The average American adult reads at an 8th-grade level.¹ Limited general literacy can affect health literacy, which is defined as the “degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions.”^2,3 Adults with limited health literacy are at risk for poorer outcomes, including overuse of the emergency department and lower adherence to preventive care recommendations.⁴

Children transitioning from hospital to home depend on their adult caregivers (and their caregivers’ health literacy) to carry out discharge instructions. During the immediate postdischarge period, complex care needs can involve new or changed medications, follow-up instructions, home care instructions, and suggestions regarding when and why to seek additional care.

The discharge education provided to patients in the hospital is often subpar because of lack of standardization and divided responsibility among providers.⁵ Communication of vital information to patients with low health literacy has been noted to be particularly poor,⁶ as many patient education materials are written at 10th-, 11th-, and 12th-grade reading levels.⁴ Evidence supports providing materials written at 6th-grade level or lower to increase comprehension.⁷ Several studies have evaluated the quality and readability of discharge instructions for hospitalized adults,^8,9 and one study found a link between poorly written instructions for adult patients and readmission risk.¹⁰ Less is known about readability in pediatrics, in which education may be more important for families of children most commonly hospitalized for acute illness.

We conducted a study to describe readability levels, understandability scores, and completeness of written instructions given to families at hospital discharge.

Study Design and Setting

In this study, we performed a cross-sectional review of discharge instructions within electronic health records at Cincinnati Children’s Hospital Medical Center (CCHMC). The study was reviewed and approved by CCHMC’s Institutional Review Board. Charts were randomly selected from all hospital medicine service discharges during two 3-month periods of high patient volume: January-March 2014 and January-March 2015.

CCHMC is a large urban academic referral center that is the sole provider of general, subspecialty, and critical pediatric inpatient care for a large geographical area. CCHMC, which has 600 beds, provides cares for many children who live in impoverished settings. Its hospital medicine service consists of 4 teams that care for approximately 7000 children hospitalized with general pediatric illnesses each year. Each team consists of 5 or 6 pediatric residents supervised by a hospital medicine attending.

Providers, most commonly pediatric interns, generate discharge instructions in electronic health records. In this nonautomated process, they use free-text or nonstandardized templates to create content. At discharge, instructions are printed as part of the postvisit summary, which includes updates on medications and scheduled follow-up appointments. Bedside nurses verbally review the instructions with families and provide printed copies for home use.

Data Collection and Analysis

A random sequence generator was used to select charts for review. Instructions written in a language other than English were excluded. Written discharge instructions and clinical information, including age, sex, primary diagnosis, insurance type, number of discharge medications, number of scheduled appointments at discharge, and hospital length of stay, were abstracted from electronic health records and anonymized before analysis. The primary outcomes assessed were discharge instruction readability, understandability, and completeness. Readability was calculated with Fry Readability Scale (FRS) scores,¹¹ which range from 1 to 17 and correspond to reading levels (score 1 = 1st-grade reading level). Health literacy experts have used the FRS to assess readability in health care environments.¹²

Understandability was measured with the Patient Education Materials Assessment Tool (PEMAT), a validated scoring system provided by the Agency for Healthcare Research and Quality.¹³ The PEMAT measures the understandability of print materials on a scale ranging from 0% to 100%. Higher scores indicate increased understandability, and scores under 70% indicate instructions are difficult to understand.

Although recent efforts have focused on the development of quality metrics for hospital-to-home transitions of pediatric patients,¹⁴ during our study there were no standard items to include in pediatric discharge instructions. Five criteria for completeness were determined by consensus of 3 pediatric hospital medicine faculty and were informed by qualitative results of work performed at our institution—work in which families noted challenges with information overload and a desire for pertinent and usable information that would enhance caregiver confidence and discharge preparedness.¹⁵ The criteria included statement of diagnosis, description of diagnosis, signs and symptoms indicative of the need for escalation of care (warning signs), the person caregivers should call if worried, and contact information for the primary care provider, subspecialist, and/or emergency department. Each set of discharge instructions was manually evaluated for completeness (presence of each individual component, number of components present, presence of all components). All charts were scored by the same investigator. A convenience sample of 20 charts was evaluated by a different investigator to ensure rating parameters were clear and classification was consistent (defined as perfect agreement). If the primary rater was undecided on a discharge instruction score, the secondary rater rated the instruction, and consensus was reached.

Means, medians, and ranges were calculated to enumerate the distribution of readability levels, understandability scores, and completeness of discharge instructions. Instructions were classified as readable if the FRS score was 6 or under, as understandable if the PEMAT score was under 70%, and as complete if all 5 criteria were satisfied. Descriptive statistics were generated for all demographic and clinical variables.

Of the study period’s 3819 discharges, 200 were randomly selected for review. Table 1 lists the demographic and clinical information of patients included in the analyses. Median FRS score was 10, indicating a 10th-grade reading level (interquartile range, 8-12; range, 1-13) (Table 2). Only 14 (7%) of 200 discharge instructions had a score of 6 or under. Median PEMAT understandability score was 73% (interquartile range, 64%-82%), and 36% of instructions had a PEMAT score under 70%. No instruction satisfied all 5 of the defined characteristics of complete discharge instructions (Table 2).

To our knowledge, this is the first study of the readability, understandability, and completeness of discharge instructions in a pediatric population. We found that the majority of discharge instruction readability levels were 10th grade or higher, that many instructions were difficult to understand, and that important information was missing from many instructions.

Discharge instruction readability levels were higher than the literacy level of many families in surrounding communities. The high school dropout rates in Cincinnati are staggering; they range from 22% to 64% in the 10 neighborhoods with the largest proportion of residents not completing high school.¹⁶ However, such findings are not unique to Cincinnati; low literacy is prevalent throughout the United States. Caregivers with limited literacy skills may struggle to navigate complex health systems, understand medical instructions and anticipatory guidance, perform child care and self-care tasks, and understand issues related to consent, medical authorization, and risk communication.¹⁷

Although readability is important, other factors also correlate with comprehension and execution of discharge tasks.¹⁸ Information must be understandable, or presented in a way that makes sense and can inform appropriate action. In many cases in our study, instructions were incomplete, despite previous investigators’ emphasizing caregivers’ desire and need for written instructions that are complete, informative, and inclusive of clearly outlined contingency plans.^15,19 In addition, families may differ in the level of support needed after discharge; standardizing elements and including families in the development of discharge instructions may improve communication.⁸

This study had several limitations. First, the discharge instructions randomly selected for review were all written during the winter months. As the census on the hospital medicine teams is particularly high during that time, authors with competing responsibilities may not have had enough time to write effective discharge instructions then. We selected the winter period in order to capture real-world instructions written during a busy clinical time, when providers care for a high volume of patients. Second, caregiver health literacy and English-language proficiency were not assessed, and information regarding caregivers’ race/ethnicity, educational attainment, and socioeconomic status was unavailable. Third, interrater agreement was not formally evaluated. Fourth, this was a single-center study with results that may not be generalizable.

In conclusion, discharge instructions for pediatric patients are often difficult to read and understand, and incomplete. Efforts to address these communication gaps—including educational initiatives for physician trainees focused on health literacy, and quality improvement work directed at standardization and creation of readable, understandable, and complete discharge instructions—are crucial in providing safe, high-value care. Researchers need to evaluate the relationship between discharge instruction quality and outcomes, including unplanned office visits, emergency department visits, and readmissions.

Disclosure

Nothing to report.

The average American adult reads at an 8th-grade level.¹ Limited general literacy can affect health literacy, which is defined as the “degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions.”^2,3 Adults with limited health literacy are at risk for poorer outcomes, including overuse of the emergency department and lower adherence to preventive care recommendations.⁴

Children transitioning from hospital to home depend on their adult caregivers (and their caregivers’ health literacy) to carry out discharge instructions. During the immediate postdischarge period, complex care needs can involve new or changed medications, follow-up instructions, home care instructions, and suggestions regarding when and why to seek additional care.

The discharge education provided to patients in the hospital is often subpar because of lack of standardization and divided responsibility among providers.⁵ Communication of vital information to patients with low health literacy has been noted to be particularly poor,⁶ as many patient education materials are written at 10th-, 11th-, and 12th-grade reading levels.⁴ Evidence supports providing materials written at 6th-grade level or lower to increase comprehension.⁷ Several studies have evaluated the quality and readability of discharge instructions for hospitalized adults,^8,9 and one study found a link between poorly written instructions for adult patients and readmission risk.¹⁰ Less is known about readability in pediatrics, in which education may be more important for families of children most commonly hospitalized for acute illness.

We conducted a study to describe readability levels, understandability scores, and completeness of written instructions given to families at hospital discharge.

Study Design and Setting

In this study, we performed a cross-sectional review of discharge instructions within electronic health records at Cincinnati Children’s Hospital Medical Center (CCHMC). The study was reviewed and approved by CCHMC’s Institutional Review Board. Charts were randomly selected from all hospital medicine service discharges during two 3-month periods of high patient volume: January-March 2014 and January-March 2015.

CCHMC is a large urban academic referral center that is the sole provider of general, subspecialty, and critical pediatric inpatient care for a large geographical area. CCHMC, which has 600 beds, provides cares for many children who live in impoverished settings. Its hospital medicine service consists of 4 teams that care for approximately 7000 children hospitalized with general pediatric illnesses each year. Each team consists of 5 or 6 pediatric residents supervised by a hospital medicine attending.

Providers, most commonly pediatric interns, generate discharge instructions in electronic health records. In this nonautomated process, they use free-text or nonstandardized templates to create content. At discharge, instructions are printed as part of the postvisit summary, which includes updates on medications and scheduled follow-up appointments. Bedside nurses verbally review the instructions with families and provide printed copies for home use.

Data Collection and Analysis

A random sequence generator was used to select charts for review. Instructions written in a language other than English were excluded. Written discharge instructions and clinical information, including age, sex, primary diagnosis, insurance type, number of discharge medications, number of scheduled appointments at discharge, and hospital length of stay, were abstracted from electronic health records and anonymized before analysis. The primary outcomes assessed were discharge instruction readability, understandability, and completeness. Readability was calculated with Fry Readability Scale (FRS) scores,¹¹ which range from 1 to 17 and correspond to reading levels (score 1 = 1st-grade reading level). Health literacy experts have used the FRS to assess readability in health care environments.¹²

Understandability was measured with the Patient Education Materials Assessment Tool (PEMAT), a validated scoring system provided by the Agency for Healthcare Research and Quality.¹³ The PEMAT measures the understandability of print materials on a scale ranging from 0% to 100%. Higher scores indicate increased understandability, and scores under 70% indicate instructions are difficult to understand.

Although recent efforts have focused on the development of quality metrics for hospital-to-home transitions of pediatric patients,¹⁴ during our study there were no standard items to include in pediatric discharge instructions. Five criteria for completeness were determined by consensus of 3 pediatric hospital medicine faculty and were informed by qualitative results of work performed at our institution—work in which families noted challenges with information overload and a desire for pertinent and usable information that would enhance caregiver confidence and discharge preparedness.¹⁵ The criteria included statement of diagnosis, description of diagnosis, signs and symptoms indicative of the need for escalation of care (warning signs), the person caregivers should call if worried, and contact information for the primary care provider, subspecialist, and/or emergency department. Each set of discharge instructions was manually evaluated for completeness (presence of each individual component, number of components present, presence of all components). All charts were scored by the same investigator. A convenience sample of 20 charts was evaluated by a different investigator to ensure rating parameters were clear and classification was consistent (defined as perfect agreement). If the primary rater was undecided on a discharge instruction score, the secondary rater rated the instruction, and consensus was reached.

Means, medians, and ranges were calculated to enumerate the distribution of readability levels, understandability scores, and completeness of discharge instructions. Instructions were classified as readable if the FRS score was 6 or under, as understandable if the PEMAT score was under 70%, and as complete if all 5 criteria were satisfied. Descriptive statistics were generated for all demographic and clinical variables.

Of the study period’s 3819 discharges, 200 were randomly selected for review. Table 1 lists the demographic and clinical information of patients included in the analyses. Median FRS score was 10, indicating a 10th-grade reading level (interquartile range, 8-12; range, 1-13) (Table 2). Only 14 (7%) of 200 discharge instructions had a score of 6 or under. Median PEMAT understandability score was 73% (interquartile range, 64%-82%), and 36% of instructions had a PEMAT score under 70%. No instruction satisfied all 5 of the defined characteristics of complete discharge instructions (Table 2).

To our knowledge, this is the first study of the readability, understandability, and completeness of discharge instructions in a pediatric population. We found that the majority of discharge instruction readability levels were 10th grade or higher, that many instructions were difficult to understand, and that important information was missing from many instructions.

Discharge instruction readability levels were higher than the literacy level of many families in surrounding communities. The high school dropout rates in Cincinnati are staggering; they range from 22% to 64% in the 10 neighborhoods with the largest proportion of residents not completing high school.¹⁶ However, such findings are not unique to Cincinnati; low literacy is prevalent throughout the United States. Caregivers with limited literacy skills may struggle to navigate complex health systems, understand medical instructions and anticipatory guidance, perform child care and self-care tasks, and understand issues related to consent, medical authorization, and risk communication.¹⁷

Although readability is important, other factors also correlate with comprehension and execution of discharge tasks.¹⁸ Information must be understandable, or presented in a way that makes sense and can inform appropriate action. In many cases in our study, instructions were incomplete, despite previous investigators’ emphasizing caregivers’ desire and need for written instructions that are complete, informative, and inclusive of clearly outlined contingency plans.^15,19 In addition, families may differ in the level of support needed after discharge; standardizing elements and including families in the development of discharge instructions may improve communication.⁸

This study had several limitations. First, the discharge instructions randomly selected for review were all written during the winter months. As the census on the hospital medicine teams is particularly high during that time, authors with competing responsibilities may not have had enough time to write effective discharge instructions then. We selected the winter period in order to capture real-world instructions written during a busy clinical time, when providers care for a high volume of patients. Second, caregiver health literacy and English-language proficiency were not assessed, and information regarding caregivers’ race/ethnicity, educational attainment, and socioeconomic status was unavailable. Third, interrater agreement was not formally evaluated. Fourth, this was a single-center study with results that may not be generalizable.

In conclusion, discharge instructions for pediatric patients are often difficult to read and understand, and incomplete. Efforts to address these communication gaps—including educational initiatives for physician trainees focused on health literacy, and quality improvement work directed at standardization and creation of readable, understandable, and complete discharge instructions—are crucial in providing safe, high-value care. Researchers need to evaluate the relationship between discharge instruction quality and outcomes, including unplanned office visits, emergency department visits, and readmissions.

Disclosure

Nothing to report.

The average American adult reads at an 8th-grade level.¹ Limited general literacy can affect health literacy, which is defined as the “degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions.”^2,3 Adults with limited health literacy are at risk for poorer outcomes, including overuse of the emergency department and lower adherence to preventive care recommendations.⁴

Children transitioning from hospital to home depend on their adult caregivers (and their caregivers’ health literacy) to carry out discharge instructions. During the immediate postdischarge period, complex care needs can involve new or changed medications, follow-up instructions, home care instructions, and suggestions regarding when and why to seek additional care.

The discharge education provided to patients in the hospital is often subpar because of lack of standardization and divided responsibility among providers.⁵ Communication of vital information to patients with low health literacy has been noted to be particularly poor,⁶ as many patient education materials are written at 10th-, 11th-, and 12th-grade reading levels.⁴ Evidence supports providing materials written at 6th-grade level or lower to increase comprehension.⁷ Several studies have evaluated the quality and readability of discharge instructions for hospitalized adults,^8,9 and one study found a link between poorly written instructions for adult patients and readmission risk.¹⁰ Less is known about readability in pediatrics, in which education may be more important for families of children most commonly hospitalized for acute illness.

We conducted a study to describe readability levels, understandability scores, and completeness of written instructions given to families at hospital discharge.

Study Design and Setting

In this study, we performed a cross-sectional review of discharge instructions within electronic health records at Cincinnati Children’s Hospital Medical Center (CCHMC). The study was reviewed and approved by CCHMC’s Institutional Review Board. Charts were randomly selected from all hospital medicine service discharges during two 3-month periods of high patient volume: January-March 2014 and January-March 2015.

CCHMC is a large urban academic referral center that is the sole provider of general, subspecialty, and critical pediatric inpatient care for a large geographical area. CCHMC, which has 600 beds, provides cares for many children who live in impoverished settings. Its hospital medicine service consists of 4 teams that care for approximately 7000 children hospitalized with general pediatric illnesses each year. Each team consists of 5 or 6 pediatric residents supervised by a hospital medicine attending.

Providers, most commonly pediatric interns, generate discharge instructions in electronic health records. In this nonautomated process, they use free-text or nonstandardized templates to create content. At discharge, instructions are printed as part of the postvisit summary, which includes updates on medications and scheduled follow-up appointments. Bedside nurses verbally review the instructions with families and provide printed copies for home use.

Data Collection and Analysis

A random sequence generator was used to select charts for review. Instructions written in a language other than English were excluded. Written discharge instructions and clinical information, including age, sex, primary diagnosis, insurance type, number of discharge medications, number of scheduled appointments at discharge, and hospital length of stay, were abstracted from electronic health records and anonymized before analysis. The primary outcomes assessed were discharge instruction readability, understandability, and completeness. Readability was calculated with Fry Readability Scale (FRS) scores,¹¹ which range from 1 to 17 and correspond to reading levels (score 1 = 1st-grade reading level). Health literacy experts have used the FRS to assess readability in health care environments.¹²

Understandability was measured with the Patient Education Materials Assessment Tool (PEMAT), a validated scoring system provided by the Agency for Healthcare Research and Quality.¹³ The PEMAT measures the understandability of print materials on a scale ranging from 0% to 100%. Higher scores indicate increased understandability, and scores under 70% indicate instructions are difficult to understand.

Although recent efforts have focused on the development of quality metrics for hospital-to-home transitions of pediatric patients,¹⁴ during our study there were no standard items to include in pediatric discharge instructions. Five criteria for completeness were determined by consensus of 3 pediatric hospital medicine faculty and were informed by qualitative results of work performed at our institution—work in which families noted challenges with information overload and a desire for pertinent and usable information that would enhance caregiver confidence and discharge preparedness.¹⁵ The criteria included statement of diagnosis, description of diagnosis, signs and symptoms indicative of the need for escalation of care (warning signs), the person caregivers should call if worried, and contact information for the primary care provider, subspecialist, and/or emergency department. Each set of discharge instructions was manually evaluated for completeness (presence of each individual component, number of components present, presence of all components). All charts were scored by the same investigator. A convenience sample of 20 charts was evaluated by a different investigator to ensure rating parameters were clear and classification was consistent (defined as perfect agreement). If the primary rater was undecided on a discharge instruction score, the secondary rater rated the instruction, and consensus was reached.

Means, medians, and ranges were calculated to enumerate the distribution of readability levels, understandability scores, and completeness of discharge instructions. Instructions were classified as readable if the FRS score was 6 or under, as understandable if the PEMAT score was under 70%, and as complete if all 5 criteria were satisfied. Descriptive statistics were generated for all demographic and clinical variables.

Of the study period’s 3819 discharges, 200 were randomly selected for review. Table 1 lists the demographic and clinical information of patients included in the analyses. Median FRS score was 10, indicating a 10th-grade reading level (interquartile range, 8-12; range, 1-13) (Table 2). Only 14 (7%) of 200 discharge instructions had a score of 6 or under. Median PEMAT understandability score was 73% (interquartile range, 64%-82%), and 36% of instructions had a PEMAT score under 70%. No instruction satisfied all 5 of the defined characteristics of complete discharge instructions (Table 2).

To our knowledge, this is the first study of the readability, understandability, and completeness of discharge instructions in a pediatric population. We found that the majority of discharge instruction readability levels were 10th grade or higher, that many instructions were difficult to understand, and that important information was missing from many instructions.

Discharge instruction readability levels were higher than the literacy level of many families in surrounding communities. The high school dropout rates in Cincinnati are staggering; they range from 22% to 64% in the 10 neighborhoods with the largest proportion of residents not completing high school.¹⁶ However, such findings are not unique to Cincinnati; low literacy is prevalent throughout the United States. Caregivers with limited literacy skills may struggle to navigate complex health systems, understand medical instructions and anticipatory guidance, perform child care and self-care tasks, and understand issues related to consent, medical authorization, and risk communication.¹⁷

Although readability is important, other factors also correlate with comprehension and execution of discharge tasks.¹⁸ Information must be understandable, or presented in a way that makes sense and can inform appropriate action. In many cases in our study, instructions were incomplete, despite previous investigators’ emphasizing caregivers’ desire and need for written instructions that are complete, informative, and inclusive of clearly outlined contingency plans.^15,19 In addition, families may differ in the level of support needed after discharge; standardizing elements and including families in the development of discharge instructions may improve communication.⁸

This study had several limitations. First, the discharge instructions randomly selected for review were all written during the winter months. As the census on the hospital medicine teams is particularly high during that time, authors with competing responsibilities may not have had enough time to write effective discharge instructions then. We selected the winter period in order to capture real-world instructions written during a busy clinical time, when providers care for a high volume of patients. Second, caregiver health literacy and English-language proficiency were not assessed, and information regarding caregivers’ race/ethnicity, educational attainment, and socioeconomic status was unavailable. Third, interrater agreement was not formally evaluated. Fourth, this was a single-center study with results that may not be generalizable.

