Modern‐day continuity of patient care in teaching hospitals, once remarkably high because of a cadre of sleep‐deprived residents, is now peppered with breaks, each accompanied by the transfer of patient care responsibility from one resident to another; a process often referred to as a handoff. Such transitions have long been a part of medical practice but have recently received increased attention because of restrictions in the duty hours of house staff. In July 2003 the Accreditation Council for Graduate Medical Education (ACGME) mandated reduced duty hours for all trainees in hopes of improving resident education and well‐being and patient safety.1 In fact, some studies have shown improved resident well‐being2 and fewer medical errors with reductions in duty hours,3, 4 but the growing consensus about the negative consequences of resident fatigue on patient safety has been accompanied by parallel concerns about the potential for information loss with each break in the continuity of care.5, 6

Although the tradeoff of increased discontinuity of care for fewer hours worked is sometimes characterized as an unintended consequence of duty hour regulations, it is in fact predictable and essential. As individuals work fewer hours, discontinuity must necessarily increase (assuming 24‐hour coverage).7 The extent to which this occurs may vary, but the link is consistent. At the University of California, San Francisco (UCSF), for example, we found that compliance with new duty hour requirements for internal medicine resulted in an average of 15 handoffs per patient during a 5‐day hospitalization. Each individual intern was involved in more than 300 handoffs in an average month‐long rotation, an increase of 40% since system changes were introduced to decrease duty hours. We found similar increases at Brigham and Women's Hospital (BWH) and the University of Chicago. Because U.S. teaching hospitals care for more than 6 million patients each year,8 the impact of these handoffs on the quality and efficiency of care is tremendous.

Discontinuity of care is currently managed by sign‐out, or the transfer of patient information from one physician to another. Recognizing the importance of information transfer at these vulnerable transition times for patients, the Joint Commission on Accreditation of Hospital Organizations (JCAHO) issued the 2006 National Patient Safety Goal 2E: Implement a standardized approach to hand off communications, including an opportunity to ask and respond to questions.9 Hospitals have little data to draw on to determine how to comply with this mandate and even less data to guide them in how to achieve its intended goals of improving communication and thus patient safety.

In an effort to better understand sign‐outs and ways to improve this process for house staff on in‐patient services, we reviewed data from the fields of aviation, communications, systems engineering, and human factors research, and we also searched the medical literature using key words pass‐off, handoff, sign‐out, duty hours, work hours, and discontinuity of care and MeSH headings Continuity of Patient Care Internship and Residency/*organization & administration, Personnel Staffing and Scheduling/*organization & administration, and Quality of Health Care. We also searched the websites of the Agency of Healthcare Quality and Research and the National Patient Safety Foundation. On the basis of these reviews, our experiences as hospitalist medical educators organizing resident sign‐out efforts at the University of California, San Francisco, the University of Chicago, and Brigham and Women's Hospital, and our efforts leading national training sessions on sign‐outs at the Society of General Internal Medicine (2004 and 2005), the Society of Hospital Medicine (2004), and the Association of Program Directors in Internal Medicine (2005, 2006), we propose a set of best practices regarding the content and process of sign‐out in an effort to improve communication between residents caring for hospitalized patients, assist programs in building safe and effective sign‐out systems, and improve the quality of patient care.

Effects of Discontinuity on Patient Safety

Research on the effects of discontinuity of care, although limited, suggests it has a negative impact on patient safety. In a study that investigated the institution of code 405 (the regulation that reduced duty hours in New York State), researchers found that the presumed increase in discontinuity with decreased duty hours resulted in delayed test ordering and an increased number of hospital complications.10 Another study found that the number of potentially preventable adverse events doubled when patients were under the care of a physician from a nonprimary team (eg, the cross‐covering intern).11 Studies have also linked resident discontinuity with longer length of stay, increased laboratory testing, and increased medication errors.12, 13

Managing Discontinuity: Sign‐Out as the Means of Information Transfer

In theory, more effective sign‐out systems should mitigate the potential for patient harm, but there is little in the literature describing current effective sign‐out practices or the best ways to design and implement such systems in the health care field. Examining information transfer mechanisms used in fields outside health care can assist in developing these systems.

The Current Practice of Sign‐Out

In examining sign‐outs at our 3 institutions, we found them to be unstructured and unstandardized. From discussion with faculty participating in national workshops on sign‐out, we found that most sign‐outs are conducted by interns, usually with little or no formal training. Templates, checklists, or other methods to standardize the content of the information transferred were rarely used.

We also noted that the vehicle for written sign‐out is highly variable. At UCSF, different residency training programs used a variety of modalities for written sign‐outs, including index cards, Excel spreadsheets, Word documents, and loose sheets of paper. Recently, the UCSF Department of Medicine designed a simple database (on Filemaker Pro) that allows members of the house staff to update their sign‐out information, share it with other house staff and nurses, and access it at locations throughout the hospital (Fig. 1). Although this database is not yet linked to the hospital information system (planned for 2006), anecdotally resident satisfaction with sign‐out has vastly improved since its implementation. The cost of design and implementation was approximately $10,000. At the University of Chicago, interns used Microsoft Word to create sign‐out sheets containing patient summaries to transfer information. However, during structured interviews, 95% of the interns reported that these sheets were frequently lost or misplaced.7 Although medicine residents at BWH use a computerized system to produce sign‐out sheets, this system did not guarantee complete and structured information. For example, a survey at BWH found that 56% of cross‐covering residents said that when paged about a patient overnight, the relevant information needed to care for that patient was present less than half the time; and 27% of residents reported being paged more than 3 times in the previous 2 weeks about a test result or consultant recommendation that they did not know was pending.36

Figure 1

The process of sign‐out also varied across disciplines and institutions. From our experiences at our sites and at the sites of faculty nationally, we found limited standardization about whether sign‐out was verbal, the data transmitted, and the setting in which it was transmitted. In fact, at UCSF most residents signed out verbally on the fly, wherever and whenever they could find the cross‐coverage intern. At BWH, only 37% of residents said that sign‐out occurred in a quiet place most of the time, and only 52% signed out on every patient both orally and in writing.36 At the University of Chicago, the sign‐out process was characterized by outright failures in communication because of omission of needed information (ie, medications, active or anticipated medical problems, etc.) or by failure‐prone communication (ie, lack of face‐to‐face communication, illegible writing). These failures often led to uncertainty in making patient care decisions, potentially resulting in inefficient or suboptimal care.35

Strategies for Safe and Effective Sign‐Out

Given the current landscape of variability in sign‐outs, the recognition that information lost during sign‐out may result in harm to patients, and evidence of improvements in information transfer in areas outside health care, we aimed to develop mechanisms to improve the sign‐out process for residents working in a hospital setting. These strategies are based on our review of the existing literature supplemented by our experiences at our 3 institutions.

Content of Sign‐Out

The elements of content necessary for safe and effective sign‐out can be divided into 5 broad categories (Table 1), contained in the mnemonic ANTICipate: Administrative information, New clinical information, specific Tasks to be performed, assessment of severity of Illness, and Contingency plans or anticipated problems (Table 1, Fig. 2).

Table 1.Checklist for Elements of a Safe and Effective Written Sign‐outANTICipate

✓ Administrative data
□ Patient name, age, sex
□ Medical record number
□ Room number
□ Admission date
□ Primary inpatient medical team, primary care physician
□ Family contact information
✓ New information (clinical update)
□ Chief complaint, brief HPI, and diagnosis (or differential diagnosis)
□ Updated list of medications with doses, updated allergies
□ Updated, brief assessment by system/problem, with dates
□ Current baseline status (eg, mental status, cardiopulmonary, vital signs, especially if abnormal but stable)
□ Recent procedures and significant events
✓ Tasks (what needs to be done)
□ Specific, using if‐then statements
□ Prepare cross‐coverage (eg, patient consent for blood transfusion)
□ Alert to incoming information (eg, study results, consultant recommendations), and what action, if any, needs to be taken during the cross‐coverage
✓ Illness
□ Is the patient sick?
✓ Contingency planning/Code status
□ What may go wrong and what to do about it
□ What has or has not worked before (eg, responds to 40 mg IV furosemide)
□ Difficult family or psychosocial situations
□ Code status, especially recent changes or family discussions

Figure 2

Several general points about this list should be noted. First, the sign‐out content is not meant to replace the chart. The information included reflects the goal of a sign‐out, namely, to provide enough information to allow for a safe transition in patient care. Information we believe is not essential to the sign‐out includes: a complete history and physical exam from the day of admission, a list of tasks already completed, and data necessary only to complete a discharge summary.

Sign‐out must be also be a closed loopthe process of signing in is as important as the process of signing out. This usually entails members of the primary team obtaining information from the cross‐covering physician when they resume care of the patient. The information conveyed in this case is different and includes details on events during cross‐coverage such as: 1) time called to assess patient; 2) reason for call; 3) a brief assessment of the patient, including vital signs; 4) actions taken, for example, medications given and tests ordered; and 5) rationale for those actions. Some of this information may also be included in the chart as an event note (see Fig. 3).

Figure 3

CONCLUSIONS

Sign‐outs are a part of the current landscape of academic medical centers as well as hospitals at large. Interns, residents, and consulting fellows, not to mention nurses, physical therapists, and nutritionists, transfer patient care information at each transition point. There are few resources that can assist these caregivers in identifying and implementing the most effective ways to transfer patient care information. Hospitals and other care facilities are now mandated to develop standards and systems to improve sign‐out. On the basis of the limited literature to date and our own experiences, we have proposed standards and best practices to assist hospitals, training programs, and institutional leaders in designing safe and usable sign‐out systems. Effective implementation of the standards must include appropriate allocation of resources, individualization to meet specific needs of each program or institution, intensive training, and ongoing evaluation. Future research should focus on developing valid surrogate measures of continuity of care, conducting rigorous trials to determine the elements of sign‐out that lead to the best patient outcomes, and studying the most effective ways of implementing these improvements. By improving the content and process of sign‐out, we can meet the challenges of the new health care landscape while putting patient safety at the forefront.

Modern‐day continuity of patient care in teaching hospitals, once remarkably high because of a cadre of sleep‐deprived residents, is now peppered with breaks, each accompanied by the transfer of patient care responsibility from one resident to another; a process often referred to as a handoff. Such transitions have long been a part of medical practice but have recently received increased attention because of restrictions in the duty hours of house staff. In July 2003 the Accreditation Council for Graduate Medical Education (ACGME) mandated reduced duty hours for all trainees in hopes of improving resident education and well‐being and patient safety.1 In fact, some studies have shown improved resident well‐being2 and fewer medical errors with reductions in duty hours,3, 4 but the growing consensus about the negative consequences of resident fatigue on patient safety has been accompanied by parallel concerns about the potential for information loss with each break in the continuity of care.5, 6

Although the tradeoff of increased discontinuity of care for fewer hours worked is sometimes characterized as an unintended consequence of duty hour regulations, it is in fact predictable and essential. As individuals work fewer hours, discontinuity must necessarily increase (assuming 24‐hour coverage).7 The extent to which this occurs may vary, but the link is consistent. At the University of California, San Francisco (UCSF), for example, we found that compliance with new duty hour requirements for internal medicine resulted in an average of 15 handoffs per patient during a 5‐day hospitalization. Each individual intern was involved in more than 300 handoffs in an average month‐long rotation, an increase of 40% since system changes were introduced to decrease duty hours. We found similar increases at Brigham and Women's Hospital (BWH) and the University of Chicago. Because U.S. teaching hospitals care for more than 6 million patients each year,8 the impact of these handoffs on the quality and efficiency of care is tremendous.

Discontinuity of care is currently managed by sign‐out, or the transfer of patient information from one physician to another. Recognizing the importance of information transfer at these vulnerable transition times for patients, the Joint Commission on Accreditation of Hospital Organizations (JCAHO) issued the 2006 National Patient Safety Goal 2E: Implement a standardized approach to hand off communications, including an opportunity to ask and respond to questions.9 Hospitals have little data to draw on to determine how to comply with this mandate and even less data to guide them in how to achieve its intended goals of improving communication and thus patient safety.

In an effort to better understand sign‐outs and ways to improve this process for house staff on in‐patient services, we reviewed data from the fields of aviation, communications, systems engineering, and human factors research, and we also searched the medical literature using key words pass‐off, handoff, sign‐out, duty hours, work hours, and discontinuity of care and MeSH headings Continuity of Patient Care Internship and Residency/*organization & administration, Personnel Staffing and Scheduling/*organization & administration, and Quality of Health Care. We also searched the websites of the Agency of Healthcare Quality and Research and the National Patient Safety Foundation. On the basis of these reviews, our experiences as hospitalist medical educators organizing resident sign‐out efforts at the University of California, San Francisco, the University of Chicago, and Brigham and Women's Hospital, and our efforts leading national training sessions on sign‐outs at the Society of General Internal Medicine (2004 and 2005), the Society of Hospital Medicine (2004), and the Association of Program Directors in Internal Medicine (2005, 2006), we propose a set of best practices regarding the content and process of sign‐out in an effort to improve communication between residents caring for hospitalized patients, assist programs in building safe and effective sign‐out systems, and improve the quality of patient care.

Effects of Discontinuity on Patient Safety

Research on the effects of discontinuity of care, although limited, suggests it has a negative impact on patient safety. In a study that investigated the institution of code 405 (the regulation that reduced duty hours in New York State), researchers found that the presumed increase in discontinuity with decreased duty hours resulted in delayed test ordering and an increased number of hospital complications.10 Another study found that the number of potentially preventable adverse events doubled when patients were under the care of a physician from a nonprimary team (eg, the cross‐covering intern).11 Studies have also linked resident discontinuity with longer length of stay, increased laboratory testing, and increased medication errors.12, 13

Managing Discontinuity: Sign‐Out as the Means of Information Transfer

In theory, more effective sign‐out systems should mitigate the potential for patient harm, but there is little in the literature describing current effective sign‐out practices or the best ways to design and implement such systems in the health care field. Examining information transfer mechanisms used in fields outside health care can assist in developing these systems.

The Current Practice of Sign‐Out

In examining sign‐outs at our 3 institutions, we found them to be unstructured and unstandardized. From discussion with faculty participating in national workshops on sign‐out, we found that most sign‐outs are conducted by interns, usually with little or no formal training. Templates, checklists, or other methods to standardize the content of the information transferred were rarely used.

We also noted that the vehicle for written sign‐out is highly variable. At UCSF, different residency training programs used a variety of modalities for written sign‐outs, including index cards, Excel spreadsheets, Word documents, and loose sheets of paper. Recently, the UCSF Department of Medicine designed a simple database (on Filemaker Pro) that allows members of the house staff to update their sign‐out information, share it with other house staff and nurses, and access it at locations throughout the hospital (Fig. 1). Although this database is not yet linked to the hospital information system (planned for 2006), anecdotally resident satisfaction with sign‐out has vastly improved since its implementation. The cost of design and implementation was approximately $10,000. At the University of Chicago, interns used Microsoft Word to create sign‐out sheets containing patient summaries to transfer information. However, during structured interviews, 95% of the interns reported that these sheets were frequently lost or misplaced.7 Although medicine residents at BWH use a computerized system to produce sign‐out sheets, this system did not guarantee complete and structured information. For example, a survey at BWH found that 56% of cross‐covering residents said that when paged about a patient overnight, the relevant information needed to care for that patient was present less than half the time; and 27% of residents reported being paged more than 3 times in the previous 2 weeks about a test result or consultant recommendation that they did not know was pending.36

Figure 1

The process of sign‐out also varied across disciplines and institutions. From our experiences at our sites and at the sites of faculty nationally, we found limited standardization about whether sign‐out was verbal, the data transmitted, and the setting in which it was transmitted. In fact, at UCSF most residents signed out verbally on the fly, wherever and whenever they could find the cross‐coverage intern. At BWH, only 37% of residents said that sign‐out occurred in a quiet place most of the time, and only 52% signed out on every patient both orally and in writing.36 At the University of Chicago, the sign‐out process was characterized by outright failures in communication because of omission of needed information (ie, medications, active or anticipated medical problems, etc.) or by failure‐prone communication (ie, lack of face‐to‐face communication, illegible writing). These failures often led to uncertainty in making patient care decisions, potentially resulting in inefficient or suboptimal care.35

Strategies for Safe and Effective Sign‐Out

Given the current landscape of variability in sign‐outs, the recognition that information lost during sign‐out may result in harm to patients, and evidence of improvements in information transfer in areas outside health care, we aimed to develop mechanisms to improve the sign‐out process for residents working in a hospital setting. These strategies are based on our review of the existing literature supplemented by our experiences at our 3 institutions.

Content of Sign‐Out

The elements of content necessary for safe and effective sign‐out can be divided into 5 broad categories (Table 1), contained in the mnemonic ANTICipate: Administrative information, New clinical information, specific Tasks to be performed, assessment of severity of Illness, and Contingency plans or anticipated problems (Table 1, Fig. 2).

