Studies have shown that a majority of patients remain confused about their health care plans after being discharged from the hospital.^1,2 Furthermore, most patients do not recognize their lack of comprehension.² A substantial proportion of medical information is forgotten immediately after discharge. Kessels found that when larger amounts of information were presented, less was recalled, and almost half of the recalled information was incorrect.³ Researchers also have found that health information that was focused on individual needs not only increased patients’ understanding of their health needs and improved their health literacy, but supported self-management and promoted health outcomes for adults with chronic illness.^4,5

Health literacy is the “capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions.”⁶ To read instructions on a prescription bottle, patients need an intermediate level of health literacy. Even for patients with such a level of health literacy, comprehending and managing a health care plan for a chronic disease can be challenging. About 35% of Americans had lower than an intermediate level of health literacy.⁷ Insufficient health literacy is associated with increased health system use and costs, health disparities, and poor health outcomes.⁸ As a result, it is crucial to gear oral instructions to patients’ health literacy levels to ensure that patients understand health information and instructions and perform self-care at home. The teach-back method, a technique for verifying patients’ understanding of their health information, has been recommended by the Agency for Healthcare Research and Quality (AHRQ) and the Institute for Healthcare Improvement (IHI) as a strategy for taking universal precautions for health literacy. Patients are asked to repeat the instructions they receive from their health care professionals (HCPs). HCPs should use caring and plain language in a shame-free environment during patient education. By using the teach-back method, HCPs can assess patients’ understanding, and reteach or modify teaching if comprehension is not demonstrated. Patients have an important role in their health and their ability to understand health information has a significant impact on their health behavior and outcomes.

In our systematic research, we examined the effectiveness of using the teach-back method to understand health education as well as the impact of this method on patients’ disease self-management and health outcomes.

Methods

In the teach-back method, patients explain health information in their own words.⁹ To gauge the use and effectiveness of this method, investigators have studied patient perceptions and acknowledgments of the method as well as the effects of the method on health interventions. According to Dorothea Orem’s self-care deficit nursing theory, disease self-management is an “executive ability” to “control, handle, direct or govern” self-care activities.¹⁰ We define disease self-management as disease knowledge and disease management changes that promote self-care activities. In addition, we define health outcomes as health changes that result from the teach-back method, such as changes in postdischarge readmission rates, patient satisfaction, and health behavior.

Inclusion Criteria

We systematically reviewed evidence regarding the teach-back method as an educational intervention for patients aged ≥ 18 years. We included articles if they reported the process and outcomes of using the method alone or in combination with other educational strategies. The literature search focused on English-language articles published in peer-reviewed journals. Included in the review were qualitative, randomized controlled trials (RCTs); quasi-experimental studies; cohort studies; and pretest–posttest studies on the effects of the teach-back method. As the method can be applied in any health care setting, we used studies conducted in a variety of settings, including primary care, inpatient, outpatient, emergency department (ED), and community, in any time frame. Study participants had heart failure, diabetes mellitus (DM), hypertension, asthma, or other chronic diseases.

Exclusion Criteria

Studies that used the teach-back method as an outcome measurement but not an intervention were excluded. For example, those that used the method to measure patients’ postintervention understanding were excluded. Also excluded were those that used the method to examine HCP training or to measure HCP outcomes (ie, studies that did not use the method for patient education or outcomes).

Literature Search

In September 2017, we searched 4 databases: Ovid Medline, PubMed, EBSCO (Elton B. Stephens Co), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ProQuest. Also included were relevant studies from cited reference searching (Figure).

This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline for searches and formatting results. The literature search was performed with the term teach-back and terms from the structured PICO (population, intervention, comparison, outcomes) statement. The study population consisted of patients who received the teach-back intervention as part of the patient education process in a medical care setting, and the comparator population consisted of patients who did not receive the intervention in their patient education. Target outcomes were disease self-management, self-care, patient satisfaction, patient perception and acknowledgment of the teach-back method, and other health outcomes.

Data Collection

Data collected included authors, publication date, and journal; purpose; study design; setting, sample, and population; intervention; and outcomes.

The methodologic quality of papers retrieved for review was determined with Critical Appraisals Skills Programme (CASP) guidelines (casp-uk.net/casp-tools-checklists). CASP randomised controlled trial, cohort study, case control study, and qualitative checklists were used. The authors assessed the full texts for eligibility. Disagreements were resolved through discussion.

The initial literature search found 112, 135, and 161 articles from EBSCO CINAHL, Ovid Medline, and PubMed, respectively. Five articles from ProQuest were identified through the EBSCO CINAHL search. After inclusion and exclusion criteria were applied, duplicate articles removed, a cited reference added, and CASP criteria assessed, 26 articles remained in the review. The 26 studies consisted of 15 cohort studies, 5 case–control studies, 5 RCTs, and 1 qualitative interview. Twenty-two of the articles were published in the US, the other 4 in Australia and Iran (2 each).^11-14 All 26 studies used the teach-back method with other educational interventions to reinforce learning (eg, the method was used after heart failure or DM education). Of the 26 studies, 10 used a pretest–posttest intervention design,^15-24 and 10 used a quasi-experimental or experimental design.^{11,13,14,25-31}

Results

The common outcome measures used in the 26 studies fall into 5 categories: patient satisfaction; postdischarge readmission; patient perception of teach-back method effectiveness; disease knowledge and disease management improvements; and intervention effects on health-related quality of life (HR-QOL). A summary of included articles, study setting, design, outcomes, and details is available from the author.

Patient Satisfaction

Ten studies examined the impact of the teach-back method on patient satisfaction.^{15,17,19,21,23,26,27,29,31,32} Of these 10 studies, 6 explored the influence of the method on Hospital Consumer Assessment of Healthcare Providers and Systems survey scores.^{15,17,19,21,22,26} All included studies indicated improved satisfaction with medication education, discharge information, and health management—except for the Silva study, who found an upward trend but not a statistically significant improvement in patient understanding of the purpose of a medication.²³

Grice and colleagues also found that community-dwelling seniors expressed satisfaction with using the teach-back method while being evaluated and assessed for health services at home.³² Improvement or a positive trend in teach-back groups was reported in a majority of the studies except for those by Hyrkas and Wiggins, and Griffey and colleagues.^27,29 Hyrkas and Wiggins found the method slightly improved patients’ medication confidence after hospital discharge, though patient satisfaction scores were associated with patient–nurse relationships, not with use of the teach-back method and a motivational interview.²⁷ Similarly, Griffey and colleagues found that patients who had limited health literacy and received a standard discharge with teach-back scored higher on medication comprehension, compared with patients who received only a standard discharge, but there was no difference in patient satisfaction after an ED visit.²⁹

Postdischarge Readmission

Results emphasized the importance of teach-back in reinforcing discharge instructions and improving postdischarge readmission rates. Of the 6 studies on the effect that teach-back with discharge summary had on readmission rates, 2 found statistically significant improvement for patients with heart failure at 12 months (teach-back, 59%; non-teach-back, 44%; P = .005) and patients with coronary artery bypass grafting (CABG) at 30 days (preintervention, 25%; postintervention, 12%; P = .02).^11,16 In addition, 3 of the 6 studies reported improvement but did not provide P values.^18,20,22 One study indicated improvement in other measured outcomes but found no significant difference for patients who received teach-back with their discharge summaries.²⁷ In all studies, teach-back was added to an intervention and used to confirm and promote knowledge and self-care management.

Patient Perception of Teach-Back Effectiveness

In 2 qualitative studies, patients indicated teach-back was an effective educational method.^16,33 For patients with CABG, Bates and colleagues added a scheduled cardiology follow-up appointment and teach-back patient education to their State Action on Avoidable Rehospitalizations interventions; 96% of participants rated teach-back effective or highly effective.¹⁶ In the other study, Samuels-Kalow and colleagues interviewed 51 patients and parents who received teach-back as part of the discharge process in 2 EDs; participants indicated teach-back helped them remember what they learned from their HCPs, and gave them the opportunity to connect with their HCPs, though some with lower health literacy expressed concerns about perceived judgment by HCPs.³³

Disease Knowledge and Management

Thirteen studies examined knowledge improvement after interventions that included teach-back. Study participants answered most questions correctly after receiving teach-back.^20,32,34,35 Slater and colleagues found ED patients who received discharge instructions with teach-back had significantly higher scores measuring knowledge of diagnosis (P < .001), signs and symptoms indicating a need to return to the ED (P < .001), and follow-up instructions (P = .03); scores measuring knowledge of medication were higher as well, but were not statistically different (P = .14).²⁴ In multiple studies, improvement was not always statistically significant in terms of knowledge retention.^{12,25,29-31,36} Studies that compared medication adherence found teach-back was more effective than motivational interviews (P = .56).²⁷

Teach-back has been widely used in primary care, inpatient, and ED settings. Two studies on the effect of teach-back in primary care sampled patients with DM.^28,36 Kandula and colleagues found that participants who answered questions incorrectly after watching a multimedia DM education program could significantly improve their DM knowledge by engaging in teach-back immediately after the intervention; however, knowledge retention was not improved at 2-week follow-up (phone call).²⁸ In contrast, Swavely and colleagues compared patients who completed a 13-hour DM education program with or without teach-back and found that teach-back patients demonstrated significantly improved DM knowledge and self-care activities at 3 months.³⁶

Effects of Interventions on HR-QOL

The teach-back method had been used with QOL improvement programs and other interventions. Ahmadidarrehsima and colleagues incorporated teach-back into their medical self-management program (8 to 11 sessions, each lasting 1.5 to 2 hours) for women with breast cancer and found that the mean happiness score increased to 62.9 from 37.2 (P < .001) in the intervention group, whereas the score for the usual-care group decreased from 41.4 to 29.8.¹³ Ghiasvand and colleagues compared QOL of postpartum mothers who received routine care with QOL of those who received routine care plus 2 sessions of postpartum self-care with teach-back; mean QOL scores were significantly (P < .001) higher for the teach-back group (124.73) than for the no teach-back group (115.03).¹⁴

Discussion

This review examined the use and effectiveness of the teach-back method in health education and its influence in patients’ disease self-management and health outcomes. Results showed positive effects of teach-back on patient satisfaction, patient perceptions and acknowledgments, postdischarge readmissions, disease self-management and knowledge, and HR-QOL.

The teach-back method has been widely used in inpatient, outpatient, ED, and community settings as part of health education programs and interventions. It has been paired with educational interventions ranging from short instructions to 20-hour programs. These differences reflect the broad application of the method in patient education. Many studies have found that teach-back improves disease knowledge and self-management, though their results are not always statistically significant. In an RCT of patients with low health literacy, Griffey and colleagues studied the effect of ED discharge education with and without teach-back and found teach-back did not increase post-ED comprehension of diagnoses, medical examinations, and treatments or perceived comprehension of treatment and care; however, compared with the no teach-back group, the teach-back group had significantly higher scores on comprehension of post-ED self-care (P < .02), follow-up (P < .0001), and medication (P = .054).²⁹ This finding indicates teach-back is an effective method for helping patients understand self-care and disease self-management at home.

Comprehending medical diagnoses, examinations, and treatments involves acquiring, analyzing, and comparing multiple pieces of health information. Because comprehension requires a level of abstract thinking usually present in patients with intermediate and proficient health literacy,improvements might be more difficult to see in patients with low health literacy.⁸ Press and colleagues found that asthma patients who repeated respiratory inhaler instructions with teach-back during discharge education had less misuse of (P = .01) metered-dose and Diskus (P = .05) inhalers and lower 30-day readmission rates (P = .02) compared with the misuse of patients who received only 1 set of oral and written instructions.³¹ Even though the Diskus result was not statistically significant, it demonstrated teach-back can be used to improve patient self-care and education.³¹

Most participants in the reviewed studies improved their disease knowledge with teach-back, though the evidence regarding improved health care knowledge retention was limited. For example, the 2 studies on use of teach-back in primary care clinics had contradictory knowledge retention results.^28,36 As both studies incorporated teach-back into existing interventions, these results could be associated with those interventions and not with the teach-back method.

Health literacy is achieved through a complicated process of obtaining, analyzing, choosing, and communicating health information. Even though its knowledge retention results are inconsistent, the teach-back method is recommended by the American Academy of Family Physicians at strength of recommendation taxonomy level C.⁸ Such a designation indicates that the recommendation is based on expert opinion, bench research, consensus guideline, usual practice, clinical experience, or a case series and is appropriate for assessment of patient comprehension.³⁷ Teach-back is also suggested by AHRQ and IHI for university precautions regarding health literacy and as such should remain a standard of practice. More study is needed to understand the inconsistent results of knowledge retention and the long-term effects of the teach-back method.

Limitations

Although this review did not limit the publication years of its articles, no pre-2011 articles were found. The teach-back method has been used to measure patients’ postintervention understanding and to educate HCPs on ways to improve patient communication. As this review did not include studies of teach-back as an outcome measurement or studies of training and adaptation of teach-back in HCP or nurse education, other study results may have a bearing on the current findings. Teach-back has been used to close communication gaps between patients and HCPs.

All articles included in this review used the teach-back method with other educational or organizational interventions. The outcomes found in this review may be associated with those interventions and not with teach-back itself. Data reported here have not demonstrated a definite association between teach-back and the measured outcomes; therefore, caution should be exercised when drawing conclusions based on these data. In addition, most of the studies considered in this review were cohort or case–control studies; only 5 RCTs were included. Other confounding factors, including patient health literacy levels, HCP types, HCP competencies in use of teach-back, and type and duration of interventions used before teach-back, may have contributed to this review’s findings.

Conclusion

Findings of this systematic review support use of the teach-back method as effective in reinforcing or confirming patient education. As none of the included studies reported harmful outcomes, the teach-back method poses little risk with respect to increasing patients’ understanding of their education. The findings emphasize the importance of conducting more studies to try to understand the inconsistent results of knowledge retention and determine ways to preserve the long-term effects of teach-back.

Studies have shown that a majority of patients remain confused about their health care plans after being discharged from the hospital.^1,2 Furthermore, most patients do not recognize their lack of comprehension.² A substantial proportion of medical information is forgotten immediately after discharge. Kessels found that when larger amounts of information were presented, less was recalled, and almost half of the recalled information was incorrect.³ Researchers also have found that health information that was focused on individual needs not only increased patients’ understanding of their health needs and improved their health literacy, but supported self-management and promoted health outcomes for adults with chronic illness.^4,5

Health literacy is the “capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions.”⁶ To read instructions on a prescription bottle, patients need an intermediate level of health literacy. Even for patients with such a level of health literacy, comprehending and managing a health care plan for a chronic disease can be challenging. About 35% of Americans had lower than an intermediate level of health literacy.⁷ Insufficient health literacy is associated with increased health system use and costs, health disparities, and poor health outcomes.⁸ As a result, it is crucial to gear oral instructions to patients’ health literacy levels to ensure that patients understand health information and instructions and perform self-care at home. The teach-back method, a technique for verifying patients’ understanding of their health information, has been recommended by the Agency for Healthcare Research and Quality (AHRQ) and the Institute for Healthcare Improvement (IHI) as a strategy for taking universal precautions for health literacy. Patients are asked to repeat the instructions they receive from their health care professionals (HCPs). HCPs should use caring and plain language in a shame-free environment during patient education. By using the teach-back method, HCPs can assess patients’ understanding, and reteach or modify teaching if comprehension is not demonstrated. Patients have an important role in their health and their ability to understand health information has a significant impact on their health behavior and outcomes.

In our systematic research, we examined the effectiveness of using the teach-back method to understand health education as well as the impact of this method on patients’ disease self-management and health outcomes.

Methods

In the teach-back method, patients explain health information in their own words.⁹ To gauge the use and effectiveness of this method, investigators have studied patient perceptions and acknowledgments of the method as well as the effects of the method on health interventions. According to Dorothea Orem’s self-care deficit nursing theory, disease self-management is an “executive ability” to “control, handle, direct or govern” self-care activities.¹⁰ We define disease self-management as disease knowledge and disease management changes that promote self-care activities. In addition, we define health outcomes as health changes that result from the teach-back method, such as changes in postdischarge readmission rates, patient satisfaction, and health behavior.

Inclusion Criteria

We systematically reviewed evidence regarding the teach-back method as an educational intervention for patients aged ≥ 18 years. We included articles if they reported the process and outcomes of using the method alone or in combination with other educational strategies. The literature search focused on English-language articles published in peer-reviewed journals. Included in the review were qualitative, randomized controlled trials (RCTs); quasi-experimental studies; cohort studies; and pretest–posttest studies on the effects of the teach-back method. As the method can be applied in any health care setting, we used studies conducted in a variety of settings, including primary care, inpatient, outpatient, emergency department (ED), and community, in any time frame. Study participants had heart failure, diabetes mellitus (DM), hypertension, asthma, or other chronic diseases.

Exclusion Criteria

Studies that used the teach-back method as an outcome measurement but not an intervention were excluded. For example, those that used the method to measure patients’ postintervention understanding were excluded. Also excluded were those that used the method to examine HCP training or to measure HCP outcomes (ie, studies that did not use the method for patient education or outcomes).

Literature Search

In September 2017, we searched 4 databases: Ovid Medline, PubMed, EBSCO (Elton B. Stephens Co), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ProQuest. Also included were relevant studies from cited reference searching (Figure).

This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline for searches and formatting results. The literature search was performed with the term teach-back and terms from the structured PICO (population, intervention, comparison, outcomes) statement. The study population consisted of patients who received the teach-back intervention as part of the patient education process in a medical care setting, and the comparator population consisted of patients who did not receive the intervention in their patient education. Target outcomes were disease self-management, self-care, patient satisfaction, patient perception and acknowledgment of the teach-back method, and other health outcomes.

Data Collection

Data collected included authors, publication date, and journal; purpose; study design; setting, sample, and population; intervention; and outcomes.

The methodologic quality of papers retrieved for review was determined with Critical Appraisals Skills Programme (CASP) guidelines (casp-uk.net/casp-tools-checklists). CASP randomised controlled trial, cohort study, case control study, and qualitative checklists were used. The authors assessed the full texts for eligibility. Disagreements were resolved through discussion.

The initial literature search found 112, 135, and 161 articles from EBSCO CINAHL, Ovid Medline, and PubMed, respectively. Five articles from ProQuest were identified through the EBSCO CINAHL search. After inclusion and exclusion criteria were applied, duplicate articles removed, a cited reference added, and CASP criteria assessed, 26 articles remained in the review. The 26 studies consisted of 15 cohort studies, 5 case–control studies, 5 RCTs, and 1 qualitative interview. Twenty-two of the articles were published in the US, the other 4 in Australia and Iran (2 each).^11-14 All 26 studies used the teach-back method with other educational interventions to reinforce learning (eg, the method was used after heart failure or DM education). Of the 26 studies, 10 used a pretest–posttest intervention design,^15-24 and 10 used a quasi-experimental or experimental design.^{11,13,14,25-31}

Results

The common outcome measures used in the 26 studies fall into 5 categories: patient satisfaction; postdischarge readmission; patient perception of teach-back method effectiveness; disease knowledge and disease management improvements; and intervention effects on health-related quality of life (HR-QOL). A summary of included articles, study setting, design, outcomes, and details is available from the author.