In conclusion, discharge instructions for pediatric patients are often difficult to read and understand, and incomplete. Efforts to address these communication gaps—including educational initiatives for physician trainees focused on health literacy, and quality improvement work directed at standardization and creation of readable, understandable, and complete discharge instructions—are crucial in providing safe, high-value care. Researchers need to evaluate the relationship between discharge instruction quality and outcomes, including unplanned office visits, emergency department visits, and readmissions.

Disclosure

Nothing to report.

During internal medicine (IM) clerkships, course directors are responsible for ensuring that medical students attain basic competency in patient management through use of risk–benefit, cost–benefit, and evidence-based considerations.¹ However, the students’ primary teachers—IM residents and attendings—consistently role-model high-value care (HVC) perhaps only half the time.² The inconsistency may have a few sources, including unawareness of the costs of tests and treatments ordered and little formal training in HVC.^3-5 In addition, the environment at some academic institutions may reward learners for performing tests that may be unnecessary.⁶

We conducted a study to assess medical students’ perceptions of unnecessary testing and the adequacy–inadequacy of HVC instruction, as well as their observations of behavior that may hinder the practice of HVC during the IM clerkship.

When students completed their third-year IM clerkships at The Johns Hopkins University School of Medicine, the Icahn School of Medicine at Mount Sinai, the University of Alabama at Birmingham School of Medicine, and the Tulane University School of Medicine, we sent them a recruitment email asking them to complete an anonymous survey regarding their clerkship experiences with HVC. The clerkships’ directors, who collaborated on survey development, searched the literature to quantify behavior thought to decrease the practice of HVC. The survey was tested several times with different learners and faculty to increase response process validity.

The SurveyMonkey online platform was used to administer the survey. Students were given 1 week after the end of their clerkship to complete the survey. Data were collected for the period October 2013 to December 2014. Each student was offered a $10 gift certificate for survey completion. Each institution received exempt approval from its institutional review board.

Survey respondents were divided into those who perceived HVC education as adequate and those who perceived it as inadequate. Chi-square tests were performed with Stata Version 12 (College Station, TX) to determine whether a student’s perception of HVC education being adequate or inadequate was significantly associated with the other survey questions.

Of 577 eligible students, 307 (53%) completed the survey. About 83% of the respondents reported noticing the ordering of laboratory or radiologic tests they considered unnecessary, and a majority (81%) of those students noticed this activity at least once a week. Overall, 51% of the respondents thought their HVC education was inadequate. Significantly more of the students who perceived their HVC education as inadequate were uncomfortable bringing an unnecessary test to the attention of the ward team, rarely discussed costs, and rarely observed team members being praised for forgoing unnecessary tests (Table). Two significant associations were found: between institution attended and perceived adequacy–inadequacy of HVC education and between institution and frequency of cost discussions.

Most (78.5%) students thought an HVC curriculum should be added to the IM clerkship, and 34.5% thought the HVC curriculum should be incorporated into daily rounds. In regards to additions to the clerkship curriculum, most students wanted to round with phlebotomy (29%) or discuss costs of testing on patients (26%).

Students attributed the ordering of unnecessary tests and treatments to several factors: residents investigating “interesting diagnoses” (46%), teams practicing defensive medicine (43%), consultants making requests (40%), attendings investigating “interesting diagnoses” (27%), and patients making requests (8%).

About 51% of the students thought their HVC education was inadequate, and about 83% noticed unnecessary testing. Our study findings reaffirm those of a single-site study in which 93% of students noted unnecessary testing.⁷

In this study, many students perceived HVC education as inadequate and reported wanting HVC principles added to their training and an HVC curriculum incorporated into daily rounds. Students who perceived HVC education as inadequate were significantly less comfortable bringing an unnecessary test to the attention of the ward team and noticed less discussion about costs and less praise for avoiding unnecessary tests. One institution had a significantly higher proportion of students perceiving their HVC education as adequate and noticing more discussions about test costs. This institution was the only one that incorporated discussions about test costs into its curriculum during the study period—which may account for its students’ perceptions.

This study had a few limitations. First, as the survey was administered after the IM clerkships, students’ responses may have been subject to recall bias. We minimized this bias by allowing 1 week for survey completion. Second, given the 53% response rate, there may have been response bias. However, one institution’s demographics showed no significant differences between responders and nonresponders with respect to age, sex, ethnicity, or type of degree. Third, students’ understanding of what tests and treatments are necessary and unnecessary may be relatively underdeveloped, given their training level. One study found that medical students with minimal clinical experience were able to identify unnecessary tests and treatments, but this study has not been validated at other institutions.⁷

Efforts to increase HVC education and practice have focused on residents and attendings, but our study findings reaffirm that HVC training is much needed and wanted in undergraduate medical education. Studies are needed to test the effectiveness of HVC curricula in medical school and the ability of these curricula to give students the tools they need to practice HVC.

Disclosures

Dr. Pahwa received support from the Johns Hopkins Hospitalist Scholars Fund, and Dr. Cayea is supported by the Daniel and Jeanette Hendin Schapiro Geriatric Medical Education Center. The sponsors had no role in study design, methods, subject recruitment, data collection, data analysis, or manuscript preparation. The authors have no conflicts of interest to disclose.

During internal medicine (IM) clerkships, course directors are responsible for ensuring that medical students attain basic competency in patient management through use of risk–benefit, cost–benefit, and evidence-based considerations.¹ However, the students’ primary teachers—IM residents and attendings—consistently role-model high-value care (HVC) perhaps only half the time.² The inconsistency may have a few sources, including unawareness of the costs of tests and treatments ordered and little formal training in HVC.^3-5 In addition, the environment at some academic institutions may reward learners for performing tests that may be unnecessary.⁶

We conducted a study to assess medical students’ perceptions of unnecessary testing and the adequacy–inadequacy of HVC instruction, as well as their observations of behavior that may hinder the practice of HVC during the IM clerkship.

When students completed their third-year IM clerkships at The Johns Hopkins University School of Medicine, the Icahn School of Medicine at Mount Sinai, the University of Alabama at Birmingham School of Medicine, and the Tulane University School of Medicine, we sent them a recruitment email asking them to complete an anonymous survey regarding their clerkship experiences with HVC. The clerkships’ directors, who collaborated on survey development, searched the literature to quantify behavior thought to decrease the practice of HVC. The survey was tested several times with different learners and faculty to increase response process validity.

The SurveyMonkey online platform was used to administer the survey. Students were given 1 week after the end of their clerkship to complete the survey. Data were collected for the period October 2013 to December 2014. Each student was offered a $10 gift certificate for survey completion. Each institution received exempt approval from its institutional review board.

Survey respondents were divided into those who perceived HVC education as adequate and those who perceived it as inadequate. Chi-square tests were performed with Stata Version 12 (College Station, TX) to determine whether a student’s perception of HVC education being adequate or inadequate was significantly associated with the other survey questions.

Of 577 eligible students, 307 (53%) completed the survey. About 83% of the respondents reported noticing the ordering of laboratory or radiologic tests they considered unnecessary, and a majority (81%) of those students noticed this activity at least once a week. Overall, 51% of the respondents thought their HVC education was inadequate. Significantly more of the students who perceived their HVC education as inadequate were uncomfortable bringing an unnecessary test to the attention of the ward team, rarely discussed costs, and rarely observed team members being praised for forgoing unnecessary tests (Table). Two significant associations were found: between institution attended and perceived adequacy–inadequacy of HVC education and between institution and frequency of cost discussions.

Most (78.5%) students thought an HVC curriculum should be added to the IM clerkship, and 34.5% thought the HVC curriculum should be incorporated into daily rounds. In regards to additions to the clerkship curriculum, most students wanted to round with phlebotomy (29%) or discuss costs of testing on patients (26%).

Students attributed the ordering of unnecessary tests and treatments to several factors: residents investigating “interesting diagnoses” (46%), teams practicing defensive medicine (43%), consultants making requests (40%), attendings investigating “interesting diagnoses” (27%), and patients making requests (8%).

About 51% of the students thought their HVC education was inadequate, and about 83% noticed unnecessary testing. Our study findings reaffirm those of a single-site study in which 93% of students noted unnecessary testing.⁷

In this study, many students perceived HVC education as inadequate and reported wanting HVC principles added to their training and an HVC curriculum incorporated into daily rounds. Students who perceived HVC education as inadequate were significantly less comfortable bringing an unnecessary test to the attention of the ward team and noticed less discussion about costs and less praise for avoiding unnecessary tests. One institution had a significantly higher proportion of students perceiving their HVC education as adequate and noticing more discussions about test costs. This institution was the only one that incorporated discussions about test costs into its curriculum during the study period—which may account for its students’ perceptions.

This study had a few limitations. First, as the survey was administered after the IM clerkships, students’ responses may have been subject to recall bias. We minimized this bias by allowing 1 week for survey completion. Second, given the 53% response rate, there may have been response bias. However, one institution’s demographics showed no significant differences between responders and nonresponders with respect to age, sex, ethnicity, or type of degree. Third, students’ understanding of what tests and treatments are necessary and unnecessary may be relatively underdeveloped, given their training level. One study found that medical students with minimal clinical experience were able to identify unnecessary tests and treatments, but this study has not been validated at other institutions.⁷

Efforts to increase HVC education and practice have focused on residents and attendings, but our study findings reaffirm that HVC training is much needed and wanted in undergraduate medical education. Studies are needed to test the effectiveness of HVC curricula in medical school and the ability of these curricula to give students the tools they need to practice HVC.

Disclosures

Dr. Pahwa received support from the Johns Hopkins Hospitalist Scholars Fund, and Dr. Cayea is supported by the Daniel and Jeanette Hendin Schapiro Geriatric Medical Education Center. The sponsors had no role in study design, methods, subject recruitment, data collection, data analysis, or manuscript preparation. The authors have no conflicts of interest to disclose.

During internal medicine (IM) clerkships, course directors are responsible for ensuring that medical students attain basic competency in patient management through use of risk–benefit, cost–benefit, and evidence-based considerations.¹ However, the students’ primary teachers—IM residents and attendings—consistently role-model high-value care (HVC) perhaps only half the time.² The inconsistency may have a few sources, including unawareness of the costs of tests and treatments ordered and little formal training in HVC.^3-5 In addition, the environment at some academic institutions may reward learners for performing tests that may be unnecessary.⁶

We conducted a study to assess medical students’ perceptions of unnecessary testing and the adequacy–inadequacy of HVC instruction, as well as their observations of behavior that may hinder the practice of HVC during the IM clerkship.

When students completed their third-year IM clerkships at The Johns Hopkins University School of Medicine, the Icahn School of Medicine at Mount Sinai, the University of Alabama at Birmingham School of Medicine, and the Tulane University School of Medicine, we sent them a recruitment email asking them to complete an anonymous survey regarding their clerkship experiences with HVC. The clerkships’ directors, who collaborated on survey development, searched the literature to quantify behavior thought to decrease the practice of HVC. The survey was tested several times with different learners and faculty to increase response process validity.

The SurveyMonkey online platform was used to administer the survey. Students were given 1 week after the end of their clerkship to complete the survey. Data were collected for the period October 2013 to December 2014. Each student was offered a $10 gift certificate for survey completion. Each institution received exempt approval from its institutional review board.

Survey respondents were divided into those who perceived HVC education as adequate and those who perceived it as inadequate. Chi-square tests were performed with Stata Version 12 (College Station, TX) to determine whether a student’s perception of HVC education being adequate or inadequate was significantly associated with the other survey questions.

Of 577 eligible students, 307 (53%) completed the survey. About 83% of the respondents reported noticing the ordering of laboratory or radiologic tests they considered unnecessary, and a majority (81%) of those students noticed this activity at least once a week. Overall, 51% of the respondents thought their HVC education was inadequate. Significantly more of the students who perceived their HVC education as inadequate were uncomfortable bringing an unnecessary test to the attention of the ward team, rarely discussed costs, and rarely observed team members being praised for forgoing unnecessary tests (Table). Two significant associations were found: between institution attended and perceived adequacy–inadequacy of HVC education and between institution and frequency of cost discussions.

Most (78.5%) students thought an HVC curriculum should be added to the IM clerkship, and 34.5% thought the HVC curriculum should be incorporated into daily rounds. In regards to additions to the clerkship curriculum, most students wanted to round with phlebotomy (29%) or discuss costs of testing on patients (26%).

Students attributed the ordering of unnecessary tests and treatments to several factors: residents investigating “interesting diagnoses” (46%), teams practicing defensive medicine (43%), consultants making requests (40%), attendings investigating “interesting diagnoses” (27%), and patients making requests (8%).

About 51% of the students thought their HVC education was inadequate, and about 83% noticed unnecessary testing. Our study findings reaffirm those of a single-site study in which 93% of students noted unnecessary testing.⁷

In this study, many students perceived HVC education as inadequate and reported wanting HVC principles added to their training and an HVC curriculum incorporated into daily rounds. Students who perceived HVC education as inadequate were significantly less comfortable bringing an unnecessary test to the attention of the ward team and noticed less discussion about costs and less praise for avoiding unnecessary tests. One institution had a significantly higher proportion of students perceiving their HVC education as adequate and noticing more discussions about test costs. This institution was the only one that incorporated discussions about test costs into its curriculum during the study period—which may account for its students’ perceptions.

This study had a few limitations. First, as the survey was administered after the IM clerkships, students’ responses may have been subject to recall bias. We minimized this bias by allowing 1 week for survey completion. Second, given the 53% response rate, there may have been response bias. However, one institution’s demographics showed no significant differences between responders and nonresponders with respect to age, sex, ethnicity, or type of degree. Third, students’ understanding of what tests and treatments are necessary and unnecessary may be relatively underdeveloped, given their training level. One study found that medical students with minimal clinical experience were able to identify unnecessary tests and treatments, but this study has not been validated at other institutions.⁷

Efforts to increase HVC education and practice have focused on residents and attendings, but our study findings reaffirm that HVC training is much needed and wanted in undergraduate medical education. Studies are needed to test the effectiveness of HVC curricula in medical school and the ability of these curricula to give students the tools they need to practice HVC.

Disclosures

Dr. Pahwa received support from the Johns Hopkins Hospitalist Scholars Fund, and Dr. Cayea is supported by the Daniel and Jeanette Hendin Schapiro Geriatric Medical Education Center. The sponsors had no role in study design, methods, subject recruitment, data collection, data analysis, or manuscript preparation. The authors have no conflicts of interest to disclose.

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. The bolded text represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts.

A 75-year-old man was brought by ambulance to the emergency department (ED) after the acute onset of palpitations, lightheadedness, and confusion. His medical history, provided by his wife, included osteoarthritis and remote cholecystectomy. He was not a smoker but drank 2 to 4 cans of beer daily. His medications were aspirin 162 mg daily and naproxen as needed. There was no history of bruising, diarrhea, melena, or bleeding.

Palpitations may represent an arrhythmia arising from an ischemic or alcoholic cardiomyopathy. Mental status changes usually have metabolic, infectious, structural (eg, hemorrhage, tumor), or toxic causes. Lightheadedness and confusion could occur with arrhythmia-associated cerebral hypoperfusion or a seizure. Daily alcohol use could cause confusion through acute intoxication, thiamine or B₁₂ deficiency, repeated head trauma, or liver failure.

The patient’s systolic blood pressure (BP) was 60 mm Hg, heart rate (HR) was 120 beats per minute (bpm), and oral temperature was 98.4°F. Rousing him was difficult. There were no localizing neurologic abnormalities, and the rest of the physical examination findings were normal. Point-of-care blood glucose level was 155 mg/dL. Blood cultures were obtained and broad-spectrum antibiotics initiated. After fluid resuscitation, BP improved to 116/87 mm Hg, HR fell to 105 bpm, and the patient became alert and oriented. He denied chest pain, fever, or diaphoresis.

The patient’s improvement with intravenous (IV) fluids makes cardiogenic shock unlikely but does not exclude an underlying compensated cardiomyopathy that may be predisposing to arrhythmia. Hypotension, tachycardia, and somnolence may represent sepsis, but the near normalization of vital signs and mental status shortly after administration of IV fluids, the normal temperature, and the absence of localizing signs of infection favor withholding additional antibiotics. Other causes of hypotension are hypovolemia, medication effects, adrenal insufficiency, anaphylaxis, and autonomic insufficiency. There was no reported nausea, vomiting, diarrhea, bleeding, polyuria, or impaired oral intake to support hypovolemia, though the response to IV fluids suggests hypovolemia may still be playing a role.

White blood cell (WBC) count was 15,450/µL with a normal differential; hemoglobin level was 15.8 g/dL; and platelet count was 176,000/µL. Electrolytes, liver function tests, cardiac enzymes, and urinalysis were normal. Electrocardiogram showed sinus tachycardia with premature atrial complexes and no ST-segment abnormalities. Radiograph of the chest and computed tomography scan of the head were normal. Echocardiogram showed moderate left ventricular hypertrophy with a normal ejection fraction and no valvular abnormalities. Exercise nuclear cardiac stress test was negative for ischemia. Blood cultures were sterile. The patient quickly became asymptomatic and remained so during his 3-day hospitalization. There were no arrhythmias on telemetry. The patient was discharged with follow-up scheduled with his primary care physician.

The nonlocalizing history and physical examination findings, normal chest radiograph and urinalysis, absence of fevers, negative blood cultures, and quick recovery make infection unlikely, despite the moderate leukocytosis. Conditions that present with acute and transient hypotension and altered mental status include arrhythmias, seizures, and reactions to drugs or toxins. Given the cardiac test results, a chronic cardiomyopathy seems unlikely, but arrhythmia is still possible. Continuous outpatient monitoring is required to assess the palpitations and the frequency of the premature atrial complexes.

Two days after discharge, the patient suddenly became diaphoretic and lost consciousness while walking to the bathroom. He was taken to the ED, where his BP was 90/60 mm Hg and HR was 108 bpm. Family members reported that he had appeared flushed during the syncopal episode, showed no seizure activity, and been unconscious for 15 to 20 minutes. The patient denied chest pain, dyspnea, fever, bowel or bladder incontinence, focal weakness, slurred speech, visual changes, nausea or vomiting either before or after the episode. Physical examination revealed a tongue laceration and facial erythema; all other findings were normal. In the ED, there was an asymptomatic 7-beat run of nonsustained ventricular tachycardia, and the hypotension resolved after fluid resuscitation. The patient now reported 2 similar syncopal episodes in the past. The first occurred in a restaurant 6 years earlier, and the second occurred 3 years later, at which time he was hospitalized and no etiology was found.

The loss of consciousness is attributable to cerebral hypoperfusion. Hypotension has 3 principal categories: hypovolemic, cardiogenic, and distributive. With syncopal episodes recurring over several years, hypovolemia seems unlikely. Given the palpitations and ventricular tachycardia, it is reasonable to suspect a cardiogenic cause. Although his heart appears to be structurally normal on echocardiogram, genetic, electrophysiologic, or magnetic resonance imaging (MRI) testing will occasionally reveal an unsuspected substrate for arrhythmia.

The recurring yet self-limited nature, diaphoresis, flushing, and facial erythema suggest a non-sepsis distributive cause of hypotension. It is possible the patient is recurrently exposed to a toxin (eg, alcohol) that causes both flushing and dehydration. Flushing disorders include carcinoid syndrome, pheochromocytoma, drug reaction with eosinophilia and systemic symptoms (DRESS), and mastocytosis. Carcinoid syndrome is characterized by bronchospasm and diarrhea and, in some cases, right-sided valvulopathy, all of which are absent in this patient. Pheochromocytoma is associated with orthostasis, but patients typically are hypertensive at baseline. DRESS, which may arise from nonsteroidal anti-inflammatory drug (NSAID) or aspirin use, can cause facial erythema and swelling but is also characterized by liver, renal, and hematologic abnormalities, none of which was demonstrated. Furthermore, DRESS typically does not cause hypotension. Mastocytosis can manifest as isolated or recurrent anaphylaxis.

It is important to investigate antecedents of these syncopal episodes. If the earlier episodes were food-related—one occurred at a restaurant—then deglutition syncope (syncope precipitated by swallowing) should be considered. If an NSAID or aspirin was ingested before each episode, then medication hypersensitivity or mast cell degranulation (which can be triggered by these medications) should be further examined. Loss of consciousness lasting 20 minutes without causing any neurologic sequelae is unusual for most causes of recurrent syncope. This feature raises the possibility that a toxin or mediator might still be present in the patient’s system.

Serial cardiac enzymes and electrocardiogram were normal. A tilt-table study was negative. The cortisol response to ACTH (cosyntropin) stimulation was normal. The level of serum tryptase, drawn 2 days after syncope, was 18.4 ng/dL (normal, <11.5 ng/dL). Computed tomography scan of chest and abdomen was negative for pulmonary embolism but showed a 1.4×1.3-cm hypervascular lesion in the tail of pancreas. The following neuroendocrine tests were within normal limits: serum and urine catecholamines; urine 5-hydroxyindoleacetic acid (5-HIAA); and serum chromogranin A, insulin, serotonin, vasoactive intestinal polypeptide (VIP), and somatostatin (Table 1). The patient remained asymptomatic during his hospital stay and was discharged home with appointments for cardiology follow-up and endoscopic ultrasound-guided biopsy of the pancreatic mass.