Table 1.Checklist for Elements of a Safe and Effective Written Sign‐outANTICipate

✓ Administrative data
□ Patient name, age, sex
□ Medical record number
□ Room number
□ Admission date
□ Primary inpatient medical team, primary care physician
□ Family contact information
✓ New information (clinical update)
□ Chief complaint, brief HPI, and diagnosis (or differential diagnosis)
□ Updated list of medications with doses, updated allergies
□ Updated, brief assessment by system/problem, with dates
□ Current baseline status (eg, mental status, cardiopulmonary, vital signs, especially if abnormal but stable)
□ Recent procedures and significant events
✓ Tasks (what needs to be done)
□ Specific, using if‐then statements
□ Prepare cross‐coverage (eg, patient consent for blood transfusion)
□ Alert to incoming information (eg, study results, consultant recommendations), and what action, if any, needs to be taken during the cross‐coverage
✓ Illness
□ Is the patient sick?
✓ Contingency planning/Code status
□ What may go wrong and what to do about it
□ What has or has not worked before (eg, responds to 40 mg IV furosemide)
□ Difficult family or psychosocial situations
□ Code status, especially recent changes or family discussions

Figure 2

Several general points about this list should be noted. First, the sign‐out content is not meant to replace the chart. The information included reflects the goal of a sign‐out, namely, to provide enough information to allow for a safe transition in patient care. Information we believe is not essential to the sign‐out includes: a complete history and physical exam from the day of admission, a list of tasks already completed, and data necessary only to complete a discharge summary.

Sign‐out must be also be a closed loopthe process of signing in is as important as the process of signing out. This usually entails members of the primary team obtaining information from the cross‐covering physician when they resume care of the patient. The information conveyed in this case is different and includes details on events during cross‐coverage such as: 1) time called to assess patient; 2) reason for call; 3) a brief assessment of the patient, including vital signs; 4) actions taken, for example, medications given and tests ordered; and 5) rationale for those actions. Some of this information may also be included in the chart as an event note (see Fig. 3).

Figure 3

CONCLUSIONS

Sign‐outs are a part of the current landscape of academic medical centers as well as hospitals at large. Interns, residents, and consulting fellows, not to mention nurses, physical therapists, and nutritionists, transfer patient care information at each transition point. There are few resources that can assist these caregivers in identifying and implementing the most effective ways to transfer patient care information. Hospitals and other care facilities are now mandated to develop standards and systems to improve sign‐out. On the basis of the limited literature to date and our own experiences, we have proposed standards and best practices to assist hospitals, training programs, and institutional leaders in designing safe and usable sign‐out systems. Effective implementation of the standards must include appropriate allocation of resources, individualization to meet specific needs of each program or institution, intensive training, and ongoing evaluation. Future research should focus on developing valid surrogate measures of continuity of care, conducting rigorous trials to determine the elements of sign‐out that lead to the best patient outcomes, and studying the most effective ways of implementing these improvements. By improving the content and process of sign‐out, we can meet the challenges of the new health care landscape while putting patient safety at the forefront.

Modern‐day continuity of patient care in teaching hospitals, once remarkably high because of a cadre of sleep‐deprived residents, is now peppered with breaks, each accompanied by the transfer of patient care responsibility from one resident to another; a process often referred to as a handoff. Such transitions have long been a part of medical practice but have recently received increased attention because of restrictions in the duty hours of house staff. In July 2003 the Accreditation Council for Graduate Medical Education (ACGME) mandated reduced duty hours for all trainees in hopes of improving resident education and well‐being and patient safety.1 In fact, some studies have shown improved resident well‐being2 and fewer medical errors with reductions in duty hours,3, 4 but the growing consensus about the negative consequences of resident fatigue on patient safety has been accompanied by parallel concerns about the potential for information loss with each break in the continuity of care.5, 6

Although the tradeoff of increased discontinuity of care for fewer hours worked is sometimes characterized as an unintended consequence of duty hour regulations, it is in fact predictable and essential. As individuals work fewer hours, discontinuity must necessarily increase (assuming 24‐hour coverage).7 The extent to which this occurs may vary, but the link is consistent. At the University of California, San Francisco (UCSF), for example, we found that compliance with new duty hour requirements for internal medicine resulted in an average of 15 handoffs per patient during a 5‐day hospitalization. Each individual intern was involved in more than 300 handoffs in an average month‐long rotation, an increase of 40% since system changes were introduced to decrease duty hours. We found similar increases at Brigham and Women's Hospital (BWH) and the University of Chicago. Because U.S. teaching hospitals care for more than 6 million patients each year,8 the impact of these handoffs on the quality and efficiency of care is tremendous.

Discontinuity of care is currently managed by sign‐out, or the transfer of patient information from one physician to another. Recognizing the importance of information transfer at these vulnerable transition times for patients, the Joint Commission on Accreditation of Hospital Organizations (JCAHO) issued the 2006 National Patient Safety Goal 2E: Implement a standardized approach to hand off communications, including an opportunity to ask and respond to questions.9 Hospitals have little data to draw on to determine how to comply with this mandate and even less data to guide them in how to achieve its intended goals of improving communication and thus patient safety.

In an effort to better understand sign‐outs and ways to improve this process for house staff on in‐patient services, we reviewed data from the fields of aviation, communications, systems engineering, and human factors research, and we also searched the medical literature using key words pass‐off, handoff, sign‐out, duty hours, work hours, and discontinuity of care and MeSH headings Continuity of Patient Care Internship and Residency/*organization & administration, Personnel Staffing and Scheduling/*organization & administration, and Quality of Health Care. We also searched the websites of the Agency of Healthcare Quality and Research and the National Patient Safety Foundation. On the basis of these reviews, our experiences as hospitalist medical educators organizing resident sign‐out efforts at the University of California, San Francisco, the University of Chicago, and Brigham and Women's Hospital, and our efforts leading national training sessions on sign‐outs at the Society of General Internal Medicine (2004 and 2005), the Society of Hospital Medicine (2004), and the Association of Program Directors in Internal Medicine (2005, 2006), we propose a set of best practices regarding the content and process of sign‐out in an effort to improve communication between residents caring for hospitalized patients, assist programs in building safe and effective sign‐out systems, and improve the quality of patient care.

Effects of Discontinuity on Patient Safety

Research on the effects of discontinuity of care, although limited, suggests it has a negative impact on patient safety. In a study that investigated the institution of code 405 (the regulation that reduced duty hours in New York State), researchers found that the presumed increase in discontinuity with decreased duty hours resulted in delayed test ordering and an increased number of hospital complications.10 Another study found that the number of potentially preventable adverse events doubled when patients were under the care of a physician from a nonprimary team (eg, the cross‐covering intern).11 Studies have also linked resident discontinuity with longer length of stay, increased laboratory testing, and increased medication errors.12, 13

Managing Discontinuity: Sign‐Out as the Means of Information Transfer

In theory, more effective sign‐out systems should mitigate the potential for patient harm, but there is little in the literature describing current effective sign‐out practices or the best ways to design and implement such systems in the health care field. Examining information transfer mechanisms used in fields outside health care can assist in developing these systems.

The Current Practice of Sign‐Out

In examining sign‐outs at our 3 institutions, we found them to be unstructured and unstandardized. From discussion with faculty participating in national workshops on sign‐out, we found that most sign‐outs are conducted by interns, usually with little or no formal training. Templates, checklists, or other methods to standardize the content of the information transferred were rarely used.

We also noted that the vehicle for written sign‐out is highly variable. At UCSF, different residency training programs used a variety of modalities for written sign‐outs, including index cards, Excel spreadsheets, Word documents, and loose sheets of paper. Recently, the UCSF Department of Medicine designed a simple database (on Filemaker Pro) that allows members of the house staff to update their sign‐out information, share it with other house staff and nurses, and access it at locations throughout the hospital (Fig. 1). Although this database is not yet linked to the hospital information system (planned for 2006), anecdotally resident satisfaction with sign‐out has vastly improved since its implementation. The cost of design and implementation was approximately $10,000. At the University of Chicago, interns used Microsoft Word to create sign‐out sheets containing patient summaries to transfer information. However, during structured interviews, 95% of the interns reported that these sheets were frequently lost or misplaced.7 Although medicine residents at BWH use a computerized system to produce sign‐out sheets, this system did not guarantee complete and structured information. For example, a survey at BWH found that 56% of cross‐covering residents said that when paged about a patient overnight, the relevant information needed to care for that patient was present less than half the time; and 27% of residents reported being paged more than 3 times in the previous 2 weeks about a test result or consultant recommendation that they did not know was pending.36

Figure 1

The process of sign‐out also varied across disciplines and institutions. From our experiences at our sites and at the sites of faculty nationally, we found limited standardization about whether sign‐out was verbal, the data transmitted, and the setting in which it was transmitted. In fact, at UCSF most residents signed out verbally on the fly, wherever and whenever they could find the cross‐coverage intern. At BWH, only 37% of residents said that sign‐out occurred in a quiet place most of the time, and only 52% signed out on every patient both orally and in writing.36 At the University of Chicago, the sign‐out process was characterized by outright failures in communication because of omission of needed information (ie, medications, active or anticipated medical problems, etc.) or by failure‐prone communication (ie, lack of face‐to‐face communication, illegible writing). These failures often led to uncertainty in making patient care decisions, potentially resulting in inefficient or suboptimal care.35

Strategies for Safe and Effective Sign‐Out

Given the current landscape of variability in sign‐outs, the recognition that information lost during sign‐out may result in harm to patients, and evidence of improvements in information transfer in areas outside health care, we aimed to develop mechanisms to improve the sign‐out process for residents working in a hospital setting. These strategies are based on our review of the existing literature supplemented by our experiences at our 3 institutions.

Content of Sign‐Out

The elements of content necessary for safe and effective sign‐out can be divided into 5 broad categories (Table 1), contained in the mnemonic ANTICipate: Administrative information, New clinical information, specific Tasks to be performed, assessment of severity of Illness, and Contingency plans or anticipated problems (Table 1, Fig. 2).

Table 1.Checklist for Elements of a Safe and Effective Written Sign‐outANTICipate

✓ Administrative data
□ Patient name, age, sex
□ Medical record number
□ Room number
□ Admission date
□ Primary inpatient medical team, primary care physician
□ Family contact information
✓ New information (clinical update)
□ Chief complaint, brief HPI, and diagnosis (or differential diagnosis)
□ Updated list of medications with doses, updated allergies
□ Updated, brief assessment by system/problem, with dates
□ Current baseline status (eg, mental status, cardiopulmonary, vital signs, especially if abnormal but stable)
□ Recent procedures and significant events
✓ Tasks (what needs to be done)
□ Specific, using if‐then statements
□ Prepare cross‐coverage (eg, patient consent for blood transfusion)
□ Alert to incoming information (eg, study results, consultant recommendations), and what action, if any, needs to be taken during the cross‐coverage
✓ Illness
□ Is the patient sick?
✓ Contingency planning/Code status
□ What may go wrong and what to do about it
□ What has or has not worked before (eg, responds to 40 mg IV furosemide)
□ Difficult family or psychosocial situations
□ Code status, especially recent changes or family discussions

Figure 2

Several general points about this list should be noted. First, the sign‐out content is not meant to replace the chart. The information included reflects the goal of a sign‐out, namely, to provide enough information to allow for a safe transition in patient care. Information we believe is not essential to the sign‐out includes: a complete history and physical exam from the day of admission, a list of tasks already completed, and data necessary only to complete a discharge summary.

Sign‐out must be also be a closed loopthe process of signing in is as important as the process of signing out. This usually entails members of the primary team obtaining information from the cross‐covering physician when they resume care of the patient. The information conveyed in this case is different and includes details on events during cross‐coverage such as: 1) time called to assess patient; 2) reason for call; 3) a brief assessment of the patient, including vital signs; 4) actions taken, for example, medications given and tests ordered; and 5) rationale for those actions. Some of this information may also be included in the chart as an event note (see Fig. 3).

Figure 3

CONCLUSIONS

Sign‐outs are a part of the current landscape of academic medical centers as well as hospitals at large. Interns, residents, and consulting fellows, not to mention nurses, physical therapists, and nutritionists, transfer patient care information at each transition point. There are few resources that can assist these caregivers in identifying and implementing the most effective ways to transfer patient care information. Hospitals and other care facilities are now mandated to develop standards and systems to improve sign‐out. On the basis of the limited literature to date and our own experiences, we have proposed standards and best practices to assist hospitals, training programs, and institutional leaders in designing safe and usable sign‐out systems. Effective implementation of the standards must include appropriate allocation of resources, individualization to meet specific needs of each program or institution, intensive training, and ongoing evaluation. Future research should focus on developing valid surrogate measures of continuity of care, conducting rigorous trials to determine the elements of sign‐out that lead to the best patient outcomes, and studying the most effective ways of implementing these improvements. By improving the content and process of sign‐out, we can meet the challenges of the new health care landscape while putting patient safety at the forefront.

A 45‐year‐old man who immigrated to Canada from Ghana at the age of 33 presented with a 2‐year history of progressive cognitive changes. He had bifrontal headache, right‐sided scalp paresthesias, and a 40‐pound weight loss. He was unable to perform his job as an auto parts worker. His wife noticed short‐ and long‐term memory problems and poor concentration. On physical exam he had no focal neurological findings but his score on the Mini‐Mental Status Exam (MMSE) was 23/30, with deficits in attention and recall.

The first important element of this illness is its chronicity. His symptoms progressed slowly over 2 years. Second, aside from his neurological problems, he is an otherwise healthy young, African‐born male. This clinical picture could be the early presentation of a demyelinating, infiltrative, or vascular illness. If vascular, it is more likely a vasculitis than atherosclerotic disease. Malignancy and infection are definitely in the differential, but at this point, I think they are less likely to be the cause, given the tempo of presentation. I would begin my investigations with basic blood work and a computerized tomography (CT) scan of his brain.

A CT scan of the head with contrast demonstrated an enlarged left lateral ventricle with no evidence of obstruction in the foramen of Munro.

The radiological findings of communicating hydrocephalus with normal parenchyma imply a disease that affects the leptomeningeal space. Given that we are looking at an illness that can change cerebral spinal fluid (CSF) flow rather than primary parenchymal disease, demyelinating and vascular illnesses are less likely etiologies, and infiltrative diseases move up on my list. Malignancy and infectious diseases remain in the differential.

He disappeared to follow up for 1 year, during which he returned to Ghana and experienced progressive neurological deterioration, with incontinence, gait instability, and inability to converse clearly and perform activities of daily living. On his return to Canada, an urgent CT scan and magnetic resonance imaging (MRI) of the brain demonstrated ongoing and unchanged hydrocephalus with aqueductal stenosis. A referral was made to a neurosurgeon for insertion of a ventriculoperitoneal shunt. A routine preoperative chest radiograph demonstrated new bilateral upper‐zone reticulonodular changes.

He had no respiratory symptoms, fevers, or lymphadenopathy. His occupational history revealed no exposure to asbestos, silica, farms, or mines. He had no history of either respiratory or neurological illness in the past and no travel other than to Ghana and Toronto. When he immigrated to Toronto, Canada, 12 years before, he had a normal chest radiograph and negative PPD tuberculin skin test.

Many illnesses produce asymptomatic changes on chest x‐ray. Oslerian principles would suggest that we should think of a single diagnosis to explain both nodular lung disease and more than 3 years of a progressive disease affecting the leptomeninges. It is unlikely that tuberculosis, other fungal diseases, or malignancy would result in the chest and brain pathology over a 3‐year period without other sequelae. Sarcoidosis could cause both chronic leptomeningeal changes and the radiographic lung findings. The next steps in investigating this patient should include measurement of angiotensin‐converting enzyme (ACE) and serum calcium and pulmonary function tests. I would ultimately send him for a pathological biopsy of his lung tissue to confirm noncaseating granuloma and exclude infection and malignancy.

Complete blood count, renal and liver biochemistry, and calcium were normal. An ACE level was elevated at 69 g/L (normal < 40 g/L). A human immunodeficiency virus (HIV‐1 and HIV‐2) test, tuberculin skin test, and syphilis serology were negative. A CT scan of the chest demonstrated bilateral upper‐zone reticulonodular changes and diffuse lymphadenopathy (Fig. 1). Pulmonary function tests (PFTs) demonstrated a forced expiratory volume 1 (FEV1) of 3.4 L (94%), forced vital capacity (FVC) of 4.0 L (83%), an FEV1/FVC of 87%, total lung capacity (TLC) of 92% predicted, and diffusion capacity (DLCO) of 67% predicted. An MRI with gadolinium (Fig. 2) demonstrated hydrocephalus, mild basal leptomeningeal enhancement around the perivascular spaces into the subinsular region, and an increased T2 signal in periventricular white matter.

Figure 1

Figure 2

A bronchoscopy with bronchoalveolar lavage and transbronchial biopsies were performed. Pathology (Fig. 3) demonstrated non‐caseating epitheliod granulomas, with negative special stains for acid‐fast bacilli (AFB) and fungus, and negative fungal and AFB cultures of the bronchial alveolar lavage.

With negative tests for infectious causes such as tuberculosis, I think there is now enough evidence that this patient has sarcoidosis involving the lung and leptomeninges. At this point I would start therapy with steroids.

Figure 3

The patient was started on prednisone 40 mg po qd, and his neurological symptoms improved markedly over the course of 1‐2 months, with normalization of his MMSE and a return to cognitive baseline. As his symptoms stabilized with no change in CT imaging, he returned to work, and over the course of 2 years his prednisone dosage was tapered to 10 mg po od. While on prednisone he developed hypertension and hyperglycemia. He continued to have no respiratory symptoms.

He was cognitively at baseline until 20 months later, when he was readmitted to the hospital with a 2‐week history of worsening headache, increased confusion, poor memory, and wandering. His MMSE had deteriorated to 19/30, with deficits again in memory and attention.

