretics. Very few patients were prepared to waive consent and grant their physicians the absolute right to administer therapies such as thrombolysis, even if the risk of bleeding was estimated to be less than 5%. Whereas the elderly patients were less likely to prefer being asked to consent to treatments than were younger patients, most would want to be informed of even trivial therapies if time allowed.

In some situations older patients (65 years old) were more likely than younger patients (<65 years old) to allow their physicians to make unilateral decisions regarding their health care. This could be explained by those age 65 and older having grown up when physician paternalism was more prevalent in American medicine. In the 1970s physician paternalism waned, and respect for patient autonomy emerged as the dominant physicianpatient model. Patients who became adults after 1970 know only this relationship with their physician, and so it makes sense that they would be more inclined to prefer a participatory model.

These data complement and extend a series of studies we conducted with patients admitted to Bridgeport Hospital. Our data suggest that our patients wish to consent for end‐of‐life decisions,1, 2 invasive procedures,3 and, now, to be apprised of medical therapies administered during hospitalization. At the same time, we have found that consent practices at many centers are not consistent with these patient predilections.1, 2, 4 Our study suffered from having a small sample size obtained in one geographic location; so results should be generalized cautiously. Nonetheless, insofar as the expectations of patients for participation are not being met by the health care system in Connecticut (and we suspect elsewhere), clinicians, hospital administrators, and health care policy makers might consider whether more rigorous and explicit consent practices and policies are required. Another important limitation of the study was that patients included may not have entirely understood the implications of their answers (ie, how cumbersome to the system and bothersome to the patient seeking consent for every therapy could become). In fact, we cannot be certain that all patients truly understood the questions, some of which were complex. Nonetheless, these results support that considered in the abstract, most patients prefer to consent for medical therapies. Had the implications for safety and expediency been explained in detail, it is possible that patients would have waived the need to give consent for treatments with minimal risk. The questionnaire also presents an abbreviated list of risks and benefits for each intervention, and although it refers to the formal process of informed consent in its preamble, it uses terminology (ie, permission) that may not reflect the complexity of informed consent. Nonetheless, our goal was to examine the degree to which patients wished to participate in their medical decision making. Notwithstanding these weaknesses of the survey instrument, the data suggest patients want to be in the loop whenever possible.

There are no national standards of consent for medical treatments. The Veterans' Administration, which has led the way in many areas of patients' rights, has a policy:

Compliance with this standard (ie, consent for every new medication) is not routine in most acute care hospitals. Although some clinicians obtain formal consent for high‐risk therapies (perhaps out of respect for autonomy, perhaps to reduce medical‐legal liability), there are no explicit decision rules to guide clinicians regarding for which treatments they should obtain formal consent. Accordingly, some might obtain formal consent for thrombolysis for massive pulmonary embolus, and others might not. It is not clear that the consent‐to‐treat form signed during hospital admission would legally cover all medical therapies during hospitalization. The legal standard for informed consent is what any reasonable patient would want to consent for. Our data suggest that most reasonable patients wish to at least assent and perhaps consent for much of what they receive during hospitalization. Although we have been unable to find case law predicated entirely on failure to obtain consent prior to administration of a therapy that caused a complication, it is plausible that the reasonable patient standard could be used in this manner. Regardless, it is impractical to require consent for the thousands of medical therapies administered each day in hospitals. Requiring consent for all therapies, if respected rigidly, would threaten the safety and efficiency of American hospitals. Naturally, a balance betweem respect for autonomy, that is, informed consent for the riskiest therapies, and efficiency is necessary. Explicit guidelines issued by accrediting agencies or the federal government would be helpful. The rules for consent (and/or assent) should be more explicit and less arbitrary, that is, determined independently by each clinician.

In conclusion, these data demonstrate that when considered in the abstract, that is, without explaining the logistical hurdles that it would create, inpatients wish to participate in decision making for both low‐ and high‐risk treatments. Clinicians are faced with demands and obligations that preclude full consent for the myriad low‐risk treatments administered daily to hospitalized patients. Some treatments are likely to be covered implicitly under the general consent‐to‐treat process and paperwork. Nonetheless, clinicians should consider explaining the principal risks and benefits of moderate‐risk treatments in order to secure informed assent. Full informed consent may be most appropriate for very high‐risk therapies. Patients expect and deserve frequent communication with caregivers that balances their safety with their right to self‐determination.

The cornerstones of American medical ethics include respect for patient autonomy and beneficence. Although informed consent is required for surgical procedures and transfusion of blood products, the overwhelming majority of medical treatments administered by physicians to hospitalized patients are given without discussing risks, benefits, and alternatives. Although patients may sign a general permission‐to‐treat form on admission to the hospital, informed consent for medical treatments is generally ad hoc, and there are no national standards or mandates. We hypothesized that given the choice, hospitalized patients would want to participate in informed decision making, especially for therapies associated with substantial risks and benefits.

METHODS

The Institutional Review Board of Bridgeport Hospital approved this study. Each day between June and August 2006, the hospital's admitting department provided investigators with a list that included names and locations of all patients admitted to the Department of Medicine inpatient service. All the patients were eligible for participation in the study. Patients were excluded if they were in a comatose state, were encephalopathic, or were judged to be severely demented. In addition, patients were assessed during the scripted intervention to ascertain whether they had the capacity to make informed decisions based on their ability: (a) to understand the presented information, (b) to consider the information in relation to their personal values, and (c) to communicate their wishes. If personnel doubted an individual's capacity in any of these 3 areas, they were not included in the study.

Study personnel read directly from the script (see Appendix) and recorded answers. Study personnel were permitted to reread questions but did not provide additional guidance beyond the questionnaire. Patients whose primary language was not English were interviewed through in‐house or 3‐way telephone (remote) translators.

Statistical analyses included the chi‐square test to examine responses across the 3 categories of answers (ie, always consent, qualified consent, waive consent) and simple comparisons of percentages. A P value < .05 was considered statistically significant.

RESULTS

A total of 634 patients were admitted to the medicine service during the study period June‐August 2006. Of these, 158 were judged to lack sufficient capacity by study personnel and were excluded from the study. Ninety‐five refused to participate, and 171 were discharged before the questionnaire could be administered. Two hundred and ten patients answered the questionnaire. They ranged in age from 18 to 96 years (mean age standard error, 63.3 1.1 years). One hundred and three (49%) were men, and 107 (51%) were women. A majority (67.5%) were white, 20% (42) were African American, and 11.9% (25) were Hispanic. Most (87.6%) had at least a high school education, and 35% had a college‐/graduate‐level education. Sixty‐seven percent had at least 2 comorbid conditions in addition to their principal reason for hospitalization. Their average acute physiology and chronic health care evaluation (APACHE II) score was 7.5 0.3 (median 7; range 0‐22).

Figure 1 shows the distribution of answers to each of the 4 questions.

Figure 1

DISCUSSION

The principal finding of this study is that most medical patients prefer to participate in making decisions about their medical care during acute hospitalization, even for relatively low‐risk treatments like potassium supplementation and administration of diuretics. Very few patients were prepared to waive consent and grant their physicians the absolute right to administer therapies such as thrombolysis, even if the risk of bleeding was estimated to be less than 5%. Whereas the elderly patients were less likely to prefer being asked to consent to treatments than were younger patients, most would want to be informed of even trivial therapies if time allowed.

In some situations older patients (65 years old) were more likely than younger patients (<65 years old) to allow their physicians to make unilateral decisions regarding their health care. This could be explained by those age 65 and older having grown up when physician paternalism was more prevalent in American medicine. In the 1970s physician paternalism waned, and respect for patient autonomy emerged as the dominant physicianpatient model. Patients who became adults after 1970 know only this relationship with their physician, and so it makes sense that they would be more inclined to prefer a participatory model.

These data complement and extend a series of studies we conducted with patients admitted to Bridgeport Hospital. Our data suggest that our patients wish to consent for end‐of‐life decisions,1, 2 invasive procedures,3 and, now, to be apprised of medical therapies administered during hospitalization. At the same time, we have found that consent practices at many centers are not consistent with these patient predilections.1, 2, 4 Our study suffered from having a small sample size obtained in one geographic location; so results should be generalized cautiously. Nonetheless, insofar as the expectations of patients for participation are not being met by the health care system in Connecticut (and we suspect elsewhere), clinicians, hospital administrators, and health care policy makers might consider whether more rigorous and explicit consent practices and policies are required. Another important limitation of the study was that patients included may not have entirely understood the implications of their answers (ie, how cumbersome to the system and bothersome to the patient seeking consent for every therapy could become). In fact, we cannot be certain that all patients truly understood the questions, some of which were complex. Nonetheless, these results support that considered in the abstract, most patients prefer to consent for medical therapies. Had the implications for safety and expediency been explained in detail, it is possible that patients would have waived the need to give consent for treatments with minimal risk. The questionnaire also presents an abbreviated list of risks and benefits for each intervention, and although it refers to the formal process of informed consent in its preamble, it uses terminology (ie, permission) that may not reflect the complexity of informed consent. Nonetheless, our goal was to examine the degree to which patients wished to participate in their medical decision making. Notwithstanding these weaknesses of the survey instrument, the data suggest patients want to be in the loop whenever possible.

There are no national standards of consent for medical treatments. The Veterans' Administration, which has led the way in many areas of patients' rights, has a policy:

Compliance with this standard (ie, consent for every new medication) is not routine in most acute care hospitals. Although some clinicians obtain formal consent for high‐risk therapies (perhaps out of respect for autonomy, perhaps to reduce medical‐legal liability), there are no explicit decision rules to guide clinicians regarding for which treatments they should obtain formal consent. Accordingly, some might obtain formal consent for thrombolysis for massive pulmonary embolus, and others might not. It is not clear that the consent‐to‐treat form signed during hospital admission would legally cover all medical therapies during hospitalization. The legal standard for informed consent is what any reasonable patient would want to consent for. Our data suggest that most reasonable patients wish to at least assent and perhaps consent for much of what they receive during hospitalization. Although we have been unable to find case law predicated entirely on failure to obtain consent prior to administration of a therapy that caused a complication, it is plausible that the reasonable patient standard could be used in this manner. Regardless, it is impractical to require consent for the thousands of medical therapies administered each day in hospitals. Requiring consent for all therapies, if respected rigidly, would threaten the safety and efficiency of American hospitals. Naturally, a balance betweem respect for autonomy, that is, informed consent for the riskiest therapies, and efficiency is necessary. Explicit guidelines issued by accrediting agencies or the federal government would be helpful. The rules for consent (and/or assent) should be more explicit and less arbitrary, that is, determined independently by each clinician.

In conclusion, these data demonstrate that when considered in the abstract, that is, without explaining the logistical hurdles that it would create, inpatients wish to participate in decision making for both low‐ and high‐risk treatments. Clinicians are faced with demands and obligations that preclude full consent for the myriad low‐risk treatments administered daily to hospitalized patients. Some treatments are likely to be covered implicitly under the general consent‐to‐treat process and paperwork. Nonetheless, clinicians should consider explaining the principal risks and benefits of moderate‐risk treatments in order to secure informed assent. Full informed consent may be most appropriate for very high‐risk therapies. Patients expect and deserve frequent communication with caregivers that balances their safety with their right to self‐determination.

Two years ago we published the first issue of the Journal of Hospital Medicine and declared, Our goal is that JHM become the premier forum for peer‐reviewed research articles and evidence‐based reviews in the specialty of hospital medicine.1 That first issue was just one of many steps toward this ambition. At the completion of its first year, JHM was selected for indexing and inclusion in the National Library of Medicine's Medical Literature Analysis and Retrieval System Online (MEDLINE), the primary component of PubMed. Following this huge step, we welcomed a remarkable increase in submissions and will have exceeded 300 in our second year, an approximately 50% increase from our first year!

As important, JHM quickly became a valuable benefit of membership in the Society of Hospital Medicine, and the innumerable compliments received by the staff reflect the diligent efforts of a remarkable editorial staff and work by our reviewers. With profound gratitude we list on page 86 these 325 reviewers who donated their priceless time and expertise to enhancing the quality of the manuscripts. To handle the marked increase in submissions, we are expanding and modifying our editorial staff. Please welcome Sunil Kripalani (Vanderbilt) and Daniel Brotman (Johns Hopkins), who join our previous six associate editors and all eight will now serve as JHM's deputy editors. Seven new associate editors also join our team. Among them, Tom Baudendistel (California Pacific Medical Center, San Francisco), Eric Alper (UMass Memorial Health Care, Worcester), Brian Harte (Cleveland Clinic), and Rehan Qayyum (Johns Hopkins) will all focus on optimizing content for practicing hospitalists. Paul Aronowitz will continue to develop our Images section as an associate editor. Recognizing the growing number of pediatric hospitalists, Lisa Zauotis (Childrens Hospital of Philadelphia) and Erin Stucky (Children's Hospital San Diego) join JHM as the other 2 new associate editors. Finally, we welcome new Editorial Board members Mary C. Ottolini (Children's National Medical Center), Douglas Carlson (St. Louis Children's Hospital), and Daniel Rauch (NYU Children's Hospital). The welcome addition of these nationally recognized academicians prepares us for continued growth in manuscript submissions to JHM.

Although we could not excel without the editors, reviewers and our terrific new managing editor, Phaedra McGuinness, we would not survive without the authors who submit their manuscripts to JHMthey are responsible for the caliber of the journal, and we are immensely indebted to them. Originally, we hoped to include individuals involved in all aspects of hospital care,1 and fortunately this is now happening. Complementing hospitalists are nurses and pharmacists2 who recognize the importance of teamwork in the care of hospitalized patients. I encourage all members of the hospital care team to send us the results of their research, teaching, and quality improvement efforts.

As the specialty of hospital medicine continues to evolve, now with more than 20,000 hospitalists, JHM will develop with it. I am honored and grateful to collaborate with such a remarkable group of colleagues as we build the premier journal for the fastest growing specialty in the history of medicine in the United States. On to year 3!

Two years ago we published the first issue of the Journal of Hospital Medicine and declared, Our goal is that JHM become the premier forum for peer‐reviewed research articles and evidence‐based reviews in the specialty of hospital medicine.1 That first issue was just one of many steps toward this ambition. At the completion of its first year, JHM was selected for indexing and inclusion in the National Library of Medicine's Medical Literature Analysis and Retrieval System Online (MEDLINE), the primary component of PubMed. Following this huge step, we welcomed a remarkable increase in submissions and will have exceeded 300 in our second year, an approximately 50% increase from our first year!

As important, JHM quickly became a valuable benefit of membership in the Society of Hospital Medicine, and the innumerable compliments received by the staff reflect the diligent efforts of a remarkable editorial staff and work by our reviewers. With profound gratitude we list on page 86 these 325 reviewers who donated their priceless time and expertise to enhancing the quality of the manuscripts. To handle the marked increase in submissions, we are expanding and modifying our editorial staff. Please welcome Sunil Kripalani (Vanderbilt) and Daniel Brotman (Johns Hopkins), who join our previous six associate editors and all eight will now serve as JHM's deputy editors. Seven new associate editors also join our team. Among them, Tom Baudendistel (California Pacific Medical Center, San Francisco), Eric Alper (UMass Memorial Health Care, Worcester), Brian Harte (Cleveland Clinic), and Rehan Qayyum (Johns Hopkins) will all focus on optimizing content for practicing hospitalists. Paul Aronowitz will continue to develop our Images section as an associate editor. Recognizing the growing number of pediatric hospitalists, Lisa Zauotis (Childrens Hospital of Philadelphia) and Erin Stucky (Children's Hospital San Diego) join JHM as the other 2 new associate editors. Finally, we welcome new Editorial Board members Mary C. Ottolini (Children's National Medical Center), Douglas Carlson (St. Louis Children's Hospital), and Daniel Rauch (NYU Children's Hospital). The welcome addition of these nationally recognized academicians prepares us for continued growth in manuscript submissions to JHM.

Although we could not excel without the editors, reviewers and our terrific new managing editor, Phaedra McGuinness, we would not survive without the authors who submit their manuscripts to JHMthey are responsible for the caliber of the journal, and we are immensely indebted to them. Originally, we hoped to include individuals involved in all aspects of hospital care,1 and fortunately this is now happening. Complementing hospitalists are nurses and pharmacists2 who recognize the importance of teamwork in the care of hospitalized patients. I encourage all members of the hospital care team to send us the results of their research, teaching, and quality improvement efforts.

As the specialty of hospital medicine continues to evolve, now with more than 20,000 hospitalists, JHM will develop with it. I am honored and grateful to collaborate with such a remarkable group of colleagues as we build the premier journal for the fastest growing specialty in the history of medicine in the United States. On to year 3!

Two years ago we published the first issue of the Journal of Hospital Medicine and declared, Our goal is that JHM become the premier forum for peer‐reviewed research articles and evidence‐based reviews in the specialty of hospital medicine.1 That first issue was just one of many steps toward this ambition. At the completion of its first year, JHM was selected for indexing and inclusion in the National Library of Medicine's Medical Literature Analysis and Retrieval System Online (MEDLINE), the primary component of PubMed. Following this huge step, we welcomed a remarkable increase in submissions and will have exceeded 300 in our second year, an approximately 50% increase from our first year!

As important, JHM quickly became a valuable benefit of membership in the Society of Hospital Medicine, and the innumerable compliments received by the staff reflect the diligent efforts of a remarkable editorial staff and work by our reviewers. With profound gratitude we list on page 86 these 325 reviewers who donated their priceless time and expertise to enhancing the quality of the manuscripts. To handle the marked increase in submissions, we are expanding and modifying our editorial staff. Please welcome Sunil Kripalani (Vanderbilt) and Daniel Brotman (Johns Hopkins), who join our previous six associate editors and all eight will now serve as JHM's deputy editors. Seven new associate editors also join our team. Among them, Tom Baudendistel (California Pacific Medical Center, San Francisco), Eric Alper (UMass Memorial Health Care, Worcester), Brian Harte (Cleveland Clinic), and Rehan Qayyum (Johns Hopkins) will all focus on optimizing content for practicing hospitalists. Paul Aronowitz will continue to develop our Images section as an associate editor. Recognizing the growing number of pediatric hospitalists, Lisa Zauotis (Childrens Hospital of Philadelphia) and Erin Stucky (Children's Hospital San Diego) join JHM as the other 2 new associate editors. Finally, we welcome new Editorial Board members Mary C. Ottolini (Children's National Medical Center), Douglas Carlson (St. Louis Children's Hospital), and Daniel Rauch (NYU Children's Hospital). The welcome addition of these nationally recognized academicians prepares us for continued growth in manuscript submissions to JHM.

Although we could not excel without the editors, reviewers and our terrific new managing editor, Phaedra McGuinness, we would not survive without the authors who submit their manuscripts to JHMthey are responsible for the caliber of the journal, and we are immensely indebted to them. Originally, we hoped to include individuals involved in all aspects of hospital care,1 and fortunately this is now happening. Complementing hospitalists are nurses and pharmacists2 who recognize the importance of teamwork in the care of hospitalized patients. I encourage all members of the hospital care team to send us the results of their research, teaching, and quality improvement efforts.

As the specialty of hospital medicine continues to evolve, now with more than 20,000 hospitalists, JHM will develop with it. I am honored and grateful to collaborate with such a remarkable group of colleagues as we build the premier journal for the fastest growing specialty in the history of medicine in the United States. On to year 3!

A 65‐year‐old man was referred for evaluation of worsening ascites and end‐stage liver disease. The patient had been well until 1 year ago, when he developed lower extremity edema and abdominal distention. After evaluation by his primary care physician, he was given a diagnosis of cryptogenic cirrhosis. He underwent several paracenteses and was placed on furosemide and spironolactone. The patient had been stable on his diuretic regimen until 2 weeks previously, when he suddenly developed worsening edema and ascites, along with dizziness, nausea, and hypotension. His physician stopped the diuretics and referred him to the hospital.

Before diagnosing a patient with cryptogenic cirrhosis, it is necessary to exclude common etiologies of cirrhosis such as alcohol, viral hepatitis, and non‐alcoholic fatty liver disease and numerous uncommon causes, including Wilson's disease, hemochromatosis, Budd‐Chiari, and biliary cirrhosis. It is also important to remember that patients with liver disease are not immune to extrahepatic causes of ascites, such as peritoneal carcinomatosis and tuberculous ascites. Simultaneously, reasons for chronic liver disease decompensating acutely must be considered: medication nonadherence, excess salt intake, hepatotoxicity from acetaminophen or alcohol, and other acute insults, such as hepatocellular carcinoma, an intervening infection (especially spontaneous bacterial peritonitis), ascending cholangitis, or a flare of chronic viral hepatitis.

Past medical and surgical history included diabetes mellitus (diagnosed 10 years previously), obstructive sleep apnea, hypertension, hypothyroidism, and mild chronic kidney disease. Medications included levothyroxine, lactulose, sulfamethoxazole, pioglitazone (started 4 months prior), and ibuprofen. Furosemide and spironolactone had been discontinued 2 weeks previously. He currently resided in the Central Valley of California. He had lived in Thailand from age 7 to 17 and traveled to India more than 1 year ago. He did not smoke and had never used intravenous drugs or received a blood transfusion. He rarely drank alcohol. He worked as a chemist. There was no family history of liver disease.