Patient Satisfaction

Ten studies examined the impact of the teach-back method on patient satisfaction.^{15,17,19,21,23,26,27,29,31,32} Of these 10 studies, 6 explored the influence of the method on Hospital Consumer Assessment of Healthcare Providers and Systems survey scores.^{15,17,19,21,22,26} All included studies indicated improved satisfaction with medication education, discharge information, and health management—except for the Silva study, who found an upward trend but not a statistically significant improvement in patient understanding of the purpose of a medication.²³

Grice and colleagues also found that community-dwelling seniors expressed satisfaction with using the teach-back method while being evaluated and assessed for health services at home.³² Improvement or a positive trend in teach-back groups was reported in a majority of the studies except for those by Hyrkas and Wiggins, and Griffey and colleagues.^27,29 Hyrkas and Wiggins found the method slightly improved patients’ medication confidence after hospital discharge, though patient satisfaction scores were associated with patient–nurse relationships, not with use of the teach-back method and a motivational interview.²⁷ Similarly, Griffey and colleagues found that patients who had limited health literacy and received a standard discharge with teach-back scored higher on medication comprehension, compared with patients who received only a standard discharge, but there was no difference in patient satisfaction after an ED visit.²⁹

Postdischarge Readmission

Results emphasized the importance of teach-back in reinforcing discharge instructions and improving postdischarge readmission rates. Of the 6 studies on the effect that teach-back with discharge summary had on readmission rates, 2 found statistically significant improvement for patients with heart failure at 12 months (teach-back, 59%; non-teach-back, 44%; P = .005) and patients with coronary artery bypass grafting (CABG) at 30 days (preintervention, 25%; postintervention, 12%; P = .02).^11,16 In addition, 3 of the 6 studies reported improvement but did not provide P values.^18,20,22 One study indicated improvement in other measured outcomes but found no significant difference for patients who received teach-back with their discharge summaries.²⁷ In all studies, teach-back was added to an intervention and used to confirm and promote knowledge and self-care management.

Patient Perception of Teach-Back Effectiveness

In 2 qualitative studies, patients indicated teach-back was an effective educational method.^16,33 For patients with CABG, Bates and colleagues added a scheduled cardiology follow-up appointment and teach-back patient education to their State Action on Avoidable Rehospitalizations interventions; 96% of participants rated teach-back effective or highly effective.¹⁶ In the other study, Samuels-Kalow and colleagues interviewed 51 patients and parents who received teach-back as part of the discharge process in 2 EDs; participants indicated teach-back helped them remember what they learned from their HCPs, and gave them the opportunity to connect with their HCPs, though some with lower health literacy expressed concerns about perceived judgment by HCPs.³³

Disease Knowledge and Management

Thirteen studies examined knowledge improvement after interventions that included teach-back. Study participants answered most questions correctly after receiving teach-back.^20,32,34,35 Slater and colleagues found ED patients who received discharge instructions with teach-back had significantly higher scores measuring knowledge of diagnosis (P < .001), signs and symptoms indicating a need to return to the ED (P < .001), and follow-up instructions (P = .03); scores measuring knowledge of medication were higher as well, but were not statistically different (P = .14).²⁴ In multiple studies, improvement was not always statistically significant in terms of knowledge retention.^{12,25,29-31,36} Studies that compared medication adherence found teach-back was more effective than motivational interviews (P = .56).²⁷

Teach-back has been widely used in primary care, inpatient, and ED settings. Two studies on the effect of teach-back in primary care sampled patients with DM.^28,36 Kandula and colleagues found that participants who answered questions incorrectly after watching a multimedia DM education program could significantly improve their DM knowledge by engaging in teach-back immediately after the intervention; however, knowledge retention was not improved at 2-week follow-up (phone call).²⁸ In contrast, Swavely and colleagues compared patients who completed a 13-hour DM education program with or without teach-back and found that teach-back patients demonstrated significantly improved DM knowledge and self-care activities at 3 months.³⁶

Effects of Interventions on HR-QOL

The teach-back method had been used with QOL improvement programs and other interventions. Ahmadidarrehsima and colleagues incorporated teach-back into their medical self-management program (8 to 11 sessions, each lasting 1.5 to 2 hours) for women with breast cancer and found that the mean happiness score increased to 62.9 from 37.2 (P < .001) in the intervention group, whereas the score for the usual-care group decreased from 41.4 to 29.8.¹³ Ghiasvand and colleagues compared QOL of postpartum mothers who received routine care with QOL of those who received routine care plus 2 sessions of postpartum self-care with teach-back; mean QOL scores were significantly (P < .001) higher for the teach-back group (124.73) than for the no teach-back group (115.03).¹⁴

Discussion

This review examined the use and effectiveness of the teach-back method in health education and its influence in patients’ disease self-management and health outcomes. Results showed positive effects of teach-back on patient satisfaction, patient perceptions and acknowledgments, postdischarge readmissions, disease self-management and knowledge, and HR-QOL.

The teach-back method has been widely used in inpatient, outpatient, ED, and community settings as part of health education programs and interventions. It has been paired with educational interventions ranging from short instructions to 20-hour programs. These differences reflect the broad application of the method in patient education. Many studies have found that teach-back improves disease knowledge and self-management, though their results are not always statistically significant. In an RCT of patients with low health literacy, Griffey and colleagues studied the effect of ED discharge education with and without teach-back and found teach-back did not increase post-ED comprehension of diagnoses, medical examinations, and treatments or perceived comprehension of treatment and care; however, compared with the no teach-back group, the teach-back group had significantly higher scores on comprehension of post-ED self-care (P < .02), follow-up (P < .0001), and medication (P = .054).²⁹ This finding indicates teach-back is an effective method for helping patients understand self-care and disease self-management at home.

Comprehending medical diagnoses, examinations, and treatments involves acquiring, analyzing, and comparing multiple pieces of health information. Because comprehension requires a level of abstract thinking usually present in patients with intermediate and proficient health literacy,improvements might be more difficult to see in patients with low health literacy.⁸ Press and colleagues found that asthma patients who repeated respiratory inhaler instructions with teach-back during discharge education had less misuse of (P = .01) metered-dose and Diskus (P = .05) inhalers and lower 30-day readmission rates (P = .02) compared with the misuse of patients who received only 1 set of oral and written instructions.³¹ Even though the Diskus result was not statistically significant, it demonstrated teach-back can be used to improve patient self-care and education.³¹

Most participants in the reviewed studies improved their disease knowledge with teach-back, though the evidence regarding improved health care knowledge retention was limited. For example, the 2 studies on use of teach-back in primary care clinics had contradictory knowledge retention results.^28,36 As both studies incorporated teach-back into existing interventions, these results could be associated with those interventions and not with the teach-back method.

Health literacy is achieved through a complicated process of obtaining, analyzing, choosing, and communicating health information. Even though its knowledge retention results are inconsistent, the teach-back method is recommended by the American Academy of Family Physicians at strength of recommendation taxonomy level C.⁸ Such a designation indicates that the recommendation is based on expert opinion, bench research, consensus guideline, usual practice, clinical experience, or a case series and is appropriate for assessment of patient comprehension.³⁷ Teach-back is also suggested by AHRQ and IHI for university precautions regarding health literacy and as such should remain a standard of practice. More study is needed to understand the inconsistent results of knowledge retention and the long-term effects of the teach-back method.

Limitations

Although this review did not limit the publication years of its articles, no pre-2011 articles were found. The teach-back method has been used to measure patients’ postintervention understanding and to educate HCPs on ways to improve patient communication. As this review did not include studies of teach-back as an outcome measurement or studies of training and adaptation of teach-back in HCP or nurse education, other study results may have a bearing on the current findings. Teach-back has been used to close communication gaps between patients and HCPs.

All articles included in this review used the teach-back method with other educational or organizational interventions. The outcomes found in this review may be associated with those interventions and not with teach-back itself. Data reported here have not demonstrated a definite association between teach-back and the measured outcomes; therefore, caution should be exercised when drawing conclusions based on these data. In addition, most of the studies considered in this review were cohort or case–control studies; only 5 RCTs were included. Other confounding factors, including patient health literacy levels, HCP types, HCP competencies in use of teach-back, and type and duration of interventions used before teach-back, may have contributed to this review’s findings.

Conclusion

Findings of this systematic review support use of the teach-back method as effective in reinforcing or confirming patient education. As none of the included studies reported harmful outcomes, the teach-back method poses little risk with respect to increasing patients’ understanding of their education. The findings emphasize the importance of conducting more studies to try to understand the inconsistent results of knowledge retention and determine ways to preserve the long-term effects of teach-back.

Studies have shown that a majority of patients remain confused about their health care plans after being discharged from the hospital.^1,2 Furthermore, most patients do not recognize their lack of comprehension.² A substantial proportion of medical information is forgotten immediately after discharge. Kessels found that when larger amounts of information were presented, less was recalled, and almost half of the recalled information was incorrect.³ Researchers also have found that health information that was focused on individual needs not only increased patients’ understanding of their health needs and improved their health literacy, but supported self-management and promoted health outcomes for adults with chronic illness.^4,5

Health literacy is the “capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions.”⁶ To read instructions on a prescription bottle, patients need an intermediate level of health literacy. Even for patients with such a level of health literacy, comprehending and managing a health care plan for a chronic disease can be challenging. About 35% of Americans had lower than an intermediate level of health literacy.⁷ Insufficient health literacy is associated with increased health system use and costs, health disparities, and poor health outcomes.⁸ As a result, it is crucial to gear oral instructions to patients’ health literacy levels to ensure that patients understand health information and instructions and perform self-care at home. The teach-back method, a technique for verifying patients’ understanding of their health information, has been recommended by the Agency for Healthcare Research and Quality (AHRQ) and the Institute for Healthcare Improvement (IHI) as a strategy for taking universal precautions for health literacy. Patients are asked to repeat the instructions they receive from their health care professionals (HCPs). HCPs should use caring and plain language in a shame-free environment during patient education. By using the teach-back method, HCPs can assess patients’ understanding, and reteach or modify teaching if comprehension is not demonstrated. Patients have an important role in their health and their ability to understand health information has a significant impact on their health behavior and outcomes.

In our systematic research, we examined the effectiveness of using the teach-back method to understand health education as well as the impact of this method on patients’ disease self-management and health outcomes.

Methods

In the teach-back method, patients explain health information in their own words.⁹ To gauge the use and effectiveness of this method, investigators have studied patient perceptions and acknowledgments of the method as well as the effects of the method on health interventions. According to Dorothea Orem’s self-care deficit nursing theory, disease self-management is an “executive ability” to “control, handle, direct or govern” self-care activities.¹⁰ We define disease self-management as disease knowledge and disease management changes that promote self-care activities. In addition, we define health outcomes as health changes that result from the teach-back method, such as changes in postdischarge readmission rates, patient satisfaction, and health behavior.

Inclusion Criteria

We systematically reviewed evidence regarding the teach-back method as an educational intervention for patients aged ≥ 18 years. We included articles if they reported the process and outcomes of using the method alone or in combination with other educational strategies. The literature search focused on English-language articles published in peer-reviewed journals. Included in the review were qualitative, randomized controlled trials (RCTs); quasi-experimental studies; cohort studies; and pretest–posttest studies on the effects of the teach-back method. As the method can be applied in any health care setting, we used studies conducted in a variety of settings, including primary care, inpatient, outpatient, emergency department (ED), and community, in any time frame. Study participants had heart failure, diabetes mellitus (DM), hypertension, asthma, or other chronic diseases.

Exclusion Criteria

Studies that used the teach-back method as an outcome measurement but not an intervention were excluded. For example, those that used the method to measure patients’ postintervention understanding were excluded. Also excluded were those that used the method to examine HCP training or to measure HCP outcomes (ie, studies that did not use the method for patient education or outcomes).

Literature Search

In September 2017, we searched 4 databases: Ovid Medline, PubMed, EBSCO (Elton B. Stephens Co), CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ProQuest. Also included were relevant studies from cited reference searching (Figure).

This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline for searches and formatting results. The literature search was performed with the term teach-back and terms from the structured PICO (population, intervention, comparison, outcomes) statement. The study population consisted of patients who received the teach-back intervention as part of the patient education process in a medical care setting, and the comparator population consisted of patients who did not receive the intervention in their patient education. Target outcomes were disease self-management, self-care, patient satisfaction, patient perception and acknowledgment of the teach-back method, and other health outcomes.

Data Collection

Data collected included authors, publication date, and journal; purpose; study design; setting, sample, and population; intervention; and outcomes.

The methodologic quality of papers retrieved for review was determined with Critical Appraisals Skills Programme (CASP) guidelines (casp-uk.net/casp-tools-checklists). CASP randomised controlled trial, cohort study, case control study, and qualitative checklists were used. The authors assessed the full texts for eligibility. Disagreements were resolved through discussion.

The initial literature search found 112, 135, and 161 articles from EBSCO CINAHL, Ovid Medline, and PubMed, respectively. Five articles from ProQuest were identified through the EBSCO CINAHL search. After inclusion and exclusion criteria were applied, duplicate articles removed, a cited reference added, and CASP criteria assessed, 26 articles remained in the review. The 26 studies consisted of 15 cohort studies, 5 case–control studies, 5 RCTs, and 1 qualitative interview. Twenty-two of the articles were published in the US, the other 4 in Australia and Iran (2 each).^11-14 All 26 studies used the teach-back method with other educational interventions to reinforce learning (eg, the method was used after heart failure or DM education). Of the 26 studies, 10 used a pretest–posttest intervention design,^15-24 and 10 used a quasi-experimental or experimental design.^{11,13,14,25-31}

Results

The common outcome measures used in the 26 studies fall into 5 categories: patient satisfaction; postdischarge readmission; patient perception of teach-back method effectiveness; disease knowledge and disease management improvements; and intervention effects on health-related quality of life (HR-QOL). A summary of included articles, study setting, design, outcomes, and details is available from the author.

Patient Satisfaction

Ten studies examined the impact of the teach-back method on patient satisfaction.^{15,17,19,21,23,26,27,29,31,32} Of these 10 studies, 6 explored the influence of the method on Hospital Consumer Assessment of Healthcare Providers and Systems survey scores.^{15,17,19,21,22,26} All included studies indicated improved satisfaction with medication education, discharge information, and health management—except for the Silva study, who found an upward trend but not a statistically significant improvement in patient understanding of the purpose of a medication.²³

Grice and colleagues also found that community-dwelling seniors expressed satisfaction with using the teach-back method while being evaluated and assessed for health services at home.³² Improvement or a positive trend in teach-back groups was reported in a majority of the studies except for those by Hyrkas and Wiggins, and Griffey and colleagues.^27,29 Hyrkas and Wiggins found the method slightly improved patients’ medication confidence after hospital discharge, though patient satisfaction scores were associated with patient–nurse relationships, not with use of the teach-back method and a motivational interview.²⁷ Similarly, Griffey and colleagues found that patients who had limited health literacy and received a standard discharge with teach-back scored higher on medication comprehension, compared with patients who received only a standard discharge, but there was no difference in patient satisfaction after an ED visit.²⁹

Postdischarge Readmission

Results emphasized the importance of teach-back in reinforcing discharge instructions and improving postdischarge readmission rates. Of the 6 studies on the effect that teach-back with discharge summary had on readmission rates, 2 found statistically significant improvement for patients with heart failure at 12 months (teach-back, 59%; non-teach-back, 44%; P = .005) and patients with coronary artery bypass grafting (CABG) at 30 days (preintervention, 25%; postintervention, 12%; P = .02).^11,16 In addition, 3 of the 6 studies reported improvement but did not provide P values.^18,20,22 One study indicated improvement in other measured outcomes but found no significant difference for patients who received teach-back with their discharge summaries.²⁷ In all studies, teach-back was added to an intervention and used to confirm and promote knowledge and self-care management.

Patient Perception of Teach-Back Effectiveness

In 2 qualitative studies, patients indicated teach-back was an effective educational method.^16,33 For patients with CABG, Bates and colleagues added a scheduled cardiology follow-up appointment and teach-back patient education to their State Action on Avoidable Rehospitalizations interventions; 96% of participants rated teach-back effective or highly effective.¹⁶ In the other study, Samuels-Kalow and colleagues interviewed 51 patients and parents who received teach-back as part of the discharge process in 2 EDs; participants indicated teach-back helped them remember what they learned from their HCPs, and gave them the opportunity to connect with their HCPs, though some with lower health literacy expressed concerns about perceived judgment by HCPs.³³

Disease Knowledge and Management

Thirteen studies examined knowledge improvement after interventions that included teach-back. Study participants answered most questions correctly after receiving teach-back.^20,32,34,35 Slater and colleagues found ED patients who received discharge instructions with teach-back had significantly higher scores measuring knowledge of diagnosis (P < .001), signs and symptoms indicating a need to return to the ED (P < .001), and follow-up instructions (P = .03); scores measuring knowledge of medication were higher as well, but were not statistically different (P = .14).²⁴ In multiple studies, improvement was not always statistically significant in terms of knowledge retention.^{12,25,29-31,36} Studies that compared medication adherence found teach-back was more effective than motivational interviews (P = .56).²⁷

Teach-back has been widely used in primary care, inpatient, and ED settings. Two studies on the effect of teach-back in primary care sampled patients with DM.^28,36 Kandula and colleagues found that participants who answered questions incorrectly after watching a multimedia DM education program could significantly improve their DM knowledge by engaging in teach-back immediately after the intervention; however, knowledge retention was not improved at 2-week follow-up (phone call).²⁸ In contrast, Swavely and colleagues compared patients who completed a 13-hour DM education program with or without teach-back and found that teach-back patients demonstrated significantly improved DM knowledge and self-care activities at 3 months.³⁶

Effects of Interventions on HR-QOL

The teach-back method had been used with QOL improvement programs and other interventions. Ahmadidarrehsima and colleagues incorporated teach-back into their medical self-management program (8 to 11 sessions, each lasting 1.5 to 2 hours) for women with breast cancer and found that the mean happiness score increased to 62.9 from 37.2 (P < .001) in the intervention group, whereas the score for the usual-care group decreased from 41.4 to 29.8.¹³ Ghiasvand and colleagues compared QOL of postpartum mothers who received routine care with QOL of those who received routine care plus 2 sessions of postpartum self-care with teach-back; mean QOL scores were significantly (P < .001) higher for the teach-back group (124.73) than for the no teach-back group (115.03).¹⁴

Discussion

This review examined the use and effectiveness of the teach-back method in health education and its influence in patients’ disease self-management and health outcomes. Results showed positive effects of teach-back on patient satisfaction, patient perceptions and acknowledgments, postdischarge readmissions, disease self-management and knowledge, and HR-QOL.

The teach-back method has been widely used in inpatient, outpatient, ED, and community settings as part of health education programs and interventions. It has been paired with educational interventions ranging from short instructions to 20-hour programs. These differences reflect the broad application of the method in patient education. Many studies have found that teach-back improves disease knowledge and self-management, though their results are not always statistically significant. In an RCT of patients with low health literacy, Griffey and colleagues studied the effect of ED discharge education with and without teach-back and found teach-back did not increase post-ED comprehension of diagnoses, medical examinations, and treatments or perceived comprehension of treatment and care; however, compared with the no teach-back group, the teach-back group had significantly higher scores on comprehension of post-ED self-care (P < .02), follow-up (P < .0001), and medication (P = .054).²⁹ This finding indicates teach-back is an effective method for helping patients understand self-care and disease self-management at home.

Comprehending medical diagnoses, examinations, and treatments involves acquiring, analyzing, and comparing multiple pieces of health information. Because comprehension requires a level of abstract thinking usually present in patients with intermediate and proficient health literacy,improvements might be more difficult to see in patients with low health literacy.⁸ Press and colleagues found that asthma patients who repeated respiratory inhaler instructions with teach-back during discharge education had less misuse of (P = .01) metered-dose and Diskus (P = .05) inhalers and lower 30-day readmission rates (P = .02) compared with the misuse of patients who received only 1 set of oral and written instructions.³¹ Even though the Diskus result was not statistically significant, it demonstrated teach-back can be used to improve patient self-care and education.³¹

Most participants in the reviewed studies improved their disease knowledge with teach-back, though the evidence regarding improved health care knowledge retention was limited. For example, the 2 studies on use of teach-back in primary care clinics had contradictory knowledge retention results.^28,36 As both studies incorporated teach-back into existing interventions, these results could be associated with those interventions and not with the teach-back method.