First, we can say with reasonable confidence that the diagnosis of sarcoid was correct. His long and sustained response to steroids, plus the absence of the unmasking of an infectious or malignant disease, supports this conclusion. However, he is now exhibiting an apparent relapse that mimics his presentation 3 years earlier. The question is whether he is suffering from a flare of his disease or whether a second illness has occurred. The most obvious second illness is an opportunistic infection after years of steroid use. I would certainly repeat the angiotensin‐converting enzyme and serum calcium tests and repeat the imaging of his lungs and central nervous system. He also warrants a lumbar puncture with CSF culture, stain, and PCR for opportunistic infections. If these studies are inconclusive and do not specifically suggest relapsing sarcoid, I would once again consider biopsy of tissue from either a lung or leptomeninges.

An MRI with gadolinium looked unchanged from the previous one. A lumbar puncture was performed, and his CSF demonstrated 3 WBCs, no RBCs, normal glucose, and elevated protein at 1.17 g/L, and tests for bacteria, TB, fungi, and viruses were all negative. Repeat blood work was unremarkable, and the ACE level was 2 g/L.

A chest radiograph (Fig. 4a) and CT chest (Fig. 4b) showed marked deterioration, with increased diffuse airspace opacities, interstitial nodularity, and small apical bullae. His PFTs showed some deterioration, with FEV1 2.52 L (73%), FVC 3.29 L (73%), FEV1/FVC 76%, TLC 70% predicted, DLCO 72% predicted. However, he still had no respiratory symptoms.

Figure 4

The changes on lumbar puncture are nonspecific. The ACE level is now very low, making sarcoidosis unlikely but not impossible. The chest imaging shows features, specifically interstitial nodularity, consistent with ongoing or relapsing sarcoidosis, but the extensive apical bullae are not characteristic. My best guess is that this patient's illness is not simply relapsing sarcoid but represents superimposed opportunistic infectious disease. I would not reintroduce steroids without pursuing a definitive diagnosis with tissue pathology.

He was placed on prednisone 60 mg po qd and started on trimethoprim‐sulfamethoxazole for Pneumocystis pneumonia (PCP) prophylaxis. He showed modest improvement in his neurological status. A repeat bronchoscopy was not performed. Four months later he was seen by his pulmonologist. He remained without respiratory symptoms and was neurologically unchanged, and a chest radiograph showed no change. He was continued on prednisone 60 mg po qd.

Three weeks later, he was admitted to the hospital with a 2‐week history of anorexia, fatigue, night sweats, right‐sided pleuritic chest pain with productive cough, increasing dyspnea, and no hemoptysis. On admission he was hypoxic with evidence of respiratory distress, and his chest radiograph showed evidence of new right‐sided airspace disease with an associated large right pleural effusion. Initial labs demonstrated a leukocytosis.

I am now very suspicious that this illness is not relapsed sarcoidosis based on his prior clinical response to high‐dose prednisone and that he currently is showing no neurological improvement. His recent clinical deterioration on this very high dose of prednisone makes me think that opportunistic lung infection or disseminated disease is definitely the cause, although the differential is broad. In addition to the typical viral and bacterial causes of community‐acquired pneumonia, this could be caused by unusual bacterial pathogens, tuberculosis, nontuberculous mycobacteria, or fungal diseases including Candida, Aspergillus and dimorphic fungi. I would begin empiric therapy with antibiotics, obtain pleural fluid for examination and culture, and blood cultures.

The patient was treated with a respiratory fluoroquinolone, and blood and sputum cultures were performed. A right thoracentesis removed 300 cc of yellow exudate, with negative gram stain and initial culture. Over the next 24 hours, the patient deteriorated rapidly, with progressive hypoxia and clinical and radiological (Fig. 5) evidence of acute respiratory distress syndrome (ARDS). He required endotracheal intubation with mechanical ventilation.

Figure 5

He has a progressive illness not responsive to broad‐spectrum antibiotics, and he has deteriorated. At this point it is imperative that he undergo bronchoscopy and transbronchial biopsy.

Bronchoscopy demonstrated secretions from the right lower lobe. Gram stain from a bronchoalveolar lavage from the right lower lobe was negative, and cultures showed no growth after 24 hours. Immediately after bronchoscopy a third‐generation cephalosporin was empirically added. The next day the patient developed hypotension and was started on norepinephrine. Over the subsequent 48 hours, he developed progressive multiorgan failure. Despite multiple vasopressors, high‐frequency oscillator ventilation, broad‐spectrum antimicrobials, and activated protein C, he died in the intensive care unit. At the time of death, all blood cultures were negative, abdominal CT scans showed no intraabdominal infections, and the BAL performed on admission demonstrated negative gram stain, fungal stain, AFB stain, and PCP and no growth from fungal or bacterial cultures.

I think it is an unavoidable conclusion that this man's progressive systemic inflammatory response syndrome and ultimate multiorgan failure was caused by an opportunistic pathogen that was not antibiotic responsive and not identified from the extensive range of infectious disease studies performed. Despite all the negative studies, there still might be either mycobacterial illness or fungal illness. With negative cultures, Candida or Aspergillus infection is unlikely. Other opportunistic fungi like Blastomyces, Histoplasma, and Cryptococcus are certainly in the differential because these organisms can be notoriously difficult to detect on routine surveying such as bronchoalveolar lavage or lumbar puncture. Blastomyces and Histoplasma are both endemic in the area of Canada where the patient resided. I would also keep the zygomycoses in the differential.

Five days after death, fungal culture was reported demonstrating Blastomyces dermatitidis. Postmortem demonstrated disseminated blastomycosis causing severe bilateral pneumonia (Fig. 6a), empyema of right lung, and involvement of the thyroid, heart, liver, spleen, and kidneys. There was also evidence of active CNS blastomycosis involving the meninges and cerebral cortex and diencephalon (Fig. 6b). As well as active blastomycosis, the leptomeninges demonstrated fibrosis and old granulomas that did not contain an organism.

Figure 6

COMMENTARY

This case describes a 45‐year‐old man who presented with chronic cognitive symptoms associated with hydrocephalus. The first step in establishing the diagnosis was made by realizing that a communicating hydrocephalus with no parenchymal CNS disease was highly suggestive of a leptomeningeal process. This narrowed the differential diagnosis to an infiltrative disease affecting the leptomeninges. The next step involved the discovery of an upper‐lobe interstitial lung process, establishing sarcoidosis as the most likely unifying diagnosis. This was confirmed with transbronchial biopsies showing noncaseating granulomas and by the sustained response to treatment with corticosteroids. Unfortunately, after a 2‐year remission, he developed a recurrence of both the neurological and respiratory findings. When his symptoms progressed despite higher doses of corticosteroids, it became apparent that the etiology of his clinical deterioration was not recurrent disease. Instead, the deterioration was caused by disseminated blastomycosis, an opportunistic infection that developed as a result of the immunosuppressants used to treat the sarcoidosis.

With the final diagnosis of blastomycosis, one question about this case becomes: Could it have been blastomycosis and not sarcoid that was responsible for his original neurological presentation? Blastomyces dermatitidis is a thermally dimorphic fungus that causes disease from inhalation of airborne spores found in soil. Areas of North America in which it is endemic include regions bordering the Mississipi and Ohio rivers, as well as the areas bordering the Great Lakes.1 The patient in this case lived in metropolitan Toronto, on Lake Ontario, where blastomycosis is an important yet underreported disease.24 He likely was exposed to blastomyces in Toronto, which in immunocompromised patients may be followed after weeks to months by dissemination to other body sites including the dermis, bones, joints, urogenital system, and, rarely, the central nervous system (CNS) and liver.5 Like sarcoidosis, infection with blastomycosis can produce pathologic evidence of noncaseating granulomatous inflammation. However, as the discussant astutely pointed out, it would be unusual for this patient to have clinically inapparent blastomycosis for almost 2 years while on high‐dose prednisone. The initial diagnosis of sarcoid likely was correct.

CNS disease caused by Blastomyces dermatitidis is quite rare, with only 22 reported cases of meningoencephalitis in the literature.6 As this case demonstrates, CNS blastomycosis is very difficult to diagnose because of the absence of sensitive serologic markers and the difficulty of isolating the organism from blood and cerebrospinal fluid. CSF sampling from lumbar puncture led to its diagnosis in only 2 of the 22 reported cases.7 Furthermore, reliable CSF cultures are usually only obtained via ventricular sampling or tissue biopsy, which itself is limited by the organism's predilection for deep structures of the cerebrum, midbrain, and basal meninges.6 Blastomyces involving the CNS rarely occurs in isolation. In the patient's case, during his neurological deterioration, there was clear radiological evidence of progressive pulmonary pathology despite his being asymptomatic, and as the discussant suggests, pulmonary investigations were warranted.

Pulmonary manifestations of blastomycosis are variable. Acute infections most commonly resemble pneumonia, whereas chronic disease may show reticulonodular changes indistinguishable from sarcoidosis. Severe cases have been shown to progress to respiratory failure with acute respiratory distress syndrome (ARDS).1 The diagnosis is usually established through culture of noninvasive (sensitivity 86%) or bronchoalveolar lavage (sensitivity 92%) specimens.8 However, blastomyces will take between 5 and 30 days to grow in culture.1 In cases where the diagnosis needs to be established quickly, a KOH smear can be done looking for broad‐based budding yeast. Although the yield of this test is lower (0%‐50%), the results can be available within 24 hours.9 As these tests are not always routinely performed, direct communication with the pathologist is recommended if a rapid diagnosis is needed.

The major challenge of this case lay in distinguishing between the recurrence of an old disease and the complications of its treatment. In this case the discussant addresses strategies that might be useful in differentiating recurrent sarcoidosis from an opportunistic infection like blastomycosis. The first issue is the steroid therapy. The exact dose of steroids required to compromise the immune system enough to yield infections is not known. However, in a meta‐analysis of 71 controlled clinical trials performed with steroids, Stuck et. al. were able to show that the occurrence of opportunistic infections depended on both the amount of daily steroid and the cumulative dose.10 Opportunistic infections were unlikely to occur in patients given a mean daily dose of less than 10 mg/day or a cumulative dose of less than 700 mg of prednisone. Although the patient in the present case was only on 10 mg/day of prednisone, his mean daily dose was more than 10 mg/day, and his cumulative dose far exceeded 700 mg. Therefore, an opportunistic infection should have been strongly considered.

The other item used to help distinguish between the 2 diseases was serum angiotensin‐converting enzyme (ACE) level. ACE is an enzyme produced by the epithelial cells of the granulomas in sarcoidosis. ACE alone is inadequate for diagnosis, with a reported sensitivity of 40%‐90%, depending on the population studied and on the definition of normal.1114 Even an ACE level more than twice the normal is not diagnostic for sarcoidosis, with elevated levels found in histoplasmosis, silicosis, tuberculosis, Gaucher's disease, and other disorders.15 Rather than as a diagnostic test, ACE level instead is used to follow disease activity in sarcoidosis, as ACE level often reflects the granuloma burden.1618 The low levels at the initial recurrence suggests the symptoms were not a result of active sarcoid, especially considering that if ACE levels are originally elevated with sarcoidosis, they are almost always elevated again when the disease recurs.14 Normal levels of ACE in sarcoid patients with previously elevated ACE levels should therefore prompt a search for an alternate diagnosis.

This case is an example of the therapy causing a complication that mimics the disease it was intended to cure. When any patient deteriorates while on steroids, the clinician must ask the age‐old question: should more steroids be prescribed or less? As in this case, the answer is not always apparent. Safe decisions in these situations demand awareness of the opportunistic infections endemic to the area and a willingness to perform early invasive procedures (in this case bronchoscopy) to obtain samples to make a definitive diagnosis. By doing so, the devastating chain of events that occurred here hopefully can be avoided.

A 45‐year‐old man who immigrated to Canada from Ghana at the age of 33 presented with a 2‐year history of progressive cognitive changes. He had bifrontal headache, right‐sided scalp paresthesias, and a 40‐pound weight loss. He was unable to perform his job as an auto parts worker. His wife noticed short‐ and long‐term memory problems and poor concentration. On physical exam he had no focal neurological findings but his score on the Mini‐Mental Status Exam (MMSE) was 23/30, with deficits in attention and recall.

The first important element of this illness is its chronicity. His symptoms progressed slowly over 2 years. Second, aside from his neurological problems, he is an otherwise healthy young, African‐born male. This clinical picture could be the early presentation of a demyelinating, infiltrative, or vascular illness. If vascular, it is more likely a vasculitis than atherosclerotic disease. Malignancy and infection are definitely in the differential, but at this point, I think they are less likely to be the cause, given the tempo of presentation. I would begin my investigations with basic blood work and a computerized tomography (CT) scan of his brain.

A CT scan of the head with contrast demonstrated an enlarged left lateral ventricle with no evidence of obstruction in the foramen of Munro.

The radiological findings of communicating hydrocephalus with normal parenchyma imply a disease that affects the leptomeningeal space. Given that we are looking at an illness that can change cerebral spinal fluid (CSF) flow rather than primary parenchymal disease, demyelinating and vascular illnesses are less likely etiologies, and infiltrative diseases move up on my list. Malignancy and infectious diseases remain in the differential.

He disappeared to follow up for 1 year, during which he returned to Ghana and experienced progressive neurological deterioration, with incontinence, gait instability, and inability to converse clearly and perform activities of daily living. On his return to Canada, an urgent CT scan and magnetic resonance imaging (MRI) of the brain demonstrated ongoing and unchanged hydrocephalus with aqueductal stenosis. A referral was made to a neurosurgeon for insertion of a ventriculoperitoneal shunt. A routine preoperative chest radiograph demonstrated new bilateral upper‐zone reticulonodular changes.

He had no respiratory symptoms, fevers, or lymphadenopathy. His occupational history revealed no exposure to asbestos, silica, farms, or mines. He had no history of either respiratory or neurological illness in the past and no travel other than to Ghana and Toronto. When he immigrated to Toronto, Canada, 12 years before, he had a normal chest radiograph and negative PPD tuberculin skin test.

Many illnesses produce asymptomatic changes on chest x‐ray. Oslerian principles would suggest that we should think of a single diagnosis to explain both nodular lung disease and more than 3 years of a progressive disease affecting the leptomeninges. It is unlikely that tuberculosis, other fungal diseases, or malignancy would result in the chest and brain pathology over a 3‐year period without other sequelae. Sarcoidosis could cause both chronic leptomeningeal changes and the radiographic lung findings. The next steps in investigating this patient should include measurement of angiotensin‐converting enzyme (ACE) and serum calcium and pulmonary function tests. I would ultimately send him for a pathological biopsy of his lung tissue to confirm noncaseating granuloma and exclude infection and malignancy.

Complete blood count, renal and liver biochemistry, and calcium were normal. An ACE level was elevated at 69 g/L (normal < 40 g/L). A human immunodeficiency virus (HIV‐1 and HIV‐2) test, tuberculin skin test, and syphilis serology were negative. A CT scan of the chest demonstrated bilateral upper‐zone reticulonodular changes and diffuse lymphadenopathy (Fig. 1). Pulmonary function tests (PFTs) demonstrated a forced expiratory volume 1 (FEV1) of 3.4 L (94%), forced vital capacity (FVC) of 4.0 L (83%), an FEV1/FVC of 87%, total lung capacity (TLC) of 92% predicted, and diffusion capacity (DLCO) of 67% predicted. An MRI with gadolinium (Fig. 2) demonstrated hydrocephalus, mild basal leptomeningeal enhancement around the perivascular spaces into the subinsular region, and an increased T2 signal in periventricular white matter.

Figure 1

Figure 2

A bronchoscopy with bronchoalveolar lavage and transbronchial biopsies were performed. Pathology (Fig. 3) demonstrated non‐caseating epitheliod granulomas, with negative special stains for acid‐fast bacilli (AFB) and fungus, and negative fungal and AFB cultures of the bronchial alveolar lavage.

With negative tests for infectious causes such as tuberculosis, I think there is now enough evidence that this patient has sarcoidosis involving the lung and leptomeninges. At this point I would start therapy with steroids.

Figure 3

The patient was started on prednisone 40 mg po qd, and his neurological symptoms improved markedly over the course of 1‐2 months, with normalization of his MMSE and a return to cognitive baseline. As his symptoms stabilized with no change in CT imaging, he returned to work, and over the course of 2 years his prednisone dosage was tapered to 10 mg po od. While on prednisone he developed hypertension and hyperglycemia. He continued to have no respiratory symptoms.

He was cognitively at baseline until 20 months later, when he was readmitted to the hospital with a 2‐week history of worsening headache, increased confusion, poor memory, and wandering. His MMSE had deteriorated to 19/30, with deficits again in memory and attention.

First, we can say with reasonable confidence that the diagnosis of sarcoid was correct. His long and sustained response to steroids, plus the absence of the unmasking of an infectious or malignant disease, supports this conclusion. However, he is now exhibiting an apparent relapse that mimics his presentation 3 years earlier. The question is whether he is suffering from a flare of his disease or whether a second illness has occurred. The most obvious second illness is an opportunistic infection after years of steroid use. I would certainly repeat the angiotensin‐converting enzyme and serum calcium tests and repeat the imaging of his lungs and central nervous system. He also warrants a lumbar puncture with CSF culture, stain, and PCR for opportunistic infections. If these studies are inconclusive and do not specifically suggest relapsing sarcoid, I would once again consider biopsy of tissue from either a lung or leptomeninges.