There is no obvious explanation for the underlying liver disease or the acute decompensation. Sulfamethoxazole is a rare cause of allergic or granulomatous hepatitis. Pioglitazone is a thiazolinedione which in earlier formulations was linked to hepatitis but can be excluded as a cause of this patient's cirrhosis because it was started after liver disease was detected. As a chemist, he might have been exposed to carbon tetrachloride, a known hepatotoxin. Obstructive sleep apnea causes pulmonary hypertension, but severe ascites and acute hepatic decompensation would be unusual. Ibuprofen might precipitate worsening renal function and fluid accumulation. Time in Thailand and India raises the possibility of tuberculous ascites.

The patient had no headache, vision changes, abdominal pain, emesis, melena, hematochezia, chest pain, palpitations, dysuria, polyuria, pruritus, dark urine, or rashes. He reported difficulty with concentration when lactulose was decreased. He noted worsening exercise tolerance with dyspnea after 10 steps and reported a weight gain of 12 pounds in the past 2 weeks.

On examination, temperature was 36.8C; blood pressure, 129/87 mm Hg; heart rate, 85 beats per minute; respirations, 20 per minute; and oxygen saturation, 94% on room air. He was uncomfortable but alert. There was no scleral icterus or conjunctival pallor. Jugular venous pressure was elevated. The lungs were clear, and the heart was regular, with no murmur, rub, or gallops. The abdomen was massively distended with a fluid wave; the liver and spleen could not be palpated. There was pitting edema of the sacrum and lower extremities. There was no asterixis, palmar erythema, spider angiomata, or skin discoloration.

The additional history and physical exam suggest that the primary problem may lie outside the liver, especially as signs of advanced liver disease (other than ascites) are absent. Dyspnea on exertion is consistent with the physical stress of a large volume of ascites or could be secondary to several pulmonary complications associated with liver disease, including portopulmonary hypertension, hepatopulmonary syndrome, or hepatic hydrothorax. Alternatively, the dyspnea raises the possibility that the ascites is not related to a primary liver disorder but rather to anemia or to a cardiac disorder, such as chronic left ventricular failure, isolated right‐sided heart failure, or constrictive pericarditis. These diagnoses are suggested by the elevated jugular venous pressure, which is atypical in cirrhosis.

Although portal hypertension accounts for most cases of ascites, peritoneal fluid should be examined to exclude peritoneal carcinomatosis and tuberculous ascites. I am interested in the results of an echocardiogram.

Initial laboratory studies demonstrated a sodium concentration of 136 mEq/dL; potassium, 4.7 mEq/dL; chloride, 99 mEq/dL; bicarbonate, 24 mEq/dL; blood urea nitrogen, 54 mg/dL; creatinine, 3.3 mg/dL (increased from baseline of 1.6 mg/dL 4 months previously); white cell count, 7000/mm³; hemoglobin, 10.5 g/dL; MCV, 89 fL; platelet count, 205,000/mm³; bilirubin, 0.6 mg/dL; aspartate aminotransferase, 15 U/L; alanine aminotransferase, 8 U/L; alkaline phosphatase, 102 U/L; albumin, 4.2 g/dL; total protein, 8.2 g/dL; international normalized ratio, 1.2; and partial thromboplastin time, 31.8 seconds. A urine dipstick demonstrated 1+ protein. The chest radiograph was normal. Electrocardiogram had borderline low voltage with nonspecific T‐wave abnormalities. Additional studies showed a serum iron concentration of 49 mg/dL, transferrin saturation of 16%, total iron binding capacity of 310 mg/dL, and ferritin of 247 mg/mL. Hemoglobin A1c was 7.0%. Acute and chronic antibodies to hepatitis A, B, and C viruses were negative. The following study results were normal or negative: antinuclear antibody, alpha‐1‐antitrypsin, ceruloplasmin, alpha‐fetoprotein, carcinoembryonic antigen, and 24‐hour urinary copper. The thyroid function studies were normal. A purified protein derivative (PPD) skin test was nonreactive.

There continues to be a paucity of evidence of a primary liver disorder. The hepatic enzymes and tests of liver synthetic function are normal, and there is no pancytopenia, as might result from hypersplenism. I remain most suspicious of either a primary cardiac or pericardial disorder with secondary hepatic congestion or a disease that simultaneously affects the heart and liver.

The reasons for the low voltage on the electrocardiogram include processes that infiltrate the myocardium (amyloidosis, sarcoidosis, hemochromatosis, and myxedema fluid) and processes that increase the distance between the myocardium and surface electrodes, such as adipose tissue, air (from emphysema or pneumothorax), or pericardial effusion. Pericardial effusion may present subacutely with predominant features of right ventricular failure. Low voltage, liver disease, and possible heart failure raise the possibility of amyloidosis or hemochromatosis. The low transferrin saturation renders hemochromatosis unlikely. Although normal alkaline phosphatase and serum albumin are not characteristic when AL amyloid affects the liver and kidneys, serum and urine protein electrophoresis and immunofixation should be considered.

With paracentesis 3.5 L of ascitic fluid was removed. The red cell count was 4000/mm³, and white blood cell count was 505/mm³, of which 25% were polymorphonuclear cells, 22% were lymphocytes, and 53% were monocytes. Additional peritoneal fluid chemistries included albumin of 3.0 g/dL and total protein of 5.3 g/dL. Abdominal ultrasound with Doppler demonstrated a liver of normal size and echogenicity with patent hepatic arteries, hepatic veins, and portal vein. There was mild splenomegaly with normal kidneys. Evaluation for a possible liver transplant was initiated. Blood, urine, and peritoneal fluid cultures demonstrated no growth. Echocardiography demonstrated borderline concentric left ventricular hypertrophy, normal right and left ventricular function, dilated superior and inferior vena cavae, and no pericardial effusion or thickening.

The serum‐ascites albumin gradient (SAAG) of 1.2 is consistent with portal hypertension as the cause of the ascites. The Doppler findings exclude postsinusoidal causes of portal hypertension from hepatic vein obstruction or thrombosis. The combination of the elevated SAAG, elevated jugular venous pressure, borderline low voltage on ECG, and elevated peritoneal total protein make cardiac and pericardial disease the leading considerations. Given the normal ventricular function, I am concerned about elevated intracardiac pressures resulting from pericardial disease or restrictive cardiomyopathy. At this point, right heart catheterization would be useful for assessing intracardiac pressures.

On the fourth hospital day, paracentesis was repeated, and 15 L of fluid was removed. A transjugular liver biopsy demonstrated diffuse patchy fibrosis consistent with early cirrhosis and minor intralobular changes with minimal ballooning. There was no steatosis, active inflammation, granulomata, iron deposition, or evidence of viral hepatitis. Right heart catheterization revealed a right atrial pressure of 18 cm H₂0, right ventricular pressure of 34/20 cm H₂0, pulmonary artery pressure of 34/18 cm H₂0 (mean 25), pulmonary capillary wedge pressure of 20 cm H₂0, cardiac output of 5.8 L/min, and cardiac index of 2.5 L/min/m².

The mild hepatic histologic abnormalities do not support an intrinsic liver disease as the cause of his massive ascites and end‐stage liver disease physiology. Cardiac catheterization demonstrates equalization of diastolic pressures, which suggests constrictive pericarditis or restrictive cardiomyopathy. Despite the normal chest radiograph and nonreactive PPD, tuberculosis would be my leading explanation for constrictive pericarditis given the time spent in areas endemic with TB. Although lateral chest radiography may demonstrate pericardial calcifications, magnetic resonance imaging (MRI) is the best imaging modality to detect constrictive pericarditis. Alternately, cardiac amyloidosis could cause restrictive cardiomyopathy and has not been definitively excluded. A cardiac MRI to assess the pericardium would be my next test, and I would request Congo red stains of the liver biopsy. If these tests are unrevealing, endomyocardial biopsy may be necessary.

The cardiac MRI revealed a severely thickened 7‐mm pericardium (normal < 3 mm) most prominent over the right atrium and ventricle. The right ventricle was described as bullet‐shaped, suggesting constrictive pericardial disease (Fig. 1). Left heart catheterization to evaluate coronary anatomy and left ventricular pressures revealed no significant coronary arterial disease and demonstrated an elevated left ventricular end‐diastolic pressure consistent with constrictive pericarditis. Endomyocardial biopsy showed no evidence of infiltrative disease, granulomata, or other significant abnormality. The following day the patient underwent pericardiectomy. Postoperatively, his ascites was easily managed with low doses of diuretics. The pericardial tissue revealed chronic inflammatory cells and dense collagenous fibrosis characteristic of constrictive pericarditis without evidence of malignancy or granulomatous disease. Pericardial cultures were negative for bacteria, viruses, fungi, and mycobacteria.

Figure 1

DISCUSSION

Constrictive pericarditis is characterized by chronic fibrous thickening of the once‐elastic pericardial sac and can occur following any disease process that affects the pericardium (Table 1).1, 2 The challenge in the diagnosis of constrictive pericarditis lies in the recognition of this slowly progressive and uncommon disease. In many cases, nonspecific symptoms of reduced cardiac output and insidious right‐sided heart failure are present for 12 months or longer before a diagnosis is established.1, 3 A typical presentation of constrictive pericarditis is peripheral edema, ascites, and hepatomegaly, a combination that may understandably lead to a misdiagnosis of chronic liver disease and even subject a patient to the unnecessary risk of a liver biopsy, as in this case.

Cryptogenic cirrhosis, the initial diagnosis of this patient, is a term used only after excluding the common and uncommon causes of cirrhosis (Table 2).46 With expanded knowledge of the causes of cirrhosis, especially nonalcoholic fatty liver disease, the number of cases of cirrhosis considered to be cryptogenic has decreased from nearly one‐third of all cases in 1960 to approximately 5% in a modern series.7, 8 Chronic or repetitive heart failure can lead to progressive hepatic fibrosis and cirrhosis. Distinguishing features compared to other causes of cirrhosis include an ascitic protein concentration greater than 2.5 g/dL, relatively preserved synthetic function, and infrequent stigmata of end‐stage liver disease such as spider angiomata or pronounced jaundice.9, 10

A key exam feature that distinguishes cardiac cirrhosis from other causes of liver failure is an elevated jugular venous pressure. Hepatic causes of cirrhosis induce increased nitric oxide production, which leads to splanchnic and peripheral arterial vasodilatation with a reduced effective circulating volume and normal or low jugular venous pressure.11, 12 Therefore, a patient with cirrhosis and ascites having an elevated jugular venous pressure should prompt echocardiographic evaluation.13 When echocardiography excludes ventricular dysfunction, valvular abnormalities, and pulmonary hypertension, constrictive pericarditis and restrictive cardiomyopathy remain important diagnostic considerations.

In both constrictive pericarditis and restrictive cardiomyopathy, ventricular filling is limited. Pressures in the chambers rise abruptly and rapidly during ventricular filling until equilibrium is reached in early diastole. This can be conceptualized as the cardiac chambers being constrained by the limitations of a rigid external box. In constrictive pericarditis, the rigid external box is the fibrosed and thickened pericardial sac, which loses its elasticity and impairs filling of the ventricles. In restrictive cardiomyopathy, the stiff myocardium limits ventricular filling.

There is considerable overlap in the clinical, echocardiographic, and hemodynamic findings of constrictive pericarditis and restrictive cardiomyopathy.14 Both may present insidiously with progressive heart failure. Echocardiography demonstrates impaired diastolic function. Cardiac hemodynamics demonstrate abrupt and rapid early diastolic filling, elevated and equal ventricular end‐diastolic pressures, and reduced stroke volume and cardiac output. A diagnosis of constrictive pericarditis is favored when a marked inspiratory increase in right ventricular pressures and decrease in left ventricular pressures are seen on heart catheterization or a similar inspiratory increase in transvalvular flow velocities across the tricuspid valve compared with the mitral valve is shown by echocardiography. This finding results from normal inspiratory increases in intrathoracic pressures, which are unable to be transmitted through the rigid pericardium but continue to augment venous return to the right side of the heart. As many as one‐third of patients with pericardial constriction lack these characteristic findings on echocardiogram.14

The results of pericardial imaging may suggest a diagnosis of constrictive pericarditis. Lateral chest radiography demonstrates pericardial calcifications in less than 30% of cases.15 Cardiac computed tomography (CT) and MRI are the best imaging modalities for detecting an increase in pericardial thickness (3 mm or greater).16 However, in as many as 20% of patients with surgically confirmed constrictive pericarditis, CT and MRI will demonstrate a pericardium of normal thickness.17

When faced with the diagnostic conundrum of constrictive pericarditis versus restrictive cardiomyopathy, strong clinical suspicion, thorough echocardiography, careful hemodynamic assessment with right and left heart catheterization,14, 18 pericardial imaging, and sometimes endomyocardial biopsy to exclude restrictive cardiomyopathy are often needed before proceeding to pericardiectomy, which carries a significant surgical risk but can also be curative.

This case highlights many of the features of constrictive pericarditis, the challenges and delay in its diagnosis, and its occasional misdiagnosis as chronic liver disease. Clinicians may recognize the typical combination of cirrhosis (or suspected cirrhosis), high SAAG ascites, and edema as characteristic of advanced intrinsic liver disease. However, they must not be seduced into immediate pattern recognition when contrary evidencesuch as elevated neck veins, elevated ascitic total protein, or relatively preserved hepatic synthetic functionaccompanies that picture. Under such circumstances, they must remember to think outside the box and bear in mind that the heart may be trapped inside a box.

A 65‐year‐old man was referred for evaluation of worsening ascites and end‐stage liver disease. The patient had been well until 1 year ago, when he developed lower extremity edema and abdominal distention. After evaluation by his primary care physician, he was given a diagnosis of cryptogenic cirrhosis. He underwent several paracenteses and was placed on furosemide and spironolactone. The patient had been stable on his diuretic regimen until 2 weeks previously, when he suddenly developed worsening edema and ascites, along with dizziness, nausea, and hypotension. His physician stopped the diuretics and referred him to the hospital.

Before diagnosing a patient with cryptogenic cirrhosis, it is necessary to exclude common etiologies of cirrhosis such as alcohol, viral hepatitis, and non‐alcoholic fatty liver disease and numerous uncommon causes, including Wilson's disease, hemochromatosis, Budd‐Chiari, and biliary cirrhosis. It is also important to remember that patients with liver disease are not immune to extrahepatic causes of ascites, such as peritoneal carcinomatosis and tuberculous ascites. Simultaneously, reasons for chronic liver disease decompensating acutely must be considered: medication nonadherence, excess salt intake, hepatotoxicity from acetaminophen or alcohol, and other acute insults, such as hepatocellular carcinoma, an intervening infection (especially spontaneous bacterial peritonitis), ascending cholangitis, or a flare of chronic viral hepatitis.

Past medical and surgical history included diabetes mellitus (diagnosed 10 years previously), obstructive sleep apnea, hypertension, hypothyroidism, and mild chronic kidney disease. Medications included levothyroxine, lactulose, sulfamethoxazole, pioglitazone (started 4 months prior), and ibuprofen. Furosemide and spironolactone had been discontinued 2 weeks previously. He currently resided in the Central Valley of California. He had lived in Thailand from age 7 to 17 and traveled to India more than 1 year ago. He did not smoke and had never used intravenous drugs or received a blood transfusion. He rarely drank alcohol. He worked as a chemist. There was no family history of liver disease.

There is no obvious explanation for the underlying liver disease or the acute decompensation. Sulfamethoxazole is a rare cause of allergic or granulomatous hepatitis. Pioglitazone is a thiazolinedione which in earlier formulations was linked to hepatitis but can be excluded as a cause of this patient's cirrhosis because it was started after liver disease was detected. As a chemist, he might have been exposed to carbon tetrachloride, a known hepatotoxin. Obstructive sleep apnea causes pulmonary hypertension, but severe ascites and acute hepatic decompensation would be unusual. Ibuprofen might precipitate worsening renal function and fluid accumulation. Time in Thailand and India raises the possibility of tuberculous ascites.

The patient had no headache, vision changes, abdominal pain, emesis, melena, hematochezia, chest pain, palpitations, dysuria, polyuria, pruritus, dark urine, or rashes. He reported difficulty with concentration when lactulose was decreased. He noted worsening exercise tolerance with dyspnea after 10 steps and reported a weight gain of 12 pounds in the past 2 weeks.

On examination, temperature was 36.8C; blood pressure, 129/87 mm Hg; heart rate, 85 beats per minute; respirations, 20 per minute; and oxygen saturation, 94% on room air. He was uncomfortable but alert. There was no scleral icterus or conjunctival pallor. Jugular venous pressure was elevated. The lungs were clear, and the heart was regular, with no murmur, rub, or gallops. The abdomen was massively distended with a fluid wave; the liver and spleen could not be palpated. There was pitting edema of the sacrum and lower extremities. There was no asterixis, palmar erythema, spider angiomata, or skin discoloration.

The additional history and physical exam suggest that the primary problem may lie outside the liver, especially as signs of advanced liver disease (other than ascites) are absent. Dyspnea on exertion is consistent with the physical stress of a large volume of ascites or could be secondary to several pulmonary complications associated with liver disease, including portopulmonary hypertension, hepatopulmonary syndrome, or hepatic hydrothorax. Alternatively, the dyspnea raises the possibility that the ascites is not related to a primary liver disorder but rather to anemia or to a cardiac disorder, such as chronic left ventricular failure, isolated right‐sided heart failure, or constrictive pericarditis. These diagnoses are suggested by the elevated jugular venous pressure, which is atypical in cirrhosis.

Although portal hypertension accounts for most cases of ascites, peritoneal fluid should be examined to exclude peritoneal carcinomatosis and tuberculous ascites. I am interested in the results of an echocardiogram.

Initial laboratory studies demonstrated a sodium concentration of 136 mEq/dL; potassium, 4.7 mEq/dL; chloride, 99 mEq/dL; bicarbonate, 24 mEq/dL; blood urea nitrogen, 54 mg/dL; creatinine, 3.3 mg/dL (increased from baseline of 1.6 mg/dL 4 months previously); white cell count, 7000/mm³; hemoglobin, 10.5 g/dL; MCV, 89 fL; platelet count, 205,000/mm³; bilirubin, 0.6 mg/dL; aspartate aminotransferase, 15 U/L; alanine aminotransferase, 8 U/L; alkaline phosphatase, 102 U/L; albumin, 4.2 g/dL; total protein, 8.2 g/dL; international normalized ratio, 1.2; and partial thromboplastin time, 31.8 seconds. A urine dipstick demonstrated 1+ protein. The chest radiograph was normal. Electrocardiogram had borderline low voltage with nonspecific T‐wave abnormalities. Additional studies showed a serum iron concentration of 49 mg/dL, transferrin saturation of 16%, total iron binding capacity of 310 mg/dL, and ferritin of 247 mg/mL. Hemoglobin A1c was 7.0%. Acute and chronic antibodies to hepatitis A, B, and C viruses were negative. The following study results were normal or negative: antinuclear antibody, alpha‐1‐antitrypsin, ceruloplasmin, alpha‐fetoprotein, carcinoembryonic antigen, and 24‐hour urinary copper. The thyroid function studies were normal. A purified protein derivative (PPD) skin test was nonreactive.

There continues to be a paucity of evidence of a primary liver disorder. The hepatic enzymes and tests of liver synthetic function are normal, and there is no pancytopenia, as might result from hypersplenism. I remain most suspicious of either a primary cardiac or pericardial disorder with secondary hepatic congestion or a disease that simultaneously affects the heart and liver.

The reasons for the low voltage on the electrocardiogram include processes that infiltrate the myocardium (amyloidosis, sarcoidosis, hemochromatosis, and myxedema fluid) and processes that increase the distance between the myocardium and surface electrodes, such as adipose tissue, air (from emphysema or pneumothorax), or pericardial effusion. Pericardial effusion may present subacutely with predominant features of right ventricular failure. Low voltage, liver disease, and possible heart failure raise the possibility of amyloidosis or hemochromatosis. The low transferrin saturation renders hemochromatosis unlikely. Although normal alkaline phosphatase and serum albumin are not characteristic when AL amyloid affects the liver and kidneys, serum and urine protein electrophoresis and immunofixation should be considered.

With paracentesis 3.5 L of ascitic fluid was removed. The red cell count was 4000/mm³, and white blood cell count was 505/mm³, of which 25% were polymorphonuclear cells, 22% were lymphocytes, and 53% were monocytes. Additional peritoneal fluid chemistries included albumin of 3.0 g/dL and total protein of 5.3 g/dL. Abdominal ultrasound with Doppler demonstrated a liver of normal size and echogenicity with patent hepatic arteries, hepatic veins, and portal vein. There was mild splenomegaly with normal kidneys. Evaluation for a possible liver transplant was initiated. Blood, urine, and peritoneal fluid cultures demonstrated no growth. Echocardiography demonstrated borderline concentric left ventricular hypertrophy, normal right and left ventricular function, dilated superior and inferior vena cavae, and no pericardial effusion or thickening.

The serum‐ascites albumin gradient (SAAG) of 1.2 is consistent with portal hypertension as the cause of the ascites. The Doppler findings exclude postsinusoidal causes of portal hypertension from hepatic vein obstruction or thrombosis. The combination of the elevated SAAG, elevated jugular venous pressure, borderline low voltage on ECG, and elevated peritoneal total protein make cardiac and pericardial disease the leading considerations. Given the normal ventricular function, I am concerned about elevated intracardiac pressures resulting from pericardial disease or restrictive cardiomyopathy. At this point, right heart catheterization would be useful for assessing intracardiac pressures.