As hypoglycemia from a pancreatic insulinoma is plausible as a cause of episodic loss of consciousness lasting 15 minutes or more, it is important to inquire if giving food or drink helped resolve previous episodes. The normal insulin level reported here is of limited value, because it is the combination of insulin and C-peptide levels at time of hypoglycemia that is diagnostic. The normal glucose level recorded during one of the earlier episodes and the hypotension argue against hypoglycemia.

The elevated tryptase level is an indicator of mast cell degranulation. Tryptase levels are transiently elevated during the initial 2 to 4 hours after an anaphylactic episode and then normalize. An elevated level many hours or days later is considered a sign of mast cell excess. Although there is no evidence of the multi-organ disease (eg, cytopenia, bone disease, hepatosplenomegaly) seen in patients with a high systemic burden of mast cells, mast cell disorders exist on a spectrum. There may be a focal excess of mast cells confined to one organ or an isolated mass.

The same day as discharge, the patient’s wife drove them to the grocery store. He remained in the car while she shopped. When she returned, she found him confused and minimally responsive with subsequent brief loss of consciousness. He was taken to an ED, where he was flushed and hypotensive (systolic BP, 60 mm Hg) and tachycardic. Other examination findings were normal. After fluid resuscitation he became alert and oriented. WBC count was 20,850/μL with 89% neutrophils, hemoglobin level was 14.6 g/dL, and platelet count was 168,000/μL. Serum lactate level was 3.7 mmol/L (normal, <2.3 mmol/L). Chest radiograph was normal. He was treated with broad-spectrum antibiotic therapy and admitted to the hospital. Blood and urine cultures were sterile. Fine-needle aspiration of the pancreatic mass demonstrated nonspecific inflammation. Four days after admission (3 days after pancreatic mass biopsy) the patient developed palpitations, felt unwell, and had marked flushing of the face and trunk, with concomitant BP of 90/50 mm Hg and HR of 140 bpm.

The salient features of this case are recurrent hypotension, tachycardia, and flushing. Autonomic insufficiency, to which elderly patients are prone, causes hemodynamic perturbations but rarely flushing. The patient does not have diabetes mellitus, Parkinson disease, or another condition that puts him at risk for dysautonomia. Pancreatic neuroendocrine tumors secrete mediators that lead to vasodilation and hypotension but are unlikely given the clinical and biochemical data.

The patient’s symptoms are consistent with anaphylaxis, though prototypical immunoglobulin E (IgE)–mediated anaphylaxis is usually accompanied by urticaria, angioedema, and wheezing, which have been absent during his presentations. There are no clear food, pharmacologic, or environmental precipitants.

Recurrent anaphylaxis can be a manifestation of mast cell excess (eg, cutaneous or systemic mastocytosis). A markedly elevated tryptase level during an anaphylactic episode is consistent with mastocytosis or IgE-mediated anaphylaxis. An elevated baseline tryptase level days after an anaphylactic episode signals increased mast cell burden. There may be a reservoir of mast cells in the bone marrow. Alternatively, the hypervascular pancreatic mass may be a mastocytoma or a mast cell sarcoma (missed because of inadequate sampling or staining).

The lactic acidosis likely reflects global tissue hypoperfusion from vasodilatory hypotension. The leukocytosis may reflect WBC mobilization secondary to endogenous corticosteroids and catecholamines in response to hypotension or may be a direct response to the release of mast cell–derived mediators of inflammation.

The patient was treated with diphenhydramine and ranitidine. Serum tryptase level was 46.8 ng/mL (normal, <11.5 ng/mL), and 24-hour urine histamine level was 95 µ g/dL (normal, <60 µ g/dL). Bone marrow biopsy results showed multifocal dense infiltrative aggregates of mast cells (>15 cells/aggregate), which were confirmed by CD117 (Kit) and tryptase positivity (Figure). Mutation analysis for Kit Asp816Val, which is present in 80% to 90% of patients with mastocytosis, was positive. He fulfilled the 2008 World Health Organization criteria for systemic mastocytosis (Table 2). Prednisone, histamine inhibitors, and montelukast were prescribed. Six months later, magnetic resonance imaging of the abdomen showed no change in the pancreatic mass, which was now characterized as a possible splenule. The patient had no additional episodes of flushing or syncope over 2 years.

Cardiovascular collapse (hypotension, tachycardia, syncope) in an elderly patient prompts clinicians to focus on life-threatening conditions, such as acute coronary syndrome, pulmonary embolus, arrhythmia, and sepsis. Each of these diagnoses was considered early in the course of this patient’s presentations, but each was deemed unlikely as it became apparent that the episodes were self-limited and recurrent over years. Incorporating flushing into the diagnostic problem representation allowed the clinicians to focus on a subset of causes of hypotension.

Flushing disorders may be classified by whether they are mediated by the autonomic nervous system (wet flushes, because they are usually accompanied by diaphoresis) or by exogenous or endogenous vasoactive substances (dry flushes).¹ Autonomic nervous system flushing is triggered by emotions, fever, exercise, perimenopause (hot flashes), and neurologic conditions (eg, Parkinson disease, spinal cord injury, multiple sclerosis). Vasoactive flushing precipitants include drugs (eg, niacin); alcohol (secondary to cutaneous vasodilation, or acetaldehyde particularly in people with insufficient acetaldehyde dehydrogenase activity)²; foods that contain capsaicin, tyramine, sulfites, or histamine (eg, eating improperly handled fish can cause scombroid poisoning); and anaphylaxis. Rare causes of vasoactive flushing include carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, VIPoma, and mastocytosis.²

Mastocytosis is a rare clonal disorder characterized by the accumulation of abnormal mast cells in the skin (cutaneous mastocytosis), in multiple organs (systemic mastocytosis), or in a solid tumor (mastocytoma). Urticaria pigmentosa is the most common form of cutaneous mastocytosis; it is seen more often in children than in adults and typically is associated with a maculopapular rash and dermatographism. Systemic mastocytosis is the most common form of the disorder in adults.³ Symptoms are related to mast cell infiltration or mast cell mediator–related effects, which range from itching, flushing, and diarrhea to hypotension and anaphylaxis. Other manifestations are fatigue, urticaria pigmentosa, osteoporosis, hepatosplenomegaly, bone pain, cytopenias, and lymphadenopathy.⁴

Systemic mastocytosis can occur at any age and should be considered in patients with recurrent unexplained flushing, syncope, or hypotension. Eighty percent to 90% of patients with systemic mastocytosis have a mutation in Kit,⁵ a transmembrane tyrosine kinase that is the receptor for stem cell factor. The Asp816Val mutation leads to increased proliferation and reduced apoptosis of mast cells.^3,6,7 Proposed diagnostic algorithms^8-11 involve measurement of serum tryptase levels and examination of bone marrow. Bone marrow biopsy and testing for the Asp816Val Kit mutation should be considered in patients with modestly elevated baseline tryptase levels (11.5-20 ng/mL) if clinical findings are consistent with mastocytosis.¹²

The primary goals of treatment are managing mast cell–mediated symptoms and, in advanced cases, achieving cytoreduction. Alcohol can trigger mast cell degranulation in indolent systemic mastocytosis and should be avoided. Mast cell–mediated symptoms are managed with histamine blockers, leukotriene antagonists, and mast cell stabilizers.¹² Targeted therapy with tyrosine kinase inhibitors (eg, imatinib) in patients with transmembrane Kit mutation (eg, Phe522Cys, Lys509Ile) associated with systemic mastocytosis has had promising results.^13,14 However, this patient’s Asp816Val mutation is in the Kit catalytic domain, not the transmembrane region, and therefore would not be expected to respond to imatinib. A recent open-label trial of the multikinase inhibitor midostaurin demonstrated resolution of organ damage, reduced bone marrow burden, and lowered serum tryptase levels in patients with advanced systemic mastocytosis.¹⁵ Interferon, cladribine, and high-dose corticosteroids are prescribed in patients for whom other therapies have been ineffective.⁸

The differential diagnosis is broad for both hypotension and for flushing, but the differential diagnosis for recurrent hypotension and flushing is limited. Recognizing that flushing was an essential feature of this patient’s hypotensive condition, and not an epiphenomenon of syncope, allowed the clinicians to focus on the overlap and make a shocking diagnosis.

Acknowledgment

The authors thank David Bosler, MD (Cleveland Clinic) for interpreting the pathology image.

Disclosure

Nothing to report.

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. The bolded text represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts.

A 75-year-old man was brought by ambulance to the emergency department (ED) after the acute onset of palpitations, lightheadedness, and confusion. His medical history, provided by his wife, included osteoarthritis and remote cholecystectomy. He was not a smoker but drank 2 to 4 cans of beer daily. His medications were aspirin 162 mg daily and naproxen as needed. There was no history of bruising, diarrhea, melena, or bleeding.

Palpitations may represent an arrhythmia arising from an ischemic or alcoholic cardiomyopathy. Mental status changes usually have metabolic, infectious, structural (eg, hemorrhage, tumor), or toxic causes. Lightheadedness and confusion could occur with arrhythmia-associated cerebral hypoperfusion or a seizure. Daily alcohol use could cause confusion through acute intoxication, thiamine or B₁₂ deficiency, repeated head trauma, or liver failure.

The patient’s systolic blood pressure (BP) was 60 mm Hg, heart rate (HR) was 120 beats per minute (bpm), and oral temperature was 98.4°F. Rousing him was difficult. There were no localizing neurologic abnormalities, and the rest of the physical examination findings were normal. Point-of-care blood glucose level was 155 mg/dL. Blood cultures were obtained and broad-spectrum antibiotics initiated. After fluid resuscitation, BP improved to 116/87 mm Hg, HR fell to 105 bpm, and the patient became alert and oriented. He denied chest pain, fever, or diaphoresis.

The patient’s improvement with intravenous (IV) fluids makes cardiogenic shock unlikely but does not exclude an underlying compensated cardiomyopathy that may be predisposing to arrhythmia. Hypotension, tachycardia, and somnolence may represent sepsis, but the near normalization of vital signs and mental status shortly after administration of IV fluids, the normal temperature, and the absence of localizing signs of infection favor withholding additional antibiotics. Other causes of hypotension are hypovolemia, medication effects, adrenal insufficiency, anaphylaxis, and autonomic insufficiency. There was no reported nausea, vomiting, diarrhea, bleeding, polyuria, or impaired oral intake to support hypovolemia, though the response to IV fluids suggests hypovolemia may still be playing a role.

White blood cell (WBC) count was 15,450/µL with a normal differential; hemoglobin level was 15.8 g/dL; and platelet count was 176,000/µL. Electrolytes, liver function tests, cardiac enzymes, and urinalysis were normal. Electrocardiogram showed sinus tachycardia with premature atrial complexes and no ST-segment abnormalities. Radiograph of the chest and computed tomography scan of the head were normal. Echocardiogram showed moderate left ventricular hypertrophy with a normal ejection fraction and no valvular abnormalities. Exercise nuclear cardiac stress test was negative for ischemia. Blood cultures were sterile. The patient quickly became asymptomatic and remained so during his 3-day hospitalization. There were no arrhythmias on telemetry. The patient was discharged with follow-up scheduled with his primary care physician.

The nonlocalizing history and physical examination findings, normal chest radiograph and urinalysis, absence of fevers, negative blood cultures, and quick recovery make infection unlikely, despite the moderate leukocytosis. Conditions that present with acute and transient hypotension and altered mental status include arrhythmias, seizures, and reactions to drugs or toxins. Given the cardiac test results, a chronic cardiomyopathy seems unlikely, but arrhythmia is still possible. Continuous outpatient monitoring is required to assess the palpitations and the frequency of the premature atrial complexes.

Two days after discharge, the patient suddenly became diaphoretic and lost consciousness while walking to the bathroom. He was taken to the ED, where his BP was 90/60 mm Hg and HR was 108 bpm. Family members reported that he had appeared flushed during the syncopal episode, showed no seizure activity, and been unconscious for 15 to 20 minutes. The patient denied chest pain, dyspnea, fever, bowel or bladder incontinence, focal weakness, slurred speech, visual changes, nausea or vomiting either before or after the episode. Physical examination revealed a tongue laceration and facial erythema; all other findings were normal. In the ED, there was an asymptomatic 7-beat run of nonsustained ventricular tachycardia, and the hypotension resolved after fluid resuscitation. The patient now reported 2 similar syncopal episodes in the past. The first occurred in a restaurant 6 years earlier, and the second occurred 3 years later, at which time he was hospitalized and no etiology was found.

The loss of consciousness is attributable to cerebral hypoperfusion. Hypotension has 3 principal categories: hypovolemic, cardiogenic, and distributive. With syncopal episodes recurring over several years, hypovolemia seems unlikely. Given the palpitations and ventricular tachycardia, it is reasonable to suspect a cardiogenic cause. Although his heart appears to be structurally normal on echocardiogram, genetic, electrophysiologic, or magnetic resonance imaging (MRI) testing will occasionally reveal an unsuspected substrate for arrhythmia.

The recurring yet self-limited nature, diaphoresis, flushing, and facial erythema suggest a non-sepsis distributive cause of hypotension. It is possible the patient is recurrently exposed to a toxin (eg, alcohol) that causes both flushing and dehydration. Flushing disorders include carcinoid syndrome, pheochromocytoma, drug reaction with eosinophilia and systemic symptoms (DRESS), and mastocytosis. Carcinoid syndrome is characterized by bronchospasm and diarrhea and, in some cases, right-sided valvulopathy, all of which are absent in this patient. Pheochromocytoma is associated with orthostasis, but patients typically are hypertensive at baseline. DRESS, which may arise from nonsteroidal anti-inflammatory drug (NSAID) or aspirin use, can cause facial erythema and swelling but is also characterized by liver, renal, and hematologic abnormalities, none of which was demonstrated. Furthermore, DRESS typically does not cause hypotension. Mastocytosis can manifest as isolated or recurrent anaphylaxis.

It is important to investigate antecedents of these syncopal episodes. If the earlier episodes were food-related—one occurred at a restaurant—then deglutition syncope (syncope precipitated by swallowing) should be considered. If an NSAID or aspirin was ingested before each episode, then medication hypersensitivity or mast cell degranulation (which can be triggered by these medications) should be further examined. Loss of consciousness lasting 20 minutes without causing any neurologic sequelae is unusual for most causes of recurrent syncope. This feature raises the possibility that a toxin or mediator might still be present in the patient’s system.

Serial cardiac enzymes and electrocardiogram were normal. A tilt-table study was negative. The cortisol response to ACTH (cosyntropin) stimulation was normal. The level of serum tryptase, drawn 2 days after syncope, was 18.4 ng/dL (normal, <11.5 ng/dL). Computed tomography scan of chest and abdomen was negative for pulmonary embolism but showed a 1.4×1.3-cm hypervascular lesion in the tail of pancreas. The following neuroendocrine tests were within normal limits: serum and urine catecholamines; urine 5-hydroxyindoleacetic acid (5-HIAA); and serum chromogranin A, insulin, serotonin, vasoactive intestinal polypeptide (VIP), and somatostatin (Table 1). The patient remained asymptomatic during his hospital stay and was discharged home with appointments for cardiology follow-up and endoscopic ultrasound-guided biopsy of the pancreatic mass.

As hypoglycemia from a pancreatic insulinoma is plausible as a cause of episodic loss of consciousness lasting 15 minutes or more, it is important to inquire if giving food or drink helped resolve previous episodes. The normal insulin level reported here is of limited value, because it is the combination of insulin and C-peptide levels at time of hypoglycemia that is diagnostic. The normal glucose level recorded during one of the earlier episodes and the hypotension argue against hypoglycemia.

The elevated tryptase level is an indicator of mast cell degranulation. Tryptase levels are transiently elevated during the initial 2 to 4 hours after an anaphylactic episode and then normalize. An elevated level many hours or days later is considered a sign of mast cell excess. Although there is no evidence of the multi-organ disease (eg, cytopenia, bone disease, hepatosplenomegaly) seen in patients with a high systemic burden of mast cells, mast cell disorders exist on a spectrum. There may be a focal excess of mast cells confined to one organ or an isolated mass.

The same day as discharge, the patient’s wife drove them to the grocery store. He remained in the car while she shopped. When she returned, she found him confused and minimally responsive with subsequent brief loss of consciousness. He was taken to an ED, where he was flushed and hypotensive (systolic BP, 60 mm Hg) and tachycardic. Other examination findings were normal. After fluid resuscitation he became alert and oriented. WBC count was 20,850/μL with 89% neutrophils, hemoglobin level was 14.6 g/dL, and platelet count was 168,000/μL. Serum lactate level was 3.7 mmol/L (normal, <2.3 mmol/L). Chest radiograph was normal. He was treated with broad-spectrum antibiotic therapy and admitted to the hospital. Blood and urine cultures were sterile. Fine-needle aspiration of the pancreatic mass demonstrated nonspecific inflammation. Four days after admission (3 days after pancreatic mass biopsy) the patient developed palpitations, felt unwell, and had marked flushing of the face and trunk, with concomitant BP of 90/50 mm Hg and HR of 140 bpm.

The salient features of this case are recurrent hypotension, tachycardia, and flushing. Autonomic insufficiency, to which elderly patients are prone, causes hemodynamic perturbations but rarely flushing. The patient does not have diabetes mellitus, Parkinson disease, or another condition that puts him at risk for dysautonomia. Pancreatic neuroendocrine tumors secrete mediators that lead to vasodilation and hypotension but are unlikely given the clinical and biochemical data.

The patient’s symptoms are consistent with anaphylaxis, though prototypical immunoglobulin E (IgE)–mediated anaphylaxis is usually accompanied by urticaria, angioedema, and wheezing, which have been absent during his presentations. There are no clear food, pharmacologic, or environmental precipitants.

Recurrent anaphylaxis can be a manifestation of mast cell excess (eg, cutaneous or systemic mastocytosis). A markedly elevated tryptase level during an anaphylactic episode is consistent with mastocytosis or IgE-mediated anaphylaxis. An elevated baseline tryptase level days after an anaphylactic episode signals increased mast cell burden. There may be a reservoir of mast cells in the bone marrow. Alternatively, the hypervascular pancreatic mass may be a mastocytoma or a mast cell sarcoma (missed because of inadequate sampling or staining).

The lactic acidosis likely reflects global tissue hypoperfusion from vasodilatory hypotension. The leukocytosis may reflect WBC mobilization secondary to endogenous corticosteroids and catecholamines in response to hypotension or may be a direct response to the release of mast cell–derived mediators of inflammation.

The patient was treated with diphenhydramine and ranitidine. Serum tryptase level was 46.8 ng/mL (normal, <11.5 ng/mL), and 24-hour urine histamine level was 95 µ g/dL (normal, <60 µ g/dL). Bone marrow biopsy results showed multifocal dense infiltrative aggregates of mast cells (>15 cells/aggregate), which were confirmed by CD117 (Kit) and tryptase positivity (Figure). Mutation analysis for Kit Asp816Val, which is present in 80% to 90% of patients with mastocytosis, was positive. He fulfilled the 2008 World Health Organization criteria for systemic mastocytosis (Table 2). Prednisone, histamine inhibitors, and montelukast were prescribed. Six months later, magnetic resonance imaging of the abdomen showed no change in the pancreatic mass, which was now characterized as a possible splenule. The patient had no additional episodes of flushing or syncope over 2 years.

Cardiovascular collapse (hypotension, tachycardia, syncope) in an elderly patient prompts clinicians to focus on life-threatening conditions, such as acute coronary syndrome, pulmonary embolus, arrhythmia, and sepsis. Each of these diagnoses was considered early in the course of this patient’s presentations, but each was deemed unlikely as it became apparent that the episodes were self-limited and recurrent over years. Incorporating flushing into the diagnostic problem representation allowed the clinicians to focus on a subset of causes of hypotension.