An MRI with gadolinium looked unchanged from the previous one. A lumbar puncture was performed, and his CSF demonstrated 3 WBCs, no RBCs, normal glucose, and elevated protein at 1.17 g/L, and tests for bacteria, TB, fungi, and viruses were all negative. Repeat blood work was unremarkable, and the ACE level was 2 g/L.

A chest radiograph (Fig. 4a) and CT chest (Fig. 4b) showed marked deterioration, with increased diffuse airspace opacities, interstitial nodularity, and small apical bullae. His PFTs showed some deterioration, with FEV1 2.52 L (73%), FVC 3.29 L (73%), FEV1/FVC 76%, TLC 70% predicted, DLCO 72% predicted. However, he still had no respiratory symptoms.

Figure 4

The changes on lumbar puncture are nonspecific. The ACE level is now very low, making sarcoidosis unlikely but not impossible. The chest imaging shows features, specifically interstitial nodularity, consistent with ongoing or relapsing sarcoidosis, but the extensive apical bullae are not characteristic. My best guess is that this patient's illness is not simply relapsing sarcoid but represents superimposed opportunistic infectious disease. I would not reintroduce steroids without pursuing a definitive diagnosis with tissue pathology.

He was placed on prednisone 60 mg po qd and started on trimethoprim‐sulfamethoxazole for Pneumocystis pneumonia (PCP) prophylaxis. He showed modest improvement in his neurological status. A repeat bronchoscopy was not performed. Four months later he was seen by his pulmonologist. He remained without respiratory symptoms and was neurologically unchanged, and a chest radiograph showed no change. He was continued on prednisone 60 mg po qd.

Three weeks later, he was admitted to the hospital with a 2‐week history of anorexia, fatigue, night sweats, right‐sided pleuritic chest pain with productive cough, increasing dyspnea, and no hemoptysis. On admission he was hypoxic with evidence of respiratory distress, and his chest radiograph showed evidence of new right‐sided airspace disease with an associated large right pleural effusion. Initial labs demonstrated a leukocytosis.

I am now very suspicious that this illness is not relapsed sarcoidosis based on his prior clinical response to high‐dose prednisone and that he currently is showing no neurological improvement. His recent clinical deterioration on this very high dose of prednisone makes me think that opportunistic lung infection or disseminated disease is definitely the cause, although the differential is broad. In addition to the typical viral and bacterial causes of community‐acquired pneumonia, this could be caused by unusual bacterial pathogens, tuberculosis, nontuberculous mycobacteria, or fungal diseases including Candida, Aspergillus and dimorphic fungi. I would begin empiric therapy with antibiotics, obtain pleural fluid for examination and culture, and blood cultures.

The patient was treated with a respiratory fluoroquinolone, and blood and sputum cultures were performed. A right thoracentesis removed 300 cc of yellow exudate, with negative gram stain and initial culture. Over the next 24 hours, the patient deteriorated rapidly, with progressive hypoxia and clinical and radiological (Fig. 5) evidence of acute respiratory distress syndrome (ARDS). He required endotracheal intubation with mechanical ventilation.

Figure 5

He has a progressive illness not responsive to broad‐spectrum antibiotics, and he has deteriorated. At this point it is imperative that he undergo bronchoscopy and transbronchial biopsy.

Bronchoscopy demonstrated secretions from the right lower lobe. Gram stain from a bronchoalveolar lavage from the right lower lobe was negative, and cultures showed no growth after 24 hours. Immediately after bronchoscopy a third‐generation cephalosporin was empirically added. The next day the patient developed hypotension and was started on norepinephrine. Over the subsequent 48 hours, he developed progressive multiorgan failure. Despite multiple vasopressors, high‐frequency oscillator ventilation, broad‐spectrum antimicrobials, and activated protein C, he died in the intensive care unit. At the time of death, all blood cultures were negative, abdominal CT scans showed no intraabdominal infections, and the BAL performed on admission demonstrated negative gram stain, fungal stain, AFB stain, and PCP and no growth from fungal or bacterial cultures.

I think it is an unavoidable conclusion that this man's progressive systemic inflammatory response syndrome and ultimate multiorgan failure was caused by an opportunistic pathogen that was not antibiotic responsive and not identified from the extensive range of infectious disease studies performed. Despite all the negative studies, there still might be either mycobacterial illness or fungal illness. With negative cultures, Candida or Aspergillus infection is unlikely. Other opportunistic fungi like Blastomyces, Histoplasma, and Cryptococcus are certainly in the differential because these organisms can be notoriously difficult to detect on routine surveying such as bronchoalveolar lavage or lumbar puncture. Blastomyces and Histoplasma are both endemic in the area of Canada where the patient resided. I would also keep the zygomycoses in the differential.

Five days after death, fungal culture was reported demonstrating Blastomyces dermatitidis. Postmortem demonstrated disseminated blastomycosis causing severe bilateral pneumonia (Fig. 6a), empyema of right lung, and involvement of the thyroid, heart, liver, spleen, and kidneys. There was also evidence of active CNS blastomycosis involving the meninges and cerebral cortex and diencephalon (Fig. 6b). As well as active blastomycosis, the leptomeninges demonstrated fibrosis and old granulomas that did not contain an organism.

Figure 6

COMMENTARY

This case describes a 45‐year‐old man who presented with chronic cognitive symptoms associated with hydrocephalus. The first step in establishing the diagnosis was made by realizing that a communicating hydrocephalus with no parenchymal CNS disease was highly suggestive of a leptomeningeal process. This narrowed the differential diagnosis to an infiltrative disease affecting the leptomeninges. The next step involved the discovery of an upper‐lobe interstitial lung process, establishing sarcoidosis as the most likely unifying diagnosis. This was confirmed with transbronchial biopsies showing noncaseating granulomas and by the sustained response to treatment with corticosteroids. Unfortunately, after a 2‐year remission, he developed a recurrence of both the neurological and respiratory findings. When his symptoms progressed despite higher doses of corticosteroids, it became apparent that the etiology of his clinical deterioration was not recurrent disease. Instead, the deterioration was caused by disseminated blastomycosis, an opportunistic infection that developed as a result of the immunosuppressants used to treat the sarcoidosis.

With the final diagnosis of blastomycosis, one question about this case becomes: Could it have been blastomycosis and not sarcoid that was responsible for his original neurological presentation? Blastomyces dermatitidis is a thermally dimorphic fungus that causes disease from inhalation of airborne spores found in soil. Areas of North America in which it is endemic include regions bordering the Mississipi and Ohio rivers, as well as the areas bordering the Great Lakes.1 The patient in this case lived in metropolitan Toronto, on Lake Ontario, where blastomycosis is an important yet underreported disease.24 He likely was exposed to blastomyces in Toronto, which in immunocompromised patients may be followed after weeks to months by dissemination to other body sites including the dermis, bones, joints, urogenital system, and, rarely, the central nervous system (CNS) and liver.5 Like sarcoidosis, infection with blastomycosis can produce pathologic evidence of noncaseating granulomatous inflammation. However, as the discussant astutely pointed out, it would be unusual for this patient to have clinically inapparent blastomycosis for almost 2 years while on high‐dose prednisone. The initial diagnosis of sarcoid likely was correct.

CNS disease caused by Blastomyces dermatitidis is quite rare, with only 22 reported cases of meningoencephalitis in the literature.6 As this case demonstrates, CNS blastomycosis is very difficult to diagnose because of the absence of sensitive serologic markers and the difficulty of isolating the organism from blood and cerebrospinal fluid. CSF sampling from lumbar puncture led to its diagnosis in only 2 of the 22 reported cases.7 Furthermore, reliable CSF cultures are usually only obtained via ventricular sampling or tissue biopsy, which itself is limited by the organism's predilection for deep structures of the cerebrum, midbrain, and basal meninges.6 Blastomyces involving the CNS rarely occurs in isolation. In the patient's case, during his neurological deterioration, there was clear radiological evidence of progressive pulmonary pathology despite his being asymptomatic, and as the discussant suggests, pulmonary investigations were warranted.

Pulmonary manifestations of blastomycosis are variable. Acute infections most commonly resemble pneumonia, whereas chronic disease may show reticulonodular changes indistinguishable from sarcoidosis. Severe cases have been shown to progress to respiratory failure with acute respiratory distress syndrome (ARDS).1 The diagnosis is usually established through culture of noninvasive (sensitivity 86%) or bronchoalveolar lavage (sensitivity 92%) specimens.8 However, blastomyces will take between 5 and 30 days to grow in culture.1 In cases where the diagnosis needs to be established quickly, a KOH smear can be done looking for broad‐based budding yeast. Although the yield of this test is lower (0%‐50%), the results can be available within 24 hours.9 As these tests are not always routinely performed, direct communication with the pathologist is recommended if a rapid diagnosis is needed.

The major challenge of this case lay in distinguishing between the recurrence of an old disease and the complications of its treatment. In this case the discussant addresses strategies that might be useful in differentiating recurrent sarcoidosis from an opportunistic infection like blastomycosis. The first issue is the steroid therapy. The exact dose of steroids required to compromise the immune system enough to yield infections is not known. However, in a meta‐analysis of 71 controlled clinical trials performed with steroids, Stuck et. al. were able to show that the occurrence of opportunistic infections depended on both the amount of daily steroid and the cumulative dose.10 Opportunistic infections were unlikely to occur in patients given a mean daily dose of less than 10 mg/day or a cumulative dose of less than 700 mg of prednisone. Although the patient in the present case was only on 10 mg/day of prednisone, his mean daily dose was more than 10 mg/day, and his cumulative dose far exceeded 700 mg. Therefore, an opportunistic infection should have been strongly considered.

The other item used to help distinguish between the 2 diseases was serum angiotensin‐converting enzyme (ACE) level. ACE is an enzyme produced by the epithelial cells of the granulomas in sarcoidosis. ACE alone is inadequate for diagnosis, with a reported sensitivity of 40%‐90%, depending on the population studied and on the definition of normal.1114 Even an ACE level more than twice the normal is not diagnostic for sarcoidosis, with elevated levels found in histoplasmosis, silicosis, tuberculosis, Gaucher's disease, and other disorders.15 Rather than as a diagnostic test, ACE level instead is used to follow disease activity in sarcoidosis, as ACE level often reflects the granuloma burden.1618 The low levels at the initial recurrence suggests the symptoms were not a result of active sarcoid, especially considering that if ACE levels are originally elevated with sarcoidosis, they are almost always elevated again when the disease recurs.14 Normal levels of ACE in sarcoid patients with previously elevated ACE levels should therefore prompt a search for an alternate diagnosis.

This case is an example of the therapy causing a complication that mimics the disease it was intended to cure. When any patient deteriorates while on steroids, the clinician must ask the age‐old question: should more steroids be prescribed or less? As in this case, the answer is not always apparent. Safe decisions in these situations demand awareness of the opportunistic infections endemic to the area and a willingness to perform early invasive procedures (in this case bronchoscopy) to obtain samples to make a definitive diagnosis. By doing so, the devastating chain of events that occurred here hopefully can be avoided.

A 45‐year‐old man who immigrated to Canada from Ghana at the age of 33 presented with a 2‐year history of progressive cognitive changes. He had bifrontal headache, right‐sided scalp paresthesias, and a 40‐pound weight loss. He was unable to perform his job as an auto parts worker. His wife noticed short‐ and long‐term memory problems and poor concentration. On physical exam he had no focal neurological findings but his score on the Mini‐Mental Status Exam (MMSE) was 23/30, with deficits in attention and recall.

The first important element of this illness is its chronicity. His symptoms progressed slowly over 2 years. Second, aside from his neurological problems, he is an otherwise healthy young, African‐born male. This clinical picture could be the early presentation of a demyelinating, infiltrative, or vascular illness. If vascular, it is more likely a vasculitis than atherosclerotic disease. Malignancy and infection are definitely in the differential, but at this point, I think they are less likely to be the cause, given the tempo of presentation. I would begin my investigations with basic blood work and a computerized tomography (CT) scan of his brain.

A CT scan of the head with contrast demonstrated an enlarged left lateral ventricle with no evidence of obstruction in the foramen of Munro.

The radiological findings of communicating hydrocephalus with normal parenchyma imply a disease that affects the leptomeningeal space. Given that we are looking at an illness that can change cerebral spinal fluid (CSF) flow rather than primary parenchymal disease, demyelinating and vascular illnesses are less likely etiologies, and infiltrative diseases move up on my list. Malignancy and infectious diseases remain in the differential.

He disappeared to follow up for 1 year, during which he returned to Ghana and experienced progressive neurological deterioration, with incontinence, gait instability, and inability to converse clearly and perform activities of daily living. On his return to Canada, an urgent CT scan and magnetic resonance imaging (MRI) of the brain demonstrated ongoing and unchanged hydrocephalus with aqueductal stenosis. A referral was made to a neurosurgeon for insertion of a ventriculoperitoneal shunt. A routine preoperative chest radiograph demonstrated new bilateral upper‐zone reticulonodular changes.

He had no respiratory symptoms, fevers, or lymphadenopathy. His occupational history revealed no exposure to asbestos, silica, farms, or mines. He had no history of either respiratory or neurological illness in the past and no travel other than to Ghana and Toronto. When he immigrated to Toronto, Canada, 12 years before, he had a normal chest radiograph and negative PPD tuberculin skin test.

Many illnesses produce asymptomatic changes on chest x‐ray. Oslerian principles would suggest that we should think of a single diagnosis to explain both nodular lung disease and more than 3 years of a progressive disease affecting the leptomeninges. It is unlikely that tuberculosis, other fungal diseases, or malignancy would result in the chest and brain pathology over a 3‐year period without other sequelae. Sarcoidosis could cause both chronic leptomeningeal changes and the radiographic lung findings. The next steps in investigating this patient should include measurement of angiotensin‐converting enzyme (ACE) and serum calcium and pulmonary function tests. I would ultimately send him for a pathological biopsy of his lung tissue to confirm noncaseating granuloma and exclude infection and malignancy.

Complete blood count, renal and liver biochemistry, and calcium were normal. An ACE level was elevated at 69 g/L (normal < 40 g/L). A human immunodeficiency virus (HIV‐1 and HIV‐2) test, tuberculin skin test, and syphilis serology were negative. A CT scan of the chest demonstrated bilateral upper‐zone reticulonodular changes and diffuse lymphadenopathy (Fig. 1). Pulmonary function tests (PFTs) demonstrated a forced expiratory volume 1 (FEV1) of 3.4 L (94%), forced vital capacity (FVC) of 4.0 L (83%), an FEV1/FVC of 87%, total lung capacity (TLC) of 92% predicted, and diffusion capacity (DLCO) of 67% predicted. An MRI with gadolinium (Fig. 2) demonstrated hydrocephalus, mild basal leptomeningeal enhancement around the perivascular spaces into the subinsular region, and an increased T2 signal in periventricular white matter.

Figure 1

Figure 2

A bronchoscopy with bronchoalveolar lavage and transbronchial biopsies were performed. Pathology (Fig. 3) demonstrated non‐caseating epitheliod granulomas, with negative special stains for acid‐fast bacilli (AFB) and fungus, and negative fungal and AFB cultures of the bronchial alveolar lavage.

With negative tests for infectious causes such as tuberculosis, I think there is now enough evidence that this patient has sarcoidosis involving the lung and leptomeninges. At this point I would start therapy with steroids.

Figure 3

The patient was started on prednisone 40 mg po qd, and his neurological symptoms improved markedly over the course of 1‐2 months, with normalization of his MMSE and a return to cognitive baseline. As his symptoms stabilized with no change in CT imaging, he returned to work, and over the course of 2 years his prednisone dosage was tapered to 10 mg po od. While on prednisone he developed hypertension and hyperglycemia. He continued to have no respiratory symptoms.

He was cognitively at baseline until 20 months later, when he was readmitted to the hospital with a 2‐week history of worsening headache, increased confusion, poor memory, and wandering. His MMSE had deteriorated to 19/30, with deficits again in memory and attention.

First, we can say with reasonable confidence that the diagnosis of sarcoid was correct. His long and sustained response to steroids, plus the absence of the unmasking of an infectious or malignant disease, supports this conclusion. However, he is now exhibiting an apparent relapse that mimics his presentation 3 years earlier. The question is whether he is suffering from a flare of his disease or whether a second illness has occurred. The most obvious second illness is an opportunistic infection after years of steroid use. I would certainly repeat the angiotensin‐converting enzyme and serum calcium tests and repeat the imaging of his lungs and central nervous system. He also warrants a lumbar puncture with CSF culture, stain, and PCR for opportunistic infections. If these studies are inconclusive and do not specifically suggest relapsing sarcoid, I would once again consider biopsy of tissue from either a lung or leptomeninges.

An MRI with gadolinium looked unchanged from the previous one. A lumbar puncture was performed, and his CSF demonstrated 3 WBCs, no RBCs, normal glucose, and elevated protein at 1.17 g/L, and tests for bacteria, TB, fungi, and viruses were all negative. Repeat blood work was unremarkable, and the ACE level was 2 g/L.

A chest radiograph (Fig. 4a) and CT chest (Fig. 4b) showed marked deterioration, with increased diffuse airspace opacities, interstitial nodularity, and small apical bullae. His PFTs showed some deterioration, with FEV1 2.52 L (73%), FVC 3.29 L (73%), FEV1/FVC 76%, TLC 70% predicted, DLCO 72% predicted. However, he still had no respiratory symptoms.