On the fourth hospital day, paracentesis was repeated, and 15 L of fluid was removed. A transjugular liver biopsy demonstrated diffuse patchy fibrosis consistent with early cirrhosis and minor intralobular changes with minimal ballooning. There was no steatosis, active inflammation, granulomata, iron deposition, or evidence of viral hepatitis. Right heart catheterization revealed a right atrial pressure of 18 cm H₂0, right ventricular pressure of 34/20 cm H₂0, pulmonary artery pressure of 34/18 cm H₂0 (mean 25), pulmonary capillary wedge pressure of 20 cm H₂0, cardiac output of 5.8 L/min, and cardiac index of 2.5 L/min/m².

The mild hepatic histologic abnormalities do not support an intrinsic liver disease as the cause of his massive ascites and end‐stage liver disease physiology. Cardiac catheterization demonstrates equalization of diastolic pressures, which suggests constrictive pericarditis or restrictive cardiomyopathy. Despite the normal chest radiograph and nonreactive PPD, tuberculosis would be my leading explanation for constrictive pericarditis given the time spent in areas endemic with TB. Although lateral chest radiography may demonstrate pericardial calcifications, magnetic resonance imaging (MRI) is the best imaging modality to detect constrictive pericarditis. Alternately, cardiac amyloidosis could cause restrictive cardiomyopathy and has not been definitively excluded. A cardiac MRI to assess the pericardium would be my next test, and I would request Congo red stains of the liver biopsy. If these tests are unrevealing, endomyocardial biopsy may be necessary.

The cardiac MRI revealed a severely thickened 7‐mm pericardium (normal < 3 mm) most prominent over the right atrium and ventricle. The right ventricle was described as bullet‐shaped, suggesting constrictive pericardial disease (Fig. 1). Left heart catheterization to evaluate coronary anatomy and left ventricular pressures revealed no significant coronary arterial disease and demonstrated an elevated left ventricular end‐diastolic pressure consistent with constrictive pericarditis. Endomyocardial biopsy showed no evidence of infiltrative disease, granulomata, or other significant abnormality. The following day the patient underwent pericardiectomy. Postoperatively, his ascites was easily managed with low doses of diuretics. The pericardial tissue revealed chronic inflammatory cells and dense collagenous fibrosis characteristic of constrictive pericarditis without evidence of malignancy or granulomatous disease. Pericardial cultures were negative for bacteria, viruses, fungi, and mycobacteria.

Figure 1

DISCUSSION

Constrictive pericarditis is characterized by chronic fibrous thickening of the once‐elastic pericardial sac and can occur following any disease process that affects the pericardium (Table 1).1, 2 The challenge in the diagnosis of constrictive pericarditis lies in the recognition of this slowly progressive and uncommon disease. In many cases, nonspecific symptoms of reduced cardiac output and insidious right‐sided heart failure are present for 12 months or longer before a diagnosis is established.1, 3 A typical presentation of constrictive pericarditis is peripheral edema, ascites, and hepatomegaly, a combination that may understandably lead to a misdiagnosis of chronic liver disease and even subject a patient to the unnecessary risk of a liver biopsy, as in this case.

Cryptogenic cirrhosis, the initial diagnosis of this patient, is a term used only after excluding the common and uncommon causes of cirrhosis (Table 2).46 With expanded knowledge of the causes of cirrhosis, especially nonalcoholic fatty liver disease, the number of cases of cirrhosis considered to be cryptogenic has decreased from nearly one‐third of all cases in 1960 to approximately 5% in a modern series.7, 8 Chronic or repetitive heart failure can lead to progressive hepatic fibrosis and cirrhosis. Distinguishing features compared to other causes of cirrhosis include an ascitic protein concentration greater than 2.5 g/dL, relatively preserved synthetic function, and infrequent stigmata of end‐stage liver disease such as spider angiomata or pronounced jaundice.9, 10

A key exam feature that distinguishes cardiac cirrhosis from other causes of liver failure is an elevated jugular venous pressure. Hepatic causes of cirrhosis induce increased nitric oxide production, which leads to splanchnic and peripheral arterial vasodilatation with a reduced effective circulating volume and normal or low jugular venous pressure.11, 12 Therefore, a patient with cirrhosis and ascites having an elevated jugular venous pressure should prompt echocardiographic evaluation.13 When echocardiography excludes ventricular dysfunction, valvular abnormalities, and pulmonary hypertension, constrictive pericarditis and restrictive cardiomyopathy remain important diagnostic considerations.

In both constrictive pericarditis and restrictive cardiomyopathy, ventricular filling is limited. Pressures in the chambers rise abruptly and rapidly during ventricular filling until equilibrium is reached in early diastole. This can be conceptualized as the cardiac chambers being constrained by the limitations of a rigid external box. In constrictive pericarditis, the rigid external box is the fibrosed and thickened pericardial sac, which loses its elasticity and impairs filling of the ventricles. In restrictive cardiomyopathy, the stiff myocardium limits ventricular filling.

There is considerable overlap in the clinical, echocardiographic, and hemodynamic findings of constrictive pericarditis and restrictive cardiomyopathy.14 Both may present insidiously with progressive heart failure. Echocardiography demonstrates impaired diastolic function. Cardiac hemodynamics demonstrate abrupt and rapid early diastolic filling, elevated and equal ventricular end‐diastolic pressures, and reduced stroke volume and cardiac output. A diagnosis of constrictive pericarditis is favored when a marked inspiratory increase in right ventricular pressures and decrease in left ventricular pressures are seen on heart catheterization or a similar inspiratory increase in transvalvular flow velocities across the tricuspid valve compared with the mitral valve is shown by echocardiography. This finding results from normal inspiratory increases in intrathoracic pressures, which are unable to be transmitted through the rigid pericardium but continue to augment venous return to the right side of the heart. As many as one‐third of patients with pericardial constriction lack these characteristic findings on echocardiogram.14

The results of pericardial imaging may suggest a diagnosis of constrictive pericarditis. Lateral chest radiography demonstrates pericardial calcifications in less than 30% of cases.15 Cardiac computed tomography (CT) and MRI are the best imaging modalities for detecting an increase in pericardial thickness (3 mm or greater).16 However, in as many as 20% of patients with surgically confirmed constrictive pericarditis, CT and MRI will demonstrate a pericardium of normal thickness.17

When faced with the diagnostic conundrum of constrictive pericarditis versus restrictive cardiomyopathy, strong clinical suspicion, thorough echocardiography, careful hemodynamic assessment with right and left heart catheterization,14, 18 pericardial imaging, and sometimes endomyocardial biopsy to exclude restrictive cardiomyopathy are often needed before proceeding to pericardiectomy, which carries a significant surgical risk but can also be curative.

This case highlights many of the features of constrictive pericarditis, the challenges and delay in its diagnosis, and its occasional misdiagnosis as chronic liver disease. Clinicians may recognize the typical combination of cirrhosis (or suspected cirrhosis), high SAAG ascites, and edema as characteristic of advanced intrinsic liver disease. However, they must not be seduced into immediate pattern recognition when contrary evidencesuch as elevated neck veins, elevated ascitic total protein, or relatively preserved hepatic synthetic functionaccompanies that picture. Under such circumstances, they must remember to think outside the box and bear in mind that the heart may be trapped inside a box.

A 65‐year‐old man was referred for evaluation of worsening ascites and end‐stage liver disease. The patient had been well until 1 year ago, when he developed lower extremity edema and abdominal distention. After evaluation by his primary care physician, he was given a diagnosis of cryptogenic cirrhosis. He underwent several paracenteses and was placed on furosemide and spironolactone. The patient had been stable on his diuretic regimen until 2 weeks previously, when he suddenly developed worsening edema and ascites, along with dizziness, nausea, and hypotension. His physician stopped the diuretics and referred him to the hospital.

Before diagnosing a patient with cryptogenic cirrhosis, it is necessary to exclude common etiologies of cirrhosis such as alcohol, viral hepatitis, and non‐alcoholic fatty liver disease and numerous uncommon causes, including Wilson's disease, hemochromatosis, Budd‐Chiari, and biliary cirrhosis. It is also important to remember that patients with liver disease are not immune to extrahepatic causes of ascites, such as peritoneal carcinomatosis and tuberculous ascites. Simultaneously, reasons for chronic liver disease decompensating acutely must be considered: medication nonadherence, excess salt intake, hepatotoxicity from acetaminophen or alcohol, and other acute insults, such as hepatocellular carcinoma, an intervening infection (especially spontaneous bacterial peritonitis), ascending cholangitis, or a flare of chronic viral hepatitis.

Past medical and surgical history included diabetes mellitus (diagnosed 10 years previously), obstructive sleep apnea, hypertension, hypothyroidism, and mild chronic kidney disease. Medications included levothyroxine, lactulose, sulfamethoxazole, pioglitazone (started 4 months prior), and ibuprofen. Furosemide and spironolactone had been discontinued 2 weeks previously. He currently resided in the Central Valley of California. He had lived in Thailand from age 7 to 17 and traveled to India more than 1 year ago. He did not smoke and had never used intravenous drugs or received a blood transfusion. He rarely drank alcohol. He worked as a chemist. There was no family history of liver disease.

There is no obvious explanation for the underlying liver disease or the acute decompensation. Sulfamethoxazole is a rare cause of allergic or granulomatous hepatitis. Pioglitazone is a thiazolinedione which in earlier formulations was linked to hepatitis but can be excluded as a cause of this patient's cirrhosis because it was started after liver disease was detected. As a chemist, he might have been exposed to carbon tetrachloride, a known hepatotoxin. Obstructive sleep apnea causes pulmonary hypertension, but severe ascites and acute hepatic decompensation would be unusual. Ibuprofen might precipitate worsening renal function and fluid accumulation. Time in Thailand and India raises the possibility of tuberculous ascites.

The patient had no headache, vision changes, abdominal pain, emesis, melena, hematochezia, chest pain, palpitations, dysuria, polyuria, pruritus, dark urine, or rashes. He reported difficulty with concentration when lactulose was decreased. He noted worsening exercise tolerance with dyspnea after 10 steps and reported a weight gain of 12 pounds in the past 2 weeks.

On examination, temperature was 36.8C; blood pressure, 129/87 mm Hg; heart rate, 85 beats per minute; respirations, 20 per minute; and oxygen saturation, 94% on room air. He was uncomfortable but alert. There was no scleral icterus or conjunctival pallor. Jugular venous pressure was elevated. The lungs were clear, and the heart was regular, with no murmur, rub, or gallops. The abdomen was massively distended with a fluid wave; the liver and spleen could not be palpated. There was pitting edema of the sacrum and lower extremities. There was no asterixis, palmar erythema, spider angiomata, or skin discoloration.

The additional history and physical exam suggest that the primary problem may lie outside the liver, especially as signs of advanced liver disease (other than ascites) are absent. Dyspnea on exertion is consistent with the physical stress of a large volume of ascites or could be secondary to several pulmonary complications associated with liver disease, including portopulmonary hypertension, hepatopulmonary syndrome, or hepatic hydrothorax. Alternatively, the dyspnea raises the possibility that the ascites is not related to a primary liver disorder but rather to anemia or to a cardiac disorder, such as chronic left ventricular failure, isolated right‐sided heart failure, or constrictive pericarditis. These diagnoses are suggested by the elevated jugular venous pressure, which is atypical in cirrhosis.

Although portal hypertension accounts for most cases of ascites, peritoneal fluid should be examined to exclude peritoneal carcinomatosis and tuberculous ascites. I am interested in the results of an echocardiogram.

Initial laboratory studies demonstrated a sodium concentration of 136 mEq/dL; potassium, 4.7 mEq/dL; chloride, 99 mEq/dL; bicarbonate, 24 mEq/dL; blood urea nitrogen, 54 mg/dL; creatinine, 3.3 mg/dL (increased from baseline of 1.6 mg/dL 4 months previously); white cell count, 7000/mm³; hemoglobin, 10.5 g/dL; MCV, 89 fL; platelet count, 205,000/mm³; bilirubin, 0.6 mg/dL; aspartate aminotransferase, 15 U/L; alanine aminotransferase, 8 U/L; alkaline phosphatase, 102 U/L; albumin, 4.2 g/dL; total protein, 8.2 g/dL; international normalized ratio, 1.2; and partial thromboplastin time, 31.8 seconds. A urine dipstick demonstrated 1+ protein. The chest radiograph was normal. Electrocardiogram had borderline low voltage with nonspecific T‐wave abnormalities. Additional studies showed a serum iron concentration of 49 mg/dL, transferrin saturation of 16%, total iron binding capacity of 310 mg/dL, and ferritin of 247 mg/mL. Hemoglobin A1c was 7.0%. Acute and chronic antibodies to hepatitis A, B, and C viruses were negative. The following study results were normal or negative: antinuclear antibody, alpha‐1‐antitrypsin, ceruloplasmin, alpha‐fetoprotein, carcinoembryonic antigen, and 24‐hour urinary copper. The thyroid function studies were normal. A purified protein derivative (PPD) skin test was nonreactive.

There continues to be a paucity of evidence of a primary liver disorder. The hepatic enzymes and tests of liver synthetic function are normal, and there is no pancytopenia, as might result from hypersplenism. I remain most suspicious of either a primary cardiac or pericardial disorder with secondary hepatic congestion or a disease that simultaneously affects the heart and liver.

The reasons for the low voltage on the electrocardiogram include processes that infiltrate the myocardium (amyloidosis, sarcoidosis, hemochromatosis, and myxedema fluid) and processes that increase the distance between the myocardium and surface electrodes, such as adipose tissue, air (from emphysema or pneumothorax), or pericardial effusion. Pericardial effusion may present subacutely with predominant features of right ventricular failure. Low voltage, liver disease, and possible heart failure raise the possibility of amyloidosis or hemochromatosis. The low transferrin saturation renders hemochromatosis unlikely. Although normal alkaline phosphatase and serum albumin are not characteristic when AL amyloid affects the liver and kidneys, serum and urine protein electrophoresis and immunofixation should be considered.

With paracentesis 3.5 L of ascitic fluid was removed. The red cell count was 4000/mm³, and white blood cell count was 505/mm³, of which 25% were polymorphonuclear cells, 22% were lymphocytes, and 53% were monocytes. Additional peritoneal fluid chemistries included albumin of 3.0 g/dL and total protein of 5.3 g/dL. Abdominal ultrasound with Doppler demonstrated a liver of normal size and echogenicity with patent hepatic arteries, hepatic veins, and portal vein. There was mild splenomegaly with normal kidneys. Evaluation for a possible liver transplant was initiated. Blood, urine, and peritoneal fluid cultures demonstrated no growth. Echocardiography demonstrated borderline concentric left ventricular hypertrophy, normal right and left ventricular function, dilated superior and inferior vena cavae, and no pericardial effusion or thickening.

The serum‐ascites albumin gradient (SAAG) of 1.2 is consistent with portal hypertension as the cause of the ascites. The Doppler findings exclude postsinusoidal causes of portal hypertension from hepatic vein obstruction or thrombosis. The combination of the elevated SAAG, elevated jugular venous pressure, borderline low voltage on ECG, and elevated peritoneal total protein make cardiac and pericardial disease the leading considerations. Given the normal ventricular function, I am concerned about elevated intracardiac pressures resulting from pericardial disease or restrictive cardiomyopathy. At this point, right heart catheterization would be useful for assessing intracardiac pressures.

On the fourth hospital day, paracentesis was repeated, and 15 L of fluid was removed. A transjugular liver biopsy demonstrated diffuse patchy fibrosis consistent with early cirrhosis and minor intralobular changes with minimal ballooning. There was no steatosis, active inflammation, granulomata, iron deposition, or evidence of viral hepatitis. Right heart catheterization revealed a right atrial pressure of 18 cm H₂0, right ventricular pressure of 34/20 cm H₂0, pulmonary artery pressure of 34/18 cm H₂0 (mean 25), pulmonary capillary wedge pressure of 20 cm H₂0, cardiac output of 5.8 L/min, and cardiac index of 2.5 L/min/m².

The mild hepatic histologic abnormalities do not support an intrinsic liver disease as the cause of his massive ascites and end‐stage liver disease physiology. Cardiac catheterization demonstrates equalization of diastolic pressures, which suggests constrictive pericarditis or restrictive cardiomyopathy. Despite the normal chest radiograph and nonreactive PPD, tuberculosis would be my leading explanation for constrictive pericarditis given the time spent in areas endemic with TB. Although lateral chest radiography may demonstrate pericardial calcifications, magnetic resonance imaging (MRI) is the best imaging modality to detect constrictive pericarditis. Alternately, cardiac amyloidosis could cause restrictive cardiomyopathy and has not been definitively excluded. A cardiac MRI to assess the pericardium would be my next test, and I would request Congo red stains of the liver biopsy. If these tests are unrevealing, endomyocardial biopsy may be necessary.

The cardiac MRI revealed a severely thickened 7‐mm pericardium (normal < 3 mm) most prominent over the right atrium and ventricle. The right ventricle was described as bullet‐shaped, suggesting constrictive pericardial disease (Fig. 1). Left heart catheterization to evaluate coronary anatomy and left ventricular pressures revealed no significant coronary arterial disease and demonstrated an elevated left ventricular end‐diastolic pressure consistent with constrictive pericarditis. Endomyocardial biopsy showed no evidence of infiltrative disease, granulomata, or other significant abnormality. The following day the patient underwent pericardiectomy. Postoperatively, his ascites was easily managed with low doses of diuretics. The pericardial tissue revealed chronic inflammatory cells and dense collagenous fibrosis characteristic of constrictive pericarditis without evidence of malignancy or granulomatous disease. Pericardial cultures were negative for bacteria, viruses, fungi, and mycobacteria.

Figure 1

DISCUSSION

Constrictive pericarditis is characterized by chronic fibrous thickening of the once‐elastic pericardial sac and can occur following any disease process that affects the pericardium (Table 1).1, 2 The challenge in the diagnosis of constrictive pericarditis lies in the recognition of this slowly progressive and uncommon disease. In many cases, nonspecific symptoms of reduced cardiac output and insidious right‐sided heart failure are present for 12 months or longer before a diagnosis is established.1, 3 A typical presentation of constrictive pericarditis is peripheral edema, ascites, and hepatomegaly, a combination that may understandably lead to a misdiagnosis of chronic liver disease and even subject a patient to the unnecessary risk of a liver biopsy, as in this case.

Cryptogenic cirrhosis, the initial diagnosis of this patient, is a term used only after excluding the common and uncommon causes of cirrhosis (Table 2).46 With expanded knowledge of the causes of cirrhosis, especially nonalcoholic fatty liver disease, the number of cases of cirrhosis considered to be cryptogenic has decreased from nearly one‐third of all cases in 1960 to approximately 5% in a modern series.7, 8 Chronic or repetitive heart failure can lead to progressive hepatic fibrosis and cirrhosis. Distinguishing features compared to other causes of cirrhosis include an ascitic protein concentration greater than 2.5 g/dL, relatively preserved synthetic function, and infrequent stigmata of end‐stage liver disease such as spider angiomata or pronounced jaundice.9, 10

A key exam feature that distinguishes cardiac cirrhosis from other causes of liver failure is an elevated jugular venous pressure. Hepatic causes of cirrhosis induce increased nitric oxide production, which leads to splanchnic and peripheral arterial vasodilatation with a reduced effective circulating volume and normal or low jugular venous pressure.11, 12 Therefore, a patient with cirrhosis and ascites having an elevated jugular venous pressure should prompt echocardiographic evaluation.13 When echocardiography excludes ventricular dysfunction, valvular abnormalities, and pulmonary hypertension, constrictive pericarditis and restrictive cardiomyopathy remain important diagnostic considerations.

In both constrictive pericarditis and restrictive cardiomyopathy, ventricular filling is limited. Pressures in the chambers rise abruptly and rapidly during ventricular filling until equilibrium is reached in early diastole. This can be conceptualized as the cardiac chambers being constrained by the limitations of a rigid external box. In constrictive pericarditis, the rigid external box is the fibrosed and thickened pericardial sac, which loses its elasticity and impairs filling of the ventricles. In restrictive cardiomyopathy, the stiff myocardium limits ventricular filling.

There is considerable overlap in the clinical, echocardiographic, and hemodynamic findings of constrictive pericarditis and restrictive cardiomyopathy.14 Both may present insidiously with progressive heart failure. Echocardiography demonstrates impaired diastolic function. Cardiac hemodynamics demonstrate abrupt and rapid early diastolic filling, elevated and equal ventricular end‐diastolic pressures, and reduced stroke volume and cardiac output. A diagnosis of constrictive pericarditis is favored when a marked inspiratory increase in right ventricular pressures and decrease in left ventricular pressures are seen on heart catheterization or a similar inspiratory increase in transvalvular flow velocities across the tricuspid valve compared with the mitral valve is shown by echocardiography. This finding results from normal inspiratory increases in intrathoracic pressures, which are unable to be transmitted through the rigid pericardium but continue to augment venous return to the right side of the heart. As many as one‐third of patients with pericardial constriction lack these characteristic findings on echocardiogram.14

The results of pericardial imaging may suggest a diagnosis of constrictive pericarditis. Lateral chest radiography demonstrates pericardial calcifications in less than 30% of cases.15 Cardiac computed tomography (CT) and MRI are the best imaging modalities for detecting an increase in pericardial thickness (3 mm or greater).16 However, in as many as 20% of patients with surgically confirmed constrictive pericarditis, CT and MRI will demonstrate a pericardium of normal thickness.17

When faced with the diagnostic conundrum of constrictive pericarditis versus restrictive cardiomyopathy, strong clinical suspicion, thorough echocardiography, careful hemodynamic assessment with right and left heart catheterization,14, 18 pericardial imaging, and sometimes endomyocardial biopsy to exclude restrictive cardiomyopathy are often needed before proceeding to pericardiectomy, which carries a significant surgical risk but can also be curative.