Health literacy is achieved through a complicated process of obtaining, analyzing, choosing, and communicating health information. Even though its knowledge retention results are inconsistent, the teach-back method is recommended by the American Academy of Family Physicians at strength of recommendation taxonomy level C.⁸ Such a designation indicates that the recommendation is based on expert opinion, bench research, consensus guideline, usual practice, clinical experience, or a case series and is appropriate for assessment of patient comprehension.³⁷ Teach-back is also suggested by AHRQ and IHI for university precautions regarding health literacy and as such should remain a standard of practice. More study is needed to understand the inconsistent results of knowledge retention and the long-term effects of the teach-back method.

Limitations

Although this review did not limit the publication years of its articles, no pre-2011 articles were found. The teach-back method has been used to measure patients’ postintervention understanding and to educate HCPs on ways to improve patient communication. As this review did not include studies of teach-back as an outcome measurement or studies of training and adaptation of teach-back in HCP or nurse education, other study results may have a bearing on the current findings. Teach-back has been used to close communication gaps between patients and HCPs.

All articles included in this review used the teach-back method with other educational or organizational interventions. The outcomes found in this review may be associated with those interventions and not with teach-back itself. Data reported here have not demonstrated a definite association between teach-back and the measured outcomes; therefore, caution should be exercised when drawing conclusions based on these data. In addition, most of the studies considered in this review were cohort or case–control studies; only 5 RCTs were included. Other confounding factors, including patient health literacy levels, HCP types, HCP competencies in use of teach-back, and type and duration of interventions used before teach-back, may have contributed to this review’s findings.

Conclusion

Findings of this systematic review support use of the teach-back method as effective in reinforcing or confirming patient education. As none of the included studies reported harmful outcomes, the teach-back method poses little risk with respect to increasing patients’ understanding of their education. The findings emphasize the importance of conducting more studies to try to understand the inconsistent results of knowledge retention and determine ways to preserve the long-term effects of teach-back.

ANSWER

The correct interpretation includes normal sinus rhythm, possible left atrial enlargement (LAE), and left ventricular hypertrophy (LVH).

Normal sinus rhythm is defined as a P for every QRS and a QRS for every P, with a normal PR interval and a rate > 60 and < 100 beats/min.

Criteria for LAE include a P wave > 120 ms in lead II and/or a biphasic P wave in lead V₁ with a downward deflection > 40 ms in length with a > 1-mm negative deflection. This ECG does not meet criteria for LAE; however, it is suspicious, particularly in the context of mitral regurgitation and LVH.

LVH is diagnosed using either the Sokolow-Lyon criteria (the sum of the S wave in V₁ and the R wave in V₅ or V₆ ≥ 35 mm) or the Cornell voltage criteria (the S in V₃ plus the R in aVL > 20 mm for women [> 28 mm for men]).

LVH is usually not a target of therapy. Management is typically directed at treating the underlying pathology. For this patient, it is important to manage her hypertension and provide follow-up—including periodic echocardiography of her left atrium, mitral valve, and left ventricle—to determine response to hypertensive therapy.

ANSWER

The correct interpretation includes normal sinus rhythm, possible left atrial enlargement (LAE), and left ventricular hypertrophy (LVH).

Normal sinus rhythm is defined as a P for every QRS and a QRS for every P, with a normal PR interval and a rate > 60 and < 100 beats/min.

Criteria for LAE include a P wave > 120 ms in lead II and/or a biphasic P wave in lead V₁ with a downward deflection > 40 ms in length with a > 1-mm negative deflection. This ECG does not meet criteria for LAE; however, it is suspicious, particularly in the context of mitral regurgitation and LVH.

LVH is diagnosed using either the Sokolow-Lyon criteria (the sum of the S wave in V₁ and the R wave in V₅ or V₆ ≥ 35 mm) or the Cornell voltage criteria (the S in V₃ plus the R in aVL > 20 mm for women [> 28 mm for men]).

LVH is usually not a target of therapy. Management is typically directed at treating the underlying pathology. For this patient, it is important to manage her hypertension and provide follow-up—including periodic echocardiography of her left atrium, mitral valve, and left ventricle—to determine response to hypertensive therapy.

ANSWER

The correct interpretation includes normal sinus rhythm, possible left atrial enlargement (LAE), and left ventricular hypertrophy (LVH).

Normal sinus rhythm is defined as a P for every QRS and a QRS for every P, with a normal PR interval and a rate > 60 and < 100 beats/min.

Criteria for LAE include a P wave > 120 ms in lead II and/or a biphasic P wave in lead V₁ with a downward deflection > 40 ms in length with a > 1-mm negative deflection. This ECG does not meet criteria for LAE; however, it is suspicious, particularly in the context of mitral regurgitation and LVH.

LVH is diagnosed using either the Sokolow-Lyon criteria (the sum of the S wave in V₁ and the R wave in V₅ or V₆ ≥ 35 mm) or the Cornell voltage criteria (the S in V₃ plus the R in aVL > 20 mm for women [> 28 mm for men]).

LVH is usually not a target of therapy. Management is typically directed at treating the underlying pathology. For this patient, it is important to manage her hypertension and provide follow-up—including periodic echocardiography of her left atrium, mitral valve, and left ventricle—to determine response to hypertensive therapy.

CHICAGO – For colorectal cancer patients with liver metastases, laparoscopic surgery has short-term advantages over open surgery, including fewer complications and better quality of life as compared to open surgery. Now, there are data to show that long-term outcomes with the laparoscopic approach aren’t any worse with the laparoscopic approach.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Åsmund Avdem Fretland, MD, discusses results of the 280-patient randomized OSLO-COMET study, including 5-year survival of 56% for the laparoscopic approach, and similarly, 57% for the open procedure.

Based on lower morbidity, and now similar life expectancy, more centers should be doing laparoscopic procedures for liver metastases, said Dr. Fretland, a surgeon in the department of HPB surgery at Oslo University Hospital.

For now, however, open surgery appears to be the dominant approach. According to a recent survey, just 22% of U.S. patients with colorectal liver metastases have laparoscopic surgery.

More data could help. Dr. Fretland said in the interview that more randomized trials are underway aimed at evaluating the long-term outcomes of laparoscopic versus open procedures.

Dr. Fretland reported honoraria from Olympus Medical Systems.

CHICAGO – For colorectal cancer patients with liver metastases, laparoscopic surgery has short-term advantages over open surgery, including fewer complications and better quality of life as compared to open surgery. Now, there are data to show that long-term outcomes with the laparoscopic approach aren’t any worse with the laparoscopic approach.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Åsmund Avdem Fretland, MD, discusses results of the 280-patient randomized OSLO-COMET study, including 5-year survival of 56% for the laparoscopic approach, and similarly, 57% for the open procedure.

Based on lower morbidity, and now similar life expectancy, more centers should be doing laparoscopic procedures for liver metastases, said Dr. Fretland, a surgeon in the department of HPB surgery at Oslo University Hospital.

For now, however, open surgery appears to be the dominant approach. According to a recent survey, just 22% of U.S. patients with colorectal liver metastases have laparoscopic surgery.

More data could help. Dr. Fretland said in the interview that more randomized trials are underway aimed at evaluating the long-term outcomes of laparoscopic versus open procedures.

Dr. Fretland reported honoraria from Olympus Medical Systems.

CHICAGO – For colorectal cancer patients with liver metastases, laparoscopic surgery has short-term advantages over open surgery, including fewer complications and better quality of life as compared to open surgery. Now, there are data to show that long-term outcomes with the laparoscopic approach aren’t any worse with the laparoscopic approach.

In a video interview at the annual meeting of the American Society of Clinical Oncology, Åsmund Avdem Fretland, MD, discusses results of the 280-patient randomized OSLO-COMET study, including 5-year survival of 56% for the laparoscopic approach, and similarly, 57% for the open procedure.

Based on lower morbidity, and now similar life expectancy, more centers should be doing laparoscopic procedures for liver metastases, said Dr. Fretland, a surgeon in the department of HPB surgery at Oslo University Hospital.

For now, however, open surgery appears to be the dominant approach. According to a recent survey, just 22% of U.S. patients with colorectal liver metastases have laparoscopic surgery.

More data could help. Dr. Fretland said in the interview that more randomized trials are underway aimed at evaluating the long-term outcomes of laparoscopic versus open procedures.

Dr. Fretland reported honoraria from Olympus Medical Systems.

To the Editor:

Solid-organ transplant recipients can develop a range of dermatologic consequences due to chronic immunosuppression, including frequent skin infections and malignancies. Atopic dermatitis (AD) and psoriasis are relatively rare in this population because many immunosuppressive therapies, such as mycophenolate mofetil and tacrolimus, also are used to treat inflammatory dermatoses.¹ In a large renal transplant population, the prevalence of AD was 1.3%.² The pathogenesis of posttransplantation AD is poorly understood, and standard treatment regimens have not been defined. Dupilumab is a novel biologic medication that has demonstrated efficacy in the treatment of AD.³ Reports of dupilumab use for AD management in solid-organ transplant recipients are limited in the literature.

A 29-year-old woman with a history of a heart transplant 4 years prior presented to our dermatology clinic with an itchy rash over the entire body. Since the transplant, she had been on long-term immunosuppression with prednisone, mycophenolate mofetil, and tacrolimus. The rash appeared after she switched from brand-name to generic versions of the medications. Physical examination revealed erythematous scaly plaques on the lateral face, back, chest, arms, and legs covering approximately 10% of the body surface area. The patient’s total serum IgE level was elevated at 711,500 µg/L (reference range, 0–1500 µg/L). Outside biopsies revealed changes consistent with spongiotic dermatitis, and patch testing performed by an outside physician was positive for sensitivity to the preservative bronopol.

The patient was switched back to brand-name tacrolimus, but the rash did not improve. Topical steroids, phototherapy, and omalizumab were ineffective. The itching was primarily managed with desoximetasone spray, mometasone cream, and loratidine. With approval from the patient’s transplant team outside of our hospital system, she was started on dupilumab 300 mg once every 14 days. Complete clearance of the rash was noted within 3 months of treatment. Besides bilateral conjunctivitis, which was treated with ophthalmic prednisolone and moxifloxacin solutions, dupilumab was well tolerated. No issues related to immunosuppressant levels or graft-related issues, including rejection, were reported at 6-, 12-, and 18-month follow-up visits.

Atopic dermatitis is characterized by activation of type 2 immune responses, skin barrier defects, and increased Staphylococcus aureus colonization.⁴ A potential mechanism for the development of AD in transplant recipients relates to their use of tacrolimus for chronic immunosuppression. Tacrolimus increases intestinal permeability and therefore allows greater absorption of allergens. This influx of allergens promotes hypersensitivity reactions, resulting in elevated IgE levels and eosinophilia. Tacrolimus also facilitates predominance of helper T cells (T_H2 cytokines) through selective inhibition of the T_H1 cytokine IL-2.⁵

Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of T_H2-mediated inflammation. In addition to downregulation of inflammatory mediators, dupilumab also increases production of epidermal barrier proteins, resulting in skin repair. It has demonstrated rapid, dose-dependent efficacy in patients with moderate to severe AD.⁶ Dupilumab boasts a good safety profile with no increase in risk for skin infections compared to placebo⁶; however, its safety has not yet been verified in transplant recipients.

Our case is notable for the severity of the patient’s AD despite considerable immunosuppression with transplant medications. Development of AD was associated with a switch from brand-name to generic drugs, which is not commonly reported. Her condition was refractory to a litany of treatments prior to a trial of dupilumab. The rapid clearance observed with this novel biologic medication highlights its potential to provide relief to patients who have particularly tenacious cases of AD. Prior to starting dupilumab, we do recommend more extensive laboratory testing in immunosuppressed patients including transplant recipients and patients with human immunodeficiency virus. We illustrate that a history of solid-organ transplant need not exclude patients from consideration for dupilumab therapy.

To the Editor:

Solid-organ transplant recipients can develop a range of dermatologic consequences due to chronic immunosuppression, including frequent skin infections and malignancies. Atopic dermatitis (AD) and psoriasis are relatively rare in this population because many immunosuppressive therapies, such as mycophenolate mofetil and tacrolimus, also are used to treat inflammatory dermatoses.¹ In a large renal transplant population, the prevalence of AD was 1.3%.² The pathogenesis of posttransplantation AD is poorly understood, and standard treatment regimens have not been defined. Dupilumab is a novel biologic medication that has demonstrated efficacy in the treatment of AD.³ Reports of dupilumab use for AD management in solid-organ transplant recipients are limited in the literature.

A 29-year-old woman with a history of a heart transplant 4 years prior presented to our dermatology clinic with an itchy rash over the entire body. Since the transplant, she had been on long-term immunosuppression with prednisone, mycophenolate mofetil, and tacrolimus. The rash appeared after she switched from brand-name to generic versions of the medications. Physical examination revealed erythematous scaly plaques on the lateral face, back, chest, arms, and legs covering approximately 10% of the body surface area. The patient’s total serum IgE level was elevated at 711,500 µg/L (reference range, 0–1500 µg/L). Outside biopsies revealed changes consistent with spongiotic dermatitis, and patch testing performed by an outside physician was positive for sensitivity to the preservative bronopol.

The patient was switched back to brand-name tacrolimus, but the rash did not improve. Topical steroids, phototherapy, and omalizumab were ineffective. The itching was primarily managed with desoximetasone spray, mometasone cream, and loratidine. With approval from the patient’s transplant team outside of our hospital system, she was started on dupilumab 300 mg once every 14 days. Complete clearance of the rash was noted within 3 months of treatment. Besides bilateral conjunctivitis, which was treated with ophthalmic prednisolone and moxifloxacin solutions, dupilumab was well tolerated. No issues related to immunosuppressant levels or graft-related issues, including rejection, were reported at 6-, 12-, and 18-month follow-up visits.

Atopic dermatitis is characterized by activation of type 2 immune responses, skin barrier defects, and increased Staphylococcus aureus colonization.⁴ A potential mechanism for the development of AD in transplant recipients relates to their use of tacrolimus for chronic immunosuppression. Tacrolimus increases intestinal permeability and therefore allows greater absorption of allergens. This influx of allergens promotes hypersensitivity reactions, resulting in elevated IgE levels and eosinophilia. Tacrolimus also facilitates predominance of helper T cells (T_H2 cytokines) through selective inhibition of the T_H1 cytokine IL-2.⁵

Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of T_H2-mediated inflammation. In addition to downregulation of inflammatory mediators, dupilumab also increases production of epidermal barrier proteins, resulting in skin repair. It has demonstrated rapid, dose-dependent efficacy in patients with moderate to severe AD.⁶ Dupilumab boasts a good safety profile with no increase in risk for skin infections compared to placebo⁶; however, its safety has not yet been verified in transplant recipients.

Our case is notable for the severity of the patient’s AD despite considerable immunosuppression with transplant medications. Development of AD was associated with a switch from brand-name to generic drugs, which is not commonly reported. Her condition was refractory to a litany of treatments prior to a trial of dupilumab. The rapid clearance observed with this novel biologic medication highlights its potential to provide relief to patients who have particularly tenacious cases of AD. Prior to starting dupilumab, we do recommend more extensive laboratory testing in immunosuppressed patients including transplant recipients and patients with human immunodeficiency virus. We illustrate that a history of solid-organ transplant need not exclude patients from consideration for dupilumab therapy.

To the Editor:

Solid-organ transplant recipients can develop a range of dermatologic consequences due to chronic immunosuppression, including frequent skin infections and malignancies. Atopic dermatitis (AD) and psoriasis are relatively rare in this population because many immunosuppressive therapies, such as mycophenolate mofetil and tacrolimus, also are used to treat inflammatory dermatoses.¹ In a large renal transplant population, the prevalence of AD was 1.3%.² The pathogenesis of posttransplantation AD is poorly understood, and standard treatment regimens have not been defined. Dupilumab is a novel biologic medication that has demonstrated efficacy in the treatment of AD.³ Reports of dupilumab use for AD management in solid-organ transplant recipients are limited in the literature.

A 29-year-old woman with a history of a heart transplant 4 years prior presented to our dermatology clinic with an itchy rash over the entire body. Since the transplant, she had been on long-term immunosuppression with prednisone, mycophenolate mofetil, and tacrolimus. The rash appeared after she switched from brand-name to generic versions of the medications. Physical examination revealed erythematous scaly plaques on the lateral face, back, chest, arms, and legs covering approximately 10% of the body surface area. The patient’s total serum IgE level was elevated at 711,500 µg/L (reference range, 0–1500 µg/L). Outside biopsies revealed changes consistent with spongiotic dermatitis, and patch testing performed by an outside physician was positive for sensitivity to the preservative bronopol.

The patient was switched back to brand-name tacrolimus, but the rash did not improve. Topical steroids, phototherapy, and omalizumab were ineffective. The itching was primarily managed with desoximetasone spray, mometasone cream, and loratidine. With approval from the patient’s transplant team outside of our hospital system, she was started on dupilumab 300 mg once every 14 days. Complete clearance of the rash was noted within 3 months of treatment. Besides bilateral conjunctivitis, which was treated with ophthalmic prednisolone and moxifloxacin solutions, dupilumab was well tolerated. No issues related to immunosuppressant levels or graft-related issues, including rejection, were reported at 6-, 12-, and 18-month follow-up visits.

Atopic dermatitis is characterized by activation of type 2 immune responses, skin barrier defects, and increased Staphylococcus aureus colonization.⁴ A potential mechanism for the development of AD in transplant recipients relates to their use of tacrolimus for chronic immunosuppression. Tacrolimus increases intestinal permeability and therefore allows greater absorption of allergens. This influx of allergens promotes hypersensitivity reactions, resulting in elevated IgE levels and eosinophilia. Tacrolimus also facilitates predominance of helper T cells (T_H2 cytokines) through selective inhibition of the T_H1 cytokine IL-2.⁵

Dupilumab is a human monoclonal antibody that blocks IL-4 and IL-13, which are key drivers of T_H2-mediated inflammation. In addition to downregulation of inflammatory mediators, dupilumab also increases production of epidermal barrier proteins, resulting in skin repair. It has demonstrated rapid, dose-dependent efficacy in patients with moderate to severe AD.⁶ Dupilumab boasts a good safety profile with no increase in risk for skin infections compared to placebo⁶; however, its safety has not yet been verified in transplant recipients.

Our case is notable for the severity of the patient’s AD despite considerable immunosuppression with transplant medications. Development of AD was associated with a switch from brand-name to generic drugs, which is not commonly reported. Her condition was refractory to a litany of treatments prior to a trial of dupilumab. The rapid clearance observed with this novel biologic medication highlights its potential to provide relief to patients who have particularly tenacious cases of AD. Prior to starting dupilumab, we do recommend more extensive laboratory testing in immunosuppressed patients including transplant recipients and patients with human immunodeficiency virus. We illustrate that a history of solid-organ transplant need not exclude patients from consideration for dupilumab therapy.

SAN DIEGO – Coffee, tea, and soda consumption are all associated with increased risk for gastroesophageal reflux disease (GERD), according to a new prospective cohort study presented at the annual Digestive Disease Week.

In an interview following the oral presentation, Raaj S. Mehta, MD, said that patients in his primary care panel at Massachusetts General Hospital, Boston, where he’s a senior resident, frequently came to him with GERD. In addition to questions about diet, patients frequently wanted to know which beverages might provoke or exacerbate their GERD.

Vidyard Video

In trying to help his patients, Dr. Mehta said he realized that there wasn’t a prospective evidence base to answer their questions about beverages and GERD, so he and his colleagues used data from the Nurses’ Health Study II (NHS II), a prospective cohort study, to look at the association between various beverages and the incidence of GERD.

“What’s exciting is that we were able to find that coffee, tea, and soda – all three – increase your risk for gastroesophageal reflux disease,” Dr. Mehta said in a video interview. “At the highest quintile level, so looking at people who consume six or more cups per day, you’re looking at maybe a 25%-35% increase in risk of reflux disease.”