Figure 4

The changes on lumbar puncture are nonspecific. The ACE level is now very low, making sarcoidosis unlikely but not impossible. The chest imaging shows features, specifically interstitial nodularity, consistent with ongoing or relapsing sarcoidosis, but the extensive apical bullae are not characteristic. My best guess is that this patient's illness is not simply relapsing sarcoid but represents superimposed opportunistic infectious disease. I would not reintroduce steroids without pursuing a definitive diagnosis with tissue pathology.

He was placed on prednisone 60 mg po qd and started on trimethoprim‐sulfamethoxazole for Pneumocystis pneumonia (PCP) prophylaxis. He showed modest improvement in his neurological status. A repeat bronchoscopy was not performed. Four months later he was seen by his pulmonologist. He remained without respiratory symptoms and was neurologically unchanged, and a chest radiograph showed no change. He was continued on prednisone 60 mg po qd.

Three weeks later, he was admitted to the hospital with a 2‐week history of anorexia, fatigue, night sweats, right‐sided pleuritic chest pain with productive cough, increasing dyspnea, and no hemoptysis. On admission he was hypoxic with evidence of respiratory distress, and his chest radiograph showed evidence of new right‐sided airspace disease with an associated large right pleural effusion. Initial labs demonstrated a leukocytosis.

I am now very suspicious that this illness is not relapsed sarcoidosis based on his prior clinical response to high‐dose prednisone and that he currently is showing no neurological improvement. His recent clinical deterioration on this very high dose of prednisone makes me think that opportunistic lung infection or disseminated disease is definitely the cause, although the differential is broad. In addition to the typical viral and bacterial causes of community‐acquired pneumonia, this could be caused by unusual bacterial pathogens, tuberculosis, nontuberculous mycobacteria, or fungal diseases including Candida, Aspergillus and dimorphic fungi. I would begin empiric therapy with antibiotics, obtain pleural fluid for examination and culture, and blood cultures.

The patient was treated with a respiratory fluoroquinolone, and blood and sputum cultures were performed. A right thoracentesis removed 300 cc of yellow exudate, with negative gram stain and initial culture. Over the next 24 hours, the patient deteriorated rapidly, with progressive hypoxia and clinical and radiological (Fig. 5) evidence of acute respiratory distress syndrome (ARDS). He required endotracheal intubation with mechanical ventilation.

Figure 5

He has a progressive illness not responsive to broad‐spectrum antibiotics, and he has deteriorated. At this point it is imperative that he undergo bronchoscopy and transbronchial biopsy.

Bronchoscopy demonstrated secretions from the right lower lobe. Gram stain from a bronchoalveolar lavage from the right lower lobe was negative, and cultures showed no growth after 24 hours. Immediately after bronchoscopy a third‐generation cephalosporin was empirically added. The next day the patient developed hypotension and was started on norepinephrine. Over the subsequent 48 hours, he developed progressive multiorgan failure. Despite multiple vasopressors, high‐frequency oscillator ventilation, broad‐spectrum antimicrobials, and activated protein C, he died in the intensive care unit. At the time of death, all blood cultures were negative, abdominal CT scans showed no intraabdominal infections, and the BAL performed on admission demonstrated negative gram stain, fungal stain, AFB stain, and PCP and no growth from fungal or bacterial cultures.

I think it is an unavoidable conclusion that this man's progressive systemic inflammatory response syndrome and ultimate multiorgan failure was caused by an opportunistic pathogen that was not antibiotic responsive and not identified from the extensive range of infectious disease studies performed. Despite all the negative studies, there still might be either mycobacterial illness or fungal illness. With negative cultures, Candida or Aspergillus infection is unlikely. Other opportunistic fungi like Blastomyces, Histoplasma, and Cryptococcus are certainly in the differential because these organisms can be notoriously difficult to detect on routine surveying such as bronchoalveolar lavage or lumbar puncture. Blastomyces and Histoplasma are both endemic in the area of Canada where the patient resided. I would also keep the zygomycoses in the differential.

Five days after death, fungal culture was reported demonstrating Blastomyces dermatitidis. Postmortem demonstrated disseminated blastomycosis causing severe bilateral pneumonia (Fig. 6a), empyema of right lung, and involvement of the thyroid, heart, liver, spleen, and kidneys. There was also evidence of active CNS blastomycosis involving the meninges and cerebral cortex and diencephalon (Fig. 6b). As well as active blastomycosis, the leptomeninges demonstrated fibrosis and old granulomas that did not contain an organism.

Figure 6

COMMENTARY

This case describes a 45‐year‐old man who presented with chronic cognitive symptoms associated with hydrocephalus. The first step in establishing the diagnosis was made by realizing that a communicating hydrocephalus with no parenchymal CNS disease was highly suggestive of a leptomeningeal process. This narrowed the differential diagnosis to an infiltrative disease affecting the leptomeninges. The next step involved the discovery of an upper‐lobe interstitial lung process, establishing sarcoidosis as the most likely unifying diagnosis. This was confirmed with transbronchial biopsies showing noncaseating granulomas and by the sustained response to treatment with corticosteroids. Unfortunately, after a 2‐year remission, he developed a recurrence of both the neurological and respiratory findings. When his symptoms progressed despite higher doses of corticosteroids, it became apparent that the etiology of his clinical deterioration was not recurrent disease. Instead, the deterioration was caused by disseminated blastomycosis, an opportunistic infection that developed as a result of the immunosuppressants used to treat the sarcoidosis.

With the final diagnosis of blastomycosis, one question about this case becomes: Could it have been blastomycosis and not sarcoid that was responsible for his original neurological presentation? Blastomyces dermatitidis is a thermally dimorphic fungus that causes disease from inhalation of airborne spores found in soil. Areas of North America in which it is endemic include regions bordering the Mississipi and Ohio rivers, as well as the areas bordering the Great Lakes.1 The patient in this case lived in metropolitan Toronto, on Lake Ontario, where blastomycosis is an important yet underreported disease.24 He likely was exposed to blastomyces in Toronto, which in immunocompromised patients may be followed after weeks to months by dissemination to other body sites including the dermis, bones, joints, urogenital system, and, rarely, the central nervous system (CNS) and liver.5 Like sarcoidosis, infection with blastomycosis can produce pathologic evidence of noncaseating granulomatous inflammation. However, as the discussant astutely pointed out, it would be unusual for this patient to have clinically inapparent blastomycosis for almost 2 years while on high‐dose prednisone. The initial diagnosis of sarcoid likely was correct.

CNS disease caused by Blastomyces dermatitidis is quite rare, with only 22 reported cases of meningoencephalitis in the literature.6 As this case demonstrates, CNS blastomycosis is very difficult to diagnose because of the absence of sensitive serologic markers and the difficulty of isolating the organism from blood and cerebrospinal fluid. CSF sampling from lumbar puncture led to its diagnosis in only 2 of the 22 reported cases.7 Furthermore, reliable CSF cultures are usually only obtained via ventricular sampling or tissue biopsy, which itself is limited by the organism's predilection for deep structures of the cerebrum, midbrain, and basal meninges.6 Blastomyces involving the CNS rarely occurs in isolation. In the patient's case, during his neurological deterioration, there was clear radiological evidence of progressive pulmonary pathology despite his being asymptomatic, and as the discussant suggests, pulmonary investigations were warranted.

Pulmonary manifestations of blastomycosis are variable. Acute infections most commonly resemble pneumonia, whereas chronic disease may show reticulonodular changes indistinguishable from sarcoidosis. Severe cases have been shown to progress to respiratory failure with acute respiratory distress syndrome (ARDS).1 The diagnosis is usually established through culture of noninvasive (sensitivity 86%) or bronchoalveolar lavage (sensitivity 92%) specimens.8 However, blastomyces will take between 5 and 30 days to grow in culture.1 In cases where the diagnosis needs to be established quickly, a KOH smear can be done looking for broad‐based budding yeast. Although the yield of this test is lower (0%‐50%), the results can be available within 24 hours.9 As these tests are not always routinely performed, direct communication with the pathologist is recommended if a rapid diagnosis is needed.

The major challenge of this case lay in distinguishing between the recurrence of an old disease and the complications of its treatment. In this case the discussant addresses strategies that might be useful in differentiating recurrent sarcoidosis from an opportunistic infection like blastomycosis. The first issue is the steroid therapy. The exact dose of steroids required to compromise the immune system enough to yield infections is not known. However, in a meta‐analysis of 71 controlled clinical trials performed with steroids, Stuck et. al. were able to show that the occurrence of opportunistic infections depended on both the amount of daily steroid and the cumulative dose.10 Opportunistic infections were unlikely to occur in patients given a mean daily dose of less than 10 mg/day or a cumulative dose of less than 700 mg of prednisone. Although the patient in the present case was only on 10 mg/day of prednisone, his mean daily dose was more than 10 mg/day, and his cumulative dose far exceeded 700 mg. Therefore, an opportunistic infection should have been strongly considered.

The other item used to help distinguish between the 2 diseases was serum angiotensin‐converting enzyme (ACE) level. ACE is an enzyme produced by the epithelial cells of the granulomas in sarcoidosis. ACE alone is inadequate for diagnosis, with a reported sensitivity of 40%‐90%, depending on the population studied and on the definition of normal.1114 Even an ACE level more than twice the normal is not diagnostic for sarcoidosis, with elevated levels found in histoplasmosis, silicosis, tuberculosis, Gaucher's disease, and other disorders.15 Rather than as a diagnostic test, ACE level instead is used to follow disease activity in sarcoidosis, as ACE level often reflects the granuloma burden.1618 The low levels at the initial recurrence suggests the symptoms were not a result of active sarcoid, especially considering that if ACE levels are originally elevated with sarcoidosis, they are almost always elevated again when the disease recurs.14 Normal levels of ACE in sarcoid patients with previously elevated ACE levels should therefore prompt a search for an alternate diagnosis.

This case is an example of the therapy causing a complication that mimics the disease it was intended to cure. When any patient deteriorates while on steroids, the clinician must ask the age‐old question: should more steroids be prescribed or less? As in this case, the answer is not always apparent. Safe decisions in these situations demand awareness of the opportunistic infections endemic to the area and a willingness to perform early invasive procedures (in this case bronchoscopy) to obtain samples to make a definitive diagnosis. By doing so, the devastating chain of events that occurred here hopefully can be avoided.

I was a newly appointed head of a department of medicine. Supervising the care of 44 patients and instructing interns and residents was a new and thrilling experience. Some patients presented complex problems, which satisfied my detective instincts and provided a stimulating intellectual challenge. Many others were less intellectually demanding, but I loved the personal interaction, the ability to change things for the better, and the endless variability.

It amazes me to reflect on how uncritical I was at the time, adopting and following common clinical practices with little questioning. It never really crossed my mind that medicine could be practiced in a different and better way. When I managed after some months to set aside one day a week to continue basic research, I was overjoyed. On that day, I became a scientist, putting each assumption to rigorous testing. At the hospital however, I was much more self‐assured and complacent. It was during a break between experiments at the research institute that I slumped wearily into an armchair in the library and picked up a shabby copy of the Green Journal. Being too tired for anything serious, I started reading what looked like a fairy tale. It was titled In a stew, by Michael LaCombe, whom I knew to be a gifted medical writer.1 Soon I found myself immersed in the story. The princess is seriously sick, and all the court doctors are baffled. She already has had 4 CT scans, 3 MRIs, and dozens of other tests. All the tests were fine, but the princess remains very sick, and the king is terribly worried. Then, somebody remembers an old, forgotten clinician who has been relegated to a small dusty den somewhere in the basement. For his services to be rendered, all he demands is that someone find him his stethoscope and that he be allowed to have a pupil. Using observation, knowledge, and wisdom (but no further tests), he elegantly elicits the relevant history and makes the correct diagnosis, which has eluded all the sophisticated court doctors armed with their batteries of high‐tech tests but with little regard for old‐fashioned clinical methods.

This was good fun, but though I enjoyed it very much, I had no idea that it would remain in my mind and shape my thinking, my practice, and my teaching. Nevertheless, I gradually found myself during rounds reflecting on this story with the patient who had had 2 CT scans done before anyone bothered to listen to him or examine him and with the patient who had been studied for months before a simple fact that should have been noted at once was finally revealed, which led to a single test that was diagnostic and to the patient's recovery.2 Then there was the patient who underwent a procedure, which looked innocent enough, but resulted in an adverse event that cascaded into months of life‐threatening illness.3 Was the procedure really necessary?

One night, a couple of years later, I woke up and instead of going back to sleep, sat in the silent living room, suddenly thinking of our departmental routine and realizing somehow that many things we physicians do may be seriously flawed: taking a superficial history and performing a perfunctory exam; having a light finger on the trigger of test ordering even if imaging and tests may mean little out of the clinical context and often beget more unnecessary testing; skipping significant information only because it is not immediately available but has to be found at another hospital or clinic or by calling the primary physician; disregarding the ubiquitous and influential emotional aspect or the patient's perspective and health literacy, which are essential for shared decisions; and the repeated underuse4 of highly effective medications and especially of proven preventive measures that are not pharmacological and hence not vigorously promoted by the large pharmaceutical companies.

The seed for this heresy was sown by the fable, and it colored my clinical life with a vein of skepticism and self‐criticism. Slowly it also grew into a long‐term commitment to teaching about and research on avoidable pitfalls in patient care.5

Thus, Lacombe's little piece often comes back to me, teaching me that a fairy tale can sometimes be more powerful than a randomized controlled study of 10,000 patients.

I was a newly appointed head of a department of medicine. Supervising the care of 44 patients and instructing interns and residents was a new and thrilling experience. Some patients presented complex problems, which satisfied my detective instincts and provided a stimulating intellectual challenge. Many others were less intellectually demanding, but I loved the personal interaction, the ability to change things for the better, and the endless variability.

It amazes me to reflect on how uncritical I was at the time, adopting and following common clinical practices with little questioning. It never really crossed my mind that medicine could be practiced in a different and better way. When I managed after some months to set aside one day a week to continue basic research, I was overjoyed. On that day, I became a scientist, putting each assumption to rigorous testing. At the hospital however, I was much more self‐assured and complacent. It was during a break between experiments at the research institute that I slumped wearily into an armchair in the library and picked up a shabby copy of the Green Journal. Being too tired for anything serious, I started reading what looked like a fairy tale. It was titled In a stew, by Michael LaCombe, whom I knew to be a gifted medical writer.1 Soon I found myself immersed in the story. The princess is seriously sick, and all the court doctors are baffled. She already has had 4 CT scans, 3 MRIs, and dozens of other tests. All the tests were fine, but the princess remains very sick, and the king is terribly worried. Then, somebody remembers an old, forgotten clinician who has been relegated to a small dusty den somewhere in the basement. For his services to be rendered, all he demands is that someone find him his stethoscope and that he be allowed to have a pupil. Using observation, knowledge, and wisdom (but no further tests), he elegantly elicits the relevant history and makes the correct diagnosis, which has eluded all the sophisticated court doctors armed with their batteries of high‐tech tests but with little regard for old‐fashioned clinical methods.

This was good fun, but though I enjoyed it very much, I had no idea that it would remain in my mind and shape my thinking, my practice, and my teaching. Nevertheless, I gradually found myself during rounds reflecting on this story with the patient who had had 2 CT scans done before anyone bothered to listen to him or examine him and with the patient who had been studied for months before a simple fact that should have been noted at once was finally revealed, which led to a single test that was diagnostic and to the patient's recovery.2 Then there was the patient who underwent a procedure, which looked innocent enough, but resulted in an adverse event that cascaded into months of life‐threatening illness.3 Was the procedure really necessary?

One night, a couple of years later, I woke up and instead of going back to sleep, sat in the silent living room, suddenly thinking of our departmental routine and realizing somehow that many things we physicians do may be seriously flawed: taking a superficial history and performing a perfunctory exam; having a light finger on the trigger of test ordering even if imaging and tests may mean little out of the clinical context and often beget more unnecessary testing; skipping significant information only because it is not immediately available but has to be found at another hospital or clinic or by calling the primary physician; disregarding the ubiquitous and influential emotional aspect or the patient's perspective and health literacy, which are essential for shared decisions; and the repeated underuse4 of highly effective medications and especially of proven preventive measures that are not pharmacological and hence not vigorously promoted by the large pharmaceutical companies.

The seed for this heresy was sown by the fable, and it colored my clinical life with a vein of skepticism and self‐criticism. Slowly it also grew into a long‐term commitment to teaching about and research on avoidable pitfalls in patient care.5

Thus, Lacombe's little piece often comes back to me, teaching me that a fairy tale can sometimes be more powerful than a randomized controlled study of 10,000 patients.

I was a newly appointed head of a department of medicine. Supervising the care of 44 patients and instructing interns and residents was a new and thrilling experience. Some patients presented complex problems, which satisfied my detective instincts and provided a stimulating intellectual challenge. Many others were less intellectually demanding, but I loved the personal interaction, the ability to change things for the better, and the endless variability.