This case highlights many of the features of constrictive pericarditis, the challenges and delay in its diagnosis, and its occasional misdiagnosis as chronic liver disease. Clinicians may recognize the typical combination of cirrhosis (or suspected cirrhosis), high SAAG ascites, and edema as characteristic of advanced intrinsic liver disease. However, they must not be seduced into immediate pattern recognition when contrary evidencesuch as elevated neck veins, elevated ascitic total protein, or relatively preserved hepatic synthetic functionaccompanies that picture. Under such circumstances, they must remember to think outside the box and bear in mind that the heart may be trapped inside a box.

We deeply appreciate the involvement of our reviewers who made the Journal of Hospital Medicine so successful in its second year. Listed below are the many reviewers and volume of their contributions. They have our sincere gratitude.

Reviewed 4 or More Articles

Thomas E. Baudendistel (7)

Renee Patrice Bullock‐Palmer (4)

Vincent W. Chiang (4)

Jasminka M. Criley (4)

Gurpreet Dhaliwal (6)

Lorenzo Di Francesco (4)

Dana Edelson, MD (7)

Kellie L. Flood (5)

Jeffrey Glasheen (5)

Jeffrey L. Greenwald (4)

Brian Harte (11)

Sunil Kripalani (4)

Matthew Landler (4)

Greg Maynard (5)

Kevin J. O'Leary (4)

Sameer Parikh (6)

James C. Pile (6)

Jason S. Schneider (4)

Doug Wright (4)

Reviewed 3 Articles

Eric Alper

Alpesh Amin

Robert Neal Axon

David L. Blazes

Douglas Carlson

Param Dedhia

Margaret Fang

Jonathan M. Flacker

Rajesh Garg

Stephanie Grossman

Daniel Payson Hunt

Christopher Seoung Kim

Christopher P. Landrigan

Kristine H. Lethert

Marcia Levetown

David Liebovitz

David Likosky

Navneet Majhail

Jennifer Myers

Janet Nagamine

Daniel A. Rauch

Steve Ross

Danielle Bowen Scheurer

Jeffrey Lawrence Schnipper

Hiren Shah

Jason Stein

Reviewed 2 Articles

Nasim Afsarmanesh

Mel L. Anderson III

Vineet Arora

John Banja

Susan S. Braithwaite

Cynthia Jean Brown

Daniel Seth Budnitz

Beril Cakir

Rachel N. Caskey

Murtaza Cassoobhoy

Eva Chittenden

Eugene Shu‐Sen Chu

Steven L. Cohn

Randolph Cole

Nathan T. Connell

Richard I. Cook

Aashish Didwania

Daniel David Dressler

Matthew Eisen

Terry England

Leonard Samuel Feldman

Regina Fink

Raminder Singh Gill

Philip H. Goodman

Mohan Gounder

Susan Grant

Paul Grant

Sajeev Handa

Jeanne M. Huddleston

Carlos Manuel Isada

Amir K. Jaffer

Peter John Kaboli

Jennifer Kapo

Ariel R. Katz

Ujjaini Khanderia

Lisa Kirkland

Cindy J. Lai

Cecilia Lansang

Michael Edwin Lazarus

Bennett Leslie

Blake J. Lesselroth

Lee Lindquist

Michael Lubin

Michelle Magee

David Malkenson

Michael Matheny

Laurence McMahon

Donna Leco Mercado

Melissa Munsell

Brahmajee Nallamothu

James Newman

Vikas Parekh

Mohammed A. Qadeer

Kara Quan

Cate E. Ranheim

Sumant Ranji

Gustavo Rivero

John James Ross

Richard Saitz

Elias G. Sakalis

Maryam Sattari

Bradley Allen Sharpe

Tamara D. Simon

Jeff Sperring

Erin Stucky

Rebecca Sudore

Patrick John Torcson

Arpana Vidyarthi

Diane B. Wayne

Chad Whelan

Stephen Wilson

Jeanie Youngwerth

Iris Yung

Lisa B. Zaoutis

Thomas Zipp

Reviewed 1 Article

Adebola Adesanya

Deborah Adey

Bianca Borges Afonso

Dewesh Agrawal

Meenakshy Aiyer

Richard Keith Albert

Shafic S. Al‐Nammari

Wendy Anderson

Ashish Aneja

Armand H. M. Antommaria

Paul Aronowitz

Deepak Asudani

Andrew Auerbach

Ann Avery

Ahmed BaHammam

Thomas W. Barrett

Jeffrey Barsuk

John Alexander Batsis

Brent Beasley

Deepti Behl

Chaim Bell

Rachelle Bernacki

Jennifer Best

Nisha L. Bhatia

Richard D. Blondell

Bema Bonsu

Thomas Bookwalter

Jeffrey Boord

Debra Boyer

Dawn Brezina

Mandy Brown Belfort

Lucinda Bryant

Alfred Paul Burger

David Busch

Bill Carruth

Brian Carter

Peter J. Cawley

Shiven B. Chabria

Kevin Chan

Carol Chenoweth

Barbara Cleary

Jennifer Cohen

Curtiss B. Cook

Otto Costantini

Kenneth Covinsky

Donald Craven

Timothy J. Crone

Yvette Marie Cua

Ethan Ulysses Cumbler

A. Mark Dalzell

Jennifer Daru

Mellar Davis

William DeMarco

Thomas Donner

Abhijit Duggal

Beatrice Edwards

David Efron

Erin Egan

Kristin Englund

Edward Etchells

Mark Fagan

Tonya Fancher

Randy Joe Ferrance

Chris Feudtner

Christopher K. Finch

Kathleen M. Finn

Alan John Forster

Michael Sebastian Galindo

Joseph Michael Geskey

Roma Y. Gianchandani

Adit A. Ginde

Alan Go

Sherita Hill Golden

Jill Deborah Goldenberg

Adrienne Green

Brian Greffe

Douglas Gregory

Merik Gross

Munish Gupta

Lakshmi Halasyamani

Leslie W. Hall

Jennifer Hanrahan

Lee Hargraves

Gregory Adam Harlan

Michael Harper

Julie Hauer

Nicola Helm

Timothy Hoff

Eric Edwin Howell

Michael Howell

Stephen Hwang

Robert Hyzy

Brian Jack

Joshua Levi Jacobs

Jay Jahanmir

Neeta Jain

William Janssen

Michael Jibson

Karnjit Johl

Robert Kalayjian

Andrew Karson

Dan Kaul

Abel Ngo Kho

Flora Kisuule

Antonios E. Kopanakis

Collin Kroen

Damon Kwan

Alan Labonte

Robert Lash

Usman Latif

Joshua Lee

Sei Lee

Joseph Li

Peter K. Lindenauer

David Ling

Ian Logan

Vanessa London

Jennifer Lukela

Eusni Rahayu M. Tohit

Alejandro E. Macias

Jennifer Mack

Brian Mandell

Efren C. Manjarrez

Brian Markoff

George Mathew

Sarah McBride

Michael McFarlane

Sylvia Cheney McKean

David Meltzer

Franklin Michota

Sherif Mossad

Joseph Munsayac

Paul Murphree

Thomas Aquinas Murphy

Nina Naeger Murphy

Eric Neurmberger

Kathrin Nicolacakis

Craig Nielsen

Lise Nigrovic

Timothy O'Brien

Mary Ottolini

Thomas Andrew Owens

Robert Pascucci

Raffaele Pesavento

Diana Pi

Ann Poncelet

Maryjo Prince‐Paul

Rehan Qayyum

Hossam A. Rahman

Vijay Rajput

Shawn Ralston

Sadat Rashid

Kimberly Rask

Mathew J. Reeves

Robert Reilly

Larry Rhein

Erinn Rhodes

Willaim David Rifkin

Hilary F. Ryder

Camille Sabella

Sandeep Sachdeva

Sanjay Saint

David Schulman

Thomas Schwenk

Gregory B. Seymann

Hasan Shabbir

Samir S. Shah

Lisa Shah

Kaveh G. Shojania

Rebecca Shunk

Eric M. Siegal

Jeffrey Simmons

Siddhartha Singh

G. Randall Smith Jr.

Lailey Sooriash

Ted Speroff

Diane Stafford

Brett Stauffer

Andrea Stracciolini

Hemali Sudhalkar

Alan Taege

Benjamin Taylor

Jay Thomas

Rachel E. Thompson

Sharlene Toney

Joan Trey

Jennifer Michelle Trujillo

Alexander Turchin

Guillermo E. Umpierrez

Bobbak Vahid

Jay Vaidya

Tamara Vesel

Sally Vitali

Polychronopoulos Vlasis

Natalia Borisovna Volkova

Heidi Wald

H. Kenneth Walker

Jeff Wiese

Jonathan Winickoff

Bradford Winters

Scott Wright

David Zipes

We deeply appreciate the involvement of our reviewers who made the Journal of Hospital Medicine so successful in its second year. Listed below are the many reviewers and volume of their contributions. They have our sincere gratitude.

Reviewed 4 or More Articles

Thomas E. Baudendistel (7)

Renee Patrice Bullock‐Palmer (4)

Vincent W. Chiang (4)

Jasminka M. Criley (4)

Gurpreet Dhaliwal (6)

Lorenzo Di Francesco (4)

Dana Edelson, MD (7)

Kellie L. Flood (5)

Jeffrey Glasheen (5)

Jeffrey L. Greenwald (4)

Brian Harte (11)

Sunil Kripalani (4)

Matthew Landler (4)

Greg Maynard (5)

Kevin J. O'Leary (4)

Sameer Parikh (6)

James C. Pile (6)

Jason S. Schneider (4)

Doug Wright (4)

Reviewed 3 Articles

Eric Alper

Alpesh Amin

Robert Neal Axon

David L. Blazes

Douglas Carlson

Param Dedhia

Margaret Fang

Jonathan M. Flacker

Rajesh Garg

Stephanie Grossman

Daniel Payson Hunt

Christopher Seoung Kim

Christopher P. Landrigan

Kristine H. Lethert

Marcia Levetown

David Liebovitz

David Likosky

Navneet Majhail

Jennifer Myers

Janet Nagamine

Daniel A. Rauch

Steve Ross

Danielle Bowen Scheurer

Jeffrey Lawrence Schnipper

Hiren Shah

Jason Stein

Reviewed 2 Articles

Nasim Afsarmanesh

Mel L. Anderson III

Vineet Arora

John Banja

Susan S. Braithwaite

Cynthia Jean Brown

Daniel Seth Budnitz

Beril Cakir

Rachel N. Caskey

Murtaza Cassoobhoy

Eva Chittenden

Eugene Shu‐Sen Chu

Steven L. Cohn

Randolph Cole

Nathan T. Connell

Richard I. Cook

Aashish Didwania

Daniel David Dressler

Matthew Eisen

Terry England

Leonard Samuel Feldman

Regina Fink

Raminder Singh Gill

Philip H. Goodman

Mohan Gounder

Susan Grant

Paul Grant

Sajeev Handa

Jeanne M. Huddleston

Carlos Manuel Isada

Amir K. Jaffer

Peter John Kaboli

Jennifer Kapo

Ariel R. Katz

Ujjaini Khanderia

Lisa Kirkland

Cindy J. Lai

Cecilia Lansang

Michael Edwin Lazarus

Bennett Leslie

Blake J. Lesselroth

Lee Lindquist

Michael Lubin

Michelle Magee

David Malkenson

Michael Matheny

Laurence McMahon

Donna Leco Mercado

Melissa Munsell

Brahmajee Nallamothu

James Newman

Vikas Parekh

Mohammed A. Qadeer

Kara Quan

Cate E. Ranheim

Sumant Ranji

Gustavo Rivero

John James Ross

Richard Saitz

Elias G. Sakalis

Maryam Sattari

Bradley Allen Sharpe

Tamara D. Simon

Jeff Sperring

Erin Stucky

Rebecca Sudore

Patrick John Torcson

Arpana Vidyarthi

Diane B. Wayne

Chad Whelan

Stephen Wilson

Jeanie Youngwerth

Iris Yung

Lisa B. Zaoutis

Thomas Zipp

Reviewed 1 Article

Adebola Adesanya

Deborah Adey

Bianca Borges Afonso

Dewesh Agrawal

Meenakshy Aiyer

Richard Keith Albert

Shafic S. Al‐Nammari

Wendy Anderson

Ashish Aneja

Armand H. M. Antommaria

Paul Aronowitz

Deepak Asudani

Andrew Auerbach

Ann Avery

Ahmed BaHammam

Thomas W. Barrett

Jeffrey Barsuk

John Alexander Batsis

Brent Beasley

Deepti Behl

Chaim Bell

Rachelle Bernacki

Jennifer Best

Nisha L. Bhatia

Richard D. Blondell

Bema Bonsu

Thomas Bookwalter

Jeffrey Boord

Debra Boyer

Dawn Brezina

Mandy Brown Belfort

Lucinda Bryant

Alfred Paul Burger

David Busch

Bill Carruth

Brian Carter

Peter J. Cawley

Shiven B. Chabria

Kevin Chan

Carol Chenoweth

Barbara Cleary

Jennifer Cohen

Curtiss B. Cook

Otto Costantini

Kenneth Covinsky

Donald Craven

Timothy J. Crone

Yvette Marie Cua

Ethan Ulysses Cumbler

A. Mark Dalzell

Jennifer Daru

Mellar Davis

William DeMarco

Thomas Donner

Abhijit Duggal

Beatrice Edwards

David Efron

Erin Egan

Kristin Englund

Edward Etchells

Mark Fagan

Tonya Fancher

Randy Joe Ferrance

Chris Feudtner

Christopher K. Finch

Kathleen M. Finn

Alan John Forster

Michael Sebastian Galindo

Joseph Michael Geskey

Roma Y. Gianchandani

Adit A. Ginde

Alan Go

Sherita Hill Golden

Jill Deborah Goldenberg

Adrienne Green

Brian Greffe

Douglas Gregory

Merik Gross

Munish Gupta

Lakshmi Halasyamani

Leslie W. Hall

Jennifer Hanrahan

Lee Hargraves

Gregory Adam Harlan

Michael Harper

Julie Hauer

Nicola Helm

Timothy Hoff

Eric Edwin Howell

Michael Howell

Stephen Hwang

Robert Hyzy

Brian Jack

Joshua Levi Jacobs

Jay Jahanmir

Neeta Jain

William Janssen

Michael Jibson

Karnjit Johl

Robert Kalayjian

Andrew Karson

Dan Kaul

Abel Ngo Kho

Flora Kisuule

Antonios E. Kopanakis

Collin Kroen

Damon Kwan

Alan Labonte

Robert Lash

Usman Latif

Joshua Lee

Sei Lee

Joseph Li

Peter K. Lindenauer

David Ling

Ian Logan

Vanessa London

Jennifer Lukela

Eusni Rahayu M. Tohit

Alejandro E. Macias

Jennifer Mack

Brian Mandell

Efren C. Manjarrez

Brian Markoff

George Mathew

Sarah McBride

Michael McFarlane

Sylvia Cheney McKean

David Meltzer

Franklin Michota

Sherif Mossad

Joseph Munsayac

Paul Murphree

Thomas Aquinas Murphy

Nina Naeger Murphy

Eric Neurmberger

Kathrin Nicolacakis

Craig Nielsen

Lise Nigrovic

Timothy O'Brien

Mary Ottolini

Thomas Andrew Owens

Robert Pascucci

Raffaele Pesavento

Diana Pi

Ann Poncelet

Maryjo Prince‐Paul

Rehan Qayyum

Hossam A. Rahman

Vijay Rajput

Shawn Ralston

Sadat Rashid

Kimberly Rask

Mathew J. Reeves

Robert Reilly

Larry Rhein

Erinn Rhodes

Willaim David Rifkin

Hilary F. Ryder

Camille Sabella

Sandeep Sachdeva

Sanjay Saint

David Schulman

Thomas Schwenk

Gregory B. Seymann

Hasan Shabbir

Samir S. Shah

Lisa Shah

Kaveh G. Shojania

Rebecca Shunk

Eric M. Siegal

Jeffrey Simmons

Siddhartha Singh

G. Randall Smith Jr.

Lailey Sooriash

Ted Speroff

Diane Stafford

Brett Stauffer

Andrea Stracciolini

Hemali Sudhalkar

Alan Taege

Benjamin Taylor

Jay Thomas

Rachel E. Thompson

Sharlene Toney

Joan Trey

Jennifer Michelle Trujillo

Alexander Turchin

Guillermo E. Umpierrez

Bobbak Vahid

Jay Vaidya

Tamara Vesel

Sally Vitali

Polychronopoulos Vlasis

Natalia Borisovna Volkova

Heidi Wald

H. Kenneth Walker

Jeff Wiese

Jonathan Winickoff

Bradford Winters

Scott Wright

David Zipes

We deeply appreciate the involvement of our reviewers who made the Journal of Hospital Medicine so successful in its second year. Listed below are the many reviewers and volume of their contributions. They have our sincere gratitude.

Reviewed 4 or More Articles

Thomas E. Baudendistel (7)

Renee Patrice Bullock‐Palmer (4)

Vincent W. Chiang (4)

Jasminka M. Criley (4)

Gurpreet Dhaliwal (6)

Lorenzo Di Francesco (4)

Dana Edelson, MD (7)

Kellie L. Flood (5)

Jeffrey Glasheen (5)

Jeffrey L. Greenwald (4)

Brian Harte (11)

Sunil Kripalani (4)

Matthew Landler (4)

Greg Maynard (5)

Kevin J. O'Leary (4)

Sameer Parikh (6)

James C. Pile (6)

Jason S. Schneider (4)

Doug Wright (4)