Flushing disorders may be classified by whether they are mediated by the autonomic nervous system (wet flushes, because they are usually accompanied by diaphoresis) or by exogenous or endogenous vasoactive substances (dry flushes).¹ Autonomic nervous system flushing is triggered by emotions, fever, exercise, perimenopause (hot flashes), and neurologic conditions (eg, Parkinson disease, spinal cord injury, multiple sclerosis). Vasoactive flushing precipitants include drugs (eg, niacin); alcohol (secondary to cutaneous vasodilation, or acetaldehyde particularly in people with insufficient acetaldehyde dehydrogenase activity)²; foods that contain capsaicin, tyramine, sulfites, or histamine (eg, eating improperly handled fish can cause scombroid poisoning); and anaphylaxis. Rare causes of vasoactive flushing include carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, VIPoma, and mastocytosis.²

Mastocytosis is a rare clonal disorder characterized by the accumulation of abnormal mast cells in the skin (cutaneous mastocytosis), in multiple organs (systemic mastocytosis), or in a solid tumor (mastocytoma). Urticaria pigmentosa is the most common form of cutaneous mastocytosis; it is seen more often in children than in adults and typically is associated with a maculopapular rash and dermatographism. Systemic mastocytosis is the most common form of the disorder in adults.³ Symptoms are related to mast cell infiltration or mast cell mediator–related effects, which range from itching, flushing, and diarrhea to hypotension and anaphylaxis. Other manifestations are fatigue, urticaria pigmentosa, osteoporosis, hepatosplenomegaly, bone pain, cytopenias, and lymphadenopathy.⁴

Systemic mastocytosis can occur at any age and should be considered in patients with recurrent unexplained flushing, syncope, or hypotension. Eighty percent to 90% of patients with systemic mastocytosis have a mutation in Kit,⁵ a transmembrane tyrosine kinase that is the receptor for stem cell factor. The Asp816Val mutation leads to increased proliferation and reduced apoptosis of mast cells.^3,6,7 Proposed diagnostic algorithms^8-11 involve measurement of serum tryptase levels and examination of bone marrow. Bone marrow biopsy and testing for the Asp816Val Kit mutation should be considered in patients with modestly elevated baseline tryptase levels (11.5-20 ng/mL) if clinical findings are consistent with mastocytosis.¹²

The primary goals of treatment are managing mast cell–mediated symptoms and, in advanced cases, achieving cytoreduction. Alcohol can trigger mast cell degranulation in indolent systemic mastocytosis and should be avoided. Mast cell–mediated symptoms are managed with histamine blockers, leukotriene antagonists, and mast cell stabilizers.¹² Targeted therapy with tyrosine kinase inhibitors (eg, imatinib) in patients with transmembrane Kit mutation (eg, Phe522Cys, Lys509Ile) associated with systemic mastocytosis has had promising results.^13,14 However, this patient’s Asp816Val mutation is in the Kit catalytic domain, not the transmembrane region, and therefore would not be expected to respond to imatinib. A recent open-label trial of the multikinase inhibitor midostaurin demonstrated resolution of organ damage, reduced bone marrow burden, and lowered serum tryptase levels in patients with advanced systemic mastocytosis.¹⁵ Interferon, cladribine, and high-dose corticosteroids are prescribed in patients for whom other therapies have been ineffective.⁸

The differential diagnosis is broad for both hypotension and for flushing, but the differential diagnosis for recurrent hypotension and flushing is limited. Recognizing that flushing was an essential feature of this patient’s hypotensive condition, and not an epiphenomenon of syncope, allowed the clinicians to focus on the overlap and make a shocking diagnosis.

Acknowledgment

The authors thank David Bosler, MD (Cleveland Clinic) for interpreting the pathology image.

Disclosure

Nothing to report.

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant. The bolded text represents the patient’s case. Each paragraph that follows represents the discussant’s thoughts.

A 75-year-old man was brought by ambulance to the emergency department (ED) after the acute onset of palpitations, lightheadedness, and confusion. His medical history, provided by his wife, included osteoarthritis and remote cholecystectomy. He was not a smoker but drank 2 to 4 cans of beer daily. His medications were aspirin 162 mg daily and naproxen as needed. There was no history of bruising, diarrhea, melena, or bleeding.

Palpitations may represent an arrhythmia arising from an ischemic or alcoholic cardiomyopathy. Mental status changes usually have metabolic, infectious, structural (eg, hemorrhage, tumor), or toxic causes. Lightheadedness and confusion could occur with arrhythmia-associated cerebral hypoperfusion or a seizure. Daily alcohol use could cause confusion through acute intoxication, thiamine or B₁₂ deficiency, repeated head trauma, or liver failure.

The patient’s systolic blood pressure (BP) was 60 mm Hg, heart rate (HR) was 120 beats per minute (bpm), and oral temperature was 98.4°F. Rousing him was difficult. There were no localizing neurologic abnormalities, and the rest of the physical examination findings were normal. Point-of-care blood glucose level was 155 mg/dL. Blood cultures were obtained and broad-spectrum antibiotics initiated. After fluid resuscitation, BP improved to 116/87 mm Hg, HR fell to 105 bpm, and the patient became alert and oriented. He denied chest pain, fever, or diaphoresis.

The patient’s improvement with intravenous (IV) fluids makes cardiogenic shock unlikely but does not exclude an underlying compensated cardiomyopathy that may be predisposing to arrhythmia. Hypotension, tachycardia, and somnolence may represent sepsis, but the near normalization of vital signs and mental status shortly after administration of IV fluids, the normal temperature, and the absence of localizing signs of infection favor withholding additional antibiotics. Other causes of hypotension are hypovolemia, medication effects, adrenal insufficiency, anaphylaxis, and autonomic insufficiency. There was no reported nausea, vomiting, diarrhea, bleeding, polyuria, or impaired oral intake to support hypovolemia, though the response to IV fluids suggests hypovolemia may still be playing a role.

White blood cell (WBC) count was 15,450/µL with a normal differential; hemoglobin level was 15.8 g/dL; and platelet count was 176,000/µL. Electrolytes, liver function tests, cardiac enzymes, and urinalysis were normal. Electrocardiogram showed sinus tachycardia with premature atrial complexes and no ST-segment abnormalities. Radiograph of the chest and computed tomography scan of the head were normal. Echocardiogram showed moderate left ventricular hypertrophy with a normal ejection fraction and no valvular abnormalities. Exercise nuclear cardiac stress test was negative for ischemia. Blood cultures were sterile. The patient quickly became asymptomatic and remained so during his 3-day hospitalization. There were no arrhythmias on telemetry. The patient was discharged with follow-up scheduled with his primary care physician.

The nonlocalizing history and physical examination findings, normal chest radiograph and urinalysis, absence of fevers, negative blood cultures, and quick recovery make infection unlikely, despite the moderate leukocytosis. Conditions that present with acute and transient hypotension and altered mental status include arrhythmias, seizures, and reactions to drugs or toxins. Given the cardiac test results, a chronic cardiomyopathy seems unlikely, but arrhythmia is still possible. Continuous outpatient monitoring is required to assess the palpitations and the frequency of the premature atrial complexes.

Two days after discharge, the patient suddenly became diaphoretic and lost consciousness while walking to the bathroom. He was taken to the ED, where his BP was 90/60 mm Hg and HR was 108 bpm. Family members reported that he had appeared flushed during the syncopal episode, showed no seizure activity, and been unconscious for 15 to 20 minutes. The patient denied chest pain, dyspnea, fever, bowel or bladder incontinence, focal weakness, slurred speech, visual changes, nausea or vomiting either before or after the episode. Physical examination revealed a tongue laceration and facial erythema; all other findings were normal. In the ED, there was an asymptomatic 7-beat run of nonsustained ventricular tachycardia, and the hypotension resolved after fluid resuscitation. The patient now reported 2 similar syncopal episodes in the past. The first occurred in a restaurant 6 years earlier, and the second occurred 3 years later, at which time he was hospitalized and no etiology was found.

The loss of consciousness is attributable to cerebral hypoperfusion. Hypotension has 3 principal categories: hypovolemic, cardiogenic, and distributive. With syncopal episodes recurring over several years, hypovolemia seems unlikely. Given the palpitations and ventricular tachycardia, it is reasonable to suspect a cardiogenic cause. Although his heart appears to be structurally normal on echocardiogram, genetic, electrophysiologic, or magnetic resonance imaging (MRI) testing will occasionally reveal an unsuspected substrate for arrhythmia.

The recurring yet self-limited nature, diaphoresis, flushing, and facial erythema suggest a non-sepsis distributive cause of hypotension. It is possible the patient is recurrently exposed to a toxin (eg, alcohol) that causes both flushing and dehydration. Flushing disorders include carcinoid syndrome, pheochromocytoma, drug reaction with eosinophilia and systemic symptoms (DRESS), and mastocytosis. Carcinoid syndrome is characterized by bronchospasm and diarrhea and, in some cases, right-sided valvulopathy, all of which are absent in this patient. Pheochromocytoma is associated with orthostasis, but patients typically are hypertensive at baseline. DRESS, which may arise from nonsteroidal anti-inflammatory drug (NSAID) or aspirin use, can cause facial erythema and swelling but is also characterized by liver, renal, and hematologic abnormalities, none of which was demonstrated. Furthermore, DRESS typically does not cause hypotension. Mastocytosis can manifest as isolated or recurrent anaphylaxis.

It is important to investigate antecedents of these syncopal episodes. If the earlier episodes were food-related—one occurred at a restaurant—then deglutition syncope (syncope precipitated by swallowing) should be considered. If an NSAID or aspirin was ingested before each episode, then medication hypersensitivity or mast cell degranulation (which can be triggered by these medications) should be further examined. Loss of consciousness lasting 20 minutes without causing any neurologic sequelae is unusual for most causes of recurrent syncope. This feature raises the possibility that a toxin or mediator might still be present in the patient’s system.

Serial cardiac enzymes and electrocardiogram were normal. A tilt-table study was negative. The cortisol response to ACTH (cosyntropin) stimulation was normal. The level of serum tryptase, drawn 2 days after syncope, was 18.4 ng/dL (normal, <11.5 ng/dL). Computed tomography scan of chest and abdomen was negative for pulmonary embolism but showed a 1.4×1.3-cm hypervascular lesion in the tail of pancreas. The following neuroendocrine tests were within normal limits: serum and urine catecholamines; urine 5-hydroxyindoleacetic acid (5-HIAA); and serum chromogranin A, insulin, serotonin, vasoactive intestinal polypeptide (VIP), and somatostatin (Table 1). The patient remained asymptomatic during his hospital stay and was discharged home with appointments for cardiology follow-up and endoscopic ultrasound-guided biopsy of the pancreatic mass.

As hypoglycemia from a pancreatic insulinoma is plausible as a cause of episodic loss of consciousness lasting 15 minutes or more, it is important to inquire if giving food or drink helped resolve previous episodes. The normal insulin level reported here is of limited value, because it is the combination of insulin and C-peptide levels at time of hypoglycemia that is diagnostic. The normal glucose level recorded during one of the earlier episodes and the hypotension argue against hypoglycemia.

The elevated tryptase level is an indicator of mast cell degranulation. Tryptase levels are transiently elevated during the initial 2 to 4 hours after an anaphylactic episode and then normalize. An elevated level many hours or days later is considered a sign of mast cell excess. Although there is no evidence of the multi-organ disease (eg, cytopenia, bone disease, hepatosplenomegaly) seen in patients with a high systemic burden of mast cells, mast cell disorders exist on a spectrum. There may be a focal excess of mast cells confined to one organ or an isolated mass.

The same day as discharge, the patient’s wife drove them to the grocery store. He remained in the car while she shopped. When she returned, she found him confused and minimally responsive with subsequent brief loss of consciousness. He was taken to an ED, where he was flushed and hypotensive (systolic BP, 60 mm Hg) and tachycardic. Other examination findings were normal. After fluid resuscitation he became alert and oriented. WBC count was 20,850/μL with 89% neutrophils, hemoglobin level was 14.6 g/dL, and platelet count was 168,000/μL. Serum lactate level was 3.7 mmol/L (normal, <2.3 mmol/L). Chest radiograph was normal. He was treated with broad-spectrum antibiotic therapy and admitted to the hospital. Blood and urine cultures were sterile. Fine-needle aspiration of the pancreatic mass demonstrated nonspecific inflammation. Four days after admission (3 days after pancreatic mass biopsy) the patient developed palpitations, felt unwell, and had marked flushing of the face and trunk, with concomitant BP of 90/50 mm Hg and HR of 140 bpm.

The salient features of this case are recurrent hypotension, tachycardia, and flushing. Autonomic insufficiency, to which elderly patients are prone, causes hemodynamic perturbations but rarely flushing. The patient does not have diabetes mellitus, Parkinson disease, or another condition that puts him at risk for dysautonomia. Pancreatic neuroendocrine tumors secrete mediators that lead to vasodilation and hypotension but are unlikely given the clinical and biochemical data.

The patient’s symptoms are consistent with anaphylaxis, though prototypical immunoglobulin E (IgE)–mediated anaphylaxis is usually accompanied by urticaria, angioedema, and wheezing, which have been absent during his presentations. There are no clear food, pharmacologic, or environmental precipitants.

Recurrent anaphylaxis can be a manifestation of mast cell excess (eg, cutaneous or systemic mastocytosis). A markedly elevated tryptase level during an anaphylactic episode is consistent with mastocytosis or IgE-mediated anaphylaxis. An elevated baseline tryptase level days after an anaphylactic episode signals increased mast cell burden. There may be a reservoir of mast cells in the bone marrow. Alternatively, the hypervascular pancreatic mass may be a mastocytoma or a mast cell sarcoma (missed because of inadequate sampling or staining).

The lactic acidosis likely reflects global tissue hypoperfusion from vasodilatory hypotension. The leukocytosis may reflect WBC mobilization secondary to endogenous corticosteroids and catecholamines in response to hypotension or may be a direct response to the release of mast cell–derived mediators of inflammation.

The patient was treated with diphenhydramine and ranitidine. Serum tryptase level was 46.8 ng/mL (normal, <11.5 ng/mL), and 24-hour urine histamine level was 95 µ g/dL (normal, <60 µ g/dL). Bone marrow biopsy results showed multifocal dense infiltrative aggregates of mast cells (>15 cells/aggregate), which were confirmed by CD117 (Kit) and tryptase positivity (Figure). Mutation analysis for Kit Asp816Val, which is present in 80% to 90% of patients with mastocytosis, was positive. He fulfilled the 2008 World Health Organization criteria for systemic mastocytosis (Table 2). Prednisone, histamine inhibitors, and montelukast were prescribed. Six months later, magnetic resonance imaging of the abdomen showed no change in the pancreatic mass, which was now characterized as a possible splenule. The patient had no additional episodes of flushing or syncope over 2 years.

Cardiovascular collapse (hypotension, tachycardia, syncope) in an elderly patient prompts clinicians to focus on life-threatening conditions, such as acute coronary syndrome, pulmonary embolus, arrhythmia, and sepsis. Each of these diagnoses was considered early in the course of this patient’s presentations, but each was deemed unlikely as it became apparent that the episodes were self-limited and recurrent over years. Incorporating flushing into the diagnostic problem representation allowed the clinicians to focus on a subset of causes of hypotension.

Flushing disorders may be classified by whether they are mediated by the autonomic nervous system (wet flushes, because they are usually accompanied by diaphoresis) or by exogenous or endogenous vasoactive substances (dry flushes).¹ Autonomic nervous system flushing is triggered by emotions, fever, exercise, perimenopause (hot flashes), and neurologic conditions (eg, Parkinson disease, spinal cord injury, multiple sclerosis). Vasoactive flushing precipitants include drugs (eg, niacin); alcohol (secondary to cutaneous vasodilation, or acetaldehyde particularly in people with insufficient acetaldehyde dehydrogenase activity)²; foods that contain capsaicin, tyramine, sulfites, or histamine (eg, eating improperly handled fish can cause scombroid poisoning); and anaphylaxis. Rare causes of vasoactive flushing include carcinoid syndrome, pheochromocytoma, medullary thyroid carcinoma, VIPoma, and mastocytosis.²

Mastocytosis is a rare clonal disorder characterized by the accumulation of abnormal mast cells in the skin (cutaneous mastocytosis), in multiple organs (systemic mastocytosis), or in a solid tumor (mastocytoma). Urticaria pigmentosa is the most common form of cutaneous mastocytosis; it is seen more often in children than in adults and typically is associated with a maculopapular rash and dermatographism. Systemic mastocytosis is the most common form of the disorder in adults.³ Symptoms are related to mast cell infiltration or mast cell mediator–related effects, which range from itching, flushing, and diarrhea to hypotension and anaphylaxis. Other manifestations are fatigue, urticaria pigmentosa, osteoporosis, hepatosplenomegaly, bone pain, cytopenias, and lymphadenopathy.⁴

Systemic mastocytosis can occur at any age and should be considered in patients with recurrent unexplained flushing, syncope, or hypotension. Eighty percent to 90% of patients with systemic mastocytosis have a mutation in Kit,⁵ a transmembrane tyrosine kinase that is the receptor for stem cell factor. The Asp816Val mutation leads to increased proliferation and reduced apoptosis of mast cells.^3,6,7 Proposed diagnostic algorithms^8-11 involve measurement of serum tryptase levels and examination of bone marrow. Bone marrow biopsy and testing for the Asp816Val Kit mutation should be considered in patients with modestly elevated baseline tryptase levels (11.5-20 ng/mL) if clinical findings are consistent with mastocytosis.¹²

The primary goals of treatment are managing mast cell–mediated symptoms and, in advanced cases, achieving cytoreduction. Alcohol can trigger mast cell degranulation in indolent systemic mastocytosis and should be avoided. Mast cell–mediated symptoms are managed with histamine blockers, leukotriene antagonists, and mast cell stabilizers.¹² Targeted therapy with tyrosine kinase inhibitors (eg, imatinib) in patients with transmembrane Kit mutation (eg, Phe522Cys, Lys509Ile) associated with systemic mastocytosis has had promising results.^13,14 However, this patient’s Asp816Val mutation is in the Kit catalytic domain, not the transmembrane region, and therefore would not be expected to respond to imatinib. A recent open-label trial of the multikinase inhibitor midostaurin demonstrated resolution of organ damage, reduced bone marrow burden, and lowered serum tryptase levels in patients with advanced systemic mastocytosis.¹⁵ Interferon, cladribine, and high-dose corticosteroids are prescribed in patients for whom other therapies have been ineffective.⁸

The differential diagnosis is broad for both hypotension and for flushing, but the differential diagnosis for recurrent hypotension and flushing is limited. Recognizing that flushing was an essential feature of this patient’s hypotensive condition, and not an epiphenomenon of syncope, allowed the clinicians to focus on the overlap and make a shocking diagnosis.

Acknowledgment

The authors thank David Bosler, MD (Cleveland Clinic) for interpreting the pathology image.

Disclosure

Nothing to report.

Patient-centered care, defined by the Institute of Medicine as “health care that establishes a partnership among practitioners, patients, and their families to ensure that decisions respect patients’ wants, needs and preferences and that patients have the education and support they need to make decisions and participate in their own care,” has been recognized as an important factor in improving care transitions after discharge from the hospital.¹ Previous efforts to improve the discharge process for hospitalized patients and reduce avoidable readmissions have focused on improving systems surrounding the patient, such as by increasing the availability of outpatient follow-up or standardizing communication between the inpatient and outpatient care teams.^1,2 In fact, successful programs such as Project BOOST and the Care Transitions Interventions™ provide healthcare institutions with a “bundle” of evidence-based transitional care guidelines for discharge: they provide postdischarge transition coaches, assistance with medication self-management, timely follow-up tips, and improved patient records in order to improve postdischarge outcomes.^3,4 Successful interventions, however, may not provide more services, but also engage the patient in their own care.^5,6 The impact of engaging the patient in his or her own care by providing patient-friendly discharge instructions alone, however, is unknown.

A patient-centered discharge may use tools that were designed with patients, or may involve engaging patients in an interactive process of reviewing discharge instructions and empowering them to manage aspects of their own care after leaving the hospital. This endeavour may lead to more effective use of discharge instructions and reduce the need for additional or more intensive (and costly) interventions. For example, a patient-centered discharge tool could include an educational intervention that uses the “teach-back” method, in which patients are asked to restate in their own words what they thought they heard, or in which staff use additional media or a visual design tool meant to enhance comprehension of discharge instructions.^6,7 Visual aids and the use of larger fonts are particularly useful design elements for improving comprehension among non-English speakers and patients with low health literacy, who tend to have poorer recall of instructions.^8-10 What may constitute essential design elements to include in a discharge instruction tool, however, is not clear.

Moreover, whether the use of discharge tools with a specific focus on patient engagement may improve postdischarge outcomes is not known. Particularly, the ability of patient-centered discharge tools to improve outcomes beyond comprehension such as self-management, adherence to discharge instructions, a reduction in unplanned visits, and a reduction in mortality has not been studied systematically. The objective of this systematic review was to review the literature on discharge instruction tools with a focus on patient engagement and their impact among hospitalized patients.

The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement was followed as a guideline for reporting throughout this review.¹¹

Data Sources

A literature search was undertaken using the following databases from January 1994 or their inception date to May 2014: Medline, Embase, SIGLE, HTA, Bioethics, ASSIA, Psych Lit, CINAHL, Cochrane Library, EconLit, ERIC, and BioMed Central. We also searched relevant design-focused journals such as Design Issues, Journal of Design Research, Information Design Journal, Innovation, Design Studies, and International Journal of Design, as well as reference lists from studies obtained by electronic searching. The following key words and combination of key words were used with the assistance of a medical librarian: patient discharge, patient-centered discharge, patient-centered design, design thinking, user based design, patient education, discharge summary, education. Additional search terms were added when identified from relevant articles (Appendix).

Inclusion Criteria

We included all English-language studies with patients admitted to the hospital irrespective of age, sex, or medical condition, which included a control group or time period and which measured patient outcomes within 3 months of discharge. The 3-month period after discharge is often cited as a time when outcomes could reasonably be associated with an intervention at discharge.²

Exclusion Criteria

Studies that did not have clear implementation of a patient-centered tool, a control group, or those whose tool was used in the emergency department or as an outpatient were excluded. Studies that included postdischarge tools such as home visits or telephone calls were excluded unless independent effects of the predischarge interventions were measured. Studies with outcomes reported after 3 months were excluded unless outcomes before 3 months were also clearly noted.