It amazes me to reflect on how uncritical I was at the time, adopting and following common clinical practices with little questioning. It never really crossed my mind that medicine could be practiced in a different and better way. When I managed after some months to set aside one day a week to continue basic research, I was overjoyed. On that day, I became a scientist, putting each assumption to rigorous testing. At the hospital however, I was much more self‐assured and complacent. It was during a break between experiments at the research institute that I slumped wearily into an armchair in the library and picked up a shabby copy of the Green Journal. Being too tired for anything serious, I started reading what looked like a fairy tale. It was titled In a stew, by Michael LaCombe, whom I knew to be a gifted medical writer.1 Soon I found myself immersed in the story. The princess is seriously sick, and all the court doctors are baffled. She already has had 4 CT scans, 3 MRIs, and dozens of other tests. All the tests were fine, but the princess remains very sick, and the king is terribly worried. Then, somebody remembers an old, forgotten clinician who has been relegated to a small dusty den somewhere in the basement. For his services to be rendered, all he demands is that someone find him his stethoscope and that he be allowed to have a pupil. Using observation, knowledge, and wisdom (but no further tests), he elegantly elicits the relevant history and makes the correct diagnosis, which has eluded all the sophisticated court doctors armed with their batteries of high‐tech tests but with little regard for old‐fashioned clinical methods.

This was good fun, but though I enjoyed it very much, I had no idea that it would remain in my mind and shape my thinking, my practice, and my teaching. Nevertheless, I gradually found myself during rounds reflecting on this story with the patient who had had 2 CT scans done before anyone bothered to listen to him or examine him and with the patient who had been studied for months before a simple fact that should have been noted at once was finally revealed, which led to a single test that was diagnostic and to the patient's recovery.2 Then there was the patient who underwent a procedure, which looked innocent enough, but resulted in an adverse event that cascaded into months of life‐threatening illness.3 Was the procedure really necessary?

One night, a couple of years later, I woke up and instead of going back to sleep, sat in the silent living room, suddenly thinking of our departmental routine and realizing somehow that many things we physicians do may be seriously flawed: taking a superficial history and performing a perfunctory exam; having a light finger on the trigger of test ordering even if imaging and tests may mean little out of the clinical context and often beget more unnecessary testing; skipping significant information only because it is not immediately available but has to be found at another hospital or clinic or by calling the primary physician; disregarding the ubiquitous and influential emotional aspect or the patient's perspective and health literacy, which are essential for shared decisions; and the repeated underuse4 of highly effective medications and especially of proven preventive measures that are not pharmacological and hence not vigorously promoted by the large pharmaceutical companies.

The seed for this heresy was sown by the fable, and it colored my clinical life with a vein of skepticism and self‐criticism. Slowly it also grew into a long‐term commitment to teaching about and research on avoidable pitfalls in patient care.5

Thus, Lacombe's little piece often comes back to me, teaching me that a fairy tale can sometimes be more powerful than a randomized controlled study of 10,000 patients.

It is widely acknowledged that the U.S. health care system is plagued by error and inefficiency and that these factors contribute to as many as 44,000‐98,000 deaths each year in U.S. hospitals. In To Err Is Human: Building a Safer Health System, the Institute of Medicine1 outlined the critical role that information technology can play in improving patient safety and highlighted computerized physician order entry (CPOE) systems for their potential to reduce the frequency of medication errors and to improve the quality of medical care.

Computerized physician order entry systems are specialized software applications that allow physicians to place orders directly into a computer. This process has a number of potential advantages over traditional handwritten ordering, including the ability to structure the ordering process to ensure the completeness of individual orders, to provide clinical decision support through diagnosis‐based order sets, and to automatically check orders for potential drugallergy, drugdrug, and drugfood interactions.2 Finally, entering orders directly into a computer eliminates the problem of transcription‐related errors that stem from the difficulty of interpreting handwriting. In clinical trials, the introduction of CPOE has been shown to reduce the frequency of medication errors, to improve the use of preventive services, and to reduce costs.36 Recognition of the benefits of these systems has not been confined to the medical community. The Leapfrog Organization, a coalition of large businesses in the United States, has chosen CPOE as one of its 3 initial safety leaps and has established a threshold that 70% of medication orders should be entered directly by physicians.7

Although the benefits of CPOE systems are widely recognized, few hospitals have implemented these systems successfully.8, 9 Those that have, have often developed the applications internally, and many have relied on house staff to do most or all of the actual ordering.10 However, most hospitals do not have the expertise for internal development and instead rely on commercially available products. Moreover, most patients hospitalized in the United States are cared for by attending physicians working without the assistance of house staff.11 In light of the importance of successfully implementing CPOE systems in such settings, we assessed the adoption of CPOE by attending physicians at 2 community hospitals where its use was voluntary and examined the characteristics and attitudes associated with use of the system to place orders.

METHODS

RESULTS

During the study period the target group of physicians placed a total of 135,692 orders, of which 69,654 (51%) were placed directly into the CPOE system, 38,878 (29%) were made using pen and paper, 7,208 (5%) were made verbally, and 19,952 (15%) were placed by telephone. Three hundred and fifty‐six (71%) of the 502 surveys sent out to physicians at the 2 hospitals were returned. Thirteen surveys were excluded from analysis because the respondent was not a physician, and 2 because we were unable to match the survey to system usage data, leaving a total of 341 surveys for analysis. Order entry rates were not computed for an additional 3 physicians who only placed verbal and telephone orders during the study period. Response rates did not differ by clinician specialty (P = .53); compared to those of nonresponders, respondents had a similar median total number of orders (111 vs. 101, P = .67) and a higher median order entry rate (66% vs. 48%, P = .03).

Characteristics and Attitudes of High, Intermediate, and Low Users

The median order entry rate of respondents was 66%. One hundred and forty‐one (42%) placed at least 80% of their orders directly into the system, whereas 109 (32%) placed no more than 20% of their orders directly in the system (Fig. 1). There was not a significant difference between the low, intermediate, and high use groups in the total number of orders that each physician placed during the study period (Table 3). Sex, years since graduation from medical school, years in practice at the study institution, and use of computers in the outpatient setting were not meaningfully different between the 3 categories of users (Table 3). On the other hand, medical specialty was strongly associated with use of the system, with anesthesiologists, pediatricians, and surgeons the specialties with the largest proportion of high users. Furthermore, physicians who were trained in a CPOE environment and those who reported daily use of computers for personal activities showed the highest levels of adoption. Physicians at Franklin Medical Center showed lower levels of order entry than their counterparts at Baystate.

Figure 1

Table 3.Characteristics of Survey Respondents (n=338) with Written and/or Direct Entry Orders in Month Preceding Survey according to Low, Intermediate, and High Usage of a CPOE System

	Low (20%) n (row %)	Intermediate (20%‐79%) n (row %)	High (80%) n (row %)	P value
a Among n = 299 with outpatient practice. b Because of missing survey responses, category values may not add up to total. c Pearson chi‐square P value. d Mantel‐Haenszel chi‐square P value. e Kruskal‐Wallis P value
	n = 109	n = 88	n = 141
Hospital				< .01c
Baystate	73 (25)	79 (27)	138 (48)
Franklin	36 (75)	9 (19)	3 (6)
Sex				.69c
Female	28 (29)	24 (25)	43 (45)
Male	81 (33)	64 (26)	98 (40)
Specialty				.0001c
Anesthesia	8 (35)	3 (13)	12 (52)
Internal medicine	45 (33)	37 (27)	53 (39)
Medicine/pediatrics	6 (46)	5 (38)	2 (15)
OB/GYN	20 (56)	12 (33)	4 (11)
Pediatrics	13 (24)	9 (17)	32 (59)
Surgery	14 (23)	21 (34)	26 (43)
Other	3 (19)	1 (6)	12 (75)
Do you use a computer in your outpatient practice?a
Yes	75 (31)	61 (25)	105 (44)	.22c
No	20 (36)	18 (33)	17 (31)
Level of personal computer useb				.045d
Rarely	11 (44)	8 (32)	6 (24)
A few times a month	7 (33)	4 (19)	10 (48)
Several times a week	28 (35)	25 (31)	28 (35)
At least once a day	62 (30)	50 (24)	97 (46)
Training at an institution that had CPOE				.037c
Yes	30 (26)	40 (34)	46 (40)
No	76 (35)	48 (22)	94 (43)
	Median (IQR)	Median (IQR)	Median (IQR)
Years since graduation from medical school	21 (16, 28)	18 (14, 25)	19 (12, 25)	.06e
Years in practice at study institution	12 (5, 19)	12 (6, 19)	12 (6, 17)	.84e
Total number of orders placed	112 (45, 306)	105 (56, 254)	113 (44, 382)	.92e

Use of the system was highly associated with physician attitudes toward CPOE, with the views of intermediate and high users consistently different than those of low users (Fig. 2). The associations found held true regardless of hospital: low, intermediate, and high users from Franklin had similar responses to those from Baystate (P > .05 for all questions), and the data from the 2 hospitals therefore were combined for presentation. Although few physicians believed that the user interface of the system supported their work flow, high and intermediate users were 3 times as likely to share this view than were low users (Q7; Fig. 2). Similarly, 19% of low users, 31% of intermediate users, and 45% of high users believed that entering orders into the system was faster than writing orders (Q1). High and intermediate users of the system were more likely than low users to believe that orders entered into the system were carried out more rapidly (Q2) and led to fewer medication (Q3) and nonmedication (Q4) errors. Regardless of their utilization pattern, most physicians believed that order sets played an important role in promoting efficiency and quality.

Figure 2

DISCUSSION

In this study of the clinical computing practices of physicians at 2 community hospitals, we observed wide variation in the adoption of CPOE by individual attendings. Although roughly one‐third rarely placed orders directly into the system, 42% had an order entry rate of at least 80%. Contrary to our initial expectation, we found little association between a physician's order entry rate with years in practice, duration of exposure to CPOE, or use of computers in the outpatient setting. On the other hand, we observed marked differences in use of the CPOE system across specialty lines and found that physicians who were exposed to CPOE during training and those who were regular users of computers for personal activities were more likely to embrace this technology. Further, we observed important differences between physicians who used the system to place some or most of their orders and those who did so only rarely in their beliefs and attitudes about the impact and benefits of CPOE. Physicians with higher order entry rates were more likely than their colleagues to believe that placing orders electronically was faster than handwriting and that use of the system led to fewer medical errors. These findings should be encouraging to hospitals hoping to implement CPOE because they suggest that successful adoption of CPOE is not limited to physicians who have just completed their residencies or to hospitals with the capability of designing and building their own systems. On the contrary, we documented that women, older physicians, and those with limited CPOE experience were as likely to be frequent users, especially if they perceived CPOE to be safer than handwriting and if they believed the user interface supported the efficient entering of orders.

On the basis of these results we recommend that in addition to purchasing systems that meet physician work‐flow needs and support the efficient entry of orders, hospital leaders should emphasize the quality and safety benefits of CPOE as part of a comprehensive change management strategy. The differences we observed in order entry rates across specialties may have resulted from several factors, including inherent differences in personality type associated with choice of specialty and in the level of customization of a system reflected in which and how many order sets are included. Such findings suggest that when it comes to CPOE, one size does not fit all, and implementation planning should be carried out at the specialty level. Finally, our observation that physicians who had exposure to CPOE during training were more likely to use the system to place orders suggests that the nation's training institutions will play an important role in fostering universal adoption of this technology.

Several earlier studies have reported on physician experiences with CPOE systems. Murff and Kannry12 surveyed 94 internal medicine house staff to compare experiences with 2 CPOE systems: the Department of Veterans Affairs Computerized Patient Record System (CPRS) and a commercially available product. They found striking differences in user satisfaction with numerous aspects of the systems, however they did not address attitudes toward safety or quality, and because house staff were required to place orders electronically they were unable to correlate responses with actual usage patterns. Weiner et al.13 compared the opinions of internal medicine house staff, attendings, fellows, and nurses about the benefits and challenges of using a computerized provider order entry system. In contrast to the findings from our study, Weiner et al. reported that more than half of physicians believed that provider order entry led to a greater number of errors, and only a minority believed the system increased quality of care overall. Finally, Lee et al.14 surveyed medical and surgical house officers and nurses at a large academic medical center about their satisfaction with a locally developed order entry system. They found that attitudes about the impact of the system on productivity and ease of use were more strongly associated with overall satisfaction than having undergone training or experience with personal computers. These findings are congruous with our own observation that beliefs about the speed with which orders are placed are closely associated with actual use of the system. They reported, as have we, that physicians placed a high value on order sets.

Our study had a number of strengths. First, we were able to offer insight into the attitudes and behaviors of a previously neglected, but critically important groupattending physicians who care for patients at community hospitals without the assistance of house staff. Second, whereas previous studies primarily assessed physician satisfaction with CPOE, we explored how physician attitudes about the impact of CPOE on work flow and on safety were associated with actual ordering habits. Information about ordering was obtained directly from the order entry system and not through self‐report. We conducted the study at 2 hospitals, a large urban community teaching hospital and a smaller rural hospital, and focused on a CPOE system that is in use at many institutions throughout the country, thereby increasing the generalizability of our findings. Although adoption of the system by physicians at the 2 hospitals differed, factors that associated with the use of CPOE to place orders were similar. Finally, we surveyed a large number of physicians, had a high response rate, and found only small differences in the utilization patterns of responders and nonresponders, suggesting that our portrayal of the attitudes of physicians was representative of the views of physicians practicing in our community.

The study had a number of weaknesses. First, we cannot be sure whether preexisting beliefs about the benefits of CPOE directly influenced physicians' use of the system or, conversely, if these attitudes developed in response to experience as users. Nevertheless, it seems practical to suggest that hospitals focus on purchasing systems that support the efficient entering of orders while simultaneously adopting a communication and change management strategy that emphasizes the safety and quality benefits of CPOE more broadly. Second, we did not attempt to validate the opinions expressed by physicians about the usability or safety benefits of the system. That said, the purpose of the study was to determine whether physician attitudes toward these issues was associated with the use of the system to place orders. Whether or not this particular CPOE system actually prevented medication errors, most physicians believed it did, a belief strongly associated with the observed order entry rates. Third, we studied a single CPOE system implemented approximately 10 years ago that does not reflect state‐of‐the‐art user interface design or functionality. Nevertheless, our observation about the importance of the user experience is probably no less relevant today. Fourth, we were unable to ascertain every order given by physicians, as some so‐called MD to RN orders may never have made it into the system. Finally, there is a small risk that some written, telephone, and verbal orders may have been randomly or systematically assigned to incorrect physicians, which would have led us to calculate inaccurate utilization rates.

CONCLUSIONS

In a voluntary community hospital environment the adoption of CPOE by attending physicians varies widely. While placing a premium on the purchase of systems that meet the work‐flow needs of physicians and support the efficient entry of orders, hospital leaders can enhance physician adoption of this technology by communicating the role of CPOE in improving quality and safety.

It is widely acknowledged that the U.S. health care system is plagued by error and inefficiency and that these factors contribute to as many as 44,000‐98,000 deaths each year in U.S. hospitals. In To Err Is Human: Building a Safer Health System, the Institute of Medicine1 outlined the critical role that information technology can play in improving patient safety and highlighted computerized physician order entry (CPOE) systems for their potential to reduce the frequency of medication errors and to improve the quality of medical care.

Computerized physician order entry systems are specialized software applications that allow physicians to place orders directly into a computer. This process has a number of potential advantages over traditional handwritten ordering, including the ability to structure the ordering process to ensure the completeness of individual orders, to provide clinical decision support through diagnosis‐based order sets, and to automatically check orders for potential drugallergy, drugdrug, and drugfood interactions.2 Finally, entering orders directly into a computer eliminates the problem of transcription‐related errors that stem from the difficulty of interpreting handwriting. In clinical trials, the introduction of CPOE has been shown to reduce the frequency of medication errors, to improve the use of preventive services, and to reduce costs.36 Recognition of the benefits of these systems has not been confined to the medical community. The Leapfrog Organization, a coalition of large businesses in the United States, has chosen CPOE as one of its 3 initial safety leaps and has established a threshold that 70% of medication orders should be entered directly by physicians.7

Although the benefits of CPOE systems are widely recognized, few hospitals have implemented these systems successfully.8, 9 Those that have, have often developed the applications internally, and many have relied on house staff to do most or all of the actual ordering.10 However, most hospitals do not have the expertise for internal development and instead rely on commercially available products. Moreover, most patients hospitalized in the United States are cared for by attending physicians working without the assistance of house staff.11 In light of the importance of successfully implementing CPOE systems in such settings, we assessed the adoption of CPOE by attending physicians at 2 community hospitals where its use was voluntary and examined the characteristics and attitudes associated with use of the system to place orders.

METHODS

RESULTS

During the study period the target group of physicians placed a total of 135,692 orders, of which 69,654 (51%) were placed directly into the CPOE system, 38,878 (29%) were made using pen and paper, 7,208 (5%) were made verbally, and 19,952 (15%) were placed by telephone. Three hundred and fifty‐six (71%) of the 502 surveys sent out to physicians at the 2 hospitals were returned. Thirteen surveys were excluded from analysis because the respondent was not a physician, and 2 because we were unable to match the survey to system usage data, leaving a total of 341 surveys for analysis. Order entry rates were not computed for an additional 3 physicians who only placed verbal and telephone orders during the study period. Response rates did not differ by clinician specialty (P = .53); compared to those of nonresponders, respondents had a similar median total number of orders (111 vs. 101, P = .67) and a higher median order entry rate (66% vs. 48%, P = .03).