Reviewed 3 Articles

Eric Alper

Alpesh Amin

Robert Neal Axon

David L. Blazes

Douglas Carlson

Param Dedhia

Margaret Fang

Jonathan M. Flacker

Rajesh Garg

Stephanie Grossman

Daniel Payson Hunt

Christopher Seoung Kim

Christopher P. Landrigan

Kristine H. Lethert

Marcia Levetown

David Liebovitz

David Likosky

Navneet Majhail

Jennifer Myers

Janet Nagamine

Daniel A. Rauch

Steve Ross

Danielle Bowen Scheurer

Jeffrey Lawrence Schnipper

Hiren Shah

Jason Stein

Reviewed 2 Articles

Nasim Afsarmanesh

Mel L. Anderson III

Vineet Arora

John Banja

Susan S. Braithwaite

Cynthia Jean Brown

Daniel Seth Budnitz

Beril Cakir

Rachel N. Caskey

Murtaza Cassoobhoy

Eva Chittenden

Eugene Shu‐Sen Chu

Steven L. Cohn

Randolph Cole

Nathan T. Connell

Richard I. Cook

Aashish Didwania

Daniel David Dressler

Matthew Eisen

Terry England

Leonard Samuel Feldman

Regina Fink

Raminder Singh Gill

Philip H. Goodman

Mohan Gounder

Susan Grant

Paul Grant

Sajeev Handa

Jeanne M. Huddleston

Carlos Manuel Isada

Amir K. Jaffer

Peter John Kaboli

Jennifer Kapo

Ariel R. Katz

Ujjaini Khanderia

Lisa Kirkland

Cindy J. Lai

Cecilia Lansang

Michael Edwin Lazarus

Bennett Leslie

Blake J. Lesselroth

Lee Lindquist

Michael Lubin

Michelle Magee

David Malkenson

Michael Matheny

Laurence McMahon

Donna Leco Mercado

Melissa Munsell

Brahmajee Nallamothu

James Newman

Vikas Parekh

Mohammed A. Qadeer

Kara Quan

Cate E. Ranheim

Sumant Ranji

Gustavo Rivero

John James Ross

Richard Saitz

Elias G. Sakalis

Maryam Sattari

Bradley Allen Sharpe

Tamara D. Simon

Jeff Sperring

Erin Stucky

Rebecca Sudore

Patrick John Torcson

Arpana Vidyarthi

Diane B. Wayne

Chad Whelan

Stephen Wilson

Jeanie Youngwerth

Iris Yung

Lisa B. Zaoutis

Thomas Zipp

Reviewed 1 Article

Adebola Adesanya

Deborah Adey

Bianca Borges Afonso

Dewesh Agrawal

Meenakshy Aiyer

Richard Keith Albert

Shafic S. Al‐Nammari

Wendy Anderson

Ashish Aneja

Armand H. M. Antommaria

Paul Aronowitz

Deepak Asudani

Andrew Auerbach

Ann Avery

Ahmed BaHammam

Thomas W. Barrett

Jeffrey Barsuk

John Alexander Batsis

Brent Beasley

Deepti Behl

Chaim Bell

Rachelle Bernacki

Jennifer Best

Nisha L. Bhatia

Richard D. Blondell

Bema Bonsu

Thomas Bookwalter

Jeffrey Boord

Debra Boyer

Dawn Brezina

Mandy Brown Belfort

Lucinda Bryant

Alfred Paul Burger

David Busch

Bill Carruth

Brian Carter

Peter J. Cawley

Shiven B. Chabria

Kevin Chan

Carol Chenoweth

Barbara Cleary

Jennifer Cohen

Curtiss B. Cook

Otto Costantini

Kenneth Covinsky

Donald Craven

Timothy J. Crone

Yvette Marie Cua

Ethan Ulysses Cumbler

A. Mark Dalzell

Jennifer Daru

Mellar Davis

William DeMarco

Thomas Donner

Abhijit Duggal

Beatrice Edwards

David Efron

Erin Egan

Kristin Englund

Edward Etchells

Mark Fagan

Tonya Fancher

Randy Joe Ferrance

Chris Feudtner

Christopher K. Finch

Kathleen M. Finn

Alan John Forster

Michael Sebastian Galindo

Joseph Michael Geskey

Roma Y. Gianchandani

Adit A. Ginde

Alan Go

Sherita Hill Golden

Jill Deborah Goldenberg

Adrienne Green

Brian Greffe

Douglas Gregory

Merik Gross

Munish Gupta

Lakshmi Halasyamani

Leslie W. Hall

Jennifer Hanrahan

Lee Hargraves

Gregory Adam Harlan

Michael Harper

Julie Hauer

Nicola Helm

Timothy Hoff

Eric Edwin Howell

Michael Howell

Stephen Hwang

Robert Hyzy

Brian Jack

Joshua Levi Jacobs

Jay Jahanmir

Neeta Jain

William Janssen

Michael Jibson

Karnjit Johl

Robert Kalayjian

Andrew Karson

Dan Kaul

Abel Ngo Kho

Flora Kisuule

Antonios E. Kopanakis

Collin Kroen

Damon Kwan

Alan Labonte

Robert Lash

Usman Latif

Joshua Lee

Sei Lee

Joseph Li

Peter K. Lindenauer

David Ling

Ian Logan

Vanessa London

Jennifer Lukela

Eusni Rahayu M. Tohit

Alejandro E. Macias

Jennifer Mack

Brian Mandell

Efren C. Manjarrez

Brian Markoff

George Mathew

Sarah McBride

Michael McFarlane

Sylvia Cheney McKean

David Meltzer

Franklin Michota

Sherif Mossad

Joseph Munsayac

Paul Murphree

Thomas Aquinas Murphy

Nina Naeger Murphy

Eric Neurmberger

Kathrin Nicolacakis

Craig Nielsen

Lise Nigrovic

Timothy O'Brien

Mary Ottolini

Thomas Andrew Owens

Robert Pascucci

Raffaele Pesavento

Diana Pi

Ann Poncelet

Maryjo Prince‐Paul

Rehan Qayyum

Hossam A. Rahman

Vijay Rajput

Shawn Ralston

Sadat Rashid

Kimberly Rask

Mathew J. Reeves

Robert Reilly

Larry Rhein

Erinn Rhodes

Willaim David Rifkin

Hilary F. Ryder

Camille Sabella

Sandeep Sachdeva

Sanjay Saint

David Schulman

Thomas Schwenk

Gregory B. Seymann

Hasan Shabbir

Samir S. Shah

Lisa Shah

Kaveh G. Shojania

Rebecca Shunk

Eric M. Siegal

Jeffrey Simmons

Siddhartha Singh

G. Randall Smith Jr.

Lailey Sooriash

Ted Speroff

Diane Stafford

Brett Stauffer

Andrea Stracciolini

Hemali Sudhalkar

Alan Taege

Benjamin Taylor

Jay Thomas

Rachel E. Thompson

Sharlene Toney

Joan Trey

Jennifer Michelle Trujillo

Alexander Turchin

Guillermo E. Umpierrez

Bobbak Vahid

Jay Vaidya

Tamara Vesel

Sally Vitali

Polychronopoulos Vlasis

Natalia Borisovna Volkova

Heidi Wald

H. Kenneth Walker

Jeff Wiese

Jonathan Winickoff

Bradford Winters

Scott Wright

David Zipes

Inappropriate antibiotic use is a major public health concern and demonstrates the need for quality improvement initiatives in the delivery of health care.16 Each year nearly 2 million patients in the United States acquire an infection in the hospital, and about 90,000 of them die from these infections.7 More than 70% of the bacteria that cause hospital‐acquired infections are resistant to at least one commonly used drug.7 Persons infected with drug‐resistant organisms have longer hospital stays and higher mortality rates.7

Inappropriate antibiotic use in the inpatient hospital setting can be classified into 5 categories. First, antibiotics may be given for illnesses for which they are not indicated (eg, viral infections). Second, broad‐spectrum antibiotics (such as piperacillin‐tazobactam and quinolones) may be overused in the empiric treatment of common infections.8 Overuse of broad‐spectrum drugs increases selective pressure for antimicrobial resistance and exposes patients to the side effects of some of these drugs, such as Clostridium difficile colitis.8 Third, clinicians occasionally prescribe intravenous (IV) antibiotics when the efficacy of oral agents would be similar. Inappropriate intravenous therapy increases the cost of care and also exposes the patient to the risk of intravenous catheters.8 Fourth, when the correct antibiotic choice is made, inappropriate antibiotic dosage, schedule, and/or duration of treatment can threaten patient safety.8 Fifth, bug‐drug mismatch occurs when susceptibility studies indicate that the drug being used is ineffective or only marginally effective.8 Beyond antimicrobial resistance and safety, these practices also usually increase costs to both the patient and the hospital.7, 910

Influencing providers' prescribing patterns is difficult.11 In this project we assessed the prescribing patterns of hospitalists in an active inpatient environment and then developed an intervention to improve the providers' use of antibiotics. The intervention utilized public health methodologyprior to implementation, we defined the problem, determined its magnitude, identified a behavior change model, and constructed a conceptual framework that identifyied the key determinants. A pilot academic detailing project addressing many determinants was developed, implemented, and evaluated.

Conceptual Model

To change prescribing behaviors is to change learned behaviors. Changing behavior is a complex process affected by several factors including beliefs, expectations, motivations, and the psychosocial environments of the target groups.12 Each of these factors must be considered when attempting to bring about behavior changes. In doing so, a theory that can be depicted in a model often emerges.13 This approach is widely used in understanding and developing public health interventions.

Formulating the Model

In any public health intervention, recognizing and engaging key stakeholders is a critical step. We identified the following stakeholders: (1) hospitalist practitioners and other prescribing providers including residents and infectious disease specialists; (2) nurses; (3) administrators who are focused on cost effectiveness; (4) patients and their families, who want to get well affordably, without side effects; (5) pharmacists; (6) risk management; and (7) society, which is fearful of the propagation of resistant microbes. In consulting with some of the stakeholders, 4 factors that influence hospitalists' prescribing patterns became apparent. These are practitioner factors, environmental factors, perceived rewards, and perceived threats (Fig. 1).

Figure 1

The practitioner factors shaping prescribing are: (1) knowledge of current best care; (2) self‐efficacy, which determines whether a provider is confident in his or her knowledge to adequately treat a specific infection; (3) habit, which causes providers to pick from a narrow repertoire of antibiotics when treating an infection; and (4) fear of liability, which forces some providers to be cautious. Four environmental factors affecting antibiotic prescriptions are: (1) published guidelines regarding organisms' sensitivity to antibiotics; (2) patient‐driven factors such as affordability, compliance with dosing regimens, side effects, and interactions between the antibiotics and other medications; (3) peer influence, in that providers are reluctant to change a prescription started by another provider (eg, emergency room physician); and (4) the formulary of the hospital, as it forces providers to prescribe within specific parameters. The perceived rewards of specific prescribing practices may include improving patient safety and reducing antibiotic resistance and costs, whereas the perceived threats are increasing antimicrobial resistance, having adverse patient outcomes, and increasing costs and hospital length of stay. We selected a high‐yield, low‐effort intervention in order to have an impact on some of the factors underlying hospitalists' prescribing patterns.

METHODS

Data Collection

We collected and assessed prescription patterns over 3 periods: preintervention, interim, and postintervention.

Detailing Procedures

After the review, a profile was assembled for each of the CIMS providers. The study team detailers (a physician and a pharmacist) met with the individual providers for 30 to 45 minutes. Each hospitalist participant completed a short survey that collected demographic information and was asked about the rationale for his or her antibiotic prescribing pattern. Next, the appraisal of the provider's prescribing pattern was reviewed. This review included looking at the costs of the prescribed antibiotics compared with those of the appropriate alternatives and a reexamination of the guidelines for the selected target drugspiperacillin‐tazobactam, vancomycin, and extended‐spectrum quinolones. These 3 antibiotics were picked because our providers had been particularly vulnerable to inappropriately prescribing them. The hospitalists were provided an antibiotic guide developed specifically for this project and based on the Johns Hopkins Antibiotic Guide14 that summarizes the consensus guidelines.

Data Analysis

The primary outcome variable was the aggregate proportion of inappropriate antibiotic prescribed (as defined earlier) before the intervention, during the interim between obtaining informed consent and intervening on all study subjects, and after the intervention. The percentage of appropriate prescriptions versus total not appropriate prescriptions (combining of the effective but inappropriate and inappropriate categories) were compared across the 3 periods. Ninety‐five percent confidence intervals for comparisons of the proportions were determined using Stata 9.0 (College Station, TX). The difference between the proportions of total not appropriate prescriptions before and after academic detailing was computed in Stata using Fisher's exact test to assess significance.

RESULTS

Demographic information and professional characteristics of the 17 providers are shown in Table 1. Their mean age was 36 years, and 76% were female. The top 4 reasons the providers gave for their prescribing practices were: (1) published guidelines, (2) easier dosing schedule for patient when discharged, (3) continuing an antibiotic course initiated in the emergency room, and (4) broad‐spectrum antibiotics cover all possible microbes.

DISCUSSION

We have demonstrated that academic detailing had a positive impact on the prescribing patterns of hospitalists. The aggregated improvement in antibiotic prescribing patterns can be attributed to improvement in the prescribing patterns of almost every hospitalist practitioner (Table 2). This study focused on aggregate prescriptions as the primary outcome measure because the hospitalists at JHBMC, like at many other institutions, function as a team, with a patient routinely having multiple providers over the course of the hospital stay. The improved prescribing patterns noted during the interim period suggest that the mere knowledge of a project can have an impact on providers. Providers informed the investigators that they were more thoughtful about their choice of antibiotics when they knew that they were being studied. The further statistically significant improvement in prescribing patterns with the intervention shows that the academic detailing itself was successful.

The greatest absolute change in practice was seen in effective but inappropriate prescribing (from 30.4% to 6%), whereas inappropriate prescribing only decreased from 26.6% to 20.6%. Although we aimed to have an impact on all inappropriate antibiotic prescribing patterns, we specifically reviewed the prescribing guidelines for piperacillin‐tazobactam, extended‐spectrum quinolones, and vancomycin. These 3 antibiotics were targeted because our providers had been particularly susceptible to inappropriately prescribing them. The focus on these antibiotics may have resulted in the larger absolute change noted in effective but inappropriate prescribing. We did not collect any data to determine if having an impact on effective but inappropriate prescribing changed the clinical course of the patients, such as shortening their hospital stays. Anecdotal evidence, however, suggests that it does. At our institution it is not uncommon for patients to be kept in the hospital for an extra day to ensure they are stable when transitioned from extended‐spectrum to narrower‐spectrum antibiotics prior to discharge. The effect of reducing effective but inappropriate prescriptions on the clinical course of patients could be an outcome measure assessed by a future, larger study.

Our one‐on‐one appraisal of each provider's prescribing patterns included a review of the cost of the prescribed antibiotics compared with that of the appropriate alternatives. Although decisions on antibiotic choice should be driven by clinical guidelines and appropriateness rather than price, we believed it was relevant to include education about costs and pricing so that providers would be reminded to ascertain whether patients would be able to afford their antibiotics. Antibiotic resistance is influenced by a patient's failure to complete the course of treatment, and noncompliance may be caused by an inability to afford the medication. Often, there are affordable, appropriate alternatives to the newest and most expensive drugs.

A hospitalist‐based academic detailing approach to improving antibiotic prescribing may have far‐reaching benefits and influence. First, it has the potential to affect other practitioners by setting an example and role modeling. In addition to that with their immediate peer group, hospitalists have close and repeated contact with house officers and emergency room physicians and often act as consultants to physicians in other departments such as surgery and psychiatry. Furthermore, some community hospitals have no infectious disease specialists readily available. So this represents an opportunity for hospitalists to promote quality in antibiotic prescribing. Practice‐based learning was very effective because it brought the practitioners face to face with their prescribing patterns. Although intellectually everyone agreed that antibiotics are often misused, this approach forced the providers to stop and reflect on their individual practices. This peer‐delivered intervention allowed for a collaborative approach to solving the problem; the peer (detailer) was approachable, nonjudgmental, and available for further discussion and guidance.

The public health quality improvement approach that we used for our intervention helped us to realize and appreciate the factors underlying prescribing patterns. Only by understanding the motivations for prescribing patterns can we hope to make sustainable changes. This coincides with our previous assertion that hospitalists are engaging in some public health practice.16 In pubic health, the programs, services, and institutions involved emphasize the prevention of disease and the health needs of the population as a whole.17 Hospitalist teams aim to make sure that the high‐quality services needed for protecting the health of their community (hospitalized patients) are available and that this population receives proper consideration in the allocation of resources. Antibiotic optimization is a key role that could fall within the mantra of public health practice for the hospitalist.

Several limitations of this pilot should be considered. First, the intervention is labor intensive. However, it is essential to use the problem‐solving paradigm and incorporate behavior change theories in order to identify interventions that can lead to sustainable change. Second, this was not a randomized controlled trial, and it is possible that there might have been some contamination by external forces. However, in reviewing the educational events at our institution, the press, and articles published during the study period, we could not identify any external factors that would have influenced antibiotic prescribing patterns. It would not have been possible to conduct a randomized trial at our institution because the hospitalists work so closely together that we could not ensure complete separation if the subjects were randomized. There would have been contamination from the intervention group to the control group. A trial with randomization at the institution level is the next step. Third, the number of months retrospectively reviewed in order to identify 20 prescriptions of a provider varied. This study assumed there were no other differences during those months that could have affected provider prescribing behavior; this may have introduced some bias. Fourth, the sustainability of this intervention's positive impact is unknown. We assessed outcome soon after the intervention, and it is unknown whether continual booster sessions are required to maintain the positive impact on prescribing patterns.

This pilot was a good starting place to show that behavior change can be realized with a well‐conceived and methodically executed intervention, even among the busiest of physicians. Audit and feedback, or practice‐based learning, appears to be a powerful educational intervention among professionals who take great pride in their work.

Inappropriate antibiotic use is a major public health concern and demonstrates the need for quality improvement initiatives in the delivery of health care.16 Each year nearly 2 million patients in the United States acquire an infection in the hospital, and about 90,000 of them die from these infections.7 More than 70% of the bacteria that cause hospital‐acquired infections are resistant to at least one commonly used drug.7 Persons infected with drug‐resistant organisms have longer hospital stays and higher mortality rates.7

Inappropriate antibiotic use in the inpatient hospital setting can be classified into 5 categories. First, antibiotics may be given for illnesses for which they are not indicated (eg, viral infections). Second, broad‐spectrum antibiotics (such as piperacillin‐tazobactam and quinolones) may be overused in the empiric treatment of common infections.8 Overuse of broad‐spectrum drugs increases selective pressure for antimicrobial resistance and exposes patients to the side effects of some of these drugs, such as Clostridium difficile colitis.8 Third, clinicians occasionally prescribe intravenous (IV) antibiotics when the efficacy of oral agents would be similar. Inappropriate intravenous therapy increases the cost of care and also exposes the patient to the risk of intravenous catheters.8 Fourth, when the correct antibiotic choice is made, inappropriate antibiotic dosage, schedule, and/or duration of treatment can threaten patient safety.8 Fifth, bug‐drug mismatch occurs when susceptibility studies indicate that the drug being used is ineffective or only marginally effective.8 Beyond antimicrobial resistance and safety, these practices also usually increase costs to both the patient and the hospital.7, 910

Influencing providers' prescribing patterns is difficult.11 In this project we assessed the prescribing patterns of hospitalists in an active inpatient environment and then developed an intervention to improve the providers' use of antibiotics. The intervention utilized public health methodologyprior to implementation, we defined the problem, determined its magnitude, identified a behavior change model, and constructed a conceptual framework that identifyied the key determinants. A pilot academic detailing project addressing many determinants was developed, implemented, and evaluated.

Conceptual Model

To change prescribing behaviors is to change learned behaviors. Changing behavior is a complex process affected by several factors including beliefs, expectations, motivations, and the psychosocial environments of the target groups.12 Each of these factors must be considered when attempting to bring about behavior changes. In doing so, a theory that can be depicted in a model often emerges.13 This approach is widely used in understanding and developing public health interventions.

Formulating the Model

In any public health intervention, recognizing and engaging key stakeholders is a critical step. We identified the following stakeholders: (1) hospitalist practitioners and other prescribing providers including residents and infectious disease specialists; (2) nurses; (3) administrators who are focused on cost effectiveness; (4) patients and their families, who want to get well affordably, without side effects; (5) pharmacists; (6) risk management; and (7) society, which is fearful of the propagation of resistant microbes. In consulting with some of the stakeholders, 4 factors that influence hospitalists' prescribing patterns became apparent. These are practitioner factors, environmental factors, perceived rewards, and perceived threats (Fig. 1).

Figure 1

The practitioner factors shaping prescribing are: (1) knowledge of current best care; (2) self‐efficacy, which determines whether a provider is confident in his or her knowledge to adequately treat a specific infection; (3) habit, which causes providers to pick from a narrow repertoire of antibiotics when treating an infection; and (4) fear of liability, which forces some providers to be cautious. Four environmental factors affecting antibiotic prescriptions are: (1) published guidelines regarding organisms' sensitivity to antibiotics; (2) patient‐driven factors such as affordability, compliance with dosing regimens, side effects, and interactions between the antibiotics and other medications; (3) peer influence, in that providers are reluctant to change a prescription started by another provider (eg, emergency room physician); and (4) the formulary of the hospital, as it forces providers to prescribe within specific parameters. The perceived rewards of specific prescribing practices may include improving patient safety and reducing antibiotic resistance and costs, whereas the perceived threats are increasing antimicrobial resistance, having adverse patient outcomes, and increasing costs and hospital length of stay. We selected a high‐yield, low‐effort intervention in order to have an impact on some of the factors underlying hospitalists' prescribing patterns.

METHODS

Data Collection

We collected and assessed prescription patterns over 3 periods: preintervention, interim, and postintervention.

Detailing Procedures

After the review, a profile was assembled for each of the CIMS providers. The study team detailers (a physician and a pharmacist) met with the individual providers for 30 to 45 minutes. Each hospitalist participant completed a short survey that collected demographic information and was asked about the rationale for his or her antibiotic prescribing pattern. Next, the appraisal of the provider's prescribing pattern was reviewed. This review included looking at the costs of the prescribed antibiotics compared with those of the appropriate alternatives and a reexamination of the guidelines for the selected target drugspiperacillin‐tazobactam, vancomycin, and extended‐spectrum quinolones. These 3 antibiotics were picked because our providers had been particularly vulnerable to inappropriately prescribing them. The hospitalists were provided an antibiotic guide developed specifically for this project and based on the Johns Hopkins Antibiotic Guide14 that summarizes the consensus guidelines.

Data Analysis

The primary outcome variable was the aggregate proportion of inappropriate antibiotic prescribed (as defined earlier) before the intervention, during the interim between obtaining informed consent and intervening on all study subjects, and after the intervention. The percentage of appropriate prescriptions versus total not appropriate prescriptions (combining of the effective but inappropriate and inappropriate categories) were compared across the 3 periods. Ninety‐five percent confidence intervals for comparisons of the proportions were determined using Stata 9.0 (College Station, TX). The difference between the proportions of total not appropriate prescriptions before and after academic detailing was computed in Stata using Fisher's exact test to assess significance.

RESULTS

Demographic information and professional characteristics of the 17 providers are shown in Table 1. Their mean age was 36 years, and 76% were female. The top 4 reasons the providers gave for their prescribing practices were: (1) published guidelines, (2) easier dosing schedule for patient when discharged, (3) continuing an antibiotic course initiated in the emergency room, and (4) broad‐spectrum antibiotics cover all possible microbes.

DISCUSSION

We have demonstrated that academic detailing had a positive impact on the prescribing patterns of hospitalists. The aggregated improvement in antibiotic prescribing patterns can be attributed to improvement in the prescribing patterns of almost every hospitalist practitioner (Table 2). This study focused on aggregate prescriptions as the primary outcome measure because the hospitalists at JHBMC, like at many other institutions, function as a team, with a patient routinely having multiple providers over the course of the hospital stay. The improved prescribing patterns noted during the interim period suggest that the mere knowledge of a project can have an impact on providers. Providers informed the investigators that they were more thoughtful about their choice of antibiotics when they knew that they were being studied. The further statistically significant improvement in prescribing patterns with the intervention shows that the academic detailing itself was successful.

The greatest absolute change in practice was seen in effective but inappropriate prescribing (from 30.4% to 6%), whereas inappropriate prescribing only decreased from 26.6% to 20.6%. Although we aimed to have an impact on all inappropriate antibiotic prescribing patterns, we specifically reviewed the prescribing guidelines for piperacillin‐tazobactam, extended‐spectrum quinolones, and vancomycin. These 3 antibiotics were targeted because our providers had been particularly susceptible to inappropriately prescribing them. The focus on these antibiotics may have resulted in the larger absolute change noted in effective but inappropriate prescribing. We did not collect any data to determine if having an impact on effective but inappropriate prescribing changed the clinical course of the patients, such as shortening their hospital stays. Anecdotal evidence, however, suggests that it does. At our institution it is not uncommon for patients to be kept in the hospital for an extra day to ensure they are stable when transitioned from extended‐spectrum to narrower‐spectrum antibiotics prior to discharge. The effect of reducing effective but inappropriate prescriptions on the clinical course of patients could be an outcome measure assessed by a future, larger study.