All searches were entered into Endnote and duplicates were removed. A 2-stage inclusion process was used. Titles and abstracts of articles were first screened for meeting inclusion and exclusion criteria by 1 reviewer. A second reviewer independently checked a 10% random sample of all the abstracts that met the initial screening criteria. If the agreement to exclude studies was less than 95%, criteria were reviewed before checking the rest of the 90% sample. In the second stage, 2 independent reviewers examined paper copies of the full articles selected in the first stage. Disagreement between reviewers was resolved by discussion or a third reviewer if no agreement could be reached.

Data Analysis and Synthesis

The following information was extracted from the full reference: type of study, population studied, control group or time period, tool used, and outcomes measured. Based on the National Health Care Quality report’s priorities and goals on patient and/or family engagement during transitions of care, educational tools were further described based on method of teaching, involvement of the care team, involvement of the patient in the design or delivery of the tool, and/or the use of visual aids.¹² All primary outcomes were classified according to 3 categories: improved knowledge/comprehension, patient experience (patient satisfaction, self-management/efficacy such as functional status, both physical and mental), and health outcomes (unscheduled visits or readmissions, adherence with medications, diet, exercise, or follow-up, and mortality).

No quantitative pooling of results or meta-analysis was done given the variability and heterogeneity of studies reviewed. However, following guidelines for Effect Practice and Organisation of Care (EPOC) Risk of Bias criteria,¹³ studies that had a higher risk of bias such as uncontrolled before-after studies or studies with only 1 intervention or control site (historical controls, eg) were excluded from the final review because of the difficulties in attributing causation. Only primary outcomes were reported in order to minimize type II errors.

Our search revealed a total of 3699 studies after duplicates had been removed (Figure). A total of 714 references were included after initial review by title and abstract and 30 studies after full-text review. Agreement on a 10% random sample of all abstracts and full text was 79% (k=0.58) and 86% (k=0.72), respectively. Discussion was needed for fewer than 100 references, and agreement was subsequently reached for 100%.

There were 22 randomized controlled trials and 8 nonrandomized studies (5 nonrandomized controlled trials and 3 controlled before-after studies). Most of these studies were conducted in the United States (13/30 studies), followed by other European countries (5 studies), and the United Kingdom (4 studies). A large number of studies were conducted among patients with cardiovascular disease or risk factors (10 studies), followed by postsurgical patients such as coronary artery bypass graft surgery or orthopaedic surgery (5 studies). Five of 30 studies were conducted among individuals older than 65 years. Most studies excluded patients who did not speak English or the country’s official language; only 3 studies included patients with limited literacy, patients who spoke other languages, or caregivers if the patients could not communicate.

Most studies tested the impact of educational discharge interventions (28 of 30 studies) (Table 1). Quite often, it was a member of the research team who carried out the patient education. Only 3 studies involved multiple members of the care team in designing or reviewing the discharge tool with the patient. Almost half (12 studies) targeted multiple aspects of postdischarge care, including medications and side effects, signs and symptoms to consider, plans for follow-up, dietary restrictions, and/or exercise modifications. Many (19 studies) provided education using one-on-one teaching in association with a discharge tool, accompanied by a written handout (13 studies), audiotape (2 studies), or video (3 studies). While 13 studies had patients involved in creating what content was discussed and 14 studies had patients involved in the delivery of the tool, only 6 studies had patients involved in both design and delivery of the tool. Nine studies also used visual aids such as pictures, larger font, or use of a tool enhanced for patients with language barriers or limited health literacy.

Our systematic review found 30 studies that engaged patients during the design or the delivery of a discharge instruction tool and that tested the effect of the tool on postdischarge outcomes.^6-10,14–38 Our review suggests that there is sufficient evidence that patient-centered discharge tools improve comprehension. However, evidence is currently insufficient to determine if patient-centered tools improve adherence with discharge instructions. Moreover, though limited studies show promising results, more studies are needed to determine if patient engagement improves self-efficacy and healthcare utilization after discharge.

A major limitation of current studies is the variability in the level of patient engagement in tool design or delivery. Patients were involved in the design mostly through targeted development of a discharge management plan and the delivery by encouraging them to ask questions. Few studies involved patients in the design of the tool such that patients were responsible for coming up with content that was of interest to them. The few that did, often with the additional use of video media, demonstrated significant outcomes. Only a minority of studies used an interactive process to assess understanding such as “teach-back” or maximize patient comprehension such as visual aids. Even fewer studies engaged patients in both developing the discharge tool and providing discharge instructions.

Several previous studies have demonstrated that most complications after discharge are the result of ineffective communication, which can be exacerbated by lack of fluency in English or by limited health literacy.^2,39-43 As a result, poor understanding of discharge instructions by patients and their caregivers can create an important care gap.⁴⁴ Therefore, the use of patient-centered tools to engage patients at discharge in their own care is needed. How to engage patients consistently and effectively is perhaps less evident, as demonstrated in this review of the literature in which different levels of patient engagement were found. Many of the tools tested placed attention on patient education, sometimes in the context of bundled care along with home visits or follow-up, all of which can require extensive resources and time. Providing patients with information that the patients themselves state is of value may be the easiest refinement to a discharge educational tool, although this was surprisingly uncommon.^{6,9,10,17,23,33,37} Only 2 studies were found that engaged patients in the initial stage of design of the discharge tool, by incorporating information of interest to them.^23,32 For example, a study testing the impact of a computer-generated written education package on poststroke outcomes designed the information by asking patients to identify which topics they would like to receive information about (along with the amount of information and font size).²³ Secondly, although most of the discharge tools reviewed included the use of one-on-one teaching and the use of media such as patient handouts, these tools were often used in such a way that patients were passive recipients. In fact, studies that used additional video media that incorporated personalized content were the most likely to demonstrate positive outcomes.^17,34 The next level of patient engagement may therefore be to involve the patient as an interactive partner when delivering the tool in order to empower patients to self-care. For example, 1 study designed a structured education program by first assessing lifestyle risk factors related to hypertension that were modifiable along with preconceived notions through open-ended questions during a one-on-one interview.³⁷ Patients were subsequently educated on any knowledge deficits regarding the management of their lifestyle. Another level of patient engagement may be to use visual aids during discussions, as a well-known complement to verbal instructions.^45,46 For example, in a controlled study that randomized a ward of elderly patients with 4 or more prescriptions to predischarge counseling, the counseling session aimed to review reasons for their prescriptions along with corresponding side effects, doses, and dosage times with the help of a medicine reminder card. Other uses of visual aid tools identified in our review included the use of pictograms or illustrations or, at minimum, attention to font size.^{7,8,16,29,33,35} In the absence of a visual aid, asking the patient to repeat or demonstrate what was just communicated can be used to assess the amount of information retained.^18,33

An important result discovered in our review of the literature was also the lack of studies that tested the impact of discharge tools on usability of discharge information once at home. Conducting an evaluation of the benefits to patients after discharge can help objectify vague outcomes like health gains or qualify benefits in patient’s views. This might also explain why many studies with documented patient engagement at the time of discharge were able to demonstrate improvements in comprehension but not adherence to instructions. Although patients and caregivers may understand the information, this comprehension does not necessarily mean they will find the information useful or adhere to it once at home. For example, in 1 study, patients discharged with at least 1 medication were randomized to a structured discharge interview during which the treatment plan was reviewed verbally and questions clarified along with a visually enhanced treatment card.²⁶ Although knowledge of medications increased, no effect was found on adherence at 1 week postdischarge. However, use of the treatment card at home was not assessed. Similarly, another study tested the effect of an individualized video of exercises and failed to find a difference in patient adherence at 4 weeks.²⁸ The authors suggested that the lack of benefit may have been because patients were not using the video once at home. This is in contrast to 2 studies that involved patients in their own care by requiring them to request their medication as part of a self-medication tool predischarge.^16,30 Patients were engaged in the process such that increasing independence was given to patients based on their demonstration of understanding and adherence to their treatment while still in the hospital, a learning tool that can be applied once at home. Feeling knowledgeable and involved, as others have suggested, may be the intermediary outcomes that led to improved adherence.⁴⁷ It is also possible that adherence to discharge instructions may vary based on complexity of the information provided, such that instructions focusing solely on medication use may require less patient engagement than discharge instructions that include information on medications, diet, exercise modifications, and follow-up.⁴⁸

Our review has a few limitations. Previous systematic reviews have demonstrated that bundled discharge interventions that include patient-centered education have a positive effect on outcomes postdischarge.^2,5 However, we sought to describe and study the individual and distinct impact of patient engagement in the creation and delivery of discharge tools on outcomes postdischarge. We hoped that this may provide others with key information regarding elements of patient engagement that were particularly useful when designing a new discharge tool. The variability of the studies we identified, however, made it difficult to ascertain what level of patient engagement is required to observe improvements in health outcomes. It is also possible that a higher level of patient engagement may have been used but not described in the studies we reviewed. As only primary outcomes were included, we may have underestimated the effect of patient-centered discharge tools on outcomes that were reported as secondary outcomes. As we were interested in reviewing as many studies of patient-centered discharge tools as possible, we did not assess the quality of the studies and cannot comment on the role of bias in these studies. However, we excluded studies with study designs known to have the highest risk of bias. Lastly, we also cannot comment on whether patient-centered tools may have an effect on outcomes more than 3 months after a hospital discharge. However, several studies included in this review suggest a sustained effect beyond this time period.^8,25,32,37

Patient-centered discharge tools in which patients were engaged in the design or the delivery were found to improve comprehension of but not adherence with discharge instructions. The perceived lack of improved adherence may be due to a lack of studies that measured the usefulness and utilization of information for patients once at home. There was also substantial variability in the extent of patient involvement in designing the style and content of information provided to patients at discharge, as well as the extent of patient engagement when receiving discharge instructions. Future studies would benefit from detailing the level of patient engagement needed in designing and delivery of discharge tools. This information may lead to the discovery of barriers and facilitators to utilization of discharge information once at home and lead to a better understanding of the patient’s journey from hospital to home and onwards.

C.M.B. and this work were funded by a CIHR Canadian Patient Safety Institute Chair in Patient Safety and Continuity of Care. Funding was provided to cover fees to obtain articles from the Donald J. Matthews Complex Care Fund of the University Health Network in Toronto, Canada. The Toronto Central Local Health Integration Network provided funding for the design and implementation of a patient-oriented discharge summary. None of the funding or supportive agencies were involved in the design or conduct of the present study, analysis, or interpretation of the data, or approval of the manuscript.

Disclosures

The authors report no conflicts of interest.

Patient-centered care, defined by the Institute of Medicine as “health care that establishes a partnership among practitioners, patients, and their families to ensure that decisions respect patients’ wants, needs and preferences and that patients have the education and support they need to make decisions and participate in their own care,” has been recognized as an important factor in improving care transitions after discharge from the hospital.¹ Previous efforts to improve the discharge process for hospitalized patients and reduce avoidable readmissions have focused on improving systems surrounding the patient, such as by increasing the availability of outpatient follow-up or standardizing communication between the inpatient and outpatient care teams.^1,2 In fact, successful programs such as Project BOOST and the Care Transitions Interventions™ provide healthcare institutions with a “bundle” of evidence-based transitional care guidelines for discharge: they provide postdischarge transition coaches, assistance with medication self-management, timely follow-up tips, and improved patient records in order to improve postdischarge outcomes.^3,4 Successful interventions, however, may not provide more services, but also engage the patient in their own care.^5,6 The impact of engaging the patient in his or her own care by providing patient-friendly discharge instructions alone, however, is unknown.

A patient-centered discharge may use tools that were designed with patients, or may involve engaging patients in an interactive process of reviewing discharge instructions and empowering them to manage aspects of their own care after leaving the hospital. This endeavour may lead to more effective use of discharge instructions and reduce the need for additional or more intensive (and costly) interventions. For example, a patient-centered discharge tool could include an educational intervention that uses the “teach-back” method, in which patients are asked to restate in their own words what they thought they heard, or in which staff use additional media or a visual design tool meant to enhance comprehension of discharge instructions.^6,7 Visual aids and the use of larger fonts are particularly useful design elements for improving comprehension among non-English speakers and patients with low health literacy, who tend to have poorer recall of instructions.^8-10 What may constitute essential design elements to include in a discharge instruction tool, however, is not clear.

Moreover, whether the use of discharge tools with a specific focus on patient engagement may improve postdischarge outcomes is not known. Particularly, the ability of patient-centered discharge tools to improve outcomes beyond comprehension such as self-management, adherence to discharge instructions, a reduction in unplanned visits, and a reduction in mortality has not been studied systematically. The objective of this systematic review was to review the literature on discharge instruction tools with a focus on patient engagement and their impact among hospitalized patients.

The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement was followed as a guideline for reporting throughout this review.¹¹

Data Sources

A literature search was undertaken using the following databases from January 1994 or their inception date to May 2014: Medline, Embase, SIGLE, HTA, Bioethics, ASSIA, Psych Lit, CINAHL, Cochrane Library, EconLit, ERIC, and BioMed Central. We also searched relevant design-focused journals such as Design Issues, Journal of Design Research, Information Design Journal, Innovation, Design Studies, and International Journal of Design, as well as reference lists from studies obtained by electronic searching. The following key words and combination of key words were used with the assistance of a medical librarian: patient discharge, patient-centered discharge, patient-centered design, design thinking, user based design, patient education, discharge summary, education. Additional search terms were added when identified from relevant articles (Appendix).

Inclusion Criteria

We included all English-language studies with patients admitted to the hospital irrespective of age, sex, or medical condition, which included a control group or time period and which measured patient outcomes within 3 months of discharge. The 3-month period after discharge is often cited as a time when outcomes could reasonably be associated with an intervention at discharge.²

Exclusion Criteria

Studies that did not have clear implementation of a patient-centered tool, a control group, or those whose tool was used in the emergency department or as an outpatient were excluded. Studies that included postdischarge tools such as home visits or telephone calls were excluded unless independent effects of the predischarge interventions were measured. Studies with outcomes reported after 3 months were excluded unless outcomes before 3 months were also clearly noted.

All searches were entered into Endnote and duplicates were removed. A 2-stage inclusion process was used. Titles and abstracts of articles were first screened for meeting inclusion and exclusion criteria by 1 reviewer. A second reviewer independently checked a 10% random sample of all the abstracts that met the initial screening criteria. If the agreement to exclude studies was less than 95%, criteria were reviewed before checking the rest of the 90% sample. In the second stage, 2 independent reviewers examined paper copies of the full articles selected in the first stage. Disagreement between reviewers was resolved by discussion or a third reviewer if no agreement could be reached.

Data Analysis and Synthesis

The following information was extracted from the full reference: type of study, population studied, control group or time period, tool used, and outcomes measured. Based on the National Health Care Quality report’s priorities and goals on patient and/or family engagement during transitions of care, educational tools were further described based on method of teaching, involvement of the care team, involvement of the patient in the design or delivery of the tool, and/or the use of visual aids.¹² All primary outcomes were classified according to 3 categories: improved knowledge/comprehension, patient experience (patient satisfaction, self-management/efficacy such as functional status, both physical and mental), and health outcomes (unscheduled visits or readmissions, adherence with medications, diet, exercise, or follow-up, and mortality).

No quantitative pooling of results or meta-analysis was done given the variability and heterogeneity of studies reviewed. However, following guidelines for Effect Practice and Organisation of Care (EPOC) Risk of Bias criteria,¹³ studies that had a higher risk of bias such as uncontrolled before-after studies or studies with only 1 intervention or control site (historical controls, eg) were excluded from the final review because of the difficulties in attributing causation. Only primary outcomes were reported in order to minimize type II errors.

Our search revealed a total of 3699 studies after duplicates had been removed (Figure). A total of 714 references were included after initial review by title and abstract and 30 studies after full-text review. Agreement on a 10% random sample of all abstracts and full text was 79% (k=0.58) and 86% (k=0.72), respectively. Discussion was needed for fewer than 100 references, and agreement was subsequently reached for 100%.

There were 22 randomized controlled trials and 8 nonrandomized studies (5 nonrandomized controlled trials and 3 controlled before-after studies). Most of these studies were conducted in the United States (13/30 studies), followed by other European countries (5 studies), and the United Kingdom (4 studies). A large number of studies were conducted among patients with cardiovascular disease or risk factors (10 studies), followed by postsurgical patients such as coronary artery bypass graft surgery or orthopaedic surgery (5 studies). Five of 30 studies were conducted among individuals older than 65 years. Most studies excluded patients who did not speak English or the country’s official language; only 3 studies included patients with limited literacy, patients who spoke other languages, or caregivers if the patients could not communicate.

Most studies tested the impact of educational discharge interventions (28 of 30 studies) (Table 1). Quite often, it was a member of the research team who carried out the patient education. Only 3 studies involved multiple members of the care team in designing or reviewing the discharge tool with the patient. Almost half (12 studies) targeted multiple aspects of postdischarge care, including medications and side effects, signs and symptoms to consider, plans for follow-up, dietary restrictions, and/or exercise modifications. Many (19 studies) provided education using one-on-one teaching in association with a discharge tool, accompanied by a written handout (13 studies), audiotape (2 studies), or video (3 studies). While 13 studies had patients involved in creating what content was discussed and 14 studies had patients involved in the delivery of the tool, only 6 studies had patients involved in both design and delivery of the tool. Nine studies also used visual aids such as pictures, larger font, or use of a tool enhanced for patients with language barriers or limited health literacy.

Our systematic review found 30 studies that engaged patients during the design or the delivery of a discharge instruction tool and that tested the effect of the tool on postdischarge outcomes.^6-10,14–38 Our review suggests that there is sufficient evidence that patient-centered discharge tools improve comprehension. However, evidence is currently insufficient to determine if patient-centered tools improve adherence with discharge instructions. Moreover, though limited studies show promising results, more studies are needed to determine if patient engagement improves self-efficacy and healthcare utilization after discharge.

A major limitation of current studies is the variability in the level of patient engagement in tool design or delivery. Patients were involved in the design mostly through targeted development of a discharge management plan and the delivery by encouraging them to ask questions. Few studies involved patients in the design of the tool such that patients were responsible for coming up with content that was of interest to them. The few that did, often with the additional use of video media, demonstrated significant outcomes. Only a minority of studies used an interactive process to assess understanding such as “teach-back” or maximize patient comprehension such as visual aids. Even fewer studies engaged patients in both developing the discharge tool and providing discharge instructions.

Several previous studies have demonstrated that most complications after discharge are the result of ineffective communication, which can be exacerbated by lack of fluency in English or by limited health literacy.^2,39-43 As a result, poor understanding of discharge instructions by patients and their caregivers can create an important care gap.⁴⁴ Therefore, the use of patient-centered tools to engage patients at discharge in their own care is needed. How to engage patients consistently and effectively is perhaps less evident, as demonstrated in this review of the literature in which different levels of patient engagement were found. Many of the tools tested placed attention on patient education, sometimes in the context of bundled care along with home visits or follow-up, all of which can require extensive resources and time. Providing patients with information that the patients themselves state is of value may be the easiest refinement to a discharge educational tool, although this was surprisingly uncommon.^{6,9,10,17,23,33,37} Only 2 studies were found that engaged patients in the initial stage of design of the discharge tool, by incorporating information of interest to them.^23,32 For example, a study testing the impact of a computer-generated written education package on poststroke outcomes designed the information by asking patients to identify which topics they would like to receive information about (along with the amount of information and font size).²³ Secondly, although most of the discharge tools reviewed included the use of one-on-one teaching and the use of media such as patient handouts, these tools were often used in such a way that patients were passive recipients. In fact, studies that used additional video media that incorporated personalized content were the most likely to demonstrate positive outcomes.^17,34 The next level of patient engagement may therefore be to involve the patient as an interactive partner when delivering the tool in order to empower patients to self-care. For example, 1 study designed a structured education program by first assessing lifestyle risk factors related to hypertension that were modifiable along with preconceived notions through open-ended questions during a one-on-one interview.³⁷ Patients were subsequently educated on any knowledge deficits regarding the management of their lifestyle. Another level of patient engagement may be to use visual aids during discussions, as a well-known complement to verbal instructions.^45,46 For example, in a controlled study that randomized a ward of elderly patients with 4 or more prescriptions to predischarge counseling, the counseling session aimed to review reasons for their prescriptions along with corresponding side effects, doses, and dosage times with the help of a medicine reminder card. Other uses of visual aid tools identified in our review included the use of pictograms or illustrations or, at minimum, attention to font size.^{7,8,16,29,33,35} In the absence of a visual aid, asking the patient to repeat or demonstrate what was just communicated can be used to assess the amount of information retained.^18,33

An important result discovered in our review of the literature was also the lack of studies that tested the impact of discharge tools on usability of discharge information once at home. Conducting an evaluation of the benefits to patients after discharge can help objectify vague outcomes like health gains or qualify benefits in patient’s views. This might also explain why many studies with documented patient engagement at the time of discharge were able to demonstrate improvements in comprehension but not adherence to instructions. Although patients and caregivers may understand the information, this comprehension does not necessarily mean they will find the information useful or adhere to it once at home. For example, in 1 study, patients discharged with at least 1 medication were randomized to a structured discharge interview during which the treatment plan was reviewed verbally and questions clarified along with a visually enhanced treatment card.²⁶ Although knowledge of medications increased, no effect was found on adherence at 1 week postdischarge. However, use of the treatment card at home was not assessed. Similarly, another study tested the effect of an individualized video of exercises and failed to find a difference in patient adherence at 4 weeks.²⁸ The authors suggested that the lack of benefit may have been because patients were not using the video once at home. This is in contrast to 2 studies that involved patients in their own care by requiring them to request their medication as part of a self-medication tool predischarge.^16,30 Patients were engaged in the process such that increasing independence was given to patients based on their demonstration of understanding and adherence to their treatment while still in the hospital, a learning tool that can be applied once at home. Feeling knowledgeable and involved, as others have suggested, may be the intermediary outcomes that led to improved adherence.⁴⁷ It is also possible that adherence to discharge instructions may vary based on complexity of the information provided, such that instructions focusing solely on medication use may require less patient engagement than discharge instructions that include information on medications, diet, exercise modifications, and follow-up.⁴⁸

Our review has a few limitations. Previous systematic reviews have demonstrated that bundled discharge interventions that include patient-centered education have a positive effect on outcomes postdischarge.^2,5 However, we sought to describe and study the individual and distinct impact of patient engagement in the creation and delivery of discharge tools on outcomes postdischarge. We hoped that this may provide others with key information regarding elements of patient engagement that were particularly useful when designing a new discharge tool. The variability of the studies we identified, however, made it difficult to ascertain what level of patient engagement is required to observe improvements in health outcomes. It is also possible that a higher level of patient engagement may have been used but not described in the studies we reviewed. As only primary outcomes were included, we may have underestimated the effect of patient-centered discharge tools on outcomes that were reported as secondary outcomes. As we were interested in reviewing as many studies of patient-centered discharge tools as possible, we did not assess the quality of the studies and cannot comment on the role of bias in these studies. However, we excluded studies with study designs known to have the highest risk of bias. Lastly, we also cannot comment on whether patient-centered tools may have an effect on outcomes more than 3 months after a hospital discharge. However, several studies included in this review suggest a sustained effect beyond this time period.^8,25,32,37

Patient-centered discharge tools in which patients were engaged in the design or the delivery were found to improve comprehension of but not adherence with discharge instructions. The perceived lack of improved adherence may be due to a lack of studies that measured the usefulness and utilization of information for patients once at home. There was also substantial variability in the extent of patient involvement in designing the style and content of information provided to patients at discharge, as well as the extent of patient engagement when receiving discharge instructions. Future studies would benefit from detailing the level of patient engagement needed in designing and delivery of discharge tools. This information may lead to the discovery of barriers and facilitators to utilization of discharge information once at home and lead to a better understanding of the patient’s journey from hospital to home and onwards.