Characteristics and Attitudes of High, Intermediate, and Low Users

The median order entry rate of respondents was 66%. One hundred and forty‐one (42%) placed at least 80% of their orders directly into the system, whereas 109 (32%) placed no more than 20% of their orders directly in the system (Fig. 1). There was not a significant difference between the low, intermediate, and high use groups in the total number of orders that each physician placed during the study period (Table 3). Sex, years since graduation from medical school, years in practice at the study institution, and use of computers in the outpatient setting were not meaningfully different between the 3 categories of users (Table 3). On the other hand, medical specialty was strongly associated with use of the system, with anesthesiologists, pediatricians, and surgeons the specialties with the largest proportion of high users. Furthermore, physicians who were trained in a CPOE environment and those who reported daily use of computers for personal activities showed the highest levels of adoption. Physicians at Franklin Medical Center showed lower levels of order entry than their counterparts at Baystate.

Figure 1

Table 3.Characteristics of Survey Respondents (n=338) with Written and/or Direct Entry Orders in Month Preceding Survey according to Low, Intermediate, and High Usage of a CPOE System

	Low (20%) n (row %)	Intermediate (20%‐79%) n (row %)	High (80%) n (row %)	P value
a Among n = 299 with outpatient practice. b Because of missing survey responses, category values may not add up to total. c Pearson chi‐square P value. d Mantel‐Haenszel chi‐square P value. e Kruskal‐Wallis P value
	n = 109	n = 88	n = 141
Hospital				< .01c
Baystate	73 (25)	79 (27)	138 (48)
Franklin	36 (75)	9 (19)	3 (6)
Sex				.69c
Female	28 (29)	24 (25)	43 (45)
Male	81 (33)	64 (26)	98 (40)
Specialty				.0001c
Anesthesia	8 (35)	3 (13)	12 (52)
Internal medicine	45 (33)	37 (27)	53 (39)
Medicine/pediatrics	6 (46)	5 (38)	2 (15)
OB/GYN	20 (56)	12 (33)	4 (11)
Pediatrics	13 (24)	9 (17)	32 (59)
Surgery	14 (23)	21 (34)	26 (43)
Other	3 (19)	1 (6)	12 (75)
Do you use a computer in your outpatient practice?a
Yes	75 (31)	61 (25)	105 (44)	.22c
No	20 (36)	18 (33)	17 (31)
Level of personal computer useb				.045d
Rarely	11 (44)	8 (32)	6 (24)
A few times a month	7 (33)	4 (19)	10 (48)
Several times a week	28 (35)	25 (31)	28 (35)
At least once a day	62 (30)	50 (24)	97 (46)
Training at an institution that had CPOE				.037c
Yes	30 (26)	40 (34)	46 (40)
No	76 (35)	48 (22)	94 (43)
	Median (IQR)	Median (IQR)	Median (IQR)
Years since graduation from medical school	21 (16, 28)	18 (14, 25)	19 (12, 25)	.06e
Years in practice at study institution	12 (5, 19)	12 (6, 19)	12 (6, 17)	.84e
Total number of orders placed	112 (45, 306)	105 (56, 254)	113 (44, 382)	.92e

Use of the system was highly associated with physician attitudes toward CPOE, with the views of intermediate and high users consistently different than those of low users (Fig. 2). The associations found held true regardless of hospital: low, intermediate, and high users from Franklin had similar responses to those from Baystate (P > .05 for all questions), and the data from the 2 hospitals therefore were combined for presentation. Although few physicians believed that the user interface of the system supported their work flow, high and intermediate users were 3 times as likely to share this view than were low users (Q7; Fig. 2). Similarly, 19% of low users, 31% of intermediate users, and 45% of high users believed that entering orders into the system was faster than writing orders (Q1). High and intermediate users of the system were more likely than low users to believe that orders entered into the system were carried out more rapidly (Q2) and led to fewer medication (Q3) and nonmedication (Q4) errors. Regardless of their utilization pattern, most physicians believed that order sets played an important role in promoting efficiency and quality.

Figure 2

DISCUSSION

In this study of the clinical computing practices of physicians at 2 community hospitals, we observed wide variation in the adoption of CPOE by individual attendings. Although roughly one‐third rarely placed orders directly into the system, 42% had an order entry rate of at least 80%. Contrary to our initial expectation, we found little association between a physician's order entry rate with years in practice, duration of exposure to CPOE, or use of computers in the outpatient setting. On the other hand, we observed marked differences in use of the CPOE system across specialty lines and found that physicians who were exposed to CPOE during training and those who were regular users of computers for personal activities were more likely to embrace this technology. Further, we observed important differences between physicians who used the system to place some or most of their orders and those who did so only rarely in their beliefs and attitudes about the impact and benefits of CPOE. Physicians with higher order entry rates were more likely than their colleagues to believe that placing orders electronically was faster than handwriting and that use of the system led to fewer medical errors. These findings should be encouraging to hospitals hoping to implement CPOE because they suggest that successful adoption of CPOE is not limited to physicians who have just completed their residencies or to hospitals with the capability of designing and building their own systems. On the contrary, we documented that women, older physicians, and those with limited CPOE experience were as likely to be frequent users, especially if they perceived CPOE to be safer than handwriting and if they believed the user interface supported the efficient entering of orders.

On the basis of these results we recommend that in addition to purchasing systems that meet physician work‐flow needs and support the efficient entry of orders, hospital leaders should emphasize the quality and safety benefits of CPOE as part of a comprehensive change management strategy. The differences we observed in order entry rates across specialties may have resulted from several factors, including inherent differences in personality type associated with choice of specialty and in the level of customization of a system reflected in which and how many order sets are included. Such findings suggest that when it comes to CPOE, one size does not fit all, and implementation planning should be carried out at the specialty level. Finally, our observation that physicians who had exposure to CPOE during training were more likely to use the system to place orders suggests that the nation's training institutions will play an important role in fostering universal adoption of this technology.

Several earlier studies have reported on physician experiences with CPOE systems. Murff and Kannry12 surveyed 94 internal medicine house staff to compare experiences with 2 CPOE systems: the Department of Veterans Affairs Computerized Patient Record System (CPRS) and a commercially available product. They found striking differences in user satisfaction with numerous aspects of the systems, however they did not address attitudes toward safety or quality, and because house staff were required to place orders electronically they were unable to correlate responses with actual usage patterns. Weiner et al.13 compared the opinions of internal medicine house staff, attendings, fellows, and nurses about the benefits and challenges of using a computerized provider order entry system. In contrast to the findings from our study, Weiner et al. reported that more than half of physicians believed that provider order entry led to a greater number of errors, and only a minority believed the system increased quality of care overall. Finally, Lee et al.14 surveyed medical and surgical house officers and nurses at a large academic medical center about their satisfaction with a locally developed order entry system. They found that attitudes about the impact of the system on productivity and ease of use were more strongly associated with overall satisfaction than having undergone training or experience with personal computers. These findings are congruous with our own observation that beliefs about the speed with which orders are placed are closely associated with actual use of the system. They reported, as have we, that physicians placed a high value on order sets.

Our study had a number of strengths. First, we were able to offer insight into the attitudes and behaviors of a previously neglected, but critically important groupattending physicians who care for patients at community hospitals without the assistance of house staff. Second, whereas previous studies primarily assessed physician satisfaction with CPOE, we explored how physician attitudes about the impact of CPOE on work flow and on safety were associated with actual ordering habits. Information about ordering was obtained directly from the order entry system and not through self‐report. We conducted the study at 2 hospitals, a large urban community teaching hospital and a smaller rural hospital, and focused on a CPOE system that is in use at many institutions throughout the country, thereby increasing the generalizability of our findings. Although adoption of the system by physicians at the 2 hospitals differed, factors that associated with the use of CPOE to place orders were similar. Finally, we surveyed a large number of physicians, had a high response rate, and found only small differences in the utilization patterns of responders and nonresponders, suggesting that our portrayal of the attitudes of physicians was representative of the views of physicians practicing in our community.

The study had a number of weaknesses. First, we cannot be sure whether preexisting beliefs about the benefits of CPOE directly influenced physicians' use of the system or, conversely, if these attitudes developed in response to experience as users. Nevertheless, it seems practical to suggest that hospitals focus on purchasing systems that support the efficient entering of orders while simultaneously adopting a communication and change management strategy that emphasizes the safety and quality benefits of CPOE more broadly. Second, we did not attempt to validate the opinions expressed by physicians about the usability or safety benefits of the system. That said, the purpose of the study was to determine whether physician attitudes toward these issues was associated with the use of the system to place orders. Whether or not this particular CPOE system actually prevented medication errors, most physicians believed it did, a belief strongly associated with the observed order entry rates. Third, we studied a single CPOE system implemented approximately 10 years ago that does not reflect state‐of‐the‐art user interface design or functionality. Nevertheless, our observation about the importance of the user experience is probably no less relevant today. Fourth, we were unable to ascertain every order given by physicians, as some so‐called MD to RN orders may never have made it into the system. Finally, there is a small risk that some written, telephone, and verbal orders may have been randomly or systematically assigned to incorrect physicians, which would have led us to calculate inaccurate utilization rates.

CONCLUSIONS

In a voluntary community hospital environment the adoption of CPOE by attending physicians varies widely. While placing a premium on the purchase of systems that meet the work‐flow needs of physicians and support the efficient entry of orders, hospital leaders can enhance physician adoption of this technology by communicating the role of CPOE in improving quality and safety.

It is widely acknowledged that the U.S. health care system is plagued by error and inefficiency and that these factors contribute to as many as 44,000‐98,000 deaths each year in U.S. hospitals. In To Err Is Human: Building a Safer Health System, the Institute of Medicine1 outlined the critical role that information technology can play in improving patient safety and highlighted computerized physician order entry (CPOE) systems for their potential to reduce the frequency of medication errors and to improve the quality of medical care.

Computerized physician order entry systems are specialized software applications that allow physicians to place orders directly into a computer. This process has a number of potential advantages over traditional handwritten ordering, including the ability to structure the ordering process to ensure the completeness of individual orders, to provide clinical decision support through diagnosis‐based order sets, and to automatically check orders for potential drugallergy, drugdrug, and drugfood interactions.2 Finally, entering orders directly into a computer eliminates the problem of transcription‐related errors that stem from the difficulty of interpreting handwriting. In clinical trials, the introduction of CPOE has been shown to reduce the frequency of medication errors, to improve the use of preventive services, and to reduce costs.36 Recognition of the benefits of these systems has not been confined to the medical community. The Leapfrog Organization, a coalition of large businesses in the United States, has chosen CPOE as one of its 3 initial safety leaps and has established a threshold that 70% of medication orders should be entered directly by physicians.7

Although the benefits of CPOE systems are widely recognized, few hospitals have implemented these systems successfully.8, 9 Those that have, have often developed the applications internally, and many have relied on house staff to do most or all of the actual ordering.10 However, most hospitals do not have the expertise for internal development and instead rely on commercially available products. Moreover, most patients hospitalized in the United States are cared for by attending physicians working without the assistance of house staff.11 In light of the importance of successfully implementing CPOE systems in such settings, we assessed the adoption of CPOE by attending physicians at 2 community hospitals where its use was voluntary and examined the characteristics and attitudes associated with use of the system to place orders.

METHODS

RESULTS

During the study period the target group of physicians placed a total of 135,692 orders, of which 69,654 (51%) were placed directly into the CPOE system, 38,878 (29%) were made using pen and paper, 7,208 (5%) were made verbally, and 19,952 (15%) were placed by telephone. Three hundred and fifty‐six (71%) of the 502 surveys sent out to physicians at the 2 hospitals were returned. Thirteen surveys were excluded from analysis because the respondent was not a physician, and 2 because we were unable to match the survey to system usage data, leaving a total of 341 surveys for analysis. Order entry rates were not computed for an additional 3 physicians who only placed verbal and telephone orders during the study period. Response rates did not differ by clinician specialty (P = .53); compared to those of nonresponders, respondents had a similar median total number of orders (111 vs. 101, P = .67) and a higher median order entry rate (66% vs. 48%, P = .03).

Characteristics and Attitudes of High, Intermediate, and Low Users

The median order entry rate of respondents was 66%. One hundred and forty‐one (42%) placed at least 80% of their orders directly into the system, whereas 109 (32%) placed no more than 20% of their orders directly in the system (Fig. 1). There was not a significant difference between the low, intermediate, and high use groups in the total number of orders that each physician placed during the study period (Table 3). Sex, years since graduation from medical school, years in practice at the study institution, and use of computers in the outpatient setting were not meaningfully different between the 3 categories of users (Table 3). On the other hand, medical specialty was strongly associated with use of the system, with anesthesiologists, pediatricians, and surgeons the specialties with the largest proportion of high users. Furthermore, physicians who were trained in a CPOE environment and those who reported daily use of computers for personal activities showed the highest levels of adoption. Physicians at Franklin Medical Center showed lower levels of order entry than their counterparts at Baystate.

Figure 1

Table 3.Characteristics of Survey Respondents (n=338) with Written and/or Direct Entry Orders in Month Preceding Survey according to Low, Intermediate, and High Usage of a CPOE System

	Low (20%) n (row %)	Intermediate (20%‐79%) n (row %)	High (80%) n (row %)	P value
a Among n = 299 with outpatient practice. b Because of missing survey responses, category values may not add up to total. c Pearson chi‐square P value. d Mantel‐Haenszel chi‐square P value. e Kruskal‐Wallis P value
	n = 109	n = 88	n = 141
Hospital				< .01c
Baystate	73 (25)	79 (27)	138 (48)
Franklin	36 (75)	9 (19)	3 (6)
Sex				.69c
Female	28 (29)	24 (25)	43 (45)
Male	81 (33)	64 (26)	98 (40)
Specialty				.0001c
Anesthesia	8 (35)	3 (13)	12 (52)
Internal medicine	45 (33)	37 (27)	53 (39)
Medicine/pediatrics	6 (46)	5 (38)	2 (15)
OB/GYN	20 (56)	12 (33)	4 (11)
Pediatrics	13 (24)	9 (17)	32 (59)
Surgery	14 (23)	21 (34)	26 (43)
Other	3 (19)	1 (6)	12 (75)
Do you use a computer in your outpatient practice?a
Yes	75 (31)	61 (25)	105 (44)	.22c
No	20 (36)	18 (33)	17 (31)
Level of personal computer useb				.045d
Rarely	11 (44)	8 (32)	6 (24)
A few times a month	7 (33)	4 (19)	10 (48)
Several times a week	28 (35)	25 (31)	28 (35)
At least once a day	62 (30)	50 (24)	97 (46)
Training at an institution that had CPOE				.037c
Yes	30 (26)	40 (34)	46 (40)
No	76 (35)	48 (22)	94 (43)
	Median (IQR)	Median (IQR)	Median (IQR)
Years since graduation from medical school	21 (16, 28)	18 (14, 25)	19 (12, 25)	.06e
Years in practice at study institution	12 (5, 19)	12 (6, 19)	12 (6, 17)	.84e
Total number of orders placed	112 (45, 306)	105 (56, 254)	113 (44, 382)	.92e

Use of the system was highly associated with physician attitudes toward CPOE, with the views of intermediate and high users consistently different than those of low users (Fig. 2). The associations found held true regardless of hospital: low, intermediate, and high users from Franklin had similar responses to those from Baystate (P > .05 for all questions), and the data from the 2 hospitals therefore were combined for presentation. Although few physicians believed that the user interface of the system supported their work flow, high and intermediate users were 3 times as likely to share this view than were low users (Q7; Fig. 2). Similarly, 19% of low users, 31% of intermediate users, and 45% of high users believed that entering orders into the system was faster than writing orders (Q1). High and intermediate users of the system were more likely than low users to believe that orders entered into the system were carried out more rapidly (Q2) and led to fewer medication (Q3) and nonmedication (Q4) errors. Regardless of their utilization pattern, most physicians believed that order sets played an important role in promoting efficiency and quality.

Figure 2

DISCUSSION

In this study of the clinical computing practices of physicians at 2 community hospitals, we observed wide variation in the adoption of CPOE by individual attendings. Although roughly one‐third rarely placed orders directly into the system, 42% had an order entry rate of at least 80%. Contrary to our initial expectation, we found little association between a physician's order entry rate with years in practice, duration of exposure to CPOE, or use of computers in the outpatient setting. On the other hand, we observed marked differences in use of the CPOE system across specialty lines and found that physicians who were exposed to CPOE during training and those who were regular users of computers for personal activities were more likely to embrace this technology. Further, we observed important differences between physicians who used the system to place some or most of their orders and those who did so only rarely in their beliefs and attitudes about the impact and benefits of CPOE. Physicians with higher order entry rates were more likely than their colleagues to believe that placing orders electronically was faster than handwriting and that use of the system led to fewer medical errors. These findings should be encouraging to hospitals hoping to implement CPOE because they suggest that successful adoption of CPOE is not limited to physicians who have just completed their residencies or to hospitals with the capability of designing and building their own systems. On the contrary, we documented that women, older physicians, and those with limited CPOE experience were as likely to be frequent users, especially if they perceived CPOE to be safer than handwriting and if they believed the user interface supported the efficient entering of orders.

On the basis of these results we recommend that in addition to purchasing systems that meet physician work‐flow needs and support the efficient entry of orders, hospital leaders should emphasize the quality and safety benefits of CPOE as part of a comprehensive change management strategy. The differences we observed in order entry rates across specialties may have resulted from several factors, including inherent differences in personality type associated with choice of specialty and in the level of customization of a system reflected in which and how many order sets are included. Such findings suggest that when it comes to CPOE, one size does not fit all, and implementation planning should be carried out at the specialty level. Finally, our observation that physicians who had exposure to CPOE during training were more likely to use the system to place orders suggests that the nation's training institutions will play an important role in fostering universal adoption of this technology.