Our one‐on‐one appraisal of each provider's prescribing patterns included a review of the cost of the prescribed antibiotics compared with that of the appropriate alternatives. Although decisions on antibiotic choice should be driven by clinical guidelines and appropriateness rather than price, we believed it was relevant to include education about costs and pricing so that providers would be reminded to ascertain whether patients would be able to afford their antibiotics. Antibiotic resistance is influenced by a patient's failure to complete the course of treatment, and noncompliance may be caused by an inability to afford the medication. Often, there are affordable, appropriate alternatives to the newest and most expensive drugs.

A hospitalist‐based academic detailing approach to improving antibiotic prescribing may have far‐reaching benefits and influence. First, it has the potential to affect other practitioners by setting an example and role modeling. In addition to that with their immediate peer group, hospitalists have close and repeated contact with house officers and emergency room physicians and often act as consultants to physicians in other departments such as surgery and psychiatry. Furthermore, some community hospitals have no infectious disease specialists readily available. So this represents an opportunity for hospitalists to promote quality in antibiotic prescribing. Practice‐based learning was very effective because it brought the practitioners face to face with their prescribing patterns. Although intellectually everyone agreed that antibiotics are often misused, this approach forced the providers to stop and reflect on their individual practices. This peer‐delivered intervention allowed for a collaborative approach to solving the problem; the peer (detailer) was approachable, nonjudgmental, and available for further discussion and guidance.

The public health quality improvement approach that we used for our intervention helped us to realize and appreciate the factors underlying prescribing patterns. Only by understanding the motivations for prescribing patterns can we hope to make sustainable changes. This coincides with our previous assertion that hospitalists are engaging in some public health practice.16 In pubic health, the programs, services, and institutions involved emphasize the prevention of disease and the health needs of the population as a whole.17 Hospitalist teams aim to make sure that the high‐quality services needed for protecting the health of their community (hospitalized patients) are available and that this population receives proper consideration in the allocation of resources. Antibiotic optimization is a key role that could fall within the mantra of public health practice for the hospitalist.

Several limitations of this pilot should be considered. First, the intervention is labor intensive. However, it is essential to use the problem‐solving paradigm and incorporate behavior change theories in order to identify interventions that can lead to sustainable change. Second, this was not a randomized controlled trial, and it is possible that there might have been some contamination by external forces. However, in reviewing the educational events at our institution, the press, and articles published during the study period, we could not identify any external factors that would have influenced antibiotic prescribing patterns. It would not have been possible to conduct a randomized trial at our institution because the hospitalists work so closely together that we could not ensure complete separation if the subjects were randomized. There would have been contamination from the intervention group to the control group. A trial with randomization at the institution level is the next step. Third, the number of months retrospectively reviewed in order to identify 20 prescriptions of a provider varied. This study assumed there were no other differences during those months that could have affected provider prescribing behavior; this may have introduced some bias. Fourth, the sustainability of this intervention's positive impact is unknown. We assessed outcome soon after the intervention, and it is unknown whether continual booster sessions are required to maintain the positive impact on prescribing patterns.

This pilot was a good starting place to show that behavior change can be realized with a well‐conceived and methodically executed intervention, even among the busiest of physicians. Audit and feedback, or practice‐based learning, appears to be a powerful educational intervention among professionals who take great pride in their work.

Inappropriate antibiotic use is a major public health concern and demonstrates the need for quality improvement initiatives in the delivery of health care.16 Each year nearly 2 million patients in the United States acquire an infection in the hospital, and about 90,000 of them die from these infections.7 More than 70% of the bacteria that cause hospital‐acquired infections are resistant to at least one commonly used drug.7 Persons infected with drug‐resistant organisms have longer hospital stays and higher mortality rates.7

Inappropriate antibiotic use in the inpatient hospital setting can be classified into 5 categories. First, antibiotics may be given for illnesses for which they are not indicated (eg, viral infections). Second, broad‐spectrum antibiotics (such as piperacillin‐tazobactam and quinolones) may be overused in the empiric treatment of common infections.8 Overuse of broad‐spectrum drugs increases selective pressure for antimicrobial resistance and exposes patients to the side effects of some of these drugs, such as Clostridium difficile colitis.8 Third, clinicians occasionally prescribe intravenous (IV) antibiotics when the efficacy of oral agents would be similar. Inappropriate intravenous therapy increases the cost of care and also exposes the patient to the risk of intravenous catheters.8 Fourth, when the correct antibiotic choice is made, inappropriate antibiotic dosage, schedule, and/or duration of treatment can threaten patient safety.8 Fifth, bug‐drug mismatch occurs when susceptibility studies indicate that the drug being used is ineffective or only marginally effective.8 Beyond antimicrobial resistance and safety, these practices also usually increase costs to both the patient and the hospital.7, 910

Influencing providers' prescribing patterns is difficult.11 In this project we assessed the prescribing patterns of hospitalists in an active inpatient environment and then developed an intervention to improve the providers' use of antibiotics. The intervention utilized public health methodologyprior to implementation, we defined the problem, determined its magnitude, identified a behavior change model, and constructed a conceptual framework that identifyied the key determinants. A pilot academic detailing project addressing many determinants was developed, implemented, and evaluated.

Conceptual Model

To change prescribing behaviors is to change learned behaviors. Changing behavior is a complex process affected by several factors including beliefs, expectations, motivations, and the psychosocial environments of the target groups.12 Each of these factors must be considered when attempting to bring about behavior changes. In doing so, a theory that can be depicted in a model often emerges.13 This approach is widely used in understanding and developing public health interventions.

Formulating the Model

In any public health intervention, recognizing and engaging key stakeholders is a critical step. We identified the following stakeholders: (1) hospitalist practitioners and other prescribing providers including residents and infectious disease specialists; (2) nurses; (3) administrators who are focused on cost effectiveness; (4) patients and their families, who want to get well affordably, without side effects; (5) pharmacists; (6) risk management; and (7) society, which is fearful of the propagation of resistant microbes. In consulting with some of the stakeholders, 4 factors that influence hospitalists' prescribing patterns became apparent. These are practitioner factors, environmental factors, perceived rewards, and perceived threats (Fig. 1).

Figure 1

The practitioner factors shaping prescribing are: (1) knowledge of current best care; (2) self‐efficacy, which determines whether a provider is confident in his or her knowledge to adequately treat a specific infection; (3) habit, which causes providers to pick from a narrow repertoire of antibiotics when treating an infection; and (4) fear of liability, which forces some providers to be cautious. Four environmental factors affecting antibiotic prescriptions are: (1) published guidelines regarding organisms' sensitivity to antibiotics; (2) patient‐driven factors such as affordability, compliance with dosing regimens, side effects, and interactions between the antibiotics and other medications; (3) peer influence, in that providers are reluctant to change a prescription started by another provider (eg, emergency room physician); and (4) the formulary of the hospital, as it forces providers to prescribe within specific parameters. The perceived rewards of specific prescribing practices may include improving patient safety and reducing antibiotic resistance and costs, whereas the perceived threats are increasing antimicrobial resistance, having adverse patient outcomes, and increasing costs and hospital length of stay. We selected a high‐yield, low‐effort intervention in order to have an impact on some of the factors underlying hospitalists' prescribing patterns.

METHODS

Data Collection

We collected and assessed prescription patterns over 3 periods: preintervention, interim, and postintervention.

Detailing Procedures

After the review, a profile was assembled for each of the CIMS providers. The study team detailers (a physician and a pharmacist) met with the individual providers for 30 to 45 minutes. Each hospitalist participant completed a short survey that collected demographic information and was asked about the rationale for his or her antibiotic prescribing pattern. Next, the appraisal of the provider's prescribing pattern was reviewed. This review included looking at the costs of the prescribed antibiotics compared with those of the appropriate alternatives and a reexamination of the guidelines for the selected target drugspiperacillin‐tazobactam, vancomycin, and extended‐spectrum quinolones. These 3 antibiotics were picked because our providers had been particularly vulnerable to inappropriately prescribing them. The hospitalists were provided an antibiotic guide developed specifically for this project and based on the Johns Hopkins Antibiotic Guide14 that summarizes the consensus guidelines.

Data Analysis

The primary outcome variable was the aggregate proportion of inappropriate antibiotic prescribed (as defined earlier) before the intervention, during the interim between obtaining informed consent and intervening on all study subjects, and after the intervention. The percentage of appropriate prescriptions versus total not appropriate prescriptions (combining of the effective but inappropriate and inappropriate categories) were compared across the 3 periods. Ninety‐five percent confidence intervals for comparisons of the proportions were determined using Stata 9.0 (College Station, TX). The difference between the proportions of total not appropriate prescriptions before and after academic detailing was computed in Stata using Fisher's exact test to assess significance.

RESULTS

Demographic information and professional characteristics of the 17 providers are shown in Table 1. Their mean age was 36 years, and 76% were female. The top 4 reasons the providers gave for their prescribing practices were: (1) published guidelines, (2) easier dosing schedule for patient when discharged, (3) continuing an antibiotic course initiated in the emergency room, and (4) broad‐spectrum antibiotics cover all possible microbes.

DISCUSSION

We have demonstrated that academic detailing had a positive impact on the prescribing patterns of hospitalists. The aggregated improvement in antibiotic prescribing patterns can be attributed to improvement in the prescribing patterns of almost every hospitalist practitioner (Table 2). This study focused on aggregate prescriptions as the primary outcome measure because the hospitalists at JHBMC, like at many other institutions, function as a team, with a patient routinely having multiple providers over the course of the hospital stay. The improved prescribing patterns noted during the interim period suggest that the mere knowledge of a project can have an impact on providers. Providers informed the investigators that they were more thoughtful about their choice of antibiotics when they knew that they were being studied. The further statistically significant improvement in prescribing patterns with the intervention shows that the academic detailing itself was successful.

The greatest absolute change in practice was seen in effective but inappropriate prescribing (from 30.4% to 6%), whereas inappropriate prescribing only decreased from 26.6% to 20.6%. Although we aimed to have an impact on all inappropriate antibiotic prescribing patterns, we specifically reviewed the prescribing guidelines for piperacillin‐tazobactam, extended‐spectrum quinolones, and vancomycin. These 3 antibiotics were targeted because our providers had been particularly susceptible to inappropriately prescribing them. The focus on these antibiotics may have resulted in the larger absolute change noted in effective but inappropriate prescribing. We did not collect any data to determine if having an impact on effective but inappropriate prescribing changed the clinical course of the patients, such as shortening their hospital stays. Anecdotal evidence, however, suggests that it does. At our institution it is not uncommon for patients to be kept in the hospital for an extra day to ensure they are stable when transitioned from extended‐spectrum to narrower‐spectrum antibiotics prior to discharge. The effect of reducing effective but inappropriate prescriptions on the clinical course of patients could be an outcome measure assessed by a future, larger study.

Our one‐on‐one appraisal of each provider's prescribing patterns included a review of the cost of the prescribed antibiotics compared with that of the appropriate alternatives. Although decisions on antibiotic choice should be driven by clinical guidelines and appropriateness rather than price, we believed it was relevant to include education about costs and pricing so that providers would be reminded to ascertain whether patients would be able to afford their antibiotics. Antibiotic resistance is influenced by a patient's failure to complete the course of treatment, and noncompliance may be caused by an inability to afford the medication. Often, there are affordable, appropriate alternatives to the newest and most expensive drugs.

A hospitalist‐based academic detailing approach to improving antibiotic prescribing may have far‐reaching benefits and influence. First, it has the potential to affect other practitioners by setting an example and role modeling. In addition to that with their immediate peer group, hospitalists have close and repeated contact with house officers and emergency room physicians and often act as consultants to physicians in other departments such as surgery and psychiatry. Furthermore, some community hospitals have no infectious disease specialists readily available. So this represents an opportunity for hospitalists to promote quality in antibiotic prescribing. Practice‐based learning was very effective because it brought the practitioners face to face with their prescribing patterns. Although intellectually everyone agreed that antibiotics are often misused, this approach forced the providers to stop and reflect on their individual practices. This peer‐delivered intervention allowed for a collaborative approach to solving the problem; the peer (detailer) was approachable, nonjudgmental, and available for further discussion and guidance.

The public health quality improvement approach that we used for our intervention helped us to realize and appreciate the factors underlying prescribing patterns. Only by understanding the motivations for prescribing patterns can we hope to make sustainable changes. This coincides with our previous assertion that hospitalists are engaging in some public health practice.16 In pubic health, the programs, services, and institutions involved emphasize the prevention of disease and the health needs of the population as a whole.17 Hospitalist teams aim to make sure that the high‐quality services needed for protecting the health of their community (hospitalized patients) are available and that this population receives proper consideration in the allocation of resources. Antibiotic optimization is a key role that could fall within the mantra of public health practice for the hospitalist.

Several limitations of this pilot should be considered. First, the intervention is labor intensive. However, it is essential to use the problem‐solving paradigm and incorporate behavior change theories in order to identify interventions that can lead to sustainable change. Second, this was not a randomized controlled trial, and it is possible that there might have been some contamination by external forces. However, in reviewing the educational events at our institution, the press, and articles published during the study period, we could not identify any external factors that would have influenced antibiotic prescribing patterns. It would not have been possible to conduct a randomized trial at our institution because the hospitalists work so closely together that we could not ensure complete separation if the subjects were randomized. There would have been contamination from the intervention group to the control group. A trial with randomization at the institution level is the next step. Third, the number of months retrospectively reviewed in order to identify 20 prescriptions of a provider varied. This study assumed there were no other differences during those months that could have affected provider prescribing behavior; this may have introduced some bias. Fourth, the sustainability of this intervention's positive impact is unknown. We assessed outcome soon after the intervention, and it is unknown whether continual booster sessions are required to maintain the positive impact on prescribing patterns.

This pilot was a good starting place to show that behavior change can be realized with a well‐conceived and methodically executed intervention, even among the busiest of physicians. Audit and feedback, or practice‐based learning, appears to be a powerful educational intervention among professionals who take great pride in their work.

Given recent changes in the goals and objectives of residency training as well as changes in the functioning of teaching hospitals, traditional educational formats may need to be supplemented or replaced.1 The Accreditation Council for Graduate Medical Education (ACGME) is promoting changes in resident education with the goal of not only enhancing trainee competency using innovative methods but also of demonstrating that these educational innovations result in enhanced quality of patient care and improved patient safety.1 A challenging aspect of these initiatives is that programs are working to implement them at a time when there are greater nonteaching demands on faculty time, mandated resident work‐hour limitations have been instituted, in some states by law, and resident patient care and educational activities are prone to disruptions inherent in caring for patients in a complex health system. Various solutions have been proposed including increased incorporation of self‐directed learning as a means of meeting modern resident educational challenges, yet the ideal tools with which to accomplish this are unknown.

Computer‐based instruction in medicine has been available since the 1960s, and although its use had initially been more widespread in medical student, nursing, allied health professional, and patient education,2, 3 it is being increasingly incorporated into resident education as well. Some studies have shown that for medical students, computer‐based teaching is at least as effective in improving knowledge as conventional lectures4 and that learners' satisfaction with computer‐based formats appears comparable with that of traditional didactic lectures.5 In recent years computer‐based teaching has been applied to resident education in various fields including surgery and surgical subspecialties, pediatrics, and obstetrics and gynecology.612 Little is known, however, about how computer‐based educational methods affect resident knowledge and especially how these methods might affect clinical practice.

Venous thromboembolism (VTE) is a common and hazardous complication of acute inpatient hospitalization.13 Recognizing that errors in proper prescribing and monitoring of anticoagulants are a major cause of acute inpatient morbidity and mortality,14 we began an initiative to educate our residents and improve their patient care practices regarding the proper use of anticoagulants. To accomplish this, we developed a CD‐ROM‐based learning module with the aim of increasing resident knowledge of anticoagulation as well as compliance with national standards for VTE prevention. In this study we assessed the impact of the CD‐ROM intervention on resident knowledge and their appropriate use of VTE prophylaxis.

METHODS

The study was approved by the institutional review board. With the participation of faculty educators in the departments of medicine, surgery, and neurology, one of the authors (H.K.) coordinated the development of a CD‐ROM containing concise modules on core topics in anticoagulation (Table 1). The presenters for these topics included the director of clinical hematology, 2 cardiologists including the director of the coronary care unit, the director of the medical intensive care unit, the director of cerebrovascular diseases, and 2 vascular surgeons, one of whom serves as vice chair of surgery. These modules, each lasting about 1 hour, had audio and slide components detailing the proper indications, monitoring, and efficacy of anticoagulants in atrial fibrillation, acute ischemic stroke, acute coronary syndromes, and VTE prevention in acutely ill hospitalized patients. The guidelines presented were based on the sixth (2000) ACCP guidelines for antithrombotic therapy for the prevention and treatment of thrombosis.15 The content of the CD‐ROM was reviewed for accuracy by the authors, though none of them were speakers. We asked that before all current residents in the departments of cardiothoracic surgery, emergency medicine, otolaryngology, internal medicine, neurosurgery, dental medicine, neurology, obstetrics and gynecology, orthopedics, surgery, and urology viewed the CD‐ROM, they complete a pretest to determine their baseline knowledge of this subject. After completing the pretest, the residents were required to view the CD‐ROM and retake the same test. We then compared pre‐ and posttest scores.

To determine whether an increase in knowledge was secondary to the CD‐ROM intervention or simply a consequence of acquired clinical experience during training, we compared test scores of residents who did and did not receive the CD‐ROM intervention. In the academic year following our initial testing, we asked the incoming categorical medical PGY‐1 classes at our hospital and at a comparable local tertiary‐care hospital in our health system 2 miles away to take an anticoagulation pretest (different from the examination given for the initial testing) during their PGY‐1 orientations. The 2 institutions are comparable in many ways including in patient demographics and size and most residents come from the same medical schools, have a similar rotation structure, and use a comparable curriculum under a unified graduate medical education office. The CD‐ROMs were only given to categorical PGY‐1 residents at our institution. Both groups then retook the same test (posttest) 3 months into their clinical training, a time chosen because it is when all PGY‐1s would be expected to have gained significant clinical experience on the medical wards and or in the intensive care units. The exam questions were generated by one of the authors (B.M.) and covered all the topics in the CD‐ROM.

An Anticoagulation Steering Committee was formed to assess whether the CD‐ROM intervention affected our residents' patient care practices. None of the members of this committee were authors of this work. Members of this committee reviewed inpatient charts and documented resident compliance with VTE prevention standards during periods before and after they had viewed the CD‐ROMs. We chose this particular portion of the CD‐ROM because at both the test and control hospitals, initiatives were underway using order sets to improve anticoagulation in cardiac, neurological, and surgical patients but not in VTE prophylaxis. Charts from the same 2 nursing units on the medical service were reviewed in each period and included patients with a discharge diagnosis of congestive heart failure, any oncologic diagnosis, or sepsis. The chart review tool was developed by the anticoagulation committee and included a thrombosis risk factor assessment section as well as a list of contraindications to anticoagulation to determine if anticoagulation was appropriately implemented. Charts were reviewed for compliance with VTE prophylaxis after the CD‐ROM intervention (given in July 2004) in August 2004. To have a comparable pre‐CD‐ROM comparison, charts of patients with the diagnoses stated above were reviewed from August of the preceding year. The same month was chosen in the previous year to minimize any impact of resident experience, which would likely be a confounding factor if charts from May or June of the academic year were used as a control, for example. To determine whether an improvement in adherence to VTE prophylaxis standards was sustained, an additional chart review was carried out 7 months after the initial CD‐ROM viewing. The same group of observers, none of whom were authors, did all the chart assessments.

RESULTS

Assessment of Independent Effect of CD‐ROM Intervention

To determine what independent effect the CD‐ROM intervention might have, given that scores may improve with the acquisition of clinical experience alone, in July 2004 we tested internal medicine categorical PGY‐1s at our institution and at another tertiary‐care hospital, as described in the Methods section. The results of testing both groups are shown in Figure 1. Nineteen medical PGY‐1s at our hospital (hospital A) completed the anticoagulation pretest, and 16 completed the posttest. Twenty‐two medical PGY‐1s completed the pretest, and 17 completed the posttest at our neighboring hospital (hospital B). Although posttest scores were higher at both institutions, the increase in scores at our institution, which received the CD‐ROM intervention, was statistically significant, whereas the increase for the group not receiving the intervention was not significant. These findings suggest that the CD‐ROM intervention may have had an independent effect on resident knowledge of anticoagulation.

Figure 1

Effect of CD‐ROM Intervention on Resident Use of VTE Prophylaxis

Appropriate use of VTE prophylaxis by residents was assessed at 3 points, as detailed in the Methods section: 1 year before the CD‐ROM intervention (baseline), immediately after the CD‐ROM intervention, and 7 months after the CD‐ROM intervention. VTE prophylaxis, one element of the CD‐ROM, was chosen as a surrogate marker for the impact of the CD‐ROM initiative. A review of 40 charts of patients with the specified diagnoses (100% of the patients with the specified diagnoses, which represented about one third of admissions to the unit) before the CD‐ROM intervention revealed that 30 patients (75%) received appropriate VTE prophylaxis. A review of 38 charts after the CD‐ROM intervention showed that 36 patients (95%) received appropriate prophylaxis; similar findings were obtained 7 months after the CD‐ROM intervention (33 of 35 patients, 94%, P = .0107). These findings, which are shown in Figure 2, suggest that the CD‐ROM intervention enhanced resident compliance with VTE prophylaxis guidelines and that this effect was sustained for at least 7 months.