There was a dose-response relationship as well: “You do see a slight increase as you go from one cup, to two, to three, and so on, all the way up to six cups” of the offending beverages, said Dr. Mehta.

Overall, the risk for GERD rose from 1.17 to 1.34 with coffee consumption as servings per day increased from less than one to six or more (P for trend less than .0001). Tea consumption was associated with increased GERD risk ranging from 1.08 to 1.26 as consumption rose (P for trend .001). For soda, the increased risk went from 1.12 at less than one serving daily, to 1.41 at four to five servings daily, and then fell to 1.29 at six or more daily servings (P for trend less than .0001).

Whether the beverages were caffeinated or not, said Dr. Mehta, only made a “minimal difference” in GERD risk.

“In contrast, we didn’t see an association for beverages like water, juice, and milk,” he said – reassuring findings in light of fruit juice’s anecdotal status as a GERD culprit.

The NHS II collected data every 2 years from 48,308 female nurses aged 42-62 years at the beginning of the study. Every 4 years dietary information was collected, and on the opposite 4-year cycle, participants answered questions about GERD. Medication use, including the incident use of proton pump inhibitors, was collected every 2 years.

Patients with baseline GERD or use of PPIs or H₂ receptor antagonists were excluded from participation.

The quantity and type of beverages were assessed by food frequency questionnaires; other demographic, dietary, and medication variables were also gathered and used to adjust the statistical analysis.

A substitution analysis answered the “what-if” question of the effect of substituting two glasses of plain water daily for either coffee, tea, or soda. Dr. Mehta and colleagues saw a modest reduction in risk for GERD with this strategy.

In addition to the prospective nature of the study (abstract 514, doi: 10.1016/S0016-5085(19)37044-1), the large sample size, high follow-up rates, and well validated dietary data were all strengths, said Dr. Mehta. However, the study’s population is relatively homogeneous, and residual confounding couldn’t be excluded. Also, GERD was defined by self-report, though participants were asked to respond to clear, validated criteria.

For Dr. Mehta, he’s glad to have a clear answer to a common clinic question. “I think that this is one additional thing that I can recommend as a primary care provider to my patients when they come into my office,” he said.

Dr. Mehta reported no conflicts of interest.

Encourage your patients to visit the AGA GI Patient Center for education by specialists for patients about GERD symptoms and treatments at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.

[email protected]

SAN DIEGO – Coffee, tea, and soda consumption are all associated with increased risk for gastroesophageal reflux disease (GERD), according to a new prospective cohort study presented at the annual Digestive Disease Week.

In an interview following the oral presentation, Raaj S. Mehta, MD, said that patients in his primary care panel at Massachusetts General Hospital, Boston, where he’s a senior resident, frequently came to him with GERD. In addition to questions about diet, patients frequently wanted to know which beverages might provoke or exacerbate their GERD.

Vidyard Video

In trying to help his patients, Dr. Mehta said he realized that there wasn’t a prospective evidence base to answer their questions about beverages and GERD, so he and his colleagues used data from the Nurses’ Health Study II (NHS II), a prospective cohort study, to look at the association between various beverages and the incidence of GERD.

“What’s exciting is that we were able to find that coffee, tea, and soda – all three – increase your risk for gastroesophageal reflux disease,” Dr. Mehta said in a video interview. “At the highest quintile level, so looking at people who consume six or more cups per day, you’re looking at maybe a 25%-35% increase in risk of reflux disease.”

There was a dose-response relationship as well: “You do see a slight increase as you go from one cup, to two, to three, and so on, all the way up to six cups” of the offending beverages, said Dr. Mehta.

Overall, the risk for GERD rose from 1.17 to 1.34 with coffee consumption as servings per day increased from less than one to six or more (P for trend less than .0001). Tea consumption was associated with increased GERD risk ranging from 1.08 to 1.26 as consumption rose (P for trend .001). For soda, the increased risk went from 1.12 at less than one serving daily, to 1.41 at four to five servings daily, and then fell to 1.29 at six or more daily servings (P for trend less than .0001).

Whether the beverages were caffeinated or not, said Dr. Mehta, only made a “minimal difference” in GERD risk.

“In contrast, we didn’t see an association for beverages like water, juice, and milk,” he said – reassuring findings in light of fruit juice’s anecdotal status as a GERD culprit.

The NHS II collected data every 2 years from 48,308 female nurses aged 42-62 years at the beginning of the study. Every 4 years dietary information was collected, and on the opposite 4-year cycle, participants answered questions about GERD. Medication use, including the incident use of proton pump inhibitors, was collected every 2 years.

Patients with baseline GERD or use of PPIs or H₂ receptor antagonists were excluded from participation.

The quantity and type of beverages were assessed by food frequency questionnaires; other demographic, dietary, and medication variables were also gathered and used to adjust the statistical analysis.

A substitution analysis answered the “what-if” question of the effect of substituting two glasses of plain water daily for either coffee, tea, or soda. Dr. Mehta and colleagues saw a modest reduction in risk for GERD with this strategy.

In addition to the prospective nature of the study (abstract 514, doi: 10.1016/S0016-5085(19)37044-1), the large sample size, high follow-up rates, and well validated dietary data were all strengths, said Dr. Mehta. However, the study’s population is relatively homogeneous, and residual confounding couldn’t be excluded. Also, GERD was defined by self-report, though participants were asked to respond to clear, validated criteria.

For Dr. Mehta, he’s glad to have a clear answer to a common clinic question. “I think that this is one additional thing that I can recommend as a primary care provider to my patients when they come into my office,” he said.

Dr. Mehta reported no conflicts of interest.

Encourage your patients to visit the AGA GI Patient Center for education by specialists for patients about GERD symptoms and treatments at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.

[email protected]

SAN DIEGO – Coffee, tea, and soda consumption are all associated with increased risk for gastroesophageal reflux disease (GERD), according to a new prospective cohort study presented at the annual Digestive Disease Week.

In an interview following the oral presentation, Raaj S. Mehta, MD, said that patients in his primary care panel at Massachusetts General Hospital, Boston, where he’s a senior resident, frequently came to him with GERD. In addition to questions about diet, patients frequently wanted to know which beverages might provoke or exacerbate their GERD.

Vidyard Video

In trying to help his patients, Dr. Mehta said he realized that there wasn’t a prospective evidence base to answer their questions about beverages and GERD, so he and his colleagues used data from the Nurses’ Health Study II (NHS II), a prospective cohort study, to look at the association between various beverages and the incidence of GERD.

“What’s exciting is that we were able to find that coffee, tea, and soda – all three – increase your risk for gastroesophageal reflux disease,” Dr. Mehta said in a video interview. “At the highest quintile level, so looking at people who consume six or more cups per day, you’re looking at maybe a 25%-35% increase in risk of reflux disease.”

There was a dose-response relationship as well: “You do see a slight increase as you go from one cup, to two, to three, and so on, all the way up to six cups” of the offending beverages, said Dr. Mehta.

Overall, the risk for GERD rose from 1.17 to 1.34 with coffee consumption as servings per day increased from less than one to six or more (P for trend less than .0001). Tea consumption was associated with increased GERD risk ranging from 1.08 to 1.26 as consumption rose (P for trend .001). For soda, the increased risk went from 1.12 at less than one serving daily, to 1.41 at four to five servings daily, and then fell to 1.29 at six or more daily servings (P for trend less than .0001).

Whether the beverages were caffeinated or not, said Dr. Mehta, only made a “minimal difference” in GERD risk.

“In contrast, we didn’t see an association for beverages like water, juice, and milk,” he said – reassuring findings in light of fruit juice’s anecdotal status as a GERD culprit.

The NHS II collected data every 2 years from 48,308 female nurses aged 42-62 years at the beginning of the study. Every 4 years dietary information was collected, and on the opposite 4-year cycle, participants answered questions about GERD. Medication use, including the incident use of proton pump inhibitors, was collected every 2 years.

Patients with baseline GERD or use of PPIs or H₂ receptor antagonists were excluded from participation.

The quantity and type of beverages were assessed by food frequency questionnaires; other demographic, dietary, and medication variables were also gathered and used to adjust the statistical analysis.

A substitution analysis answered the “what-if” question of the effect of substituting two glasses of plain water daily for either coffee, tea, or soda. Dr. Mehta and colleagues saw a modest reduction in risk for GERD with this strategy.

In addition to the prospective nature of the study (abstract 514, doi: 10.1016/S0016-5085(19)37044-1), the large sample size, high follow-up rates, and well validated dietary data were all strengths, said Dr. Mehta. However, the study’s population is relatively homogeneous, and residual confounding couldn’t be excluded. Also, GERD was defined by self-report, though participants were asked to respond to clear, validated criteria.

For Dr. Mehta, he’s glad to have a clear answer to a common clinic question. “I think that this is one additional thing that I can recommend as a primary care provider to my patients when they come into my office,” he said.

Dr. Mehta reported no conflicts of interest.

Encourage your patients to visit the AGA GI Patient Center for education by specialists for patients about GERD symptoms and treatments at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroesophageal-reflux-disease-gerd.

[email protected]

Physician burnout costs the U.S. health care system approximately $4.6 billion a year in physician turnover and reduced productivity, according to the results of a cost-consequence analysis.

In 2015, the burnout-attributable cost per physician was $7,600 – an estimate occupying the conservative middle ground between the $3,700 and $11,000 extremes produced by the study’s mathematical model.

“Traditionally, the case for ameliorating physician burnout has been made primarily on ethical grounds.” This study, believed to be the first to look at the system-wide costs of burnout, “provides tools to evaluate the economic dimension of this problem,” wrote Shasha Han, MS, of the National University of Singapore and her associates in Annals of Internal Medicine.

Individual burnout-attributable costs were higher for physicians in the younger age group (less than 55 years) in all three specialty categories: $7,100 versus $5,900 for those aged at least 55 years among primary care physicians, $10,800 versus $9,100 for surgical specialists, and $7,800 versus $6,100 for other specialists, the investigators reported.

The mathematical model used in the study focused on two productivity metrics related to burnout – cost associated with physician replacement and lost income from unfilled physician positions. “Estimated turnover costs were generally higher than costs of reduced productivity across all” the various segments of age and specialty, Ms. Han and associates wrote.

“Burnout is a problem that extends beyond physicians to nurses and other health care staff. Future work holistically investigating the costs associated with burnout in health care organizations would be valuable. Studies focusing on differences in burnout-attributable costs across provider segments other than the ones investigated in this study, including academic versus private settings, or across a finer segmentation of physician specialties also might be fruitful,” they wrote.

One investigator has received grants from the American Medical Association Accelerating Change in Medical Education Consortium, the Physicians Foundation, and the National Institutes of Health. Another received a startup grant from the National University of Singapore. Ms. Han said that she had no financial conflicts to disclose. All of the investigators’ disclosures are available online.

Learn practical tips to avoid physician burnout presented during an AGA symposium at DDW® at https://www.ddwnews.org/news/aga-symposium-provides-practical-tips-to-avoid-physician-burnout/.

[email protected]

SOURCE: Han S et al. Ann Intern Med. 2019 May 28. doi: 10.7326/M18-1422.

Physician burnout costs the U.S. health care system approximately $4.6 billion a year in physician turnover and reduced productivity, according to the results of a cost-consequence analysis.

In 2015, the burnout-attributable cost per physician was $7,600 – an estimate occupying the conservative middle ground between the $3,700 and $11,000 extremes produced by the study’s mathematical model.

“Traditionally, the case for ameliorating physician burnout has been made primarily on ethical grounds.” This study, believed to be the first to look at the system-wide costs of burnout, “provides tools to evaluate the economic dimension of this problem,” wrote Shasha Han, MS, of the National University of Singapore and her associates in Annals of Internal Medicine.

Individual burnout-attributable costs were higher for physicians in the younger age group (less than 55 years) in all three specialty categories: $7,100 versus $5,900 for those aged at least 55 years among primary care physicians, $10,800 versus $9,100 for surgical specialists, and $7,800 versus $6,100 for other specialists, the investigators reported.

The mathematical model used in the study focused on two productivity metrics related to burnout – cost associated with physician replacement and lost income from unfilled physician positions. “Estimated turnover costs were generally higher than costs of reduced productivity across all” the various segments of age and specialty, Ms. Han and associates wrote.

“Burnout is a problem that extends beyond physicians to nurses and other health care staff. Future work holistically investigating the costs associated with burnout in health care organizations would be valuable. Studies focusing on differences in burnout-attributable costs across provider segments other than the ones investigated in this study, including academic versus private settings, or across a finer segmentation of physician specialties also might be fruitful,” they wrote.

One investigator has received grants from the American Medical Association Accelerating Change in Medical Education Consortium, the Physicians Foundation, and the National Institutes of Health. Another received a startup grant from the National University of Singapore. Ms. Han said that she had no financial conflicts to disclose. All of the investigators’ disclosures are available online.

Learn practical tips to avoid physician burnout presented during an AGA symposium at DDW® at https://www.ddwnews.org/news/aga-symposium-provides-practical-tips-to-avoid-physician-burnout/.

[email protected]

SOURCE: Han S et al. Ann Intern Med. 2019 May 28. doi: 10.7326/M18-1422.

Physician burnout costs the U.S. health care system approximately $4.6 billion a year in physician turnover and reduced productivity, according to the results of a cost-consequence analysis.

In 2015, the burnout-attributable cost per physician was $7,600 – an estimate occupying the conservative middle ground between the $3,700 and $11,000 extremes produced by the study’s mathematical model.

“Traditionally, the case for ameliorating physician burnout has been made primarily on ethical grounds.” This study, believed to be the first to look at the system-wide costs of burnout, “provides tools to evaluate the economic dimension of this problem,” wrote Shasha Han, MS, of the National University of Singapore and her associates in Annals of Internal Medicine.

Individual burnout-attributable costs were higher for physicians in the younger age group (less than 55 years) in all three specialty categories: $7,100 versus $5,900 for those aged at least 55 years among primary care physicians, $10,800 versus $9,100 for surgical specialists, and $7,800 versus $6,100 for other specialists, the investigators reported.

The mathematical model used in the study focused on two productivity metrics related to burnout – cost associated with physician replacement and lost income from unfilled physician positions. “Estimated turnover costs were generally higher than costs of reduced productivity across all” the various segments of age and specialty, Ms. Han and associates wrote.

“Burnout is a problem that extends beyond physicians to nurses and other health care staff. Future work holistically investigating the costs associated with burnout in health care organizations would be valuable. Studies focusing on differences in burnout-attributable costs across provider segments other than the ones investigated in this study, including academic versus private settings, or across a finer segmentation of physician specialties also might be fruitful,” they wrote.

One investigator has received grants from the American Medical Association Accelerating Change in Medical Education Consortium, the Physicians Foundation, and the National Institutes of Health. Another received a startup grant from the National University of Singapore. Ms. Han said that she had no financial conflicts to disclose. All of the investigators’ disclosures are available online.

Learn practical tips to avoid physician burnout presented during an AGA symposium at DDW® at https://www.ddwnews.org/news/aga-symposium-provides-practical-tips-to-avoid-physician-burnout/.

[email protected]

SOURCE: Han S et al. Ann Intern Med. 2019 May 28. doi: 10.7326/M18-1422.

CHICAGO – Despite reducing risk of death by 22% versus placebo and improving progression-free survival, pembrolizumab did not meet prespecified criteria for significance of these efficacy end points in a phase 3 study in advanced hepatocellular carcinoma, an investigator reported.

The magnitude of benefit seen with pembrolizumab was nevertheless on par with results of the study that led to accelerated approval of the PD-1 inhibitor for hepatocellular carcinoma, Richard S. Finn, MD, of the University of California, Los Angeles, said at the annual meeting of the American Society of Clinical Oncology.

“These data support that the risk-benefit balance for pembrolizumab is favorable in the second line setting in hepatocellular carcinoma,” he said in an oral presentation on the phase 3 KEYNOTE-240 study.

Pembrolizumab did demonstrate “strong trends” in survival and other clinical characteristics in KEYNOTE-240, including response rate, duration of response, and a “very favorable” toxicity profile, said William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“I plan to continue to prescribe PD-1 inhibitors in the second-line setting, especially for those patients who show relative intolerance to tyrosine kinase inhibitors,” Dr. Harris said in a podium discussion of the results.

The Food and Drug Administration granted accelerated approval to the PD-1 inhibitor nivolumab in September 2017, and to pembrolizumab in November 2018, for treatment of patients with hepatocellular carcinoma who previously received sorafenib.

The accelerated approval of pembrolizumab was based on KEYNOTE-224, a single-arm, multicenter trial enrolling 104 patients with Child-Pugh Class A liver impairment who had disease progression on or after sorafenib, or were intolerant to sorafenib. Overall response rate in the study was 17%, with response durations ranging from 3.1 to 16.7 months.

The phase 3 KEYNOTE-240 study was designed to confirm the efficacy and safety of pembrolizumab in patients with hepatocellular carcinoma, Dr. Finn said. The study comprised 413 patients with Child Pugh class A, Barcelona Clinic Liver Cancer stage B/C disease who had previously received sorafenib. They were randomized 2:1 to pembrolizumab or placebo in addition to best supportive care for up to 35 cycles, or approximately 2 years of treatment.

Median overall survival was 13.9 months for the PD-1 inhibitor and 10.6 months for placebo, but the P value (.0238) did not meet a prespecified threshold of 0.0174 required to demonstrate statistical significance, according to Dr. Finn. Median progression-free survival was 3.0 months for pembrolizumab and 2.8 months for placebo, with a P value of .0186 that did not meet a prespecified value of .002.

The objective response rate was 18.3% and 4.4% for pembrolizumab and placebo, respectively (P = .00007), Dr. Finn reported. Duration of response was a median of 13.8 months for pembrolizumab, ranging from 1.5+ months to 23.6+ months, while for placebo, median duration of response was not yet reached, with a range of 2.8 to 20.4+ months, according to his report.

Rates of adverse events were similar between arms, according to Dr. Finn. While rates of grade 3-4 adverse events were higher in the pembrolizumab arm, those leading to treatment discontinuation were relatively low, he added.

About 10% of patients in the placebo arm subsequently received treatment with PD-1 or PD-L1 inhibitors, in an analysis that was prespecified in anticipation of new drugs that might be approved, according to Dr. Finn.

Ongoing now is KEYNOTE-394, another phase 3 study of pembrolizumab in previously treated, advanced hepatocellular carcinoma ongoing in the Asia Pacific region, Dr. Finn said.

Results of that phase 3 investigation could have important implications for the FDA’s subsequent analyses of pembrolizumab in this setting, according to Dr. Harris, the abstract discussant.

“I would recommend that they consider continued approval until they see results of the KEYNOTE-394 study, and take those results in sum,” he said in his presentation.

Dr. Finn reported disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, Lilly, Merck, Novartis, and Pfizer.

SOURCE: Finn RS, et al. ASCO 2019. Abstract 4004.

CHICAGO – Despite reducing risk of death by 22% versus placebo and improving progression-free survival, pembrolizumab did not meet prespecified criteria for significance of these efficacy end points in a phase 3 study in advanced hepatocellular carcinoma, an investigator reported.

The magnitude of benefit seen with pembrolizumab was nevertheless on par with results of the study that led to accelerated approval of the PD-1 inhibitor for hepatocellular carcinoma, Richard S. Finn, MD, of the University of California, Los Angeles, said at the annual meeting of the American Society of Clinical Oncology.

“These data support that the risk-benefit balance for pembrolizumab is favorable in the second line setting in hepatocellular carcinoma,” he said in an oral presentation on the phase 3 KEYNOTE-240 study.

Pembrolizumab did demonstrate “strong trends” in survival and other clinical characteristics in KEYNOTE-240, including response rate, duration of response, and a “very favorable” toxicity profile, said William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“I plan to continue to prescribe PD-1 inhibitors in the second-line setting, especially for those patients who show relative intolerance to tyrosine kinase inhibitors,” Dr. Harris said in a podium discussion of the results.