C.M.B. and this work were funded by a CIHR Canadian Patient Safety Institute Chair in Patient Safety and Continuity of Care. Funding was provided to cover fees to obtain articles from the Donald J. Matthews Complex Care Fund of the University Health Network in Toronto, Canada. The Toronto Central Local Health Integration Network provided funding for the design and implementation of a patient-oriented discharge summary. None of the funding or supportive agencies were involved in the design or conduct of the present study, analysis, or interpretation of the data, or approval of the manuscript.

Disclosures

The authors report no conflicts of interest.

Patient-centered care, defined by the Institute of Medicine as “health care that establishes a partnership among practitioners, patients, and their families to ensure that decisions respect patients’ wants, needs and preferences and that patients have the education and support they need to make decisions and participate in their own care,” has been recognized as an important factor in improving care transitions after discharge from the hospital.¹ Previous efforts to improve the discharge process for hospitalized patients and reduce avoidable readmissions have focused on improving systems surrounding the patient, such as by increasing the availability of outpatient follow-up or standardizing communication between the inpatient and outpatient care teams.^1,2 In fact, successful programs such as Project BOOST and the Care Transitions Interventions™ provide healthcare institutions with a “bundle” of evidence-based transitional care guidelines for discharge: they provide postdischarge transition coaches, assistance with medication self-management, timely follow-up tips, and improved patient records in order to improve postdischarge outcomes.^3,4 Successful interventions, however, may not provide more services, but also engage the patient in their own care.^5,6 The impact of engaging the patient in his or her own care by providing patient-friendly discharge instructions alone, however, is unknown.

A patient-centered discharge may use tools that were designed with patients, or may involve engaging patients in an interactive process of reviewing discharge instructions and empowering them to manage aspects of their own care after leaving the hospital. This endeavour may lead to more effective use of discharge instructions and reduce the need for additional or more intensive (and costly) interventions. For example, a patient-centered discharge tool could include an educational intervention that uses the “teach-back” method, in which patients are asked to restate in their own words what they thought they heard, or in which staff use additional media or a visual design tool meant to enhance comprehension of discharge instructions.^6,7 Visual aids and the use of larger fonts are particularly useful design elements for improving comprehension among non-English speakers and patients with low health literacy, who tend to have poorer recall of instructions.^8-10 What may constitute essential design elements to include in a discharge instruction tool, however, is not clear.

Moreover, whether the use of discharge tools with a specific focus on patient engagement may improve postdischarge outcomes is not known. Particularly, the ability of patient-centered discharge tools to improve outcomes beyond comprehension such as self-management, adherence to discharge instructions, a reduction in unplanned visits, and a reduction in mortality has not been studied systematically. The objective of this systematic review was to review the literature on discharge instruction tools with a focus on patient engagement and their impact among hospitalized patients.

The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Statement was followed as a guideline for reporting throughout this review.¹¹

Data Sources

A literature search was undertaken using the following databases from January 1994 or their inception date to May 2014: Medline, Embase, SIGLE, HTA, Bioethics, ASSIA, Psych Lit, CINAHL, Cochrane Library, EconLit, ERIC, and BioMed Central. We also searched relevant design-focused journals such as Design Issues, Journal of Design Research, Information Design Journal, Innovation, Design Studies, and International Journal of Design, as well as reference lists from studies obtained by electronic searching. The following key words and combination of key words were used with the assistance of a medical librarian: patient discharge, patient-centered discharge, patient-centered design, design thinking, user based design, patient education, discharge summary, education. Additional search terms were added when identified from relevant articles (Appendix).

Inclusion Criteria

We included all English-language studies with patients admitted to the hospital irrespective of age, sex, or medical condition, which included a control group or time period and which measured patient outcomes within 3 months of discharge. The 3-month period after discharge is often cited as a time when outcomes could reasonably be associated with an intervention at discharge.²

Exclusion Criteria

Studies that did not have clear implementation of a patient-centered tool, a control group, or those whose tool was used in the emergency department or as an outpatient were excluded. Studies that included postdischarge tools such as home visits or telephone calls were excluded unless independent effects of the predischarge interventions were measured. Studies with outcomes reported after 3 months were excluded unless outcomes before 3 months were also clearly noted.

All searches were entered into Endnote and duplicates were removed. A 2-stage inclusion process was used. Titles and abstracts of articles were first screened for meeting inclusion and exclusion criteria by 1 reviewer. A second reviewer independently checked a 10% random sample of all the abstracts that met the initial screening criteria. If the agreement to exclude studies was less than 95%, criteria were reviewed before checking the rest of the 90% sample. In the second stage, 2 independent reviewers examined paper copies of the full articles selected in the first stage. Disagreement between reviewers was resolved by discussion or a third reviewer if no agreement could be reached.

Data Analysis and Synthesis

The following information was extracted from the full reference: type of study, population studied, control group or time period, tool used, and outcomes measured. Based on the National Health Care Quality report’s priorities and goals on patient and/or family engagement during transitions of care, educational tools were further described based on method of teaching, involvement of the care team, involvement of the patient in the design or delivery of the tool, and/or the use of visual aids.¹² All primary outcomes were classified according to 3 categories: improved knowledge/comprehension, patient experience (patient satisfaction, self-management/efficacy such as functional status, both physical and mental), and health outcomes (unscheduled visits or readmissions, adherence with medications, diet, exercise, or follow-up, and mortality).

No quantitative pooling of results or meta-analysis was done given the variability and heterogeneity of studies reviewed. However, following guidelines for Effect Practice and Organisation of Care (EPOC) Risk of Bias criteria,¹³ studies that had a higher risk of bias such as uncontrolled before-after studies or studies with only 1 intervention or control site (historical controls, eg) were excluded from the final review because of the difficulties in attributing causation. Only primary outcomes were reported in order to minimize type II errors.

Our search revealed a total of 3699 studies after duplicates had been removed (Figure). A total of 714 references were included after initial review by title and abstract and 30 studies after full-text review. Agreement on a 10% random sample of all abstracts and full text was 79% (k=0.58) and 86% (k=0.72), respectively. Discussion was needed for fewer than 100 references, and agreement was subsequently reached for 100%.

There were 22 randomized controlled trials and 8 nonrandomized studies (5 nonrandomized controlled trials and 3 controlled before-after studies). Most of these studies were conducted in the United States (13/30 studies), followed by other European countries (5 studies), and the United Kingdom (4 studies). A large number of studies were conducted among patients with cardiovascular disease or risk factors (10 studies), followed by postsurgical patients such as coronary artery bypass graft surgery or orthopaedic surgery (5 studies). Five of 30 studies were conducted among individuals older than 65 years. Most studies excluded patients who did not speak English or the country’s official language; only 3 studies included patients with limited literacy, patients who spoke other languages, or caregivers if the patients could not communicate.

Most studies tested the impact of educational discharge interventions (28 of 30 studies) (Table 1). Quite often, it was a member of the research team who carried out the patient education. Only 3 studies involved multiple members of the care team in designing or reviewing the discharge tool with the patient. Almost half (12 studies) targeted multiple aspects of postdischarge care, including medications and side effects, signs and symptoms to consider, plans for follow-up, dietary restrictions, and/or exercise modifications. Many (19 studies) provided education using one-on-one teaching in association with a discharge tool, accompanied by a written handout (13 studies), audiotape (2 studies), or video (3 studies). While 13 studies had patients involved in creating what content was discussed and 14 studies had patients involved in the delivery of the tool, only 6 studies had patients involved in both design and delivery of the tool. Nine studies also used visual aids such as pictures, larger font, or use of a tool enhanced for patients with language barriers or limited health literacy.

Our systematic review found 30 studies that engaged patients during the design or the delivery of a discharge instruction tool and that tested the effect of the tool on postdischarge outcomes.^6-10,14–38 Our review suggests that there is sufficient evidence that patient-centered discharge tools improve comprehension. However, evidence is currently insufficient to determine if patient-centered tools improve adherence with discharge instructions. Moreover, though limited studies show promising results, more studies are needed to determine if patient engagement improves self-efficacy and healthcare utilization after discharge.

A major limitation of current studies is the variability in the level of patient engagement in tool design or delivery. Patients were involved in the design mostly through targeted development of a discharge management plan and the delivery by encouraging them to ask questions. Few studies involved patients in the design of the tool such that patients were responsible for coming up with content that was of interest to them. The few that did, often with the additional use of video media, demonstrated significant outcomes. Only a minority of studies used an interactive process to assess understanding such as “teach-back” or maximize patient comprehension such as visual aids. Even fewer studies engaged patients in both developing the discharge tool and providing discharge instructions.

Several previous studies have demonstrated that most complications after discharge are the result of ineffective communication, which can be exacerbated by lack of fluency in English or by limited health literacy.^2,39-43 As a result, poor understanding of discharge instructions by patients and their caregivers can create an important care gap.⁴⁴ Therefore, the use of patient-centered tools to engage patients at discharge in their own care is needed. How to engage patients consistently and effectively is perhaps less evident, as demonstrated in this review of the literature in which different levels of patient engagement were found. Many of the tools tested placed attention on patient education, sometimes in the context of bundled care along with home visits or follow-up, all of which can require extensive resources and time. Providing patients with information that the patients themselves state is of value may be the easiest refinement to a discharge educational tool, although this was surprisingly uncommon.^{6,9,10,17,23,33,37} Only 2 studies were found that engaged patients in the initial stage of design of the discharge tool, by incorporating information of interest to them.^23,32 For example, a study testing the impact of a computer-generated written education package on poststroke outcomes designed the information by asking patients to identify which topics they would like to receive information about (along with the amount of information and font size).²³ Secondly, although most of the discharge tools reviewed included the use of one-on-one teaching and the use of media such as patient handouts, these tools were often used in such a way that patients were passive recipients. In fact, studies that used additional video media that incorporated personalized content were the most likely to demonstrate positive outcomes.^17,34 The next level of patient engagement may therefore be to involve the patient as an interactive partner when delivering the tool in order to empower patients to self-care. For example, 1 study designed a structured education program by first assessing lifestyle risk factors related to hypertension that were modifiable along with preconceived notions through open-ended questions during a one-on-one interview.³⁷ Patients were subsequently educated on any knowledge deficits regarding the management of their lifestyle. Another level of patient engagement may be to use visual aids during discussions, as a well-known complement to verbal instructions.^45,46 For example, in a controlled study that randomized a ward of elderly patients with 4 or more prescriptions to predischarge counseling, the counseling session aimed to review reasons for their prescriptions along with corresponding side effects, doses, and dosage times with the help of a medicine reminder card. Other uses of visual aid tools identified in our review included the use of pictograms or illustrations or, at minimum, attention to font size.^{7,8,16,29,33,35} In the absence of a visual aid, asking the patient to repeat or demonstrate what was just communicated can be used to assess the amount of information retained.^18,33

An important result discovered in our review of the literature was also the lack of studies that tested the impact of discharge tools on usability of discharge information once at home. Conducting an evaluation of the benefits to patients after discharge can help objectify vague outcomes like health gains or qualify benefits in patient’s views. This might also explain why many studies with documented patient engagement at the time of discharge were able to demonstrate improvements in comprehension but not adherence to instructions. Although patients and caregivers may understand the information, this comprehension does not necessarily mean they will find the information useful or adhere to it once at home. For example, in 1 study, patients discharged with at least 1 medication were randomized to a structured discharge interview during which the treatment plan was reviewed verbally and questions clarified along with a visually enhanced treatment card.²⁶ Although knowledge of medications increased, no effect was found on adherence at 1 week postdischarge. However, use of the treatment card at home was not assessed. Similarly, another study tested the effect of an individualized video of exercises and failed to find a difference in patient adherence at 4 weeks.²⁸ The authors suggested that the lack of benefit may have been because patients were not using the video once at home. This is in contrast to 2 studies that involved patients in their own care by requiring them to request their medication as part of a self-medication tool predischarge.^16,30 Patients were engaged in the process such that increasing independence was given to patients based on their demonstration of understanding and adherence to their treatment while still in the hospital, a learning tool that can be applied once at home. Feeling knowledgeable and involved, as others have suggested, may be the intermediary outcomes that led to improved adherence.⁴⁷ It is also possible that adherence to discharge instructions may vary based on complexity of the information provided, such that instructions focusing solely on medication use may require less patient engagement than discharge instructions that include information on medications, diet, exercise modifications, and follow-up.⁴⁸

Our review has a few limitations. Previous systematic reviews have demonstrated that bundled discharge interventions that include patient-centered education have a positive effect on outcomes postdischarge.^2,5 However, we sought to describe and study the individual and distinct impact of patient engagement in the creation and delivery of discharge tools on outcomes postdischarge. We hoped that this may provide others with key information regarding elements of patient engagement that were particularly useful when designing a new discharge tool. The variability of the studies we identified, however, made it difficult to ascertain what level of patient engagement is required to observe improvements in health outcomes. It is also possible that a higher level of patient engagement may have been used but not described in the studies we reviewed. As only primary outcomes were included, we may have underestimated the effect of patient-centered discharge tools on outcomes that were reported as secondary outcomes. As we were interested in reviewing as many studies of patient-centered discharge tools as possible, we did not assess the quality of the studies and cannot comment on the role of bias in these studies. However, we excluded studies with study designs known to have the highest risk of bias. Lastly, we also cannot comment on whether patient-centered tools may have an effect on outcomes more than 3 months after a hospital discharge. However, several studies included in this review suggest a sustained effect beyond this time period.^8,25,32,37

Patient-centered discharge tools in which patients were engaged in the design or the delivery were found to improve comprehension of but not adherence with discharge instructions. The perceived lack of improved adherence may be due to a lack of studies that measured the usefulness and utilization of information for patients once at home. There was also substantial variability in the extent of patient involvement in designing the style and content of information provided to patients at discharge, as well as the extent of patient engagement when receiving discharge instructions. Future studies would benefit from detailing the level of patient engagement needed in designing and delivery of discharge tools. This information may lead to the discovery of barriers and facilitators to utilization of discharge information once at home and lead to a better understanding of the patient’s journey from hospital to home and onwards.

C.M.B. and this work were funded by a CIHR Canadian Patient Safety Institute Chair in Patient Safety and Continuity of Care. Funding was provided to cover fees to obtain articles from the Donald J. Matthews Complex Care Fund of the University Health Network in Toronto, Canada. The Toronto Central Local Health Integration Network provided funding for the design and implementation of a patient-oriented discharge summary. None of the funding or supportive agencies were involved in the design or conduct of the present study, analysis, or interpretation of the data, or approval of the manuscript.

Disclosures

The authors report no conflicts of interest.

In our current healthcare system, pressure to provide cost- and time-efficient care is immense. Inpatient care often focuses on assessing the patient’s presenting illness or injury and treating that condition in a manner that gets the patient on their feet and out of the hospital quickly. Because depression is not an indication for hospitalization so long as active suicidality is absent, inpatient physicians may view it as a problem best managed in the outpatient setting. Yet both psychosocial and physical factors associated with depression put patients at risk for rehospitalization.¹ Furthermore, hospitalization represents an unrecognized opportunity to optimize both mental and physical health outcomes.²

Indeed, poor physical and mental health often occur together. Depressed inpatients have poorer outcomes, increased length of stay, and greater vulnerability to hospital readmission.^3,4 Among elderly hospitalized patients, depression is particularly common, especially in those with poor physical health, alcoholism,⁵ hip fracture, and stroke.⁶ Yet little is known about how often depression goes unrecognized, undiagnosed, and, therefore, untreated.

The US Preventive Services Task Force (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women, and further suggests that screening should be implemented “with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.”² The USPSTF guidelines do not distinguish between inpatient and outpatient settings. However, the preponderance of evidence for screening comes from outpatient care settings, and little is known about screening among inpatient populations.⁷

This study had 2 objectives. First, we sought to examine the performance of depression screening tools in inpatient settings. If depression screening were to become routine in hospital settings, screening tools would need to be sensitive and specific as well as brief and suitable for self-administration by patients or for administration by nurses, resident physicians, or hospitalists. It is also important to consider administration by mental health professionals, who may be best trained to administer such tests. We, therefore, examined 3 types of studies: (1) studies that tested a self-administered screening instrument, (2) studies that tested screening by individuals without formal training, and (3) studies that compared screening tools administered by mental health professionals. Second, we sought to describe associations between depression and clinical or utilization outcomes among hospitalized patients.

We adhered to recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement,^8,9 including designing the analysis before performing the review. However, we did not post a protocol in an online registry, formally assess study quality, or perform a meta-analysis.

Data Sources and Searches

We searched PsycINFO and PubMed databases for articles published between 1990 and 2016 (as of July 31, 2016). In PubMed, 2 search term strings were used to capture studies of depression screening tools in inpatient settings. The first used the advanced search option to exclude studies related to primary care settings or children and adolescents, and the second used MeSH terms to ensure that a wide variety of studies were included. Specific search terms are included in the Appendix. A similar search was conducted in the PsycINFO database and these search terms are also included in the Appendix.

Study Selection

Articles were eligible if they were published in English in peer-reviewed journals, included at least 20 adults hospitalized for nonpsychiatric reasons, and described the use of at least 1 measure of depression. The studies must have either tested the validity of a depression screening tool or examined the association between depression screening and clinical or utilization outcomes. Two investigators reviewed each title, abstract, and full-text article to determine eligibility, then reached a consensus on which studies to include in this review.

Data Extraction

Two investigators reviewed each full-text article to extract information related to study design, population, and outcomes regarding screening tool analysis or clinical results. From articles that assessed the performance of depression screening tools, we extracted information related to the nature and application of the index test, the nature and application of the reference test, the prevalence of depression, and the sensitivity and specificity of the index test compared with the reference test. For articles that focused on the association between depression screening and clinical or utilization outcomes, the data on relevant clinical outcomes included symptom severity, quality of life, and daily functioning, whereas the data on utilization outcomes included length of stay, readmission, and the cost of care.

Altogether, the search identified 3226 records. After eliminating duplicates and abstracts not suitable for inclusion (Figure), 101 articles underwent full-text review and 32 were found to be eligible. Of these, 12 focused on the association between depression and clinical or utilization outcomes, while 20 assessed the performance of depression screening tools.

Depression Screening Tools

Table 1 describes the index and reference instruments as well as methods of administration, the prevalence of depression, and the sensitivity and specificity of the index instruments relative to the reference instruments. Across the 20 studies, the prevalence of depression ranged from 15% to 60%, with a median of 34%.^10–29 This finding may reflect different methods of screening or variation among diverse hospitalized populations. Many of the studies excluded patients with cognitive impairment or communication barriers.

The included studies tested a wide range of unique instruments, and compared them with diverse reference standards. Five studies examined instruments that were self-administered by patients^10–14; 9 studies assessed instruments administered by nurses, physicians, or research staff members without formal psychiatric training^15–23; and 6 studies evaluated instruments administered by mental health professionals.^24–29 Four studies compared different instruments that were administered in the same manner (eg, both self-administered by patients).^12–14,22 In the remaining studies, both instruments and methods of administration differed between the index and reference conditions.