Figure 2

DISCUSSION

Residency training is facing challenges on several fronts. In addition to substantially changed educational requirements, strict limits on the amount of time that trainees can spend in the hospital have resulted from ACGME requirements and several state laws. Residents who are on night rotations or were on call the night before often miss educational conferences or must choose between attending patient carerelated activities and educational sessions. Time constraints on faculty have compounded this problem, and for residents to effectively learn, the focus of graduate medical education may need to shift somewhat from teaching medical information toward teaching the practice of self‐directed learning, with CD‐ROMs one such mode by which this can take place. Accomplishing this will require novel teaching approaches, and residency programs will need to document their effectiveness.

In this study we demonstrated that our residents increased their knowledge and improved their patient care practices using a CD‐ROM‐based educational tool. Residents frequently make use of computer‐based educational resources in the form of journals, textbooks, informational databases such as comprehensive drug listings, and personal digital assistantbased tools. Advantages of the computer‐based learning format include increased accessibility and flexibility in viewing the material. Residents have the option of repeated screening as desired and of viewing the CD‐ROM in segments if necessary. Although residents often must choose to attend a scheduled traditional lecture or engage in a patient carerelated activity, the CD‐ROM format allows the resident to choose the ideal time and setting to engage in structured educational activities. Other advantages of the CD‐ROM format would be ease of monitoring for accuracy, applicability, and comprehensiveness as well as more flexibility in faculty time commitments. It should be noted that we have no information about how much time residents devoted to the CD‐ROM program and how often they may have returned to the module for review. It should also be noted that although there have been some reports suggesting that CD‐ROM‐based education may play a useful role in student and perhaps resident education,1618 there is no evidence to date demonstrating that widespread use of CD‐ROMs in residency training can differentially affect resident behavior compared with the use of traditional methods.

A number of variables could have affected our results. For overall test scores, the response rate was less than 50%, with variability between departments suggesting that perhaps it was more motivated residents who participated and were therefore more likely to demonstrate improvement. Although our data comparing institutions with and without the CD‐ROM intervention suggested that the CD‐ROM intervention had a discernable effect on resident knowledge, we must also consider the possibility that the 2 groups might not have been comparable, as attitudes, expectations, and other variables might have differed. All the residents were categorical trainees, and given the similarities in many aspects of the training programs in these 2 tertiary‐care hospitals, as described in the Methods section, it is hoped that any such differences were minor. Nevertheless, this must be considered a limitation of our study. Also of note, the number of trainees was small, as was the patient population studied with VTE prophylaxis; hence, we recognize that our work can best be regarded as a pilot study using an alternative learning method. We also realize that giving a group of residents a test followed by distribution of a CD‐ROM might have suggested that we were directing them toward a goal, and this may have affected the results. Heightened awareness of the importance of anticoagulation from the introduction of new guidelines and other variables also could have affected our findings. The taking of an examination itself might also have had an impact on knowledge that could affect subsequent test scores. An additional point to consider is that if knowledge and patient care did improve, we do not know whether this affects residents acquiring other knowledge or whether this will translate into improved patient care in other areas.

Although CD‐ROM‐based learning could serve a useful function in the increasingly complex environment of residency training, this learning method also has disadvantages, including not providing personal contact or having the capability of question‐and‐answer sessions between teacher and resident. This could be overcome by providing time for faculty‐precepted question‐and‐answer sessions or perhaps creating a Web‐based venue for questions to be submitted and answered. In addition, the CD‐ROMs themselves can be designed in an interactive format in which residents can provide answers to clinical questions with feedback based on their selections provided as part of the CD‐ROM program.

In summary, the CD‐ROM‐based program in this study appears to have had an effect on not only knowledge but also patient care practice and suggests that this type of format could serve a useful role in residency training. Studies of additional interventions such as this one might allow for more extensive evaluation of the utility of CD‐ROM‐based learning as a residency training tool.

Given recent changes in the goals and objectives of residency training as well as changes in the functioning of teaching hospitals, traditional educational formats may need to be supplemented or replaced.1 The Accreditation Council for Graduate Medical Education (ACGME) is promoting changes in resident education with the goal of not only enhancing trainee competency using innovative methods but also of demonstrating that these educational innovations result in enhanced quality of patient care and improved patient safety.1 A challenging aspect of these initiatives is that programs are working to implement them at a time when there are greater nonteaching demands on faculty time, mandated resident work‐hour limitations have been instituted, in some states by law, and resident patient care and educational activities are prone to disruptions inherent in caring for patients in a complex health system. Various solutions have been proposed including increased incorporation of self‐directed learning as a means of meeting modern resident educational challenges, yet the ideal tools with which to accomplish this are unknown.

Computer‐based instruction in medicine has been available since the 1960s, and although its use had initially been more widespread in medical student, nursing, allied health professional, and patient education,2, 3 it is being increasingly incorporated into resident education as well. Some studies have shown that for medical students, computer‐based teaching is at least as effective in improving knowledge as conventional lectures4 and that learners' satisfaction with computer‐based formats appears comparable with that of traditional didactic lectures.5 In recent years computer‐based teaching has been applied to resident education in various fields including surgery and surgical subspecialties, pediatrics, and obstetrics and gynecology.612 Little is known, however, about how computer‐based educational methods affect resident knowledge and especially how these methods might affect clinical practice.

Venous thromboembolism (VTE) is a common and hazardous complication of acute inpatient hospitalization.13 Recognizing that errors in proper prescribing and monitoring of anticoagulants are a major cause of acute inpatient morbidity and mortality,14 we began an initiative to educate our residents and improve their patient care practices regarding the proper use of anticoagulants. To accomplish this, we developed a CD‐ROM‐based learning module with the aim of increasing resident knowledge of anticoagulation as well as compliance with national standards for VTE prevention. In this study we assessed the impact of the CD‐ROM intervention on resident knowledge and their appropriate use of VTE prophylaxis.

METHODS

The study was approved by the institutional review board. With the participation of faculty educators in the departments of medicine, surgery, and neurology, one of the authors (H.K.) coordinated the development of a CD‐ROM containing concise modules on core topics in anticoagulation (Table 1). The presenters for these topics included the director of clinical hematology, 2 cardiologists including the director of the coronary care unit, the director of the medical intensive care unit, the director of cerebrovascular diseases, and 2 vascular surgeons, one of whom serves as vice chair of surgery. These modules, each lasting about 1 hour, had audio and slide components detailing the proper indications, monitoring, and efficacy of anticoagulants in atrial fibrillation, acute ischemic stroke, acute coronary syndromes, and VTE prevention in acutely ill hospitalized patients. The guidelines presented were based on the sixth (2000) ACCP guidelines for antithrombotic therapy for the prevention and treatment of thrombosis.15 The content of the CD‐ROM was reviewed for accuracy by the authors, though none of them were speakers. We asked that before all current residents in the departments of cardiothoracic surgery, emergency medicine, otolaryngology, internal medicine, neurosurgery, dental medicine, neurology, obstetrics and gynecology, orthopedics, surgery, and urology viewed the CD‐ROM, they complete a pretest to determine their baseline knowledge of this subject. After completing the pretest, the residents were required to view the CD‐ROM and retake the same test. We then compared pre‐ and posttest scores.

To determine whether an increase in knowledge was secondary to the CD‐ROM intervention or simply a consequence of acquired clinical experience during training, we compared test scores of residents who did and did not receive the CD‐ROM intervention. In the academic year following our initial testing, we asked the incoming categorical medical PGY‐1 classes at our hospital and at a comparable local tertiary‐care hospital in our health system 2 miles away to take an anticoagulation pretest (different from the examination given for the initial testing) during their PGY‐1 orientations. The 2 institutions are comparable in many ways including in patient demographics and size and most residents come from the same medical schools, have a similar rotation structure, and use a comparable curriculum under a unified graduate medical education office. The CD‐ROMs were only given to categorical PGY‐1 residents at our institution. Both groups then retook the same test (posttest) 3 months into their clinical training, a time chosen because it is when all PGY‐1s would be expected to have gained significant clinical experience on the medical wards and or in the intensive care units. The exam questions were generated by one of the authors (B.M.) and covered all the topics in the CD‐ROM.

An Anticoagulation Steering Committee was formed to assess whether the CD‐ROM intervention affected our residents' patient care practices. None of the members of this committee were authors of this work. Members of this committee reviewed inpatient charts and documented resident compliance with VTE prevention standards during periods before and after they had viewed the CD‐ROMs. We chose this particular portion of the CD‐ROM because at both the test and control hospitals, initiatives were underway using order sets to improve anticoagulation in cardiac, neurological, and surgical patients but not in VTE prophylaxis. Charts from the same 2 nursing units on the medical service were reviewed in each period and included patients with a discharge diagnosis of congestive heart failure, any oncologic diagnosis, or sepsis. The chart review tool was developed by the anticoagulation committee and included a thrombosis risk factor assessment section as well as a list of contraindications to anticoagulation to determine if anticoagulation was appropriately implemented. Charts were reviewed for compliance with VTE prophylaxis after the CD‐ROM intervention (given in July 2004) in August 2004. To have a comparable pre‐CD‐ROM comparison, charts of patients with the diagnoses stated above were reviewed from August of the preceding year. The same month was chosen in the previous year to minimize any impact of resident experience, which would likely be a confounding factor if charts from May or June of the academic year were used as a control, for example. To determine whether an improvement in adherence to VTE prophylaxis standards was sustained, an additional chart review was carried out 7 months after the initial CD‐ROM viewing. The same group of observers, none of whom were authors, did all the chart assessments.

RESULTS

Assessment of Independent Effect of CD‐ROM Intervention

To determine what independent effect the CD‐ROM intervention might have, given that scores may improve with the acquisition of clinical experience alone, in July 2004 we tested internal medicine categorical PGY‐1s at our institution and at another tertiary‐care hospital, as described in the Methods section. The results of testing both groups are shown in Figure 1. Nineteen medical PGY‐1s at our hospital (hospital A) completed the anticoagulation pretest, and 16 completed the posttest. Twenty‐two medical PGY‐1s completed the pretest, and 17 completed the posttest at our neighboring hospital (hospital B). Although posttest scores were higher at both institutions, the increase in scores at our institution, which received the CD‐ROM intervention, was statistically significant, whereas the increase for the group not receiving the intervention was not significant. These findings suggest that the CD‐ROM intervention may have had an independent effect on resident knowledge of anticoagulation.

Figure 1

Effect of CD‐ROM Intervention on Resident Use of VTE Prophylaxis

Appropriate use of VTE prophylaxis by residents was assessed at 3 points, as detailed in the Methods section: 1 year before the CD‐ROM intervention (baseline), immediately after the CD‐ROM intervention, and 7 months after the CD‐ROM intervention. VTE prophylaxis, one element of the CD‐ROM, was chosen as a surrogate marker for the impact of the CD‐ROM initiative. A review of 40 charts of patients with the specified diagnoses (100% of the patients with the specified diagnoses, which represented about one third of admissions to the unit) before the CD‐ROM intervention revealed that 30 patients (75%) received appropriate VTE prophylaxis. A review of 38 charts after the CD‐ROM intervention showed that 36 patients (95%) received appropriate prophylaxis; similar findings were obtained 7 months after the CD‐ROM intervention (33 of 35 patients, 94%, P = .0107). These findings, which are shown in Figure 2, suggest that the CD‐ROM intervention enhanced resident compliance with VTE prophylaxis guidelines and that this effect was sustained for at least 7 months.

Figure 2

DISCUSSION

Residency training is facing challenges on several fronts. In addition to substantially changed educational requirements, strict limits on the amount of time that trainees can spend in the hospital have resulted from ACGME requirements and several state laws. Residents who are on night rotations or were on call the night before often miss educational conferences or must choose between attending patient carerelated activities and educational sessions. Time constraints on faculty have compounded this problem, and for residents to effectively learn, the focus of graduate medical education may need to shift somewhat from teaching medical information toward teaching the practice of self‐directed learning, with CD‐ROMs one such mode by which this can take place. Accomplishing this will require novel teaching approaches, and residency programs will need to document their effectiveness.

In this study we demonstrated that our residents increased their knowledge and improved their patient care practices using a CD‐ROM‐based educational tool. Residents frequently make use of computer‐based educational resources in the form of journals, textbooks, informational databases such as comprehensive drug listings, and personal digital assistantbased tools. Advantages of the computer‐based learning format include increased accessibility and flexibility in viewing the material. Residents have the option of repeated screening as desired and of viewing the CD‐ROM in segments if necessary. Although residents often must choose to attend a scheduled traditional lecture or engage in a patient carerelated activity, the CD‐ROM format allows the resident to choose the ideal time and setting to engage in structured educational activities. Other advantages of the CD‐ROM format would be ease of monitoring for accuracy, applicability, and comprehensiveness as well as more flexibility in faculty time commitments. It should be noted that we have no information about how much time residents devoted to the CD‐ROM program and how often they may have returned to the module for review. It should also be noted that although there have been some reports suggesting that CD‐ROM‐based education may play a useful role in student and perhaps resident education,1618 there is no evidence to date demonstrating that widespread use of CD‐ROMs in residency training can differentially affect resident behavior compared with the use of traditional methods.

A number of variables could have affected our results. For overall test scores, the response rate was less than 50%, with variability between departments suggesting that perhaps it was more motivated residents who participated and were therefore more likely to demonstrate improvement. Although our data comparing institutions with and without the CD‐ROM intervention suggested that the CD‐ROM intervention had a discernable effect on resident knowledge, we must also consider the possibility that the 2 groups might not have been comparable, as attitudes, expectations, and other variables might have differed. All the residents were categorical trainees, and given the similarities in many aspects of the training programs in these 2 tertiary‐care hospitals, as described in the Methods section, it is hoped that any such differences were minor. Nevertheless, this must be considered a limitation of our study. Also of note, the number of trainees was small, as was the patient population studied with VTE prophylaxis; hence, we recognize that our work can best be regarded as a pilot study using an alternative learning method. We also realize that giving a group of residents a test followed by distribution of a CD‐ROM might have suggested that we were directing them toward a goal, and this may have affected the results. Heightened awareness of the importance of anticoagulation from the introduction of new guidelines and other variables also could have affected our findings. The taking of an examination itself might also have had an impact on knowledge that could affect subsequent test scores. An additional point to consider is that if knowledge and patient care did improve, we do not know whether this affects residents acquiring other knowledge or whether this will translate into improved patient care in other areas.

Although CD‐ROM‐based learning could serve a useful function in the increasingly complex environment of residency training, this learning method also has disadvantages, including not providing personal contact or having the capability of question‐and‐answer sessions between teacher and resident. This could be overcome by providing time for faculty‐precepted question‐and‐answer sessions or perhaps creating a Web‐based venue for questions to be submitted and answered. In addition, the CD‐ROMs themselves can be designed in an interactive format in which residents can provide answers to clinical questions with feedback based on their selections provided as part of the CD‐ROM program.

In summary, the CD‐ROM‐based program in this study appears to have had an effect on not only knowledge but also patient care practice and suggests that this type of format could serve a useful role in residency training. Studies of additional interventions such as this one might allow for more extensive evaluation of the utility of CD‐ROM‐based learning as a residency training tool.

Given recent changes in the goals and objectives of residency training as well as changes in the functioning of teaching hospitals, traditional educational formats may need to be supplemented or replaced.1 The Accreditation Council for Graduate Medical Education (ACGME) is promoting changes in resident education with the goal of not only enhancing trainee competency using innovative methods but also of demonstrating that these educational innovations result in enhanced quality of patient care and improved patient safety.1 A challenging aspect of these initiatives is that programs are working to implement them at a time when there are greater nonteaching demands on faculty time, mandated resident work‐hour limitations have been instituted, in some states by law, and resident patient care and educational activities are prone to disruptions inherent in caring for patients in a complex health system. Various solutions have been proposed including increased incorporation of self‐directed learning as a means of meeting modern resident educational challenges, yet the ideal tools with which to accomplish this are unknown.

Computer‐based instruction in medicine has been available since the 1960s, and although its use had initially been more widespread in medical student, nursing, allied health professional, and patient education,2, 3 it is being increasingly incorporated into resident education as well. Some studies have shown that for medical students, computer‐based teaching is at least as effective in improving knowledge as conventional lectures4 and that learners' satisfaction with computer‐based formats appears comparable with that of traditional didactic lectures.5 In recent years computer‐based teaching has been applied to resident education in various fields including surgery and surgical subspecialties, pediatrics, and obstetrics and gynecology.612 Little is known, however, about how computer‐based educational methods affect resident knowledge and especially how these methods might affect clinical practice.

Venous thromboembolism (VTE) is a common and hazardous complication of acute inpatient hospitalization.13 Recognizing that errors in proper prescribing and monitoring of anticoagulants are a major cause of acute inpatient morbidity and mortality,14 we began an initiative to educate our residents and improve their patient care practices regarding the proper use of anticoagulants. To accomplish this, we developed a CD‐ROM‐based learning module with the aim of increasing resident knowledge of anticoagulation as well as compliance with national standards for VTE prevention. In this study we assessed the impact of the CD‐ROM intervention on resident knowledge and their appropriate use of VTE prophylaxis.

METHODS

The study was approved by the institutional review board. With the participation of faculty educators in the departments of medicine, surgery, and neurology, one of the authors (H.K.) coordinated the development of a CD‐ROM containing concise modules on core topics in anticoagulation (Table 1). The presenters for these topics included the director of clinical hematology, 2 cardiologists including the director of the coronary care unit, the director of the medical intensive care unit, the director of cerebrovascular diseases, and 2 vascular surgeons, one of whom serves as vice chair of surgery. These modules, each lasting about 1 hour, had audio and slide components detailing the proper indications, monitoring, and efficacy of anticoagulants in atrial fibrillation, acute ischemic stroke, acute coronary syndromes, and VTE prevention in acutely ill hospitalized patients. The guidelines presented were based on the sixth (2000) ACCP guidelines for antithrombotic therapy for the prevention and treatment of thrombosis.15 The content of the CD‐ROM was reviewed for accuracy by the authors, though none of them were speakers. We asked that before all current residents in the departments of cardiothoracic surgery, emergency medicine, otolaryngology, internal medicine, neurosurgery, dental medicine, neurology, obstetrics and gynecology, orthopedics, surgery, and urology viewed the CD‐ROM, they complete a pretest to determine their baseline knowledge of this subject. After completing the pretest, the residents were required to view the CD‐ROM and retake the same test. We then compared pre‐ and posttest scores.

To determine whether an increase in knowledge was secondary to the CD‐ROM intervention or simply a consequence of acquired clinical experience during training, we compared test scores of residents who did and did not receive the CD‐ROM intervention. In the academic year following our initial testing, we asked the incoming categorical medical PGY‐1 classes at our hospital and at a comparable local tertiary‐care hospital in our health system 2 miles away to take an anticoagulation pretest (different from the examination given for the initial testing) during their PGY‐1 orientations. The 2 institutions are comparable in many ways including in patient demographics and size and most residents come from the same medical schools, have a similar rotation structure, and use a comparable curriculum under a unified graduate medical education office. The CD‐ROMs were only given to categorical PGY‐1 residents at our institution. Both groups then retook the same test (posttest) 3 months into their clinical training, a time chosen because it is when all PGY‐1s would be expected to have gained significant clinical experience on the medical wards and or in the intensive care units. The exam questions were generated by one of the authors (B.M.) and covered all the topics in the CD‐ROM.

An Anticoagulation Steering Committee was formed to assess whether the CD‐ROM intervention affected our residents' patient care practices. None of the members of this committee were authors of this work. Members of this committee reviewed inpatient charts and documented resident compliance with VTE prevention standards during periods before and after they had viewed the CD‐ROMs. We chose this particular portion of the CD‐ROM because at both the test and control hospitals, initiatives were underway using order sets to improve anticoagulation in cardiac, neurological, and surgical patients but not in VTE prophylaxis. Charts from the same 2 nursing units on the medical service were reviewed in each period and included patients with a discharge diagnosis of congestive heart failure, any oncologic diagnosis, or sepsis. The chart review tool was developed by the anticoagulation committee and included a thrombosis risk factor assessment section as well as a list of contraindications to anticoagulation to determine if anticoagulation was appropriately implemented. Charts were reviewed for compliance with VTE prophylaxis after the CD‐ROM intervention (given in July 2004) in August 2004. To have a comparable pre‐CD‐ROM comparison, charts of patients with the diagnoses stated above were reviewed from August of the preceding year. The same month was chosen in the previous year to minimize any impact of resident experience, which would likely be a confounding factor if charts from May or June of the academic year were used as a control, for example. To determine whether an improvement in adherence to VTE prophylaxis standards was sustained, an additional chart review was carried out 7 months after the initial CD‐ROM viewing. The same group of observers, none of whom were authors, did all the chart assessments.

RESULTS

Assessment of Independent Effect of CD‐ROM Intervention

To determine what independent effect the CD‐ROM intervention might have, given that scores may improve with the acquisition of clinical experience alone, in July 2004 we tested internal medicine categorical PGY‐1s at our institution and at another tertiary‐care hospital, as described in the Methods section. The results of testing both groups are shown in Figure 1. Nineteen medical PGY‐1s at our hospital (hospital A) completed the anticoagulation pretest, and 16 completed the posttest. Twenty‐two medical PGY‐1s completed the pretest, and 17 completed the posttest at our neighboring hospital (hospital B). Although posttest scores were higher at both institutions, the increase in scores at our institution, which received the CD‐ROM intervention, was statistically significant, whereas the increase for the group not receiving the intervention was not significant. These findings suggest that the CD‐ROM intervention may have had an independent effect on resident knowledge of anticoagulation.