Several earlier studies have reported on physician experiences with CPOE systems. Murff and Kannry12 surveyed 94 internal medicine house staff to compare experiences with 2 CPOE systems: the Department of Veterans Affairs Computerized Patient Record System (CPRS) and a commercially available product. They found striking differences in user satisfaction with numerous aspects of the systems, however they did not address attitudes toward safety or quality, and because house staff were required to place orders electronically they were unable to correlate responses with actual usage patterns. Weiner et al.13 compared the opinions of internal medicine house staff, attendings, fellows, and nurses about the benefits and challenges of using a computerized provider order entry system. In contrast to the findings from our study, Weiner et al. reported that more than half of physicians believed that provider order entry led to a greater number of errors, and only a minority believed the system increased quality of care overall. Finally, Lee et al.14 surveyed medical and surgical house officers and nurses at a large academic medical center about their satisfaction with a locally developed order entry system. They found that attitudes about the impact of the system on productivity and ease of use were more strongly associated with overall satisfaction than having undergone training or experience with personal computers. These findings are congruous with our own observation that beliefs about the speed with which orders are placed are closely associated with actual use of the system. They reported, as have we, that physicians placed a high value on order sets.

Our study had a number of strengths. First, we were able to offer insight into the attitudes and behaviors of a previously neglected, but critically important groupattending physicians who care for patients at community hospitals without the assistance of house staff. Second, whereas previous studies primarily assessed physician satisfaction with CPOE, we explored how physician attitudes about the impact of CPOE on work flow and on safety were associated with actual ordering habits. Information about ordering was obtained directly from the order entry system and not through self‐report. We conducted the study at 2 hospitals, a large urban community teaching hospital and a smaller rural hospital, and focused on a CPOE system that is in use at many institutions throughout the country, thereby increasing the generalizability of our findings. Although adoption of the system by physicians at the 2 hospitals differed, factors that associated with the use of CPOE to place orders were similar. Finally, we surveyed a large number of physicians, had a high response rate, and found only small differences in the utilization patterns of responders and nonresponders, suggesting that our portrayal of the attitudes of physicians was representative of the views of physicians practicing in our community.

The study had a number of weaknesses. First, we cannot be sure whether preexisting beliefs about the benefits of CPOE directly influenced physicians' use of the system or, conversely, if these attitudes developed in response to experience as users. Nevertheless, it seems practical to suggest that hospitals focus on purchasing systems that support the efficient entering of orders while simultaneously adopting a communication and change management strategy that emphasizes the safety and quality benefits of CPOE more broadly. Second, we did not attempt to validate the opinions expressed by physicians about the usability or safety benefits of the system. That said, the purpose of the study was to determine whether physician attitudes toward these issues was associated with the use of the system to place orders. Whether or not this particular CPOE system actually prevented medication errors, most physicians believed it did, a belief strongly associated with the observed order entry rates. Third, we studied a single CPOE system implemented approximately 10 years ago that does not reflect state‐of‐the‐art user interface design or functionality. Nevertheless, our observation about the importance of the user experience is probably no less relevant today. Fourth, we were unable to ascertain every order given by physicians, as some so‐called MD to RN orders may never have made it into the system. Finally, there is a small risk that some written, telephone, and verbal orders may have been randomly or systematically assigned to incorrect physicians, which would have led us to calculate inaccurate utilization rates.

CONCLUSIONS

In a voluntary community hospital environment the adoption of CPOE by attending physicians varies widely. While placing a premium on the purchase of systems that meet the work‐flow needs of physicians and support the efficient entry of orders, hospital leaders can enhance physician adoption of this technology by communicating the role of CPOE in improving quality and safety.

Aortocervicocephalic atherosclerotic disease and coronary artery disease share common risk factors, and patients with one condition are at high risk of harboring or developing the other.1, 2 Over the past decade, several randomized clinical trials of lipid‐lowering medications designed to reduce low‐density lipoprotein cholesterol (LDL‐C) have shown a significant decrease in the risk of coronary events and ischemic stroke among patients who have a history of or are at risk for coronary artery disease, regardless of whether serum cholesterol is elevated.3, 4 Results from more than 3000 stroke patients enrolled in the Heart Protection Study also provide evidence that aggressive lipid‐lowering therapy may prevent recurrent vascular events in individuals who have a total cholesterol level as low as 135 mg/dL and cerebrovascular disease, with or without known coronary artery disease.5

Guidelines from the National Cholesterol Evaluation Program Adult Treatment Panel (ATP) provide target LDL‐C levels for persons with atherosclerotic disease depending on the extent of their vascular risk.6 However, despite the broad dissemination of these guidelines, several published studies of patients with coronary artery disease or dyslipidemia have shown that a large proportion of patients with high vascular risk continue to be underscreened, underdiagnosed, and undertreated for dyslipidemia.79

Few studies have evaluated the quality of cholesterol management among hospitalized patients who have experienced an acute ischemic cerebrovascular event10, 11 So the data are scarce on the management of patients hospitalized for ischemic stroke or transient ischemic attack (TIA) who are, according to ATP criteria, at high risk for future coronary events and on the factors that may govern that management. Systematic reviews have suggested that incorporating a lipid profile during acute stroke presentation could assure baseline assessment and serve as a potential cue for physicians to change their behavior,12 and an American Stroke Association advisory recommends lipid treatment during hospitalization for most patients with ischemic stroke or TIA as it may increase the rate of long‐term use.13

The objectives of this study were to determine the rates of testing for and treatment of dyslipidemia according to national cholesterol guidelines among individuals hospitalized with acute ischemic stroke or TIA and to identify predictors of performance.

METHODS

The California Acute Stroke Prototype Registry (CASPR) is a Centers for Disease Controlsponsored cohort that captured detailed data on patients admitted to 11 hospitals over a 2‐year period. The methods of study have been described elsewhere.14 In brief, CASPR prospectively collected information on acute stroke care at 11 representative hospitals in 5 major population regions of California. Data were collected on diagnostic evaluation, appropriate use of treatment strategies, and disposition on discharge from the hospital. The main goal of CASPR was to pilot‐test a prototype prospective registry of acute stroke and transient ischemic attack to be used as a quality improvement tool. The study population was patients with an admitting or discharge diagnosis of suspected stroke or TIA from November 1, 2002, through January 31, 2003, and from November 1, 2003, through January 31, 2004. The human subjects review board at each participating center approved the study.

For the present analysis, data on all patients with a discharge diagnosis of ischemic stroke or TIA who were admitted during either period were included. We examined the possible association of several variables with 2 primary outcomes: (1) testing lipid profile during hospitalization (as indicated by a documented LDL‐C level) and (2) prescribing lipid‐lowering medication at discharge. In those analyses in which lipid profile testing was the outcome, no variables were considered acceptable reasons for not performing an LDL‐C assessment.

The distribution of LDL‐C levels in this portion of the cohort was determined. Patients were then categorized according to their risk for future coronary events. Patients were classified as at risk for coronary events (ACE) if they either had a documented history of myocardial infarction, coronary artery disease, or diabetes or had undergone carotid endarterectomy or carotid angioplasty/stenting during hospitalization. Criteria for initiating lipid‐lowering therapy were defined according to the ATP III guidelines,6 which were in effect during both CASPR study periods. Continuing the recommendation in ATP II, the ATP III recommendations emphasized that persons with documented coronary artery disease (CAD) receive the most aggressive lipid‐lowering treatment. But this recommendation was expanded to include patients without established CAD, whose coronary risk is equivalent to that of patients with diagnosed CAD.6

As per the ATP III guidelines, CASPR‐ACE patients were considered optimally treated if they were prescribed a lipid‐lowering agent at discharge or if their documented LDL‐C was less than 130 mg/dL. A concurrent history of liver disease, abnormal prothrombin time, life expectancy of less than 1 year, and terminal illness were each considered a valid contraindication to treatment with lipid‐lowering medication. Optimal treatment for non‐ACE patients was defined as receipt of lipid‐lowering medication at discharge or a documented LDL‐C of 160 mg/dL. The rate of optimal treatment of ACE patients was compared to that of non‐ACE patients. The ACE and non‐ACE patients were then further categorized into 1 of 4 groups according to LDL‐C level<100, 100130, 130160, and >160 mg/dLand an assessment for trend of the rate of treatment in each of the 4 categories in the ACE and non‐ACE groups was performed.

RESULTS

Data were available from the 11 CASPR hospitals for 764 patients diagnosed with either ischemic stroke or TIA. Overall, 53.4% of subjects were women, and the average age at hospitalization of 70.4 ( 15.4) years. In the cohort, 55.3% of the patients were non‐Hispanic white, 9.7% were African American, 13.4% were Hispanic, 13% were Asian, and 8.6% were classified as other. Three hundred and nine individuals (40.5% of the cohort) were classified as at risk for coronary events. Of these, 148 (47.8%) had diabetes only, and 160 (51.8%) had a history of MI, CAD, or both. One patient (0.4%) had undergone angioplasty/stenting during hospitalization but had no history of MI, CAD, or diabetes. Only 4 patients (0.52% of the entire cohort) had undergone a carotid endarterectomy or angioplasty/stenting during hospitalization. Rates of lipid assessment and optimal treatment varied widely between hospitals, but testing and treatment were correlated for each hospital. Overall, however, testing and treatment were correlated (Pearson correlation coefficient = 0.35, P < .0001). On an individual hospital level, the correlation was positive and significant for 6 hospitals, positive but not significant for 2 hospitals, and negative but not significant for 3 hospitals.

Overall, LDL‐C levels were determined in 383 patients (50.1%). The likelihood that a patient would have an LDL‐C test performed during hospitalization varied widely by hospital, ranging from 12% to 88% (P < .0001). Univariate variables significantly associated with documented LDL‐C measurement in the overall cohort at the = .10 level were diagnosis of ischemic stroke (as compared to TIA) and history of dyslipidemia (Table 1). In the CASPR cohort, 53% of the ACE subjects received a lipid profile assessment compared to 48% in the rest of the cohort (P = .14). In multivariate analysis, diagnosis of ischemic stroke and history of dyslipidemia remained significantly associated with documented LDL‐C measurement (Table 1).

Lipid‐lowering drugs were prescribed at discharge to 370 patients (48.4%); however, treatment rate varied among hospitals, from a low of 13% of patients to a high of 84% of patients (P < .0001). Univariate factors associated with a higher treatment rate at the = .10 level were diagnosis of ischemic stroke, history of stroke/TIA, history of diabetes, hypertension, history of dyslipidemia, independent ambulation at discharge, and ACE status (Table 2). Patients were less likely to receive lipid‐lowering medication if they had a history of heart failure. Fifty‐nine percent of the CASPR ACE subjects were discharged on lipid‐modifying agents compared to 42% in the rest of the cohort (P = .0006). Multivariate analyses revealed several independent predictors of treatment with lipid‐lowering medication. Diagnosis of ischemic stroke, ACE status, and history of heart failure were negative predictors (less likely to be treated), and history of dyslipidemia was a positive predictor (Table 2). Status as an academic hospital was a hospital characteristic for which a significant association was found. Academic hospitals were significantly more likely to both perform LDL profiles and administer lipid‐lowering medications at discharge than were nonacademic hospitals. This association was found in a logistic regression analysis that did not account for between‐hospital variance. However, when we used GEE analysis, which adjusted for the variance, the difference between academic and nonacademic hospitals was no longer significant.

Three of the patients with documented LDL‐C levels (0.8%) had documented contraindications to therapy. Among all those who had documented LDL‐C levels, the rate of appropriate treatment with lipid‐lowering medications was high in both the ACE and non‐ACE groups (94.6% and 98.6%, respectively; P = .02). However, because only a small number of patients did not receive optimal treatment, the odds ratio of 0.24 had a fairly wide confidence interval (95% CI = 0.06, 0.91). Although a trend toward a higher rate of treatment with increasing LDL‐C level was seen in both the ACE and non‐ACE groups, this trend was only significant for the group with non‐ACE patients (Figure 1).

Figure 1

DISCUSSION

We found that only half the patients hospitalized for ischemic stroke or TIA had LDL‐C levels tested while in the hospital, even among those identified by the ATP guidelines as at high risk for future coronary events. Our findings are in accord with those of the Coverdell Project, which evaluated key features of acute stroke care from 4 prototype registries, those in Georgia, Massachusetts, Michigan, and Ohio, finding that fewer than 40% of acute stroke patients had had lipid profiles checked during hospitalization.11 Our study also evaluated predictors for in‐hospital lipid testing and lipid‐lowering treatment during hospitalization for an acute ischemic cerebrovascular event. We found that lipid testing was correlated with treatment during stroke or TIA hospitalization, suggesting that in‐hospital lipid management is related to an overall appreciation of the importance of lipids.

Understanding the factors resulting in such underperformance is critical for improving patient care and outcomes. Lipid assessment and treatment rates varied widely between CASPR hospitals, reflecting dramatic differences in hospital practice. This finding is similar to that noted in a recent study performed in Europe10 and underscores the need to promote a more uniform approach to in‐hospital care of patients with ischemic stroke or TIA. Our study also found that ischemic stroke patients were much more likely to have their lipid level measured and to be discharged on a lipid‐lowering agent than were TIA patients. This may be so because many treating health care professionals perceive TIAs as benign events that carry a more favorable prognosis than do strokes, or it could be that the length of stay for a TIA, often shorter than that for a stroke, limited in‐hospital testing or planning for patient follow‐up.

A high proportion of non‐ACE, lipid‐tested stroke/TIA patients received lipid‐lowering drug treatment, even when their lipid levels were within the treatment range categorized as nonpharmacologic by the national guidelines. This finding could be a result of one of the goals of the primary study.15 In the primary study, the effect of standardized orders implemented during the second observational period were analyzed by comparing them to those in place during the first observational period to see if they had improved the in‐hospital stroke care process. One of the study goals was optimal discharge utilization of a lipid‐lowering agent, defined as prescription of a lipid modifier or an LDL < 100 mg/dL. There was a significant increase in the number of prescriptions for lipid modifiers at discharge after implementing the standardized orders.15 However, as this study has shown, when existing national cholesterol guidelines were strictly applied to all the patients,6 overall there was a suboptimal rate of utilization of lipid modifiers at discharge.

Lipid profile assessment during stroke admission is one of the 10 performance measures in the performance measure set of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) Stroke Disease‐Specific Care.16 Initiating therapy with lipid‐lowering agents before discharge may help to maintain continuity of care and clarify therapeutic intent, especially when a different physician is responsible for care after discharge from the hospital. Recent studies indicated that in‐hospital initiation of medication following admission for a vascular event tends to improve longer‐term patient adherence to treatment,17, 18 as well as vascular outcomes,19, 20 and is a strategy favored by the American Stroke Association.13, 21

This study had several limitations. Our definitions of dyslipidemia and of adherence to ATP III goals were based on single measurements of LDL‐C, rather than multiple determinations of lipoprotein subfractions. However, we believe that this approach parallels actual clinical practice more closely. Although LDL‐C is the most important of all the components of the lipid profile,6 because lipid subfractions other than LDL‐C were not collected in the CASPR registry, we may have misclassified a few patients. For instance, extremely high trigylceride levels can render LDL‐C levels inaccurate, and as such, not having a documented LDL‐C may not have always indicated that a lipid panel was not performed. It is also conceivable that physicians might actually have been more thorough in measuring LDL‐C, identifying contraindications to lipid‐lowering therapy, or instituting lipid‐lowering therapy than were noted in the hospital charts. However, for quality assurance purposes, what is documented is the only traceable record of what was actually asked for or done. As such, health care professionals are frequently encouraged to keep updated chart notes. This study was an assessment of in‐hospital behavior; the low utilization of lipid‐lowering agents observed may underestimate the final treatment rate, as we did not evaluate the postdischarge rate of therapy. However, recent data suggest in‐hospital prescription patterns are a major predictor of longer‐term care in the community.17, 22 Last, the CASPR investigators did not collect data on the rate of utilization of lipid agents prior to hospitalization or on the mechanisms by which the strokes and TIAs had occurred. Prehospital utilization of lipid agents has previously been revealed to influence the prescribing of lipid‐lowering agents at discharge.10 Knowledge of the mechanisms of the stroke and TIA events would have increased the number of those eligible for lipid treatment, particularly those whose events were to the result of an atherosclerotic mechanism per ATP III's more expansive definition of CHD risk equivalents, which includes carotid and other forms of clinical atherosclerotic disease.6 However, because the results of other studies that evaluated lipid management in all hospitalized stroke patients (regardless of mechanism)11, 23 or in all patients with any form of clinical atherosclerotic disease24 were in accord with those of our study, it would appear unlikely that such information would have made an overwhelming difference to our results.

In conclusion, the results of the present study suggest that considerable improvement is needed in identifying appropriate candidates among those who have had stroke or TIA and treating them with lipid‐lowering agents. Performing lipid testing in individuals hospitalized with ischemic stroke or TIA is important because it may inform the identification of persons for whom treatment should be initiated or modified. Lipid assessment during hospitalization for stroke/TIA and initiation of lipid‐lowering therapy when indicated are major management steps that all patients with ischemic cerebrovascular events should receive.