The Food and Drug Administration granted accelerated approval to the PD-1 inhibitor nivolumab in September 2017, and to pembrolizumab in November 2018, for treatment of patients with hepatocellular carcinoma who previously received sorafenib.

The accelerated approval of pembrolizumab was based on KEYNOTE-224, a single-arm, multicenter trial enrolling 104 patients with Child-Pugh Class A liver impairment who had disease progression on or after sorafenib, or were intolerant to sorafenib. Overall response rate in the study was 17%, with response durations ranging from 3.1 to 16.7 months.

The phase 3 KEYNOTE-240 study was designed to confirm the efficacy and safety of pembrolizumab in patients with hepatocellular carcinoma, Dr. Finn said. The study comprised 413 patients with Child Pugh class A, Barcelona Clinic Liver Cancer stage B/C disease who had previously received sorafenib. They were randomized 2:1 to pembrolizumab or placebo in addition to best supportive care for up to 35 cycles, or approximately 2 years of treatment.

Median overall survival was 13.9 months for the PD-1 inhibitor and 10.6 months for placebo, but the P value (.0238) did not meet a prespecified threshold of 0.0174 required to demonstrate statistical significance, according to Dr. Finn. Median progression-free survival was 3.0 months for pembrolizumab and 2.8 months for placebo, with a P value of .0186 that did not meet a prespecified value of .002.

The objective response rate was 18.3% and 4.4% for pembrolizumab and placebo, respectively (P = .00007), Dr. Finn reported. Duration of response was a median of 13.8 months for pembrolizumab, ranging from 1.5+ months to 23.6+ months, while for placebo, median duration of response was not yet reached, with a range of 2.8 to 20.4+ months, according to his report.

Rates of adverse events were similar between arms, according to Dr. Finn. While rates of grade 3-4 adverse events were higher in the pembrolizumab arm, those leading to treatment discontinuation were relatively low, he added.

About 10% of patients in the placebo arm subsequently received treatment with PD-1 or PD-L1 inhibitors, in an analysis that was prespecified in anticipation of new drugs that might be approved, according to Dr. Finn.

Ongoing now is KEYNOTE-394, another phase 3 study of pembrolizumab in previously treated, advanced hepatocellular carcinoma ongoing in the Asia Pacific region, Dr. Finn said.

Results of that phase 3 investigation could have important implications for the FDA’s subsequent analyses of pembrolizumab in this setting, according to Dr. Harris, the abstract discussant.

“I would recommend that they consider continued approval until they see results of the KEYNOTE-394 study, and take those results in sum,” he said in his presentation.

Dr. Finn reported disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, Lilly, Merck, Novartis, and Pfizer.

SOURCE: Finn RS, et al. ASCO 2019. Abstract 4004.

CHICAGO – Despite reducing risk of death by 22% versus placebo and improving progression-free survival, pembrolizumab did not meet prespecified criteria for significance of these efficacy end points in a phase 3 study in advanced hepatocellular carcinoma, an investigator reported.

The magnitude of benefit seen with pembrolizumab was nevertheless on par with results of the study that led to accelerated approval of the PD-1 inhibitor for hepatocellular carcinoma, Richard S. Finn, MD, of the University of California, Los Angeles, said at the annual meeting of the American Society of Clinical Oncology.

“These data support that the risk-benefit balance for pembrolizumab is favorable in the second line setting in hepatocellular carcinoma,” he said in an oral presentation on the phase 3 KEYNOTE-240 study.

Pembrolizumab did demonstrate “strong trends” in survival and other clinical characteristics in KEYNOTE-240, including response rate, duration of response, and a “very favorable” toxicity profile, said William P. Harris, MD, of the University of Washington and Fred Hutchinson Cancer Research Center, Seattle.

“I plan to continue to prescribe PD-1 inhibitors in the second-line setting, especially for those patients who show relative intolerance to tyrosine kinase inhibitors,” Dr. Harris said in a podium discussion of the results.

The Food and Drug Administration granted accelerated approval to the PD-1 inhibitor nivolumab in September 2017, and to pembrolizumab in November 2018, for treatment of patients with hepatocellular carcinoma who previously received sorafenib.

The accelerated approval of pembrolizumab was based on KEYNOTE-224, a single-arm, multicenter trial enrolling 104 patients with Child-Pugh Class A liver impairment who had disease progression on or after sorafenib, or were intolerant to sorafenib. Overall response rate in the study was 17%, with response durations ranging from 3.1 to 16.7 months.

The phase 3 KEYNOTE-240 study was designed to confirm the efficacy and safety of pembrolizumab in patients with hepatocellular carcinoma, Dr. Finn said. The study comprised 413 patients with Child Pugh class A, Barcelona Clinic Liver Cancer stage B/C disease who had previously received sorafenib. They were randomized 2:1 to pembrolizumab or placebo in addition to best supportive care for up to 35 cycles, or approximately 2 years of treatment.

Median overall survival was 13.9 months for the PD-1 inhibitor and 10.6 months for placebo, but the P value (.0238) did not meet a prespecified threshold of 0.0174 required to demonstrate statistical significance, according to Dr. Finn. Median progression-free survival was 3.0 months for pembrolizumab and 2.8 months for placebo, with a P value of .0186 that did not meet a prespecified value of .002.

The objective response rate was 18.3% and 4.4% for pembrolizumab and placebo, respectively (P = .00007), Dr. Finn reported. Duration of response was a median of 13.8 months for pembrolizumab, ranging from 1.5+ months to 23.6+ months, while for placebo, median duration of response was not yet reached, with a range of 2.8 to 20.4+ months, according to his report.

Rates of adverse events were similar between arms, according to Dr. Finn. While rates of grade 3-4 adverse events were higher in the pembrolizumab arm, those leading to treatment discontinuation were relatively low, he added.

About 10% of patients in the placebo arm subsequently received treatment with PD-1 or PD-L1 inhibitors, in an analysis that was prespecified in anticipation of new drugs that might be approved, according to Dr. Finn.

Ongoing now is KEYNOTE-394, another phase 3 study of pembrolizumab in previously treated, advanced hepatocellular carcinoma ongoing in the Asia Pacific region, Dr. Finn said.

Results of that phase 3 investigation could have important implications for the FDA’s subsequent analyses of pembrolizumab in this setting, according to Dr. Harris, the abstract discussant.

“I would recommend that they consider continued approval until they see results of the KEYNOTE-394 study, and take those results in sum,” he said in his presentation.

Dr. Finn reported disclosures related to AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Exelixis, Genentech/Roche, Lilly, Merck, Novartis, and Pfizer.

SOURCE: Finn RS, et al. ASCO 2019. Abstract 4004.

Providing consistent and high-quality services to gender diverse patients is a top priority for health care systems, including the Veterans Health Administration (VHA).¹ Over the past decade, awareness of transgender and gender nonconforming (TGNC) people in the US has increased. Gender identity refers to a person’s inner sense of where that person belongs on a continuum of masculine to androgynous to feminine traits. This identity range can additionally include nonbinary identifications, such as “gender fluid” or “genderqueer.” A goal of patient-centered care is for health care providers (HCPs) to refer to TGNC individuals, like their cisgender counterparts, according to their gender identity. Gender identity for TGNC individuals may be different from their birth sex. Birth sex, commonly referred to as “sex assigned at birth,” is the biologic and physiologic characteristics that are reflected on a person’s original birth certificate and described as male or female.

Background

In the electronic health record (EHR), birth sex is an important, structured variable that is used to facilitate effective patient care that is efficient, equitable, and patient-centered. Birth sex in an EHR often is used to cue automatic timely generation of health screens (eg, pap smears, prostate exams) and calculation of medication dosages and laboratory test ranges by adjusting for a person’s typical hormonal history and anatomy.

Gender identity fields are independently helpful to include in the EHR, because clinicians can use this information to ensure proper pronoun use and avoid misgendering a patient. Additionally, the gender identity field informs HCPs who may conduct more frequent or different health screenings to evaluate specific health risks that are more prevalent in gender minority (ie, lesbian, gay, bisexual) patients.^2,3

EHRs rely on structured data elements to standardize data about patients for clinical care, quality improvement, data sharing, and patient safety.^4,5 However, health care organizations are grappling with how to incorporate gender identity and birth sex information into EHRs.³ A 2011 Veterans Health Administration (VHA) directive required staff and providers to address and provide care to veterans based on their gender identity. Like other health systems, VHA had 1 demographic data field in the EHR to indicate birth sex, with no field for gender identity. A HCP could enter gender identity information into a progress note, but this addition might not be noticed by other HCPs. Consequently, staff and providers had no effective way of knowing a veteran’s gender identity from the EHR, which contributed to misgendering TGNC veterans.

With the singular demographic field of sex representing both birth sex and gender identity, some TGNC veterans chose to change their birth sex information to align with their gender identity. This change assured TGNC veterans that staff and providers would not misgender them because the birth sex field is easily observed and would allow providers to use respectful, gender-consistent pronouns when speaking with them. However, changing the birth sex field can misalign natal sex–based clinical reminders, medication dosages, and laboratory test values, which created potential patient safety risks. Thus, birth sex created potential hazards to quality and safety when used as a marker even with other variables—such as current anatomy, height, and weight—for health screenings, medication dosing, and other medical decisions.

In this article, we: (1) outline several patient safety issues that can arise with the birth sex field serving as an indicator for both birth sex and gender identity; (2) present case examples that illustrate the benefits of self-identified gender identity (SIGI) in an EHR; (3) describe the process of work-group development of patient-provider communication tools to improve patient safety; and (4) provide a brief overview of resources rolled out as a part of SIGI. This report serves as a guide for other federal organizations that wish to increase affirmative care and safe practices for transgender consumers. We will provide an overview of the tasks leading up to SIGI implementation, deliverables from the project, and lessons learned.

Veterans Affairs SIGI EHR Field

In 2016, the US Department of Veterans Affairs (VA) began implementing a SIGI demographic field across all EHRs, requiring administrative staff to ask enrolled and new veterans their gender identity (full implementation of SIGI has not yet occurred and will occur when a later EHR upgrade displays SIGI in the EHR). The initiation of SIGI did not change any information in the birth sex field, meaning that some veterans continue to have birth sex field information that results in problematic automatic medical reminders and dosing values. Consequently, the National Center for Patient Safety (NCPS) noted that this discrepancy may be a pertinent patient safety issue. The NCPS and Lesbian, Gay Bisexual, and Transgender (LGBT) Health national program offices worked to provide documentation to TGNC veterans to inform them of the clinical health care implications of having their birth sex demographic field reflect gender identity that is inconsistent with their natal sex (ie, original birth certificate record of sex).

Patient Safety Issues

Conversations between transgender patients and their HCPs about transition goals, necessary medical tests, and laboratory ranges based on their current anatomy and physiology can improve patient safety and satisfaction with medical care. Prior to the availability of the SIGI field, VA facilities varied in their documentation of gender identity in the patient chart. LGBT veteran care coordinators discussed diverse suggestions that ranged from informally documenting SIGI in each progress note to using flags to draw attention to use certain sections of local EHRs. These suggestions, though well intentioned, were not adequate for documenting gender identity at the national level because of regional variations in EHR customization options. Furthermore, the use of flags for drawing clinical attention to gender identity posed a potential for stigma toward patients, given that flags are typically reserved for behavioral or other risk concerns.

Several problems can emerge when HCPs are not equipped with accurate information about patient birth sex and SIGI. For instance, TGNC patients lack a way of being known from clinic to clinic by proper pronouns or self-labels. Providers may misgender veterans, which is a negative experience for TGNC veterans linked with increased barriers to care and decreased frequency of health care visits.⁴ Moreover, the quality and personalization of care across clinic locations in the facility’s system is variable without a consistent method of documenting birth sex and SIGI. For example, in clinics where the veteran is well known (eg, primary care), staff may be more affirming of the veteran’s gender identity than those in specialty care clinics that lack prior patient contact.

Furthermore, depending on hormone and surgical interventions, some health screenings may be irrelevant for TGNC patients. To determine appropriate health screens and assess potential risks associated with hormone therapy, providers must have access to current information regarding a patient’s physiologic anatomy.⁶ Health screenings and laboratory results in sophisticated EHRs (ie, EHRs that might autodetermine normative values) may populate incorrect treatment recommendations, such as sex-based medication dosages. Furthermore, laboratory test results could be incorrectly paired with a different assumed hormonal history, potentially putting the patient at risk.

Case Examples

An important element of EHRs facilitating the goal of patient-centered care is that patients have their EHR validate their sense of self, and their providers can use names and pronouns that correspond to the patient’s SIGI. Some patients have spent a great amount of effort altering their name and sex in legal records and may want their birth sex field to conform to their gender identity. To that end, patients may seek to alter their birth sex information so that it is congruent with how they see themselves to affirm their identity, despite patient safety risks. Several scenarios below demonstrate the potential costs and benefits to patients altering birth sex and SIGI in the EHR.

Case 1 Presentation

A young transman is working with his therapist on engaging in self-validating behaviors. This veteran has met with his PCP and informed the provider of his decision to alter the birth sex field in his EHR from female to male.

Ideally, the patient would begin to have regular conversations with his HCPs about his birth sex and gender identity, so that medical professionals can provide relevant screenings and affirm the patient’s gender identity while acknowledging his right to list his birth sex as he chooses. However, particular attention will need to be paid to assuring that natal sex–based health screenings (eg, pap smears, mammograms) are conducted on an appropriate schedule and that the veteran continues to discuss his current anatomy with providers.

Case 2 Presentation

A veteran has a male birth sex, identifies as a transwoman, and uses nongendered plural pronouns “they/them/theirs.” The word “they,” used as a singular pronoun may feel uncomfortable to some providers, but it validates the veteran’s sense of self and helps them feel welcome in the treatment environment. This patient communicated proactively with their HCPs about their transition goals and current hormone use.

They opted to have their birth sex field continue to indicate “male” because they, after a discussion with their PCP, are aware of the health implications of receiving an incorrect dose for their diabetes medication. They understand that having open communication and receiving input from their HCPs is part of good health care.

Case 3 Presentation

A patient with a sexual development disorder (intersex condition) identifies as a man (indicated as “male” in the SIGI field) and had his birth sex field changed to match his gender identity. He now seeks to change his birth sex field back to female, as he has complicated health considerations due to breast cancer.

The veteran thinks it is important that providers know about his intersex condition so that his breast cancer care is as seamless as possible. In particular, although this veteran is comfortable talking about his intersex condition and his identity with his PCP and oncologist, he wants to ensure that all people involved in his care (eg, pharmacists, radiologists) use the correct values in interpreting his medical data. Providers will need to use the female birth sex field for interpreting his medical data but use male pronouns when interacting with the veteran and documenting his care.

These case examples illustrate the need for HCPs to have patient-affirming education and appropriate clinical tools available when speaking to patients about birth sex, SIGI, and the implications of changing birth sex in the EHR. Moreover, these cases highlight that patient health needs may vary over time, due to factors such as perceived costs/benefits of a change in the sex field of the EHR as well as patient comfort with providers.

Current Status of SIGI and EHR

Although having separate fields for birth sex and SIGI in the EHR is ideal, the VHA does not yet have a fully functional SIGI field, and several TGNC veterans have changed their birth sex field to align with their gender identity. Roughly 9,700 patients have diagnostic codes related to transgender care in the VHA, meaning thousands of current patients would potentially benefit from SIGI implementation (John Blosnich, written communication, March 2018). A possible action that the VHA could take with the goal of enhancing patient safety would be to revert the birth sex field of patients who had previously changed the field back to the patient’s original birth sex. However, if this alteration to the EHR were done without the patient’s consent, numerous additional problems would result—including invalidating a veteran’s wishes—potentially driving patients away from receiving health care.

Moreover, in the absence of updated SIGI information (which only the veteran can provide), making a change in the EHR would perpetuate the misgendering of TGNC veterans who have already sought an administrative fix for this problem. Thus, the agency decided to engage patients in a discussion about their decision to keep the birth sex field consistent with their original birth certificate. In cases in which the field had been changed previously, the recommendation is for HCPs to gain patient consent to change the birth sex field back to what was on their original birth certificate. Thus, decisions about what should be listed in the EHR are made by the veteran using an informed decision-making model.

Patient Safety Education Workgroup

To begin the process of disentangling birth sex and SIGI fields in the EHR, 2 work groups were created: a technical work group (coding the patches for SIGI implementation) and a SIGI patient safety education work group. The patient safety education work group was committed to promoting affirmative VA policies that require validation of the gender identity of all veterans and pursuing best practices through clinical guidelines to promote effective, efficient, equitable, and safe veteran care. The patient safety education work group included representatives from all 3 branches of the VA (VHA, Veterans Benefits Administration, and National Cemetery Administration), including clinical media, patient safety, information technology, and education specialists. The group developed trainings for administrative staff about the appropriate ways to ask birth sex and SIGI questions, and how to record veteran-driven responses.

SIGI Fact Sheet

The patient safety education work group examined clinical literature and developed tools for staff and veterans to facilitate effective discussions about the importance and utility of documenting both birth sex and SIGI in the EHR. The patient safety education work group along with media and educational experts created basic key term definition documents to address the importance, purpose, and use of the SIGI field. The patient safety education work group developed 2 documents to facilitate communication between patients and providers.

A 1-page veteran-facing fact sheet was developed that described the differences between birth sex and SIGI fields and how these fields are used in the VA EHR system (Figure 1). In addition, a 1-page HCP-facing fact sheet was designed to inform HCPs that patients may have changed their birth sex in their EHR or might still wish to change their birth sex field, and to inform HCPs of the importance of patient-centered, gender-affirmative care (Figure 2). An additional goal of both documents was to educate veterans and HCPs on how the EHR automatically calculates laboratory results and screening notifications based on birth sex.

Review Process

As part of reviewing and finalizing the SIGI patient fact sheet, the patient safety education work group previewed the document’s content with veterans who provided feedback on drafts to improve comprehension, patient-centered care, and clinical accuracy. For instance, several patients commented that the document should address many gender identities, including intersex identities. As noted in one of the case presentations earlier, individuals who identify as intersex may have changed their birth sex to be consistent with their gender and might benefit from being informed about the EHR’s autocalculation feature. The patient safety education work group adjusted the SIGI patient fact sheet to include individuals who identify as intersex and instructed them to have a conversation with their HCP regarding potential birth sex changes in the EHR.

Much of the veteran feedback to the patient safety education work group reflected veteran concerns, more broadly, about implementation of SIGI. Many veterans were interested in how federal policy changes might affect their benefits package or clinical care within the VA. The SIGI patient fact sheet was a tool for communicating that Department of Defense (DoD) policies, specifically, do not have a bearing on VA care for LGBT veterans. Therefore, SIGI information does not affect service connection or benefits eligibility and is not shared with the DoD. Veterans found this information helpful to see reflected in the SIGI patient fact sheet.

The patient safety education work group also shared the SIGI provider fact sheet with VHA providers before finalizing the content. PCPs gave feedback to improve the specification of patient safety concerns and appropriate readership language. The patient safety education work group adjusted the SIGI provider fact sheet to be inclusive of relevant literature and an e-consultation link for assisting HCPs who are unsure how to proceed with a patient.

Implementation

The patient safety education work group also developed several materials to provide information about the birth sex and SIGI fields in the EHR. Because the SIGI demographic field is new and collected by clerical staff, training was necessary to explain the difference between birth sex and SIGI before implementation in the EHR. The training sessions educated staff about the difference between birth sex and SIGI, how to ask and respond to questions respectfully, and how to update these fields in the EHR. These trainings included a 20-minute video demonstrating best practices for asking about SIGI, a frequently asked questions document responding to 7 common questions about the new fields, and a quick reference guide for administrative staff to have handy at their desks.