Eight studies tested brief instruments with 5 or fewer items, most of which exhibited good sensitivity (range 38%–91%) and specificity (range 68%–86%) relative to longer instruments.^{12,14–19,22} In 2 of these studies, instruments were self-administered. In 1 case, a single self-administered item from the STOP-D instrument (“Over the past 2 weeks, how much have you been bothered by feeling sad, down, or uninterested in life?”) performed nearly as well as the 14-item Hospital Anxiety and Depression Scale.¹⁴ In the other 6 studies testing brief instruments, the instruments were administered by individuals without formal training.^15–19,22 In 1 such study, geriatricians asking 2 questions about depressed mood and anhedonia performed well compared with a formal psychiatric interview.¹⁷

Four studies tested variations of the Geriatric Depression Scale (GDS).^12,18,21,23 In 3 of these studies, abbreviated versions of the GDS exhibited relatively high sensitivity and specificity.^12,18,21 However, a study comparing the 15-item GDS (GDS-15) with the GDS-4 found that GDS-15 correctly classified 10% more patients with suspected depression.¹² Two studies examined variations of the Patient Health Questionnaire (PHQ). One study found that both the PHQ-2 and PHQ-9 obtained by staff nurses performed well relative to a comprehensive assessment by a trained advanced practice nurse.^13,19

When reported, positive predictive value, negative predictive value, and area under the receiver-operator curve were generally high.

Depression and Clinical or Utilization Outcomes

Of the 12 studies that reported either clinical or utilization outcomes for depression screening in an inpatient setting,^4,30–40 3 measured rates of rehospitalization.^4,31,39 The other 9 studies tested for associations between symptoms of depression and either health or treatment outcomes. Table 2 provides a more detailed description of the study designs and results.

Other studies found that depression was associated with reduced functional abilities such as mobility and self-care,^30,32–34 and increased hospital readmission³¹ as well as physical and mental health deficits.³⁷ Interestingly, although 1 study did not find that depression and hospital readmission were closely linked (frequency at 19%), it found that comorbid illness and previous hospitalizations predicted readmission.⁴

We also evaluated the associations between depression diagnosed in the inpatient studies and 2 types of outcomes. The first type includes clinical outcomes including symptom severity, quality of life, and daily functioning. Most studies we identified assessed clinical outcomes, and all detected an association between depression and worse clinical outcomes. The second type includes healthcare utilization, which can be measured with the patients’ length of hospital stay, readmission and cost of care. In 1 such study, Mitchell aet al.³¹ reported a 54% increase in readmission within 30 days of discharge among patients who screened positive for depression.³¹ Additionally, Cully et al.³⁰ found that depression may impinge on the recovery process of acute rehabilitation patients.

In our current healthcare system, pressure to provide cost- and time-efficient care is immense. Inpatient care often focuses on assessing the patient’s presenting illness or injury and treating that condition in a manner that gets the patient on their feet and out of the hospital quickly. Because depression is not an indication for hospitalization so long as active suicidality is absent, inpatient physicians may view it as a problem best managed in the outpatient setting. Yet both psychosocial and physical factors associated with depression put patients at risk for rehospitalization.¹ Furthermore, hospitalization represents an unrecognized opportunity to optimize both mental and physical health outcomes.²

Indeed, poor physical and mental health often occur together. Depressed inpatients have poorer outcomes, increased length of stay, and greater vulnerability to hospital readmission.^3,4 Among elderly hospitalized patients, depression is particularly common, especially in those with poor physical health, alcoholism,⁵ hip fracture, and stroke.⁶ Yet little is known about how often depression goes unrecognized, undiagnosed, and, therefore, untreated.

The US Preventive Services Task Force (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women, and further suggests that screening should be implemented “with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.”² The USPSTF guidelines do not distinguish between inpatient and outpatient settings. However, the preponderance of evidence for screening comes from outpatient care settings, and little is known about screening among inpatient populations.⁷

This study had 2 objectives. First, we sought to examine the performance of depression screening tools in inpatient settings. If depression screening were to become routine in hospital settings, screening tools would need to be sensitive and specific as well as brief and suitable for self-administration by patients or for administration by nurses, resident physicians, or hospitalists. It is also important to consider administration by mental health professionals, who may be best trained to administer such tests. We, therefore, examined 3 types of studies: (1) studies that tested a self-administered screening instrument, (2) studies that tested screening by individuals without formal training, and (3) studies that compared screening tools administered by mental health professionals. Second, we sought to describe associations between depression and clinical or utilization outcomes among hospitalized patients.

We adhered to recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement,^8,9 including designing the analysis before performing the review. However, we did not post a protocol in an online registry, formally assess study quality, or perform a meta-analysis.

Data Sources and Searches

We searched PsycINFO and PubMed databases for articles published between 1990 and 2016 (as of July 31, 2016). In PubMed, 2 search term strings were used to capture studies of depression screening tools in inpatient settings. The first used the advanced search option to exclude studies related to primary care settings or children and adolescents, and the second used MeSH terms to ensure that a wide variety of studies were included. Specific search terms are included in the Appendix. A similar search was conducted in the PsycINFO database and these search terms are also included in the Appendix.

Study Selection

Articles were eligible if they were published in English in peer-reviewed journals, included at least 20 adults hospitalized for nonpsychiatric reasons, and described the use of at least 1 measure of depression. The studies must have either tested the validity of a depression screening tool or examined the association between depression screening and clinical or utilization outcomes. Two investigators reviewed each title, abstract, and full-text article to determine eligibility, then reached a consensus on which studies to include in this review.

Data Extraction

Two investigators reviewed each full-text article to extract information related to study design, population, and outcomes regarding screening tool analysis or clinical results. From articles that assessed the performance of depression screening tools, we extracted information related to the nature and application of the index test, the nature and application of the reference test, the prevalence of depression, and the sensitivity and specificity of the index test compared with the reference test. For articles that focused on the association between depression screening and clinical or utilization outcomes, the data on relevant clinical outcomes included symptom severity, quality of life, and daily functioning, whereas the data on utilization outcomes included length of stay, readmission, and the cost of care.

Altogether, the search identified 3226 records. After eliminating duplicates and abstracts not suitable for inclusion (Figure), 101 articles underwent full-text review and 32 were found to be eligible. Of these, 12 focused on the association between depression and clinical or utilization outcomes, while 20 assessed the performance of depression screening tools.

Depression Screening Tools

Table 1 describes the index and reference instruments as well as methods of administration, the prevalence of depression, and the sensitivity and specificity of the index instruments relative to the reference instruments. Across the 20 studies, the prevalence of depression ranged from 15% to 60%, with a median of 34%.^10–29 This finding may reflect different methods of screening or variation among diverse hospitalized populations. Many of the studies excluded patients with cognitive impairment or communication barriers.

The included studies tested a wide range of unique instruments, and compared them with diverse reference standards. Five studies examined instruments that were self-administered by patients^10–14; 9 studies assessed instruments administered by nurses, physicians, or research staff members without formal psychiatric training^15–23; and 6 studies evaluated instruments administered by mental health professionals.^24–29 Four studies compared different instruments that were administered in the same manner (eg, both self-administered by patients).^12–14,22 In the remaining studies, both instruments and methods of administration differed between the index and reference conditions.

Eight studies tested brief instruments with 5 or fewer items, most of which exhibited good sensitivity (range 38%–91%) and specificity (range 68%–86%) relative to longer instruments.^{12,14–19,22} In 2 of these studies, instruments were self-administered. In 1 case, a single self-administered item from the STOP-D instrument (“Over the past 2 weeks, how much have you been bothered by feeling sad, down, or uninterested in life?”) performed nearly as well as the 14-item Hospital Anxiety and Depression Scale.¹⁴ In the other 6 studies testing brief instruments, the instruments were administered by individuals without formal training.^15–19,22 In 1 such study, geriatricians asking 2 questions about depressed mood and anhedonia performed well compared with a formal psychiatric interview.¹⁷

Four studies tested variations of the Geriatric Depression Scale (GDS).^12,18,21,23 In 3 of these studies, abbreviated versions of the GDS exhibited relatively high sensitivity and specificity.^12,18,21 However, a study comparing the 15-item GDS (GDS-15) with the GDS-4 found that GDS-15 correctly classified 10% more patients with suspected depression.¹² Two studies examined variations of the Patient Health Questionnaire (PHQ). One study found that both the PHQ-2 and PHQ-9 obtained by staff nurses performed well relative to a comprehensive assessment by a trained advanced practice nurse.^13,19

When reported, positive predictive value, negative predictive value, and area under the receiver-operator curve were generally high.

Depression and Clinical or Utilization Outcomes

Of the 12 studies that reported either clinical or utilization outcomes for depression screening in an inpatient setting,^4,30–40 3 measured rates of rehospitalization.^4,31,39 The other 9 studies tested for associations between symptoms of depression and either health or treatment outcomes. Table 2 provides a more detailed description of the study designs and results.

Other studies found that depression was associated with reduced functional abilities such as mobility and self-care,^30,32–34 and increased hospital readmission³¹ as well as physical and mental health deficits.³⁷ Interestingly, although 1 study did not find that depression and hospital readmission were closely linked (frequency at 19%), it found that comorbid illness and previous hospitalizations predicted readmission.⁴

We also evaluated the associations between depression diagnosed in the inpatient studies and 2 types of outcomes. The first type includes clinical outcomes including symptom severity, quality of life, and daily functioning. Most studies we identified assessed clinical outcomes, and all detected an association between depression and worse clinical outcomes. The second type includes healthcare utilization, which can be measured with the patients’ length of hospital stay, readmission and cost of care. In 1 such study, Mitchell aet al.³¹ reported a 54% increase in readmission within 30 days of discharge among patients who screened positive for depression.³¹ Additionally, Cully et al.³⁰ found that depression may impinge on the recovery process of acute rehabilitation patients.

In our current healthcare system, pressure to provide cost- and time-efficient care is immense. Inpatient care often focuses on assessing the patient’s presenting illness or injury and treating that condition in a manner that gets the patient on their feet and out of the hospital quickly. Because depression is not an indication for hospitalization so long as active suicidality is absent, inpatient physicians may view it as a problem best managed in the outpatient setting. Yet both psychosocial and physical factors associated with depression put patients at risk for rehospitalization.¹ Furthermore, hospitalization represents an unrecognized opportunity to optimize both mental and physical health outcomes.²

Indeed, poor physical and mental health often occur together. Depressed inpatients have poorer outcomes, increased length of stay, and greater vulnerability to hospital readmission.^3,4 Among elderly hospitalized patients, depression is particularly common, especially in those with poor physical health, alcoholism,⁵ hip fracture, and stroke.⁶ Yet little is known about how often depression goes unrecognized, undiagnosed, and, therefore, untreated.

The US Preventive Services Task Force (USPSTF) recommends screening for depression in the general adult population, including pregnant and postpartum women, and further suggests that screening should be implemented “with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up.”² The USPSTF guidelines do not distinguish between inpatient and outpatient settings. However, the preponderance of evidence for screening comes from outpatient care settings, and little is known about screening among inpatient populations.⁷

This study had 2 objectives. First, we sought to examine the performance of depression screening tools in inpatient settings. If depression screening were to become routine in hospital settings, screening tools would need to be sensitive and specific as well as brief and suitable for self-administration by patients or for administration by nurses, resident physicians, or hospitalists. It is also important to consider administration by mental health professionals, who may be best trained to administer such tests. We, therefore, examined 3 types of studies: (1) studies that tested a self-administered screening instrument, (2) studies that tested screening by individuals without formal training, and (3) studies that compared screening tools administered by mental health professionals. Second, we sought to describe associations between depression and clinical or utilization outcomes among hospitalized patients.

We adhered to recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement,^8,9 including designing the analysis before performing the review. However, we did not post a protocol in an online registry, formally assess study quality, or perform a meta-analysis.

Data Sources and Searches

We searched PsycINFO and PubMed databases for articles published between 1990 and 2016 (as of July 31, 2016). In PubMed, 2 search term strings were used to capture studies of depression screening tools in inpatient settings. The first used the advanced search option to exclude studies related to primary care settings or children and adolescents, and the second used MeSH terms to ensure that a wide variety of studies were included. Specific search terms are included in the Appendix. A similar search was conducted in the PsycINFO database and these search terms are also included in the Appendix.

Study Selection

Articles were eligible if they were published in English in peer-reviewed journals, included at least 20 adults hospitalized for nonpsychiatric reasons, and described the use of at least 1 measure of depression. The studies must have either tested the validity of a depression screening tool or examined the association between depression screening and clinical or utilization outcomes. Two investigators reviewed each title, abstract, and full-text article to determine eligibility, then reached a consensus on which studies to include in this review.

Data Extraction

Two investigators reviewed each full-text article to extract information related to study design, population, and outcomes regarding screening tool analysis or clinical results. From articles that assessed the performance of depression screening tools, we extracted information related to the nature and application of the index test, the nature and application of the reference test, the prevalence of depression, and the sensitivity and specificity of the index test compared with the reference test. For articles that focused on the association between depression screening and clinical or utilization outcomes, the data on relevant clinical outcomes included symptom severity, quality of life, and daily functioning, whereas the data on utilization outcomes included length of stay, readmission, and the cost of care.

Altogether, the search identified 3226 records. After eliminating duplicates and abstracts not suitable for inclusion (Figure), 101 articles underwent full-text review and 32 were found to be eligible. Of these, 12 focused on the association between depression and clinical or utilization outcomes, while 20 assessed the performance of depression screening tools.

Depression Screening Tools

Table 1 describes the index and reference instruments as well as methods of administration, the prevalence of depression, and the sensitivity and specificity of the index instruments relative to the reference instruments. Across the 20 studies, the prevalence of depression ranged from 15% to 60%, with a median of 34%.^10–29 This finding may reflect different methods of screening or variation among diverse hospitalized populations. Many of the studies excluded patients with cognitive impairment or communication barriers.

The included studies tested a wide range of unique instruments, and compared them with diverse reference standards. Five studies examined instruments that were self-administered by patients^10–14; 9 studies assessed instruments administered by nurses, physicians, or research staff members without formal psychiatric training^15–23; and 6 studies evaluated instruments administered by mental health professionals.^24–29 Four studies compared different instruments that were administered in the same manner (eg, both self-administered by patients).^12–14,22 In the remaining studies, both instruments and methods of administration differed between the index and reference conditions.

Eight studies tested brief instruments with 5 or fewer items, most of which exhibited good sensitivity (range 38%–91%) and specificity (range 68%–86%) relative to longer instruments.^{12,14–19,22} In 2 of these studies, instruments were self-administered. In 1 case, a single self-administered item from the STOP-D instrument (“Over the past 2 weeks, how much have you been bothered by feeling sad, down, or uninterested in life?”) performed nearly as well as the 14-item Hospital Anxiety and Depression Scale.¹⁴ In the other 6 studies testing brief instruments, the instruments were administered by individuals without formal training.^15–19,22 In 1 such study, geriatricians asking 2 questions about depressed mood and anhedonia performed well compared with a formal psychiatric interview.¹⁷

Four studies tested variations of the Geriatric Depression Scale (GDS).^12,18,21,23 In 3 of these studies, abbreviated versions of the GDS exhibited relatively high sensitivity and specificity.^12,18,21 However, a study comparing the 15-item GDS (GDS-15) with the GDS-4 found that GDS-15 correctly classified 10% more patients with suspected depression.¹² Two studies examined variations of the Patient Health Questionnaire (PHQ). One study found that both the PHQ-2 and PHQ-9 obtained by staff nurses performed well relative to a comprehensive assessment by a trained advanced practice nurse.^13,19

When reported, positive predictive value, negative predictive value, and area under the receiver-operator curve were generally high.

Depression and Clinical or Utilization Outcomes

Of the 12 studies that reported either clinical or utilization outcomes for depression screening in an inpatient setting,^4,30–40 3 measured rates of rehospitalization.^4,31,39 The other 9 studies tested for associations between symptoms of depression and either health or treatment outcomes. Table 2 provides a more detailed description of the study designs and results.

Other studies found that depression was associated with reduced functional abilities such as mobility and self-care,^30,32–34 and increased hospital readmission³¹ as well as physical and mental health deficits.³⁷ Interestingly, although 1 study did not find that depression and hospital readmission were closely linked (frequency at 19%), it found that comorbid illness and previous hospitalizations predicted readmission.⁴

We also evaluated the associations between depression diagnosed in the inpatient studies and 2 types of outcomes. The first type includes clinical outcomes including symptom severity, quality of life, and daily functioning. Most studies we identified assessed clinical outcomes, and all detected an association between depression and worse clinical outcomes. The second type includes healthcare utilization, which can be measured with the patients’ length of hospital stay, readmission and cost of care. In 1 such study, Mitchell aet al.³¹ reported a 54% increase in readmission within 30 days of discharge among patients who screened positive for depression.³¹ Additionally, Cully et al.³⁰ found that depression may impinge on the recovery process of acute rehabilitation patients.

Acute kidney injury (AKI) is a major contributor to morbidity and mortality in hospitalized patients across the world.¹ Affecting up to 20% of all admissions (depending on which definition of AKI is used),² AKI is the most common reason for new-inpatient nephrology consultation. Recent data suggest that AKI incidence has risen rapidly, by up to 10% per year.^3,4

AKI is associated with a variety of serious short- and long-term complications. Approximately 33% to 60% of critically ill patients who develop dialysis-requiring AKI do not survive to hospital discharge, and mortality associated with dialysis-requiring AKI is greater than that associated with other serious conditions such as myocardial infarction or acute respiratory distress syndrome.⁵ Even relatively mild AKI in the acute inpatient setting appears to be an independent risk factor for mortality.⁶

For several decades, many physicians believed that AKI was a self-limited process followed by complete recovery of renal function to pre-AKI levels among survivors. (Numerous trainees have been taught some variant of the old adage: “If the patients survive, so will their kidneys.”) But studies linking AKI with the development of new-onset chronic kidney disease (CKD) or the accelerated progression of pre-existing CKD have changed this view.⁷ One important reason the long-term impact of AKI hasn’t been appreciated is that, traditionally, clinical studies of AKI examined inhospital outcomes such as short-term mortality and resource usage and did not consider what transpired months to years after discharge. More recently, epidemiologic studies linking inpatient events with outpatient outcomes have filled this knowledge gap.⁸ Contemporary animal models of AKI have shed light on potential mechanisms of maladaptive repair after AKI, characterized by fibrosis, vascular rarefaction, tubular loss, glomerulosclerosis, and chronic interstitial inflammation, all of which result in renal function decline. So over the last decade there has been a paradigm shift in how we think about AKI and CKD. Rather than distinct entities, AKI and CKD are now viewed as interconnected syndromes since AKI is a risk factor for CKD progression and CKD is a risk factor for new episodes of AKI.⁹

Two studies published in this issue of the Journal of Hospital Medicine augment our understanding of AKI and its clinical impact in hospitalized patients. Analyzing data from the National Inpatient Sample, Silver et al.¹⁰ found that hospitalizations that include AKI are substantially costlier and associated with longer lengths of stay than hospitalizations without AKI. The authors also highlight that the additional economic costs of AKI exceeded those of many other higher-profile yet less-common acute medical conditions, such as myocardial infarction and gastrointestinal bleeding. These results re-emphasize the important economic burden of AKI at a national level and expand on prior literature by confirming findings previously limited to single-center and regional studies. Better defining the impact AKI has on our healthcare system could help ensure that adequate resources are invested to combat AKI.

The second study, by Rutter et al.,¹¹ found that among hospitalized patients with normal baseline renal function, use of vancomycin in combination with piperacillin-tazobactam is associated with a higher incidence of AKI after antibiotic exposure than use of either agent as monotherapy. This association persisted even after adjusting for potential confounders such as underlying comorbidities, exposure to nephrotoxic agents, documented hypotension, and baseline renal impairment. This study adds to a growing body of literature that suggests synergistic nephrotoxicity between vancomycin and piperacillin-tazobactam. It underscores that any medical intervention—even treatments typically envisioned as non-hazardous and frequently life-saving—involve inherent risks and should prompt the medical community to promote proper antimicrobial stewardship. Whether such exposures to vancomycin or beta-lactam derivatives cause AKI via direct tubular damage, interstitial nephritis, or some other novel mechanism remains to be elucidated. Better delineation of the contemporary causes of AKI, including increased antibiotic exposure, is the first step toward identifying ways to reduce AKI incidence.

Both of these papers serve to highlight the clinical importance of AKI among hospitalized patients. Their findings re-emphasize the need for vigilance in detecting AKI and intervening early to achieve the best clinical outcomes.