Figure 1

Effect of CD‐ROM Intervention on Resident Use of VTE Prophylaxis

Appropriate use of VTE prophylaxis by residents was assessed at 3 points, as detailed in the Methods section: 1 year before the CD‐ROM intervention (baseline), immediately after the CD‐ROM intervention, and 7 months after the CD‐ROM intervention. VTE prophylaxis, one element of the CD‐ROM, was chosen as a surrogate marker for the impact of the CD‐ROM initiative. A review of 40 charts of patients with the specified diagnoses (100% of the patients with the specified diagnoses, which represented about one third of admissions to the unit) before the CD‐ROM intervention revealed that 30 patients (75%) received appropriate VTE prophylaxis. A review of 38 charts after the CD‐ROM intervention showed that 36 patients (95%) received appropriate prophylaxis; similar findings were obtained 7 months after the CD‐ROM intervention (33 of 35 patients, 94%, P = .0107). These findings, which are shown in Figure 2, suggest that the CD‐ROM intervention enhanced resident compliance with VTE prophylaxis guidelines and that this effect was sustained for at least 7 months.

Figure 2

DISCUSSION

Residency training is facing challenges on several fronts. In addition to substantially changed educational requirements, strict limits on the amount of time that trainees can spend in the hospital have resulted from ACGME requirements and several state laws. Residents who are on night rotations or were on call the night before often miss educational conferences or must choose between attending patient carerelated activities and educational sessions. Time constraints on faculty have compounded this problem, and for residents to effectively learn, the focus of graduate medical education may need to shift somewhat from teaching medical information toward teaching the practice of self‐directed learning, with CD‐ROMs one such mode by which this can take place. Accomplishing this will require novel teaching approaches, and residency programs will need to document their effectiveness.

In this study we demonstrated that our residents increased their knowledge and improved their patient care practices using a CD‐ROM‐based educational tool. Residents frequently make use of computer‐based educational resources in the form of journals, textbooks, informational databases such as comprehensive drug listings, and personal digital assistantbased tools. Advantages of the computer‐based learning format include increased accessibility and flexibility in viewing the material. Residents have the option of repeated screening as desired and of viewing the CD‐ROM in segments if necessary. Although residents often must choose to attend a scheduled traditional lecture or engage in a patient carerelated activity, the CD‐ROM format allows the resident to choose the ideal time and setting to engage in structured educational activities. Other advantages of the CD‐ROM format would be ease of monitoring for accuracy, applicability, and comprehensiveness as well as more flexibility in faculty time commitments. It should be noted that we have no information about how much time residents devoted to the CD‐ROM program and how often they may have returned to the module for review. It should also be noted that although there have been some reports suggesting that CD‐ROM‐based education may play a useful role in student and perhaps resident education,1618 there is no evidence to date demonstrating that widespread use of CD‐ROMs in residency training can differentially affect resident behavior compared with the use of traditional methods.

A number of variables could have affected our results. For overall test scores, the response rate was less than 50%, with variability between departments suggesting that perhaps it was more motivated residents who participated and were therefore more likely to demonstrate improvement. Although our data comparing institutions with and without the CD‐ROM intervention suggested that the CD‐ROM intervention had a discernable effect on resident knowledge, we must also consider the possibility that the 2 groups might not have been comparable, as attitudes, expectations, and other variables might have differed. All the residents were categorical trainees, and given the similarities in many aspects of the training programs in these 2 tertiary‐care hospitals, as described in the Methods section, it is hoped that any such differences were minor. Nevertheless, this must be considered a limitation of our study. Also of note, the number of trainees was small, as was the patient population studied with VTE prophylaxis; hence, we recognize that our work can best be regarded as a pilot study using an alternative learning method. We also realize that giving a group of residents a test followed by distribution of a CD‐ROM might have suggested that we were directing them toward a goal, and this may have affected the results. Heightened awareness of the importance of anticoagulation from the introduction of new guidelines and other variables also could have affected our findings. The taking of an examination itself might also have had an impact on knowledge that could affect subsequent test scores. An additional point to consider is that if knowledge and patient care did improve, we do not know whether this affects residents acquiring other knowledge or whether this will translate into improved patient care in other areas.

Although CD‐ROM‐based learning could serve a useful function in the increasingly complex environment of residency training, this learning method also has disadvantages, including not providing personal contact or having the capability of question‐and‐answer sessions between teacher and resident. This could be overcome by providing time for faculty‐precepted question‐and‐answer sessions or perhaps creating a Web‐based venue for questions to be submitted and answered. In addition, the CD‐ROMs themselves can be designed in an interactive format in which residents can provide answers to clinical questions with feedback based on their selections provided as part of the CD‐ROM program.

In summary, the CD‐ROM‐based program in this study appears to have had an effect on not only knowledge but also patient care practice and suggests that this type of format could serve a useful role in residency training. Studies of additional interventions such as this one might allow for more extensive evaluation of the utility of CD‐ROM‐based learning as a residency training tool.

Hyperhemolysis syndrome is a form of atypical hemolytic transfusion reaction (HTR). It is characterized by a significant drop in hemoglobin (Hb) after seemingly compatible red blood cell transfusions, suggesting destruction of both transfused and autologous red blood cells. Its pathophysiology is not well understood, and a serologic cause is often not identified.14 In contrast, delayed HTRs are typically characterized by a positive direct antiglobulin test (DAT), suggesting that the patient's red blood cells are coated by immunoglobulin G and/or complement components and by the appearance of previously undetected red blood cell alloantibody or antibodies that developed from a secondary anamnestic response; however, autologous red cells are not destroyed.

CASE

A 48‐year‐old African American woman with sickle cell disease (SCD) was readmitted for pain crisis. Her medical history included stroke, pulmonary hypertension, and congestive heart failure. She had received several transfusions and consequently had developed antibodies to seven clinically significant red blood cell antigens. A week prior to readmission, she was discharged from the hospital with an Hb of 6.9 g/dL after a sickle cell crisis precipitated by pneumonia. She was treated with hydration, pain medications, antibiotics, and a unit of cross‐match‐compatible red blood cells (RBCs) that was antigen negative for her antibodies.

On readmission, she had an Hb of 5.6 g/dL and an uncorrected reticulocyte count of 17.6%. Her reticulocyte production index, a reticulocyte count corrected for the degree of anemia and reticulocyte maturation time, was elevated at 2.6. She was transfused with 1 unit of phenotypically matched and cross‐match‐compatible RBCs. Three hours after transfusion, she developed dark‐colored urine. The transfusion reaction investigation revealed no clerical error or incompatibility, a negative DAT, and an antibody panel identical to that from pretransfusion testing. During hospitalization, the hemolytic anemia worsened (Fig. 1). On the 10th hospital day, she became severely dyspneic as her Hb reached its nadir of 3.6 g/dL despite ongoing erythropoiesis. She developed decompensated heart failure and renal insufficiency, precipitated by the acutely worsening anemia. Along with diuretic and vasodilator therapies, she was treated with methylprednisolone at 125 mg twice daily for 3 days followed by tapering doses of prednisone for 2 weeks, intravenous immunoglobulin (IVIG) at 400 mg/kg a day for 5 days, and 4 cross‐match‐compatible RBC transfusions that were antigen negative for her antibodies. The hemolysis resolved and the patient improved. Throughout hospitalization, her DAT remained negative. The Hb remained stable at 7 g/dL until she was discharged. Ten months of follow‐up showed no new red blood cell antibody in her serum or recurrence of hyperhemolysis syndrome despite receiving subsequent transfusions.

Figure 1

DISCUSSION

Hyperhemolysis syndrome has been described in patients with SCD,14, 6, 7 suggesting that an underlying hemoglobinopathy may be a risk factor; however, a patient with anemia of chronic disease was recently described in the literature to have developed hyperhemolysis syndrome.5 Possible mechanisms include innocent bystander hemolysis through complement‐mediated lysis and/or formation of red blood cell alloantibody or autoantibody;1, 2 and hyperactive macrophages of the reticuloendothelial system that recognize Hb S RBCs of patients with SCD more avidly than normal RBCs because of the exposure of aminophosphatides in the outer layer of the sickled RBC membrane.3 In effect, red blood cells may be destroyed regardless of whether they are autologous or transfused. Additionally, transfusion‐related suppression of erythropoiesis may worsen the severity of anemia.2 Recent studies of patients with SCD suggest that the presence of free plasma Hb, as a consequence of hemolysis, reduces nitric oxide bioavailability, promotes endothelial dysfunction, and contributes to the development of pulmonary hypertension and the varying presentations of vasoocclusion.6 A common observation among patients who experience hyperhemolysis syndrome is that withholding transfusion seems beneficial, probably because immunologic reactions are not exacerbated, whereas treatment with steroids1, 2, 4 and/or IVIG3, 7 resolves hemolysis because of their immunomodulatory effects.

CONCLUSIONS

Hyperhemolysis syndrome is a potentially life‐threatening complication of RBC transfusion. It is important to recognize this syndrome when managing patients with SCD who present with worsening anemia after RBC transfusions. Although further transfusions can exacerbate hemolysis4, 7 and may be relatively contraindicated, in severe and desperate situations, simultaneous treatment with steroids and IVIG, together with RBC transfusions, may be lifesaving.

Hyperhemolysis syndrome is a form of atypical hemolytic transfusion reaction (HTR). It is characterized by a significant drop in hemoglobin (Hb) after seemingly compatible red blood cell transfusions, suggesting destruction of both transfused and autologous red blood cells. Its pathophysiology is not well understood, and a serologic cause is often not identified.14 In contrast, delayed HTRs are typically characterized by a positive direct antiglobulin test (DAT), suggesting that the patient's red blood cells are coated by immunoglobulin G and/or complement components and by the appearance of previously undetected red blood cell alloantibody or antibodies that developed from a secondary anamnestic response; however, autologous red cells are not destroyed.

CASE

A 48‐year‐old African American woman with sickle cell disease (SCD) was readmitted for pain crisis. Her medical history included stroke, pulmonary hypertension, and congestive heart failure. She had received several transfusions and consequently had developed antibodies to seven clinically significant red blood cell antigens. A week prior to readmission, she was discharged from the hospital with an Hb of 6.9 g/dL after a sickle cell crisis precipitated by pneumonia. She was treated with hydration, pain medications, antibiotics, and a unit of cross‐match‐compatible red blood cells (RBCs) that was antigen negative for her antibodies.

On readmission, she had an Hb of 5.6 g/dL and an uncorrected reticulocyte count of 17.6%. Her reticulocyte production index, a reticulocyte count corrected for the degree of anemia and reticulocyte maturation time, was elevated at 2.6. She was transfused with 1 unit of phenotypically matched and cross‐match‐compatible RBCs. Three hours after transfusion, she developed dark‐colored urine. The transfusion reaction investigation revealed no clerical error or incompatibility, a negative DAT, and an antibody panel identical to that from pretransfusion testing. During hospitalization, the hemolytic anemia worsened (Fig. 1). On the 10th hospital day, she became severely dyspneic as her Hb reached its nadir of 3.6 g/dL despite ongoing erythropoiesis. She developed decompensated heart failure and renal insufficiency, precipitated by the acutely worsening anemia. Along with diuretic and vasodilator therapies, she was treated with methylprednisolone at 125 mg twice daily for 3 days followed by tapering doses of prednisone for 2 weeks, intravenous immunoglobulin (IVIG) at 400 mg/kg a day for 5 days, and 4 cross‐match‐compatible RBC transfusions that were antigen negative for her antibodies. The hemolysis resolved and the patient improved. Throughout hospitalization, her DAT remained negative. The Hb remained stable at 7 g/dL until she was discharged. Ten months of follow‐up showed no new red blood cell antibody in her serum or recurrence of hyperhemolysis syndrome despite receiving subsequent transfusions.

Figure 1

DISCUSSION

Hyperhemolysis syndrome has been described in patients with SCD,14, 6, 7 suggesting that an underlying hemoglobinopathy may be a risk factor; however, a patient with anemia of chronic disease was recently described in the literature to have developed hyperhemolysis syndrome.5 Possible mechanisms include innocent bystander hemolysis through complement‐mediated lysis and/or formation of red blood cell alloantibody or autoantibody;1, 2 and hyperactive macrophages of the reticuloendothelial system that recognize Hb S RBCs of patients with SCD more avidly than normal RBCs because of the exposure of aminophosphatides in the outer layer of the sickled RBC membrane.3 In effect, red blood cells may be destroyed regardless of whether they are autologous or transfused. Additionally, transfusion‐related suppression of erythropoiesis may worsen the severity of anemia.2 Recent studies of patients with SCD suggest that the presence of free plasma Hb, as a consequence of hemolysis, reduces nitric oxide bioavailability, promotes endothelial dysfunction, and contributes to the development of pulmonary hypertension and the varying presentations of vasoocclusion.6 A common observation among patients who experience hyperhemolysis syndrome is that withholding transfusion seems beneficial, probably because immunologic reactions are not exacerbated, whereas treatment with steroids1, 2, 4 and/or IVIG3, 7 resolves hemolysis because of their immunomodulatory effects.

CONCLUSIONS

Hyperhemolysis syndrome is a potentially life‐threatening complication of RBC transfusion. It is important to recognize this syndrome when managing patients with SCD who present with worsening anemia after RBC transfusions. Although further transfusions can exacerbate hemolysis4, 7 and may be relatively contraindicated, in severe and desperate situations, simultaneous treatment with steroids and IVIG, together with RBC transfusions, may be lifesaving.

Hyperhemolysis syndrome is a form of atypical hemolytic transfusion reaction (HTR). It is characterized by a significant drop in hemoglobin (Hb) after seemingly compatible red blood cell transfusions, suggesting destruction of both transfused and autologous red blood cells. Its pathophysiology is not well understood, and a serologic cause is often not identified.14 In contrast, delayed HTRs are typically characterized by a positive direct antiglobulin test (DAT), suggesting that the patient's red blood cells are coated by immunoglobulin G and/or complement components and by the appearance of previously undetected red blood cell alloantibody or antibodies that developed from a secondary anamnestic response; however, autologous red cells are not destroyed.

CASE

A 48‐year‐old African American woman with sickle cell disease (SCD) was readmitted for pain crisis. Her medical history included stroke, pulmonary hypertension, and congestive heart failure. She had received several transfusions and consequently had developed antibodies to seven clinically significant red blood cell antigens. A week prior to readmission, she was discharged from the hospital with an Hb of 6.9 g/dL after a sickle cell crisis precipitated by pneumonia. She was treated with hydration, pain medications, antibiotics, and a unit of cross‐match‐compatible red blood cells (RBCs) that was antigen negative for her antibodies.

On readmission, she had an Hb of 5.6 g/dL and an uncorrected reticulocyte count of 17.6%. Her reticulocyte production index, a reticulocyte count corrected for the degree of anemia and reticulocyte maturation time, was elevated at 2.6. She was transfused with 1 unit of phenotypically matched and cross‐match‐compatible RBCs. Three hours after transfusion, she developed dark‐colored urine. The transfusion reaction investigation revealed no clerical error or incompatibility, a negative DAT, and an antibody panel identical to that from pretransfusion testing. During hospitalization, the hemolytic anemia worsened (Fig. 1). On the 10th hospital day, she became severely dyspneic as her Hb reached its nadir of 3.6 g/dL despite ongoing erythropoiesis. She developed decompensated heart failure and renal insufficiency, precipitated by the acutely worsening anemia. Along with diuretic and vasodilator therapies, she was treated with methylprednisolone at 125 mg twice daily for 3 days followed by tapering doses of prednisone for 2 weeks, intravenous immunoglobulin (IVIG) at 400 mg/kg a day for 5 days, and 4 cross‐match‐compatible RBC transfusions that were antigen negative for her antibodies. The hemolysis resolved and the patient improved. Throughout hospitalization, her DAT remained negative. The Hb remained stable at 7 g/dL until she was discharged. Ten months of follow‐up showed no new red blood cell antibody in her serum or recurrence of hyperhemolysis syndrome despite receiving subsequent transfusions.

Figure 1

DISCUSSION

Hyperhemolysis syndrome has been described in patients with SCD,14, 6, 7 suggesting that an underlying hemoglobinopathy may be a risk factor; however, a patient with anemia of chronic disease was recently described in the literature to have developed hyperhemolysis syndrome.5 Possible mechanisms include innocent bystander hemolysis through complement‐mediated lysis and/or formation of red blood cell alloantibody or autoantibody;1, 2 and hyperactive macrophages of the reticuloendothelial system that recognize Hb S RBCs of patients with SCD more avidly than normal RBCs because of the exposure of aminophosphatides in the outer layer of the sickled RBC membrane.3 In effect, red blood cells may be destroyed regardless of whether they are autologous or transfused. Additionally, transfusion‐related suppression of erythropoiesis may worsen the severity of anemia.2 Recent studies of patients with SCD suggest that the presence of free plasma Hb, as a consequence of hemolysis, reduces nitric oxide bioavailability, promotes endothelial dysfunction, and contributes to the development of pulmonary hypertension and the varying presentations of vasoocclusion.6 A common observation among patients who experience hyperhemolysis syndrome is that withholding transfusion seems beneficial, probably because immunologic reactions are not exacerbated, whereas treatment with steroids1, 2, 4 and/or IVIG3, 7 resolves hemolysis because of their immunomodulatory effects.

CONCLUSIONS

Hyperhemolysis syndrome is a potentially life‐threatening complication of RBC transfusion. It is important to recognize this syndrome when managing patients with SCD who present with worsening anemia after RBC transfusions. Although further transfusions can exacerbate hemolysis4, 7 and may be relatively contraindicated, in severe and desperate situations, simultaneous treatment with steroids and IVIG, together with RBC transfusions, may be lifesaving.

The use of hospitalists, physicians who specialize in inpatient care, has seen a rapid expansion over the last decade.1 Several studies have shown that with hospitalists there is a shorter length of stay (LOS) and decreased utilization of resources and that hospitalists play a positive role in medical education.24 However, only a few studies have examined the specific strategies employed by hospitalists to achieve improved efficiency and outcomes.

Congestive heart failure (CHF) is the most common diagnosis of hospitalized patients older than age 65, with more Medicare spending devoted to patients with CHF than to any other diagnosis‐related group (DRG).5, 6 Over the last 2 decades hospital discharges for congestive heart failure increased by 165%.7 In addition, the rate of hospital readmission of patients with CHF remains high: 2%, 20%, and 50% within 2 days, 1 month, and 6 months, respectively.8

Several previous studies have shown that patients cared for by hospitalists had improved clinical outcomes. Meltzer et al. found that 30‐day mortality of hospitalists' patients was lower than that of non‐hospitalists' patients, 4.2% versus 6.0%, respectively, in the second year of implementation of a hospitalist program.3 A study by Huddleston et al. showed a reduction of 11.8% in the rate of complications experienced by postsurgical orthopedic patients with the involvement of hospitalists in their care in conjunction with the surgeons.4

Many previous studies have pointed to improvements in economic outcomes such as LOS and costs for patients followed by hospitalists. Kulaga et al. showed that patients cared for by hospitalists had reductions of approximately 20% in LOS and 18% in total costs per case compared with those cared for by community‐based physicians.2 Meltzer et al. found a decrease in the average adjusted LOS of 0.49 days in the second year of implementation of a hospitalist program.3 Rifkin et al. found that patients with pneumonia cared for by hospitalists had a mean adjusted LOS of 5.6 days versus 6.5 days for those cared for by non‐hospitalists.9

Few previous studies have looked at specific practice patterns of hospitalists that result in improved efficiency and better outcomes. Rifkin et al., who found that patients with pneumonia cared for by hospitalists had a shorter LOS, suggested this finding was a result of the earlier recognition by hospitalists that patients were stable and more rapid conversion to oral antibiotics.9 Likewise, Stein et al. found that community‐acquired pneumonia patients treated by hospitalists had a shorter LOS than those treated by non‐hospitalists. However, they were unable to assess the differences in patient management that led to this result because of the design of the study.10

Lindenauer et al. compared quality‐of‐care indicators and resource utilization for patients with congestive heart failure treated by hospitalists and non‐hospitalist general internists. They found that patients under the care of hospitalists had a shorter LOS than those cared for by general internists but that the overall costs of care were similar between the groups.11 They compared the quality indicators developed by the Joint Commission on Accreditation of Healthcare Organizations in the Core Measures Initiative, but did not focus on patterns of practices of hospitalists and nonhospitalists. Moreover, they did not look at full‐time hospitalists but focused on physicians who spent at least 25% of their practice caring for inpatients.

We sought to identify distinct, quantifiable practices of full‐time hospitalists in the management of their patients with CHF. We hypothesized that hospitalists would adhere more closely to the current congestive heart failure guidelines and would utilize available resources more judiciously, leading to improved clinical and economic outcomes. To identify these practices, we compared utilization of well‐established therapeutic and diagnostic modalities such as use of ACE‐I, ARB, and beta‐blockers; ordering of chest x‐rays; measurement of brain natriuretic peptide (BNP); and use of medical subspecialty consultants. We also compared standard clinical and economic outcomes such as in‐hospital mortality, readmission rate, LOS, and costs per case between hospitalists and community‐based physicians.

METHODS

RESULTS