Dissemination of the SIGI patient and provider fact sheets is planned to occur, ideally, several weeks before implementation of the new patches updating the EHR fields in spring 2020. Building on existing resources, the patient safety education work group plans to disseminate the patient fact sheets via e-mail lists for the national mental health facility leaders as well as through e-mail lists for VA PCPs, nursing and clerical staff, privacy officers, facility LGBT veteran care coordinators, VISN leads, transgender e-consultation, the Office of Connected Care, the LGBT external homepage for the VA, and the training website for VA employees. The goal is to target potential points of contact for veterans who may have already changed their birth sex and might benefit medically from altering birth sex to be consistent with their original birth certificate.

The SIGI provider fact sheet will be disseminated using internal e-mails, announcements on routine LGBT veteran care coordinator calls, weekly Ask LGBT Health teleconferences, and announcements at LGBT health training events both internally and externally. Several dissemination tools have already ensured that VA employees are aware of the SIGI field in the EHR. Leadership throughout the VA will be encouraged to share SIGI trainings with clerical staff. Additionally, broad-based e-mails summarizing changes to the EHR will be provided concurrent to the SIGI patch implementation to VA staff as well as links to the resources and training materials.

Challenges

One difficulty in the development process for both SIGI fact sheets was addressing the issue of patient safety for veterans who may be at different points in their gender transition process. It was challenging for the patient safety education work group to not sound alarmist in discussing the safety implications of birth sex changes in the EHR, as this is just one factor in clinical decision making. The goal was to educate veterans from a patient safety perspective about the implications of having a state-of-the-art, automated EHR. However, text can be perceived differently by different people, which is why the patient safety education work group asked veterans to preview the patient document and clinical providers to preview the provider document.

Both work groups encountered technologic challenges, including a delay in the implementation of the SIGI field due to a systemwide delay of EHR updates. Although it released training and educational materials to the VHA, the patient safety education work group understood that at some point in the future, VA programmers will update the EHR to change the information clerks and HCPs can see in the EHR. Coordination of the fact sheet release alongside information technology has been an important part of the SIGI rollout process.

Conclusion

HCPs have a complex role in providing treatment to TGNC patients in the VHA: They must affirm a patient’s gender identity through how they address them, while openly communicating the health risks inherent in having their birth sex field be incongruent with the sex recorded on their original birth certificate. Accomplishing these tasks simultaneously is difficult without invalidating the veteran’s identity or right to choose their EHR demographic birth sex label. Furthermore, patients may ask HCPs to write letters of support for either medical or surgical intervention or other documentation changes (eg, changes to a patient’s legal name, passport changes, or a safe passage letter for TGNC patients). Navigating the dialectic of safety and validation requires strong rapport, trust, and effective communication in the patient-provider relationship and great empathy by the provider.

A future task for the SIGI patient safety education work group is to continue to communicate with the technical work group and providers in the field about how demographic fields in the EHR are utilized to enable future EHR changes. This hurdle is not easy because EHR updates change the infrastructure through which demographic content is delivered and incorporated into a patient’s treatment. The VA HCPs are tasked with thoroughly examining the results that automated systems produce to ensure safe and accurate medical services are always provided to all patients. An integral part of patient-centered care is balancing any computer-guided recommendations with an understanding that actual patient needs may differ due to presence/absence of anatomy and other factors (eg, weight, current medications).

From a systems perspective, a benefit of adding the SIGI demographic field is systemic improvement in calculating the number of transgender veterans under VA care and evaluating health outcomes for this population. SIGI is particularly important for signaling gender pronouns for veterans, regardless of whether they are receiving care for a gender-related diagnosis. In terms of scope, the SIGI project potentially will apply to > 9 million enrolled veterans and nearly 400,000 VA employees.

Improvements could be made in the SIGI field of the new EHR, such as expanding the options for self-labels. Additionally, a text field could be used to enhance the quality of personalization provided to veterans self-identifying in the EHR, including pronoun specification. Moreover, adding new fields such as “preferred name” could improve the health care experience of not only TGNC veterans but all veterans who use something other than their full legal name (eg, a nickname). It will be good practice to notify providers and staff of a veteran’s requested name and pronouns when the patient checks in at an electronic kiosk so that all staff immediately know how to address the patient. The VHA can continue to adjust the options for the SIGI field once the new EHR system is operational. Ideally, this new EHR will display birth sex and SIGI to clinicians or clerks engaged in patient interactions.

Technology will continue to automate medical care, meaning that HCPs must be vigilant about how computer programming and the accuracy of prepopulated information affect patient care. The concerns discussed in this report relating to patient safety are relatively absent in the medical literature, even though substantial health risks exist to patients who have birth sex listed incorrectly for any reason.^6,7 Additionally, administrative burden can be reduced if patients who do not need certain screenings based on their current anatomy are not contacted for unnecessary screenings. Future EHR systems might incorporate anatomical considerations from an inventory to assist in automating patient care in safe and accessible ways.

Providing consistent and high-quality services to gender diverse patients is a top priority for health care systems, including the Veterans Health Administration (VHA).¹ Over the past decade, awareness of transgender and gender nonconforming (TGNC) people in the US has increased. Gender identity refers to a person’s inner sense of where that person belongs on a continuum of masculine to androgynous to feminine traits. This identity range can additionally include nonbinary identifications, such as “gender fluid” or “genderqueer.” A goal of patient-centered care is for health care providers (HCPs) to refer to TGNC individuals, like their cisgender counterparts, according to their gender identity. Gender identity for TGNC individuals may be different from their birth sex. Birth sex, commonly referred to as “sex assigned at birth,” is the biologic and physiologic characteristics that are reflected on a person’s original birth certificate and described as male or female.

Background

In the electronic health record (EHR), birth sex is an important, structured variable that is used to facilitate effective patient care that is efficient, equitable, and patient-centered. Birth sex in an EHR often is used to cue automatic timely generation of health screens (eg, pap smears, prostate exams) and calculation of medication dosages and laboratory test ranges by adjusting for a person’s typical hormonal history and anatomy.

Gender identity fields are independently helpful to include in the EHR, because clinicians can use this information to ensure proper pronoun use and avoid misgendering a patient. Additionally, the gender identity field informs HCPs who may conduct more frequent or different health screenings to evaluate specific health risks that are more prevalent in gender minority (ie, lesbian, gay, bisexual) patients.^2,3

EHRs rely on structured data elements to standardize data about patients for clinical care, quality improvement, data sharing, and patient safety.^4,5 However, health care organizations are grappling with how to incorporate gender identity and birth sex information into EHRs.³ A 2011 Veterans Health Administration (VHA) directive required staff and providers to address and provide care to veterans based on their gender identity. Like other health systems, VHA had 1 demographic data field in the EHR to indicate birth sex, with no field for gender identity. A HCP could enter gender identity information into a progress note, but this addition might not be noticed by other HCPs. Consequently, staff and providers had no effective way of knowing a veteran’s gender identity from the EHR, which contributed to misgendering TGNC veterans.

With the singular demographic field of sex representing both birth sex and gender identity, some TGNC veterans chose to change their birth sex information to align with their gender identity. This change assured TGNC veterans that staff and providers would not misgender them because the birth sex field is easily observed and would allow providers to use respectful, gender-consistent pronouns when speaking with them. However, changing the birth sex field can misalign natal sex–based clinical reminders, medication dosages, and laboratory test values, which created potential patient safety risks. Thus, birth sex created potential hazards to quality and safety when used as a marker even with other variables—such as current anatomy, height, and weight—for health screenings, medication dosing, and other medical decisions.

In this article, we: (1) outline several patient safety issues that can arise with the birth sex field serving as an indicator for both birth sex and gender identity; (2) present case examples that illustrate the benefits of self-identified gender identity (SIGI) in an EHR; (3) describe the process of work-group development of patient-provider communication tools to improve patient safety; and (4) provide a brief overview of resources rolled out as a part of SIGI. This report serves as a guide for other federal organizations that wish to increase affirmative care and safe practices for transgender consumers. We will provide an overview of the tasks leading up to SIGI implementation, deliverables from the project, and lessons learned.

Veterans Affairs SIGI EHR Field

In 2016, the US Department of Veterans Affairs (VA) began implementing a SIGI demographic field across all EHRs, requiring administrative staff to ask enrolled and new veterans their gender identity (full implementation of SIGI has not yet occurred and will occur when a later EHR upgrade displays SIGI in the EHR). The initiation of SIGI did not change any information in the birth sex field, meaning that some veterans continue to have birth sex field information that results in problematic automatic medical reminders and dosing values. Consequently, the National Center for Patient Safety (NCPS) noted that this discrepancy may be a pertinent patient safety issue. The NCPS and Lesbian, Gay Bisexual, and Transgender (LGBT) Health national program offices worked to provide documentation to TGNC veterans to inform them of the clinical health care implications of having their birth sex demographic field reflect gender identity that is inconsistent with their natal sex (ie, original birth certificate record of sex).

Patient Safety Issues

Conversations between transgender patients and their HCPs about transition goals, necessary medical tests, and laboratory ranges based on their current anatomy and physiology can improve patient safety and satisfaction with medical care. Prior to the availability of the SIGI field, VA facilities varied in their documentation of gender identity in the patient chart. LGBT veteran care coordinators discussed diverse suggestions that ranged from informally documenting SIGI in each progress note to using flags to draw attention to use certain sections of local EHRs. These suggestions, though well intentioned, were not adequate for documenting gender identity at the national level because of regional variations in EHR customization options. Furthermore, the use of flags for drawing clinical attention to gender identity posed a potential for stigma toward patients, given that flags are typically reserved for behavioral or other risk concerns.

Several problems can emerge when HCPs are not equipped with accurate information about patient birth sex and SIGI. For instance, TGNC patients lack a way of being known from clinic to clinic by proper pronouns or self-labels. Providers may misgender veterans, which is a negative experience for TGNC veterans linked with increased barriers to care and decreased frequency of health care visits.⁴ Moreover, the quality and personalization of care across clinic locations in the facility’s system is variable without a consistent method of documenting birth sex and SIGI. For example, in clinics where the veteran is well known (eg, primary care), staff may be more affirming of the veteran’s gender identity than those in specialty care clinics that lack prior patient contact.

Furthermore, depending on hormone and surgical interventions, some health screenings may be irrelevant for TGNC patients. To determine appropriate health screens and assess potential risks associated with hormone therapy, providers must have access to current information regarding a patient’s physiologic anatomy.⁶ Health screenings and laboratory results in sophisticated EHRs (ie, EHRs that might autodetermine normative values) may populate incorrect treatment recommendations, such as sex-based medication dosages. Furthermore, laboratory test results could be incorrectly paired with a different assumed hormonal history, potentially putting the patient at risk.

Case Examples

An important element of EHRs facilitating the goal of patient-centered care is that patients have their EHR validate their sense of self, and their providers can use names and pronouns that correspond to the patient’s SIGI. Some patients have spent a great amount of effort altering their name and sex in legal records and may want their birth sex field to conform to their gender identity. To that end, patients may seek to alter their birth sex information so that it is congruent with how they see themselves to affirm their identity, despite patient safety risks. Several scenarios below demonstrate the potential costs and benefits to patients altering birth sex and SIGI in the EHR.

Case 1 Presentation

A young transman is working with his therapist on engaging in self-validating behaviors. This veteran has met with his PCP and informed the provider of his decision to alter the birth sex field in his EHR from female to male.

Ideally, the patient would begin to have regular conversations with his HCPs about his birth sex and gender identity, so that medical professionals can provide relevant screenings and affirm the patient’s gender identity while acknowledging his right to list his birth sex as he chooses. However, particular attention will need to be paid to assuring that natal sex–based health screenings (eg, pap smears, mammograms) are conducted on an appropriate schedule and that the veteran continues to discuss his current anatomy with providers.

Case 2 Presentation

A veteran has a male birth sex, identifies as a transwoman, and uses nongendered plural pronouns “they/them/theirs.” The word “they,” used as a singular pronoun may feel uncomfortable to some providers, but it validates the veteran’s sense of self and helps them feel welcome in the treatment environment. This patient communicated proactively with their HCPs about their transition goals and current hormone use.

They opted to have their birth sex field continue to indicate “male” because they, after a discussion with their PCP, are aware of the health implications of receiving an incorrect dose for their diabetes medication. They understand that having open communication and receiving input from their HCPs is part of good health care.

Case 3 Presentation

A patient with a sexual development disorder (intersex condition) identifies as a man (indicated as “male” in the SIGI field) and had his birth sex field changed to match his gender identity. He now seeks to change his birth sex field back to female, as he has complicated health considerations due to breast cancer.

The veteran thinks it is important that providers know about his intersex condition so that his breast cancer care is as seamless as possible. In particular, although this veteran is comfortable talking about his intersex condition and his identity with his PCP and oncologist, he wants to ensure that all people involved in his care (eg, pharmacists, radiologists) use the correct values in interpreting his medical data. Providers will need to use the female birth sex field for interpreting his medical data but use male pronouns when interacting with the veteran and documenting his care.

These case examples illustrate the need for HCPs to have patient-affirming education and appropriate clinical tools available when speaking to patients about birth sex, SIGI, and the implications of changing birth sex in the EHR. Moreover, these cases highlight that patient health needs may vary over time, due to factors such as perceived costs/benefits of a change in the sex field of the EHR as well as patient comfort with providers.

Current Status of SIGI and EHR

Although having separate fields for birth sex and SIGI in the EHR is ideal, the VHA does not yet have a fully functional SIGI field, and several TGNC veterans have changed their birth sex field to align with their gender identity. Roughly 9,700 patients have diagnostic codes related to transgender care in the VHA, meaning thousands of current patients would potentially benefit from SIGI implementation (John Blosnich, written communication, March 2018). A possible action that the VHA could take with the goal of enhancing patient safety would be to revert the birth sex field of patients who had previously changed the field back to the patient’s original birth sex. However, if this alteration to the EHR were done without the patient’s consent, numerous additional problems would result—including invalidating a veteran’s wishes—potentially driving patients away from receiving health care.

Moreover, in the absence of updated SIGI information (which only the veteran can provide), making a change in the EHR would perpetuate the misgendering of TGNC veterans who have already sought an administrative fix for this problem. Thus, the agency decided to engage patients in a discussion about their decision to keep the birth sex field consistent with their original birth certificate. In cases in which the field had been changed previously, the recommendation is for HCPs to gain patient consent to change the birth sex field back to what was on their original birth certificate. Thus, decisions about what should be listed in the EHR are made by the veteran using an informed decision-making model.

Patient Safety Education Workgroup

To begin the process of disentangling birth sex and SIGI fields in the EHR, 2 work groups were created: a technical work group (coding the patches for SIGI implementation) and a SIGI patient safety education work group. The patient safety education work group was committed to promoting affirmative VA policies that require validation of the gender identity of all veterans and pursuing best practices through clinical guidelines to promote effective, efficient, equitable, and safe veteran care. The patient safety education work group included representatives from all 3 branches of the VA (VHA, Veterans Benefits Administration, and National Cemetery Administration), including clinical media, patient safety, information technology, and education specialists. The group developed trainings for administrative staff about the appropriate ways to ask birth sex and SIGI questions, and how to record veteran-driven responses.

SIGI Fact Sheet

The patient safety education work group examined clinical literature and developed tools for staff and veterans to facilitate effective discussions about the importance and utility of documenting both birth sex and SIGI in the EHR. The patient safety education work group along with media and educational experts created basic key term definition documents to address the importance, purpose, and use of the SIGI field. The patient safety education work group developed 2 documents to facilitate communication between patients and providers.

A 1-page veteran-facing fact sheet was developed that described the differences between birth sex and SIGI fields and how these fields are used in the VA EHR system (Figure 1). In addition, a 1-page HCP-facing fact sheet was designed to inform HCPs that patients may have changed their birth sex in their EHR or might still wish to change their birth sex field, and to inform HCPs of the importance of patient-centered, gender-affirmative care (Figure 2). An additional goal of both documents was to educate veterans and HCPs on how the EHR automatically calculates laboratory results and screening notifications based on birth sex.

Review Process

As part of reviewing and finalizing the SIGI patient fact sheet, the patient safety education work group previewed the document’s content with veterans who provided feedback on drafts to improve comprehension, patient-centered care, and clinical accuracy. For instance, several patients commented that the document should address many gender identities, including intersex identities. As noted in one of the case presentations earlier, individuals who identify as intersex may have changed their birth sex to be consistent with their gender and might benefit from being informed about the EHR’s autocalculation feature. The patient safety education work group adjusted the SIGI patient fact sheet to include individuals who identify as intersex and instructed them to have a conversation with their HCP regarding potential birth sex changes in the EHR.

Much of the veteran feedback to the patient safety education work group reflected veteran concerns, more broadly, about implementation of SIGI. Many veterans were interested in how federal policy changes might affect their benefits package or clinical care within the VA. The SIGI patient fact sheet was a tool for communicating that Department of Defense (DoD) policies, specifically, do not have a bearing on VA care for LGBT veterans. Therefore, SIGI information does not affect service connection or benefits eligibility and is not shared with the DoD. Veterans found this information helpful to see reflected in the SIGI patient fact sheet.

The patient safety education work group also shared the SIGI provider fact sheet with VHA providers before finalizing the content. PCPs gave feedback to improve the specification of patient safety concerns and appropriate readership language. The patient safety education work group adjusted the SIGI provider fact sheet to be inclusive of relevant literature and an e-consultation link for assisting HCPs who are unsure how to proceed with a patient.

Implementation

The patient safety education work group also developed several materials to provide information about the birth sex and SIGI fields in the EHR. Because the SIGI demographic field is new and collected by clerical staff, training was necessary to explain the difference between birth sex and SIGI before implementation in the EHR. The training sessions educated staff about the difference between birth sex and SIGI, how to ask and respond to questions respectfully, and how to update these fields in the EHR. These trainings included a 20-minute video demonstrating best practices for asking about SIGI, a frequently asked questions document responding to 7 common questions about the new fields, and a quick reference guide for administrative staff to have handy at their desks.

Dissemination of the SIGI patient and provider fact sheets is planned to occur, ideally, several weeks before implementation of the new patches updating the EHR fields in spring 2020. Building on existing resources, the patient safety education work group plans to disseminate the patient fact sheets via e-mail lists for the national mental health facility leaders as well as through e-mail lists for VA PCPs, nursing and clerical staff, privacy officers, facility LGBT veteran care coordinators, VISN leads, transgender e-consultation, the Office of Connected Care, the LGBT external homepage for the VA, and the training website for VA employees. The goal is to target potential points of contact for veterans who may have already changed their birth sex and might benefit medically from altering birth sex to be consistent with their original birth certificate.

The SIGI provider fact sheet will be disseminated using internal e-mails, announcements on routine LGBT veteran care coordinator calls, weekly Ask LGBT Health teleconferences, and announcements at LGBT health training events both internally and externally. Several dissemination tools have already ensured that VA employees are aware of the SIGI field in the EHR. Leadership throughout the VA will be encouraged to share SIGI trainings with clerical staff. Additionally, broad-based e-mails summarizing changes to the EHR will be provided concurrent to the SIGI patch implementation to VA staff as well as links to the resources and training materials.

Challenges

One difficulty in the development process for both SIGI fact sheets was addressing the issue of patient safety for veterans who may be at different points in their gender transition process. It was challenging for the patient safety education work group to not sound alarmist in discussing the safety implications of birth sex changes in the EHR, as this is just one factor in clinical decision making. The goal was to educate veterans from a patient safety perspective about the implications of having a state-of-the-art, automated EHR. However, text can be perceived differently by different people, which is why the patient safety education work group asked veterans to preview the patient document and clinical providers to preview the provider document.

Both work groups encountered technologic challenges, including a delay in the implementation of the SIGI field due to a systemwide delay of EHR updates. Although it released training and educational materials to the VHA, the patient safety education work group understood that at some point in the future, VA programmers will update the EHR to change the information clerks and HCPs can see in the EHR. Coordination of the fact sheet release alongside information technology has been an important part of the SIGI rollout process.