Given recent understanding that survivors of AKI are at greater risk for more rapid loss of renal function long after hospital discharge, one goal the US Department of Health and Human Services put forth for Healthy People 2020 is to “increase the proportion of hospital patients who incurred AKI who have follow-up renal evaluation in 6 months post-discharge” (10% improvement targeted).¹² Transitions of care after hospitalizations complicated by AKI require special attention to ensure that patients’ needs are optimally monitored and managed during the critical post-discharge period. One recent study analyzing discharge documentation for hospitalizations including AKI found that fewer than half of the discharge summaries and patient instructions commented on the presence, cause, or course of AKI, indicating clear room for improvement.¹³ And currently, it appears that only a minority of patients with AKI—even AKI severe enough to require dialysis—are seen by a nephrologist within 90 days of discharge.¹⁴

Hospitalists play a crucial role in coordinating care as vulnerable patients transition from the inpatient to outpatient setting. We suggest that AKI should be properly documented in the discharge summary. In addition, patients should be informed that they experienced AKI so they can discuss with future caregivers potential strategies to avoid additional renal insults. Discharge referrals to nephrology should be arranged for high-risk patients, including those whose renal function remains decreased at discharge or those who had recurrent AKI episodes during prior hospitalizations. For patients with pre-hospitalization baseline CKD, nephrology should be consulted before indefinitely discontinuing medications like angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. These medications are indispensable in retarding the progression of proteinuric CKD, even though they may predispose patients to AKI under certain circumstances (eg, in states of decreased renal perfusion). Adopting these simple steps may substantially improve the long-term outcomes of patients who experience AKI during hospitalization.

Acknowledgments

The authors are supported by NIH-NIDDK Grants T32DK007219 (BJL) and K24DK92291 (CYH).

Disclosure

Nothing to report.

Acute kidney injury (AKI) is a major contributor to morbidity and mortality in hospitalized patients across the world.¹ Affecting up to 20% of all admissions (depending on which definition of AKI is used),² AKI is the most common reason for new-inpatient nephrology consultation. Recent data suggest that AKI incidence has risen rapidly, by up to 10% per year.^3,4

AKI is associated with a variety of serious short- and long-term complications. Approximately 33% to 60% of critically ill patients who develop dialysis-requiring AKI do not survive to hospital discharge, and mortality associated with dialysis-requiring AKI is greater than that associated with other serious conditions such as myocardial infarction or acute respiratory distress syndrome.⁵ Even relatively mild AKI in the acute inpatient setting appears to be an independent risk factor for mortality.⁶

For several decades, many physicians believed that AKI was a self-limited process followed by complete recovery of renal function to pre-AKI levels among survivors. (Numerous trainees have been taught some variant of the old adage: “If the patients survive, so will their kidneys.”) But studies linking AKI with the development of new-onset chronic kidney disease (CKD) or the accelerated progression of pre-existing CKD have changed this view.⁷ One important reason the long-term impact of AKI hasn’t been appreciated is that, traditionally, clinical studies of AKI examined inhospital outcomes such as short-term mortality and resource usage and did not consider what transpired months to years after discharge. More recently, epidemiologic studies linking inpatient events with outpatient outcomes have filled this knowledge gap.⁸ Contemporary animal models of AKI have shed light on potential mechanisms of maladaptive repair after AKI, characterized by fibrosis, vascular rarefaction, tubular loss, glomerulosclerosis, and chronic interstitial inflammation, all of which result in renal function decline. So over the last decade there has been a paradigm shift in how we think about AKI and CKD. Rather than distinct entities, AKI and CKD are now viewed as interconnected syndromes since AKI is a risk factor for CKD progression and CKD is a risk factor for new episodes of AKI.⁹

Two studies published in this issue of the Journal of Hospital Medicine augment our understanding of AKI and its clinical impact in hospitalized patients. Analyzing data from the National Inpatient Sample, Silver et al.¹⁰ found that hospitalizations that include AKI are substantially costlier and associated with longer lengths of stay than hospitalizations without AKI. The authors also highlight that the additional economic costs of AKI exceeded those of many other higher-profile yet less-common acute medical conditions, such as myocardial infarction and gastrointestinal bleeding. These results re-emphasize the important economic burden of AKI at a national level and expand on prior literature by confirming findings previously limited to single-center and regional studies. Better defining the impact AKI has on our healthcare system could help ensure that adequate resources are invested to combat AKI.

The second study, by Rutter et al.,¹¹ found that among hospitalized patients with normal baseline renal function, use of vancomycin in combination with piperacillin-tazobactam is associated with a higher incidence of AKI after antibiotic exposure than use of either agent as monotherapy. This association persisted even after adjusting for potential confounders such as underlying comorbidities, exposure to nephrotoxic agents, documented hypotension, and baseline renal impairment. This study adds to a growing body of literature that suggests synergistic nephrotoxicity between vancomycin and piperacillin-tazobactam. It underscores that any medical intervention—even treatments typically envisioned as non-hazardous and frequently life-saving—involve inherent risks and should prompt the medical community to promote proper antimicrobial stewardship. Whether such exposures to vancomycin or beta-lactam derivatives cause AKI via direct tubular damage, interstitial nephritis, or some other novel mechanism remains to be elucidated. Better delineation of the contemporary causes of AKI, including increased antibiotic exposure, is the first step toward identifying ways to reduce AKI incidence.

Both of these papers serve to highlight the clinical importance of AKI among hospitalized patients. Their findings re-emphasize the need for vigilance in detecting AKI and intervening early to achieve the best clinical outcomes.

Given recent understanding that survivors of AKI are at greater risk for more rapid loss of renal function long after hospital discharge, one goal the US Department of Health and Human Services put forth for Healthy People 2020 is to “increase the proportion of hospital patients who incurred AKI who have follow-up renal evaluation in 6 months post-discharge” (10% improvement targeted).¹² Transitions of care after hospitalizations complicated by AKI require special attention to ensure that patients’ needs are optimally monitored and managed during the critical post-discharge period. One recent study analyzing discharge documentation for hospitalizations including AKI found that fewer than half of the discharge summaries and patient instructions commented on the presence, cause, or course of AKI, indicating clear room for improvement.¹³ And currently, it appears that only a minority of patients with AKI—even AKI severe enough to require dialysis—are seen by a nephrologist within 90 days of discharge.¹⁴

Hospitalists play a crucial role in coordinating care as vulnerable patients transition from the inpatient to outpatient setting. We suggest that AKI should be properly documented in the discharge summary. In addition, patients should be informed that they experienced AKI so they can discuss with future caregivers potential strategies to avoid additional renal insults. Discharge referrals to nephrology should be arranged for high-risk patients, including those whose renal function remains decreased at discharge or those who had recurrent AKI episodes during prior hospitalizations. For patients with pre-hospitalization baseline CKD, nephrology should be consulted before indefinitely discontinuing medications like angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. These medications are indispensable in retarding the progression of proteinuric CKD, even though they may predispose patients to AKI under certain circumstances (eg, in states of decreased renal perfusion). Adopting these simple steps may substantially improve the long-term outcomes of patients who experience AKI during hospitalization.

Acknowledgments

The authors are supported by NIH-NIDDK Grants T32DK007219 (BJL) and K24DK92291 (CYH).

Disclosure

Nothing to report.

Acute kidney injury (AKI) is a major contributor to morbidity and mortality in hospitalized patients across the world.¹ Affecting up to 20% of all admissions (depending on which definition of AKI is used),² AKI is the most common reason for new-inpatient nephrology consultation. Recent data suggest that AKI incidence has risen rapidly, by up to 10% per year.^3,4

AKI is associated with a variety of serious short- and long-term complications. Approximately 33% to 60% of critically ill patients who develop dialysis-requiring AKI do not survive to hospital discharge, and mortality associated with dialysis-requiring AKI is greater than that associated with other serious conditions such as myocardial infarction or acute respiratory distress syndrome.⁵ Even relatively mild AKI in the acute inpatient setting appears to be an independent risk factor for mortality.⁶

For several decades, many physicians believed that AKI was a self-limited process followed by complete recovery of renal function to pre-AKI levels among survivors. (Numerous trainees have been taught some variant of the old adage: “If the patients survive, so will their kidneys.”) But studies linking AKI with the development of new-onset chronic kidney disease (CKD) or the accelerated progression of pre-existing CKD have changed this view.⁷ One important reason the long-term impact of AKI hasn’t been appreciated is that, traditionally, clinical studies of AKI examined inhospital outcomes such as short-term mortality and resource usage and did not consider what transpired months to years after discharge. More recently, epidemiologic studies linking inpatient events with outpatient outcomes have filled this knowledge gap.⁸ Contemporary animal models of AKI have shed light on potential mechanisms of maladaptive repair after AKI, characterized by fibrosis, vascular rarefaction, tubular loss, glomerulosclerosis, and chronic interstitial inflammation, all of which result in renal function decline. So over the last decade there has been a paradigm shift in how we think about AKI and CKD. Rather than distinct entities, AKI and CKD are now viewed as interconnected syndromes since AKI is a risk factor for CKD progression and CKD is a risk factor for new episodes of AKI.⁹

Two studies published in this issue of the Journal of Hospital Medicine augment our understanding of AKI and its clinical impact in hospitalized patients. Analyzing data from the National Inpatient Sample, Silver et al.¹⁰ found that hospitalizations that include AKI are substantially costlier and associated with longer lengths of stay than hospitalizations without AKI. The authors also highlight that the additional economic costs of AKI exceeded those of many other higher-profile yet less-common acute medical conditions, such as myocardial infarction and gastrointestinal bleeding. These results re-emphasize the important economic burden of AKI at a national level and expand on prior literature by confirming findings previously limited to single-center and regional studies. Better defining the impact AKI has on our healthcare system could help ensure that adequate resources are invested to combat AKI.

The second study, by Rutter et al.,¹¹ found that among hospitalized patients with normal baseline renal function, use of vancomycin in combination with piperacillin-tazobactam is associated with a higher incidence of AKI after antibiotic exposure than use of either agent as monotherapy. This association persisted even after adjusting for potential confounders such as underlying comorbidities, exposure to nephrotoxic agents, documented hypotension, and baseline renal impairment. This study adds to a growing body of literature that suggests synergistic nephrotoxicity between vancomycin and piperacillin-tazobactam. It underscores that any medical intervention—even treatments typically envisioned as non-hazardous and frequently life-saving—involve inherent risks and should prompt the medical community to promote proper antimicrobial stewardship. Whether such exposures to vancomycin or beta-lactam derivatives cause AKI via direct tubular damage, interstitial nephritis, or some other novel mechanism remains to be elucidated. Better delineation of the contemporary causes of AKI, including increased antibiotic exposure, is the first step toward identifying ways to reduce AKI incidence.

Both of these papers serve to highlight the clinical importance of AKI among hospitalized patients. Their findings re-emphasize the need for vigilance in detecting AKI and intervening early to achieve the best clinical outcomes.

Given recent understanding that survivors of AKI are at greater risk for more rapid loss of renal function long after hospital discharge, one goal the US Department of Health and Human Services put forth for Healthy People 2020 is to “increase the proportion of hospital patients who incurred AKI who have follow-up renal evaluation in 6 months post-discharge” (10% improvement targeted).¹² Transitions of care after hospitalizations complicated by AKI require special attention to ensure that patients’ needs are optimally monitored and managed during the critical post-discharge period. One recent study analyzing discharge documentation for hospitalizations including AKI found that fewer than half of the discharge summaries and patient instructions commented on the presence, cause, or course of AKI, indicating clear room for improvement.¹³ And currently, it appears that only a minority of patients with AKI—even AKI severe enough to require dialysis—are seen by a nephrologist within 90 days of discharge.¹⁴

Hospitalists play a crucial role in coordinating care as vulnerable patients transition from the inpatient to outpatient setting. We suggest that AKI should be properly documented in the discharge summary. In addition, patients should be informed that they experienced AKI so they can discuss with future caregivers potential strategies to avoid additional renal insults. Discharge referrals to nephrology should be arranged for high-risk patients, including those whose renal function remains decreased at discharge or those who had recurrent AKI episodes during prior hospitalizations. For patients with pre-hospitalization baseline CKD, nephrology should be consulted before indefinitely discontinuing medications like angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. These medications are indispensable in retarding the progression of proteinuric CKD, even though they may predispose patients to AKI under certain circumstances (eg, in states of decreased renal perfusion). Adopting these simple steps may substantially improve the long-term outcomes of patients who experience AKI during hospitalization.

Acknowledgments

The authors are supported by NIH-NIDDK Grants T32DK007219 (BJL) and K24DK92291 (CYH).

Disclosure

Nothing to report.

HOUSTON – Surgical aortic valve replacement can be performed in intermediate-risk elderly patients with an operative mortality rate of 4.1%, which is better than expected, according to results from a large multicenter analysis. However, the rate of in-hospital stroke was 5.4% – twice what was expected.

“This is most likely secondary to neurologic assessment [that was conducted] for all patients postoperatively,” Vinod H. Thourani, MD, said at the annual meeting of the Society of Thoracic Surgeons.

Doug Brunk/Frontline Medical News

[email protected]

HOUSTON – Surgical aortic valve replacement can be performed in intermediate-risk elderly patients with an operative mortality rate of 4.1%, which is better than expected, according to results from a large multicenter analysis. However, the rate of in-hospital stroke was 5.4% – twice what was expected.

“This is most likely secondary to neurologic assessment [that was conducted] for all patients postoperatively,” Vinod H. Thourani, MD, said at the annual meeting of the Society of Thoracic Surgeons.

Doug Brunk/Frontline Medical News

[email protected]

HOUSTON – Surgical aortic valve replacement can be performed in intermediate-risk elderly patients with an operative mortality rate of 4.1%, which is better than expected, according to results from a large multicenter analysis. However, the rate of in-hospital stroke was 5.4% – twice what was expected.

“This is most likely secondary to neurologic assessment [that was conducted] for all patients postoperatively,” Vinod H. Thourani, MD, said at the annual meeting of the Society of Thoracic Surgeons.

Doug Brunk/Frontline Medical News

[email protected]

The Diagnosis

Carcinosarcoma is a rare malignant entity, representing less than 2% of all esophageal neoplasms. It usually shows a bulky appearance of an intraluminal polypoid lesion owing to predominant sarcomatous development with little stromal proliferation.

References

1. Hung J.J., Li A.F., Liu J.S., et al. Esophageal carcinosarcoma with basaloid squamous cell carcinoma and osteosarcoma. Ann Thorac Surg. 2008;85[3]:1102-4.

2. Madan A.K., Long A.E., Weldon C.B., et al. Esophageal carcinosarcoma. J Gastrointest Surg. 2001;5[4]:414-7.

The Diagnosis

Carcinosarcoma is a rare malignant entity, representing less than 2% of all esophageal neoplasms. It usually shows a bulky appearance of an intraluminal polypoid lesion owing to predominant sarcomatous development with little stromal proliferation.

References

1. Hung J.J., Li A.F., Liu J.S., et al. Esophageal carcinosarcoma with basaloid squamous cell carcinoma and osteosarcoma. Ann Thorac Surg. 2008;85[3]:1102-4.

2. Madan A.K., Long A.E., Weldon C.B., et al. Esophageal carcinosarcoma. J Gastrointest Surg. 2001;5[4]:414-7.

The Diagnosis

Carcinosarcoma is a rare malignant entity, representing less than 2% of all esophageal neoplasms. It usually shows a bulky appearance of an intraluminal polypoid lesion owing to predominant sarcomatous development with little stromal proliferation.

References

1. Hung J.J., Li A.F., Liu J.S., et al. Esophageal carcinosarcoma with basaloid squamous cell carcinoma and osteosarcoma. Ann Thorac Surg. 2008;85[3]:1102-4.

2. Madan A.K., Long A.E., Weldon C.B., et al. Esophageal carcinosarcoma. J Gastrointest Surg. 2001;5[4]:414-7.

Research with mice and rats in Germany may have found a new way to treat high blood pressure.

Using epifluorescence intravital video microscopy imaging, researchers examined mice to whom they had given angiotensin II hormones to induce arterial hypertension.

They determined that the mice with low levels of thrombin-driven factor XI (FXI) – either naturally or inhibited by antisense oligonucleotides – had healthier endothelium.

“Specificity of the effects of FXI depletion was confirmed by continuous in vivo supplementation with human FXI,” wrote Sabine Kossmann, PhD, of the Center for Thrombosis and Hemostasis, University Medical Center, Mainz (Germany), and her coauthors (Sci Transl Med. 2017 Feb 1. doi: 10.1126/scitranslmed.aah4923).

Targeting the “feedback loop” between the FXI and a receptor that helps thrombin propagate on platelets reduced both vascular inflammation and blood pressure.

“Our findings suggest that inhibiting the ... thrombin-FXI–amplifying loop may provide added cardiovascular benefits that are synergistic with those of established platelet inhibitors,” the authors wrote.

This work was supported by grants from the Stiftung Pathobiochemie und Molekulare Diagnostik and the Federal Ministry of Education and Research. The authors disclosed funding and grants from the German Research Society, the European Research Council, NIH, and other sources. One of the researchers is inventor of five patents related to the FXI inhibitor and equity holder in Aronora, and may have financial interest in the findings of the research.

[email protected]

Research with mice and rats in Germany may have found a new way to treat high blood pressure.

Using epifluorescence intravital video microscopy imaging, researchers examined mice to whom they had given angiotensin II hormones to induce arterial hypertension.

They determined that the mice with low levels of thrombin-driven factor XI (FXI) – either naturally or inhibited by antisense oligonucleotides – had healthier endothelium.

“Specificity of the effects of FXI depletion was confirmed by continuous in vivo supplementation with human FXI,” wrote Sabine Kossmann, PhD, of the Center for Thrombosis and Hemostasis, University Medical Center, Mainz (Germany), and her coauthors (Sci Transl Med. 2017 Feb 1. doi: 10.1126/scitranslmed.aah4923).

Targeting the “feedback loop” between the FXI and a receptor that helps thrombin propagate on platelets reduced both vascular inflammation and blood pressure.

“Our findings suggest that inhibiting the ... thrombin-FXI–amplifying loop may provide added cardiovascular benefits that are synergistic with those of established platelet inhibitors,” the authors wrote.

This work was supported by grants from the Stiftung Pathobiochemie und Molekulare Diagnostik and the Federal Ministry of Education and Research. The authors disclosed funding and grants from the German Research Society, the European Research Council, NIH, and other sources. One of the researchers is inventor of five patents related to the FXI inhibitor and equity holder in Aronora, and may have financial interest in the findings of the research.

[email protected]

Research with mice and rats in Germany may have found a new way to treat high blood pressure.

Using epifluorescence intravital video microscopy imaging, researchers examined mice to whom they had given angiotensin II hormones to induce arterial hypertension.

They determined that the mice with low levels of thrombin-driven factor XI (FXI) – either naturally or inhibited by antisense oligonucleotides – had healthier endothelium.

“Specificity of the effects of FXI depletion was confirmed by continuous in vivo supplementation with human FXI,” wrote Sabine Kossmann, PhD, of the Center for Thrombosis and Hemostasis, University Medical Center, Mainz (Germany), and her coauthors (Sci Transl Med. 2017 Feb 1. doi: 10.1126/scitranslmed.aah4923).

Targeting the “feedback loop” between the FXI and a receptor that helps thrombin propagate on platelets reduced both vascular inflammation and blood pressure.

“Our findings suggest that inhibiting the ... thrombin-FXI–amplifying loop may provide added cardiovascular benefits that are synergistic with those of established platelet inhibitors,” the authors wrote.

This work was supported by grants from the Stiftung Pathobiochemie und Molekulare Diagnostik and the Federal Ministry of Education and Research. The authors disclosed funding and grants from the German Research Society, the European Research Council, NIH, and other sources. One of the researchers is inventor of five patents related to the FXI inhibitor and equity holder in Aronora, and may have financial interest in the findings of the research.

[email protected]

Doubt is being cast on the efficacy of Diclegis – the only prescription drug approved in the United States for treating nausea and vomiting in pregnancy – after researchers exposed flaws in previously unpublished data that served as the basis for the drug’s approval.

But the larger point, according to the researcher who brought the unpublished study to light, is the danger of relying too heavily on hidden data.

“It’s not like there’s some special concern over the safety of Diclegis. It’s that there is this commonly prescribed medication that hasn’t been proven to be effective,” Navindra Persaud, MD, a family physician and researcher at St. Michael’s Hospital in Toronto, said in an interview.

©monkeybusinessimages/thinkstockphotos.com

[email protected]

On Twitter @whitneymcknight

Doubt is being cast on the efficacy of Diclegis – the only prescription drug approved in the United States for treating nausea and vomiting in pregnancy – after researchers exposed flaws in previously unpublished data that served as the basis for the drug’s approval.

But the larger point, according to the researcher who brought the unpublished study to light, is the danger of relying too heavily on hidden data.

“It’s not like there’s some special concern over the safety of Diclegis. It’s that there is this commonly prescribed medication that hasn’t been proven to be effective,” Navindra Persaud, MD, a family physician and researcher at St. Michael’s Hospital in Toronto, said in an interview.

©monkeybusinessimages/thinkstockphotos.com

[email protected]

On Twitter @whitneymcknight

Doubt is being cast on the efficacy of Diclegis – the only prescription drug approved in the United States for treating nausea and vomiting in pregnancy – after researchers exposed flaws in previously unpublished data that served as the basis for the drug’s approval.

But the larger point, according to the researcher who brought the unpublished study to light, is the danger of relying too heavily on hidden data.

“It’s not like there’s some special concern over the safety of Diclegis. It’s that there is this commonly prescribed medication that hasn’t been proven to be effective,” Navindra Persaud, MD, a family physician and researcher at St. Michael’s Hospital in Toronto, said in an interview.

©monkeybusinessimages/thinkstockphotos.com

[email protected]

On Twitter @whitneymcknight