Conclusion

HCPs have a complex role in providing treatment to TGNC patients in the VHA: They must affirm a patient’s gender identity through how they address them, while openly communicating the health risks inherent in having their birth sex field be incongruent with the sex recorded on their original birth certificate. Accomplishing these tasks simultaneously is difficult without invalidating the veteran’s identity or right to choose their EHR demographic birth sex label. Furthermore, patients may ask HCPs to write letters of support for either medical or surgical intervention or other documentation changes (eg, changes to a patient’s legal name, passport changes, or a safe passage letter for TGNC patients). Navigating the dialectic of safety and validation requires strong rapport, trust, and effective communication in the patient-provider relationship and great empathy by the provider.

A future task for the SIGI patient safety education work group is to continue to communicate with the technical work group and providers in the field about how demographic fields in the EHR are utilized to enable future EHR changes. This hurdle is not easy because EHR updates change the infrastructure through which demographic content is delivered and incorporated into a patient’s treatment. The VA HCPs are tasked with thoroughly examining the results that automated systems produce to ensure safe and accurate medical services are always provided to all patients. An integral part of patient-centered care is balancing any computer-guided recommendations with an understanding that actual patient needs may differ due to presence/absence of anatomy and other factors (eg, weight, current medications).

From a systems perspective, a benefit of adding the SIGI demographic field is systemic improvement in calculating the number of transgender veterans under VA care and evaluating health outcomes for this population. SIGI is particularly important for signaling gender pronouns for veterans, regardless of whether they are receiving care for a gender-related diagnosis. In terms of scope, the SIGI project potentially will apply to > 9 million enrolled veterans and nearly 400,000 VA employees.

Improvements could be made in the SIGI field of the new EHR, such as expanding the options for self-labels. Additionally, a text field could be used to enhance the quality of personalization provided to veterans self-identifying in the EHR, including pronoun specification. Moreover, adding new fields such as “preferred name” could improve the health care experience of not only TGNC veterans but all veterans who use something other than their full legal name (eg, a nickname). It will be good practice to notify providers and staff of a veteran’s requested name and pronouns when the patient checks in at an electronic kiosk so that all staff immediately know how to address the patient. The VHA can continue to adjust the options for the SIGI field once the new EHR system is operational. Ideally, this new EHR will display birth sex and SIGI to clinicians or clerks engaged in patient interactions.

Technology will continue to automate medical care, meaning that HCPs must be vigilant about how computer programming and the accuracy of prepopulated information affect patient care. The concerns discussed in this report relating to patient safety are relatively absent in the medical literature, even though substantial health risks exist to patients who have birth sex listed incorrectly for any reason.^6,7 Additionally, administrative burden can be reduced if patients who do not need certain screenings based on their current anatomy are not contacted for unnecessary screenings. Future EHR systems might incorporate anatomical considerations from an inventory to assist in automating patient care in safe and accessible ways.

Providing consistent and high-quality services to gender diverse patients is a top priority for health care systems, including the Veterans Health Administration (VHA).¹ Over the past decade, awareness of transgender and gender nonconforming (TGNC) people in the US has increased. Gender identity refers to a person’s inner sense of where that person belongs on a continuum of masculine to androgynous to feminine traits. This identity range can additionally include nonbinary identifications, such as “gender fluid” or “genderqueer.” A goal of patient-centered care is for health care providers (HCPs) to refer to TGNC individuals, like their cisgender counterparts, according to their gender identity. Gender identity for TGNC individuals may be different from their birth sex. Birth sex, commonly referred to as “sex assigned at birth,” is the biologic and physiologic characteristics that are reflected on a person’s original birth certificate and described as male or female.

Background

In the electronic health record (EHR), birth sex is an important, structured variable that is used to facilitate effective patient care that is efficient, equitable, and patient-centered. Birth sex in an EHR often is used to cue automatic timely generation of health screens (eg, pap smears, prostate exams) and calculation of medication dosages and laboratory test ranges by adjusting for a person’s typical hormonal history and anatomy.

Gender identity fields are independently helpful to include in the EHR, because clinicians can use this information to ensure proper pronoun use and avoid misgendering a patient. Additionally, the gender identity field informs HCPs who may conduct more frequent or different health screenings to evaluate specific health risks that are more prevalent in gender minority (ie, lesbian, gay, bisexual) patients.^2,3

EHRs rely on structured data elements to standardize data about patients for clinical care, quality improvement, data sharing, and patient safety.^4,5 However, health care organizations are grappling with how to incorporate gender identity and birth sex information into EHRs.³ A 2011 Veterans Health Administration (VHA) directive required staff and providers to address and provide care to veterans based on their gender identity. Like other health systems, VHA had 1 demographic data field in the EHR to indicate birth sex, with no field for gender identity. A HCP could enter gender identity information into a progress note, but this addition might not be noticed by other HCPs. Consequently, staff and providers had no effective way of knowing a veteran’s gender identity from the EHR, which contributed to misgendering TGNC veterans.

With the singular demographic field of sex representing both birth sex and gender identity, some TGNC veterans chose to change their birth sex information to align with their gender identity. This change assured TGNC veterans that staff and providers would not misgender them because the birth sex field is easily observed and would allow providers to use respectful, gender-consistent pronouns when speaking with them. However, changing the birth sex field can misalign natal sex–based clinical reminders, medication dosages, and laboratory test values, which created potential patient safety risks. Thus, birth sex created potential hazards to quality and safety when used as a marker even with other variables—such as current anatomy, height, and weight—for health screenings, medication dosing, and other medical decisions.

In this article, we: (1) outline several patient safety issues that can arise with the birth sex field serving as an indicator for both birth sex and gender identity; (2) present case examples that illustrate the benefits of self-identified gender identity (SIGI) in an EHR; (3) describe the process of work-group development of patient-provider communication tools to improve patient safety; and (4) provide a brief overview of resources rolled out as a part of SIGI. This report serves as a guide for other federal organizations that wish to increase affirmative care and safe practices for transgender consumers. We will provide an overview of the tasks leading up to SIGI implementation, deliverables from the project, and lessons learned.

Veterans Affairs SIGI EHR Field

In 2016, the US Department of Veterans Affairs (VA) began implementing a SIGI demographic field across all EHRs, requiring administrative staff to ask enrolled and new veterans their gender identity (full implementation of SIGI has not yet occurred and will occur when a later EHR upgrade displays SIGI in the EHR). The initiation of SIGI did not change any information in the birth sex field, meaning that some veterans continue to have birth sex field information that results in problematic automatic medical reminders and dosing values. Consequently, the National Center for Patient Safety (NCPS) noted that this discrepancy may be a pertinent patient safety issue. The NCPS and Lesbian, Gay Bisexual, and Transgender (LGBT) Health national program offices worked to provide documentation to TGNC veterans to inform them of the clinical health care implications of having their birth sex demographic field reflect gender identity that is inconsistent with their natal sex (ie, original birth certificate record of sex).

Patient Safety Issues

Conversations between transgender patients and their HCPs about transition goals, necessary medical tests, and laboratory ranges based on their current anatomy and physiology can improve patient safety and satisfaction with medical care. Prior to the availability of the SIGI field, VA facilities varied in their documentation of gender identity in the patient chart. LGBT veteran care coordinators discussed diverse suggestions that ranged from informally documenting SIGI in each progress note to using flags to draw attention to use certain sections of local EHRs. These suggestions, though well intentioned, were not adequate for documenting gender identity at the national level because of regional variations in EHR customization options. Furthermore, the use of flags for drawing clinical attention to gender identity posed a potential for stigma toward patients, given that flags are typically reserved for behavioral or other risk concerns.

Several problems can emerge when HCPs are not equipped with accurate information about patient birth sex and SIGI. For instance, TGNC patients lack a way of being known from clinic to clinic by proper pronouns or self-labels. Providers may misgender veterans, which is a negative experience for TGNC veterans linked with increased barriers to care and decreased frequency of health care visits.⁴ Moreover, the quality and personalization of care across clinic locations in the facility’s system is variable without a consistent method of documenting birth sex and SIGI. For example, in clinics where the veteran is well known (eg, primary care), staff may be more affirming of the veteran’s gender identity than those in specialty care clinics that lack prior patient contact.

Furthermore, depending on hormone and surgical interventions, some health screenings may be irrelevant for TGNC patients. To determine appropriate health screens and assess potential risks associated with hormone therapy, providers must have access to current information regarding a patient’s physiologic anatomy.⁶ Health screenings and laboratory results in sophisticated EHRs (ie, EHRs that might autodetermine normative values) may populate incorrect treatment recommendations, such as sex-based medication dosages. Furthermore, laboratory test results could be incorrectly paired with a different assumed hormonal history, potentially putting the patient at risk.

Case Examples

An important element of EHRs facilitating the goal of patient-centered care is that patients have their EHR validate their sense of self, and their providers can use names and pronouns that correspond to the patient’s SIGI. Some patients have spent a great amount of effort altering their name and sex in legal records and may want their birth sex field to conform to their gender identity. To that end, patients may seek to alter their birth sex information so that it is congruent with how they see themselves to affirm their identity, despite patient safety risks. Several scenarios below demonstrate the potential costs and benefits to patients altering birth sex and SIGI in the EHR.

Case 1 Presentation

A young transman is working with his therapist on engaging in self-validating behaviors. This veteran has met with his PCP and informed the provider of his decision to alter the birth sex field in his EHR from female to male.

Ideally, the patient would begin to have regular conversations with his HCPs about his birth sex and gender identity, so that medical professionals can provide relevant screenings and affirm the patient’s gender identity while acknowledging his right to list his birth sex as he chooses. However, particular attention will need to be paid to assuring that natal sex–based health screenings (eg, pap smears, mammograms) are conducted on an appropriate schedule and that the veteran continues to discuss his current anatomy with providers.

Case 2 Presentation

A veteran has a male birth sex, identifies as a transwoman, and uses nongendered plural pronouns “they/them/theirs.” The word “they,” used as a singular pronoun may feel uncomfortable to some providers, but it validates the veteran’s sense of self and helps them feel welcome in the treatment environment. This patient communicated proactively with their HCPs about their transition goals and current hormone use.

They opted to have their birth sex field continue to indicate “male” because they, after a discussion with their PCP, are aware of the health implications of receiving an incorrect dose for their diabetes medication. They understand that having open communication and receiving input from their HCPs is part of good health care.

Case 3 Presentation

A patient with a sexual development disorder (intersex condition) identifies as a man (indicated as “male” in the SIGI field) and had his birth sex field changed to match his gender identity. He now seeks to change his birth sex field back to female, as he has complicated health considerations due to breast cancer.

The veteran thinks it is important that providers know about his intersex condition so that his breast cancer care is as seamless as possible. In particular, although this veteran is comfortable talking about his intersex condition and his identity with his PCP and oncologist, he wants to ensure that all people involved in his care (eg, pharmacists, radiologists) use the correct values in interpreting his medical data. Providers will need to use the female birth sex field for interpreting his medical data but use male pronouns when interacting with the veteran and documenting his care.

These case examples illustrate the need for HCPs to have patient-affirming education and appropriate clinical tools available when speaking to patients about birth sex, SIGI, and the implications of changing birth sex in the EHR. Moreover, these cases highlight that patient health needs may vary over time, due to factors such as perceived costs/benefits of a change in the sex field of the EHR as well as patient comfort with providers.

Current Status of SIGI and EHR

Although having separate fields for birth sex and SIGI in the EHR is ideal, the VHA does not yet have a fully functional SIGI field, and several TGNC veterans have changed their birth sex field to align with their gender identity. Roughly 9,700 patients have diagnostic codes related to transgender care in the VHA, meaning thousands of current patients would potentially benefit from SIGI implementation (John Blosnich, written communication, March 2018). A possible action that the VHA could take with the goal of enhancing patient safety would be to revert the birth sex field of patients who had previously changed the field back to the patient’s original birth sex. However, if this alteration to the EHR were done without the patient’s consent, numerous additional problems would result—including invalidating a veteran’s wishes—potentially driving patients away from receiving health care.

Moreover, in the absence of updated SIGI information (which only the veteran can provide), making a change in the EHR would perpetuate the misgendering of TGNC veterans who have already sought an administrative fix for this problem. Thus, the agency decided to engage patients in a discussion about their decision to keep the birth sex field consistent with their original birth certificate. In cases in which the field had been changed previously, the recommendation is for HCPs to gain patient consent to change the birth sex field back to what was on their original birth certificate. Thus, decisions about what should be listed in the EHR are made by the veteran using an informed decision-making model.

Patient Safety Education Workgroup

To begin the process of disentangling birth sex and SIGI fields in the EHR, 2 work groups were created: a technical work group (coding the patches for SIGI implementation) and a SIGI patient safety education work group. The patient safety education work group was committed to promoting affirmative VA policies that require validation of the gender identity of all veterans and pursuing best practices through clinical guidelines to promote effective, efficient, equitable, and safe veteran care. The patient safety education work group included representatives from all 3 branches of the VA (VHA, Veterans Benefits Administration, and National Cemetery Administration), including clinical media, patient safety, information technology, and education specialists. The group developed trainings for administrative staff about the appropriate ways to ask birth sex and SIGI questions, and how to record veteran-driven responses.

SIGI Fact Sheet

The patient safety education work group examined clinical literature and developed tools for staff and veterans to facilitate effective discussions about the importance and utility of documenting both birth sex and SIGI in the EHR. The patient safety education work group along with media and educational experts created basic key term definition documents to address the importance, purpose, and use of the SIGI field. The patient safety education work group developed 2 documents to facilitate communication between patients and providers.

A 1-page veteran-facing fact sheet was developed that described the differences between birth sex and SIGI fields and how these fields are used in the VA EHR system (Figure 1). In addition, a 1-page HCP-facing fact sheet was designed to inform HCPs that patients may have changed their birth sex in their EHR or might still wish to change their birth sex field, and to inform HCPs of the importance of patient-centered, gender-affirmative care (Figure 2). An additional goal of both documents was to educate veterans and HCPs on how the EHR automatically calculates laboratory results and screening notifications based on birth sex.

Review Process

As part of reviewing and finalizing the SIGI patient fact sheet, the patient safety education work group previewed the document’s content with veterans who provided feedback on drafts to improve comprehension, patient-centered care, and clinical accuracy. For instance, several patients commented that the document should address many gender identities, including intersex identities. As noted in one of the case presentations earlier, individuals who identify as intersex may have changed their birth sex to be consistent with their gender and might benefit from being informed about the EHR’s autocalculation feature. The patient safety education work group adjusted the SIGI patient fact sheet to include individuals who identify as intersex and instructed them to have a conversation with their HCP regarding potential birth sex changes in the EHR.

Much of the veteran feedback to the patient safety education work group reflected veteran concerns, more broadly, about implementation of SIGI. Many veterans were interested in how federal policy changes might affect their benefits package or clinical care within the VA. The SIGI patient fact sheet was a tool for communicating that Department of Defense (DoD) policies, specifically, do not have a bearing on VA care for LGBT veterans. Therefore, SIGI information does not affect service connection or benefits eligibility and is not shared with the DoD. Veterans found this information helpful to see reflected in the SIGI patient fact sheet.

The patient safety education work group also shared the SIGI provider fact sheet with VHA providers before finalizing the content. PCPs gave feedback to improve the specification of patient safety concerns and appropriate readership language. The patient safety education work group adjusted the SIGI provider fact sheet to be inclusive of relevant literature and an e-consultation link for assisting HCPs who are unsure how to proceed with a patient.

Implementation

The patient safety education work group also developed several materials to provide information about the birth sex and SIGI fields in the EHR. Because the SIGI demographic field is new and collected by clerical staff, training was necessary to explain the difference between birth sex and SIGI before implementation in the EHR. The training sessions educated staff about the difference between birth sex and SIGI, how to ask and respond to questions respectfully, and how to update these fields in the EHR. These trainings included a 20-minute video demonstrating best practices for asking about SIGI, a frequently asked questions document responding to 7 common questions about the new fields, and a quick reference guide for administrative staff to have handy at their desks.

Dissemination of the SIGI patient and provider fact sheets is planned to occur, ideally, several weeks before implementation of the new patches updating the EHR fields in spring 2020. Building on existing resources, the patient safety education work group plans to disseminate the patient fact sheets via e-mail lists for the national mental health facility leaders as well as through e-mail lists for VA PCPs, nursing and clerical staff, privacy officers, facility LGBT veteran care coordinators, VISN leads, transgender e-consultation, the Office of Connected Care, the LGBT external homepage for the VA, and the training website for VA employees. The goal is to target potential points of contact for veterans who may have already changed their birth sex and might benefit medically from altering birth sex to be consistent with their original birth certificate.

The SIGI provider fact sheet will be disseminated using internal e-mails, announcements on routine LGBT veteran care coordinator calls, weekly Ask LGBT Health teleconferences, and announcements at LGBT health training events both internally and externally. Several dissemination tools have already ensured that VA employees are aware of the SIGI field in the EHR. Leadership throughout the VA will be encouraged to share SIGI trainings with clerical staff. Additionally, broad-based e-mails summarizing changes to the EHR will be provided concurrent to the SIGI patch implementation to VA staff as well as links to the resources and training materials.

Challenges

One difficulty in the development process for both SIGI fact sheets was addressing the issue of patient safety for veterans who may be at different points in their gender transition process. It was challenging for the patient safety education work group to not sound alarmist in discussing the safety implications of birth sex changes in the EHR, as this is just one factor in clinical decision making. The goal was to educate veterans from a patient safety perspective about the implications of having a state-of-the-art, automated EHR. However, text can be perceived differently by different people, which is why the patient safety education work group asked veterans to preview the patient document and clinical providers to preview the provider document.

Both work groups encountered technologic challenges, including a delay in the implementation of the SIGI field due to a systemwide delay of EHR updates. Although it released training and educational materials to the VHA, the patient safety education work group understood that at some point in the future, VA programmers will update the EHR to change the information clerks and HCPs can see in the EHR. Coordination of the fact sheet release alongside information technology has been an important part of the SIGI rollout process.

Conclusion

HCPs have a complex role in providing treatment to TGNC patients in the VHA: They must affirm a patient’s gender identity through how they address them, while openly communicating the health risks inherent in having their birth sex field be incongruent with the sex recorded on their original birth certificate. Accomplishing these tasks simultaneously is difficult without invalidating the veteran’s identity or right to choose their EHR demographic birth sex label. Furthermore, patients may ask HCPs to write letters of support for either medical or surgical intervention or other documentation changes (eg, changes to a patient’s legal name, passport changes, or a safe passage letter for TGNC patients). Navigating the dialectic of safety and validation requires strong rapport, trust, and effective communication in the patient-provider relationship and great empathy by the provider.

A future task for the SIGI patient safety education work group is to continue to communicate with the technical work group and providers in the field about how demographic fields in the EHR are utilized to enable future EHR changes. This hurdle is not easy because EHR updates change the infrastructure through which demographic content is delivered and incorporated into a patient’s treatment. The VA HCPs are tasked with thoroughly examining the results that automated systems produce to ensure safe and accurate medical services are always provided to all patients. An integral part of patient-centered care is balancing any computer-guided recommendations with an understanding that actual patient needs may differ due to presence/absence of anatomy and other factors (eg, weight, current medications).

From a systems perspective, a benefit of adding the SIGI demographic field is systemic improvement in calculating the number of transgender veterans under VA care and evaluating health outcomes for this population. SIGI is particularly important for signaling gender pronouns for veterans, regardless of whether they are receiving care for a gender-related diagnosis. In terms of scope, the SIGI project potentially will apply to > 9 million enrolled veterans and nearly 400,000 VA employees.

Improvements could be made in the SIGI field of the new EHR, such as expanding the options for self-labels. Additionally, a text field could be used to enhance the quality of personalization provided to veterans self-identifying in the EHR, including pronoun specification. Moreover, adding new fields such as “preferred name” could improve the health care experience of not only TGNC veterans but all veterans who use something other than their full legal name (eg, a nickname). It will be good practice to notify providers and staff of a veteran’s requested name and pronouns when the patient checks in at an electronic kiosk so that all staff immediately know how to address the patient. The VHA can continue to adjust the options for the SIGI field once the new EHR system is operational. Ideally, this new EHR will display birth sex and SIGI to clinicians or clerks engaged in patient interactions.

Technology will continue to automate medical care, meaning that HCPs must be vigilant about how computer programming and the accuracy of prepopulated information affect patient care. The concerns discussed in this report relating to patient safety are relatively absent in the medical literature, even though substantial health risks exist to patients who have birth sex listed incorrectly for any reason.^6,7 Additionally, administrative burden can be reduced if patients who do not need certain screenings based on their current anatomy are not contacted for unnecessary screenings. Future EHR systems might incorporate anatomical considerations from an inventory to assist in automating patient care in safe and accessible ways.

Colorectal cancer (CRC) ranks among the most common causes of cancer and cancer-related death in the US. The US Multi-Society Task Force (USMSTF) on Colorectal Cancer thus strongly endorsed using several available screening options.¹ The published guidelines largely rely on age to define the target population (Table 1). For average-risk individuals, national and Veterans Health Administration (VHA) guidelines currently recommend CRC screening in individuals aged between 50 and 75 years with a life expectancy of > 5 years.¹

Although case-control studies also point to a potential benefit in persons aged > 75 years,^2,3 the USMSTF cited less convincing evidence and suggested an individualized approach that should consider relative cancer risk and comorbidity burden. Such an approach is supported by modeling studies, which suggest reduced benefit and increased risk of screening with increasing age. The reduced benefit also is significantly affected by comorbidity and relative cancer risk.⁴ The VHA has successfully implemented CRC screening, capturing the majority of eligible patients based on age criteria. A recent survey showed that more than three-quarters of veterans between age 50 and 75 years had undergone some screening test for CRC as part of routine preventive care. Colonoscopy clearly emerged as the dominant modality chosen for CRC screening and accounted for nearly 84% of these screening tests.⁵ Consistent with these data, a case-control study confirmed that the widespread implementation of colonoscopy as CRC screening method reduced cancer-related mortality in veterans for cases of left but not right-sided colon cancer.⁶

With calls to expand the age range of CRC screening beyond aged 75 years, we decided to assess survival rates of a cohort of veterans who underwent a screening or surveillance colonoscopy between 2008 and 2014.⁷ The goals were to characterize the portion of the cohort that had died, the time between a screening colonoscopy and death, the portion of deaths that were aged ≥ 80 years, and the causes of the deaths. In addition, we focused on a subgroup of the cohort, defined by death within 2 years after the index colonoscopy, to identify predictors of early death that were independent of age.

Methods

We queried the endoscopy reporting system (EndoWorks; Olympus America, Center Valley, PA) for all colonoscopies performed by 2 of 14 physicians at the George Wahlen VA Medical Center (GWVAMC) in Salt Lake City, Utah, who performed endoscopic procedures between January 1, 2008 and December 1, 2014. These physicians had focused their clinical practice exclusively on elective outpatient colonoscopies and accounted for 37.4% of the examinations at GWVAMC during the study period. All colonoscopy requests were triaged and assigned based on availability of open and appropriate procedure time slots without direct physician-specific referral, thus reducing the chance of skewing results. The reports were filtered through a text search to focus on examinations that listed screening or surveillance as indication. The central patient electronic health record was then reviewed to extract basic demographic data, survival status (as of August 1, 2018), and survival time in years after the index or subsequent colonoscopy. For deceased veterans, the age at the time of death, cause of death, and comorbidities were queried.

This study compared cases and control across the study. Cases were persons who clearly died early (defined as > 2 years following the index examination). They were matched with controls who lived for ≥ 5 years after their colonoscopy. These periods were selected because the USMSTF recommended that CRC screening or surveillance colonoscopy should be discontinued in persons with a life expectancy of < 5 years, and most study patients underwent their index procedure ≥ 5 years before August 2018. Cases and controls underwent a colonoscopy in the same year and were matched for age, sex, and presence of underlying inflammatory bowel disease (IBD). For cases and controls, we identified the ordering health care provider specialty, (ie, primary care, gastroenterology, or other).

In addition, we reviewed the encounter linked to the order and abstracted relevant comorbidities listed at that time, noted the use of anticoagulants, opioid analgesics, and benzodiazepines. The comorbidity burden was quantified using the Charlson Comorbidity Index.⁸ In addition, we denoted the presence of psychiatric problems (eg, anxiety, depression, bipolar disease, psychosis, substance abuse), the diagnosis of atrial fibrillation (AF) or other cardiac arrhythmias, and whether the patient had previously been treated for a malignancy that was in apparent clinical remission. Finally, we searched for routine laboratory tests at the time of this visit or, when not obtained, within 6 months of the encounter, and abstracted serum creatinine, hemoglobin (Hgb), platelet number, serum protein, and albumin. In clinical practice, cutoff values of test results are often more helpful in decision making. We, therefore, dichotomized results for Hgb (cutoff: 10 g/dL), creatinine (cutoff: 2 mg/dL), and albumin (cutoff: 3.2 mg/dL).

Descriptive and analytical statistics were obtained with Stata Version 14.1 (College Station, TX). Unless indicated otherwise, continuous data are shown as mean with 95% CIs. For dichotomous data, we used percentages with their 95% CIs. Analytic statistics were performed with the t test for continuous variables and the 2-tailed test for proportions. A P < .05 was considered a significant difference. To determine independent predictors of early death, we performed a logistic regression analysis with results being expressed as odds ratio with 95% CIs. Survival status was chosen as a dependent variable, and we entered variables that significantly correlated with survival in the bivariate analysis as independent variables.

The study was designed and conducted as a quality improvement project to assess colonoscopy performance and outcomes with the Salt Lake City Specialty Care Center of Innovation (COI), one of 5 regional COIs with an operational mission to improve health care access, utilization, and quality. Our work related to colonoscopy and access within the COI region, including Salt Lake City, has been reviewed and acknowledged by the GWVAMC Institutional Review Board as quality improvement. Andrew Gawron has an operational appointment in the GWVAMC COI, which is part of a US Department of Veterans Affairs (VA) central office initiative established in 2015. The COIs are charged with identifying best practices within the VA and applying those practices throughout the COI region. This local project to identify practice patterns and outcomes locally was sponsored by the GWVAMC COI with a focus to generate information to improve colonoscopy referral quality in patients at Salt Lake City and inform regional and national efforts in this domain.

Results

During the study period, 4,879 veterans (96.9% male) underwent at least 1 colonoscopy for screening or surveillance by 1 of the 2 providers. A total of 306 persons (6.3%) were aged > 80 years. The indication for surveillance colonoscopies included IBD in 78 (1.6%) veterans 2 of whom were women. The mean (SD) follow-up period between the index colonoscopy and study closure or death was 7.4 years (1.7). During the study time, 1,439 persons underwent a repeat examination for surveillance. The percentage of veterans with at least 1 additional colonoscopy after the index test was significantly higher in patients with known IBD compared with those without IBD (78.2% vs 28.7%; P < .01).

Between the index colonoscopy and August 2018, 974 patients (20.0%) died (Figure). The mean (SD) time between the colonoscopy and recorded year of death was 4.4 years (4.1). The fraction of women in the cohort that died (n = 18) was lower compared with 132 for the group of persons still alive (1.8% vs 3.4%; P < .05). The fraction of veterans with IBD who died by August 2018 did not differ from that of patients with IBD in the cohort of individuals who survived (19.2% vs 20.0%; P = .87). The cohort of veterans who died before study closure included 107 persons who were aged > 80 years at the time of their index colonoscopy, which is significantly more than in the cohort of persons still alive (11.0% vs 5.1%; P < .01).

Cause of Death

In 209 of the 974 (21.5%) veteran deaths a cause was recorded. Malignancies accounted for 88 of the deaths (42.1%), and CRCs were responsible for 14 (6.7%) deaths (Table 2). In 8 of these patients, the cancer had been identified at an advanced stage, not allowing for curative therapy. One patient had been asked to return for a repeat test as residual fecal matter did not allow proper visualization. He died 1 year later due to complications of sepsis after colonic perforation caused by a proximal colon cancer. Five patients underwent surgery with curative intent but suffered recurrences. In addition to malignancies, advanced diseases, such as cardiovascular, bronchopulmonary illnesses, and infections, were other commonly listed causes of death.

We also abstracted comorbidities that were known at the time of death or the most recent encounter within the VHA system. Hypertension was most commonly listed (549) followed by a current or prior diagnosis of malignancies (355) and diabetes mellitus (DM) (Table 3). Prostate cancer was the most commonly diagnosed malignancy (80), 17 of whom had a second malignancy. CRC accounted for 54 of the malignancies, 1 of which developed in a patient with long-standing ulcerative colitis, 2 were a manifestation of a known hereditary cancer syndrome (Lynch syndrome), and the remaining 51 cases were various cancers without known predisposition. The diagnosis of CRC was made during the study period in 29 veterans. In the remaining 25 patients, the colonoscopy was performed as a surveillance examination after previous surgery for CRC.

Potential Predictors of Early Death

To better define potential predictors of early death, we focused on the 258 persons (5.3%) who died within 2 years after the index procedure and paired them with matched controls. One patient underwent a colonoscopy for surveillance of previously treated cancer and was excluded due to very advanced age, as no matched control could be identified. The mean (SD) age of this male-predominant cohort was 68.2 (9.6) vs 67.9 (9.4) years for cases and controls, respectively. At the time of referral for the test, 29 persons (11.3%) were aged > 80 years, which is significantly more than seen for the overall cohort with 306 (6.3%; P < .001). While primary care providers accounted for most referrals in cases (85.2%) and controls (93.0%), the fraction of veterans referred by gastroenterologists or other specialty care providers was significantly higher in the case group compared with that in the controls (14.8% vs 7.0%; P < .05).

In our age-matched analysis, we examined other potential factors that could influence survival. The burden of comorbid conditions summarized in the Charlson Comorbidity Index significantly correlated with survival status (Table 4). As this composite index does not include psychiatric conditions, we separately examined the impact of anxiety, depression, bipolar disease, psychotic disorders, and substance abuse. The diagnoses of depression and substance use disorders (SUDs) were associated with higher rates of early death. Considering concerns about SUDs, we also assessed the association between prescription for opioids or benzodiazepines and survival status, which showed a marginal correlation. Anticoagulant use, a likely surrogate for cardiovascular disorders, were more commonly listed in the cases than they were in the controls.

Looking at specific comorbid conditions, significant problems affecting key organ systems from heart to lung, liver, kidneys, or brain (dementia) were all predictors of poor outcome. Similarly, DM with secondary complication correlated with early death after the index procedure. In contrast, a history of prior myocardial infarction, prior cancer treatment without evidence of persistent or recurrent disease, or prior peptic ulcer disease did not differ between cases and controls. Focusing on routine blood tests, we noted marginal, but statistically different results for Hgb, serum creatinine, and albumin in cases compared with controls.

Next we performed a logistic regression to identify independent predictors of survival status. The referring provider specialty, Charlson Comorbidity Index, the diagnosis of a SUD, current benzodiazepine use, and significant anemia or hypoalbuminemia independently predicted death within 2 years of the index examination (Table 5). Considering the composite nature of the Charlson Comorbidity Index, we separately examined the relative importance of different comorbid conditions using a logistic regression analysis. Consistent with the univariate analyses, a known malignancy; severe liver, lung, or kidney disease; and DM with secondary complications were associated with poor outcome. Only arrhythmias other than AF were independent marginal predictors of early death, whereas other variables related to cardiac performance did not reach the level of significance (Table 6). As was true for our analysis examining the composite comorbidity index, the diagnosis of a SUD remained significant as a predictor of death within 2 years of the index colonoscopy.

Discussion

This retrospective analysis followed patients for a mean time of 7 years after a colonoscopy for CRC screening or polyp surveillance. We noted a high rate of all-cause mortality, with 20% of the cohort dying within the period studied. Malignancies, cardiovascular diseases, and advanced lung diseases were most commonly listed causes of death. As expected, CRC was among the 3 most common malignancies and was the cause of death in 6.7% of the group with sufficiently detailed information. While these results fall within the expected range for the mortality related to CRC,⁹ the results do not allow us to assess the impact of screening, which has been shown to decrease cancer-related mortality in veterans.⁶ This was limited because the sample size was too small to assess the impact of screening and the cause of death was ascertained for a small percentage of the sample.

Although our findings are limited to a subset of patients seen in a single center, they suggest the importance of appropriate eligibility criteria for screening tests, as also defined in national guidelines.¹ As a key anchoring point that describes the target population, age contributed to the rate of relatively early death after the index procedure. Consistent with previously published data, we saw a significant impact of comorbid diseases.^10,11 However, our findings go beyond prior reports and show the important impact of psychiatric disease burden, most important the role of SUDs. The predictive value of a summary score, such as the Charlson Comorbidity Index, supports the idea of a cumulative impact, with an increasing disease burden decreasing life expectancy.^10-14 It is important to consider the ongoing impact of such coexisting illnesses. Our analysis shows, the mere history of prior problems did not independently predict survival status in our cohort.

Although age is the key anchoring point that defines the target population for CRC screening programs, the benefit of earlier cancer detection or, in the context of colonoscopy with polypectomy, cancer prevention comes with a delay. Thus, cancer risk, procedural risk, and life expectancy should all be weighed when discussing and deciding on the appropriateness of CRC screening. When we disregard inherited cancer syndromes, CRC is clearly a disease of the second half of life with the incidence increasing with age.¹⁵ However, other disease burdens rise, which may affects the risk of screening and treatment should cancer be found.

Using our understanding of disease development, researchers have introduced the concept of time to benefit or lag time to help decisions about screening strategies. The period defines the likely time for a precursor or early form of cancer potentially detected by screening to manifest as a clinically relevant lesion. This lag time becomes an especially important consideration in screening of older and/or chronically ill adults with life expectancies that may be close to or even less than the time to benefit.¹⁶ Modeling studies suggest that 1,000 flexible sigmoidoscopy screenings are needed to prevent 1 cancer that would manifest about 10 years after the index examination.^17,18 The mean life expectancy of a healthy person aged 75 years exceeds 10 years but drops with comorbidity burden. Consistent with these considerations, an analysis of Medicare claims data concluded that individuals with ≥ 3 significant comorbidities do not derive any benefit from screening colonoscopy.¹⁴ Looking at the impact of comorbidities, mathematical models concluded that colorectal cancer screening should not be continued in persons with moderate or severe comorbid conditions aged 66 years and 72 years, respectively.¹⁹ In contrast, modeling results suggest a benefit of continued screening up to and even above the age of 80 years if persons have an increased cancer risk and if there are no confounding comorbidities.⁴

Life expectancy and time to benefit describe probabilities. Although such probabilities are relevant in public policy decision, providers and patients may struggle with probabilistic thinking when faced with decisions that involve probabilities of individual health care vs population health care. Both are concerned about the seemingly gloomy or pessimistic undertone of discussing life expectancy and the inherent uncertainty of prognostic tools.^20,21 Prior research indicates that this reluctance translates into clinical practice. When faced with vignettes, most clinicians would offer CRC screening to healthy persons aged 80 years with rates falling when the description included a significant comorbid burden; however, more than 40% would still consider screening in octogenarians with poor health.²²

Consistent with these responses to theoretical scenarios, CRC screening of veterans dropped with age but was still continued in persons with significant comorbidity.²³ Large studies of the veteran population suggest that about 10% of veterans aged > 70 years have chronic medical problems that limit their life expectancy to < 5 years; nonetheless, more than 40% of this cohort underwent colonoscopies for CRC screening.^24,25 Interestingly, more illness burden and more clinical encounters translated into more screening examinations in older sick veterans compared with that of the cohort of healthier older persons, suggesting an impact of clinical reminders and the key role of age as the main anchoring variable.²³

Ongoing screening despite limited or even no benefit is not unique to CRC. Using validated tools, Pollock and colleagues showed comparable screening rates for breast and prostate cancer when they examined cohorts at either high or low risk of early mortality.²⁶ Similar results have been reported in veterans with about one-third of elderly males with poor life expectancy still undergoing prostate cancer screening.²⁷ Interestingly, inappropriate screening is more common in nonacademic centers and influenced by provider characteristics: nurse practitioner, physician assistants, older attending physicians and male physicians were more likely to order such tests.^27,28

Limitations

In this study, we examined a cohort of veterans enrolled in CRC screening within a single institution and obtained survival data for a mean follow-up of > 7 years. We also restricted our study to patients undergoing examinations that explicitly listed screening as indication or polyp surveillance for the test. However, inclusion was based on the indication listed in the report, which may differ from the intent of the ordering provider. Reporting systems often come with default settings, which may skew data. Comorbidities for the entire cohort of veterans who died within the time frame of the study were extracted from the chart without controlling for time-dependent changes, which may more appropriately describe the comorbidity burden at the time of the test. Using a case-control design, we addressed this potential caveat and included only illnesses recorded in the encounter linked to the colonoscopy order. Despite these limitations, our results highlight the importance to more effectively define and target appropriate candidates for CRC screening.

Conclusion

This study shows that age is a simple but not sufficiently accurate criterion to define potential candidates for CRC screening. As automated reminders often prompt discussions about and referral to screening examinations, we should develop algorithms that estimate the individual cancer risk and/or integrate an automatically calculated comorbidity index with these alerts or insert such a tool into order-sets. In addition, providers and patients need to be educated about the rationale and need for a more comprehensive approach to CRC screening that considers anticipated life expectancy. On an individual and health system level, our goal should be to reduce overall mortality rather than only cancer-specific death rates.

Colorectal cancer (CRC) ranks among the most common causes of cancer and cancer-related death in the US. The US Multi-Society Task Force (USMSTF) on Colorectal Cancer thus strongly endorsed using several available screening options.¹ The published guidelines largely rely on age to define the target population (Table 1). For average-risk individuals, national and Veterans Health Administration (VHA) guidelines currently recommend CRC screening in individuals aged between 50 and 75 years with a life expectancy of > 5 years.¹

Although case-control studies also point to a potential benefit in persons aged > 75 years,^2,3 the USMSTF cited less convincing evidence and suggested an individualized approach that should consider relative cancer risk and comorbidity burden. Such an approach is supported by modeling studies, which suggest reduced benefit and increased risk of screening with increasing age. The reduced benefit also is significantly affected by comorbidity and relative cancer risk.⁴ The VHA has successfully implemented CRC screening, capturing the majority of eligible patients based on age criteria. A recent survey showed that more than three-quarters of veterans between age 50 and 75 years had undergone some screening test for CRC as part of routine preventive care. Colonoscopy clearly emerged as the dominant modality chosen for CRC screening and accounted for nearly 84% of these screening tests.⁵ Consistent with these data, a case-control study confirmed that the widespread implementation of colonoscopy as CRC screening method reduced cancer-related mortality in veterans for cases of left but not right-sided colon cancer.⁶

With calls to expand the age range of CRC screening beyond aged 75 years, we decided to assess survival rates of a cohort of veterans who underwent a screening or surveillance colonoscopy between 2008 and 2014.⁷ The goals were to characterize the portion of the cohort that had died, the time between a screening colonoscopy and death, the portion of deaths that were aged ≥ 80 years, and the causes of the deaths. In addition, we focused on a subgroup of the cohort, defined by death within 2 years after the index colonoscopy, to identify predictors of early death that were independent of age.

Methods

We queried the endoscopy reporting system (EndoWorks; Olympus America, Center Valley, PA) for all colonoscopies performed by 2 of 14 physicians at the George Wahlen VA Medical Center (GWVAMC) in Salt Lake City, Utah, who performed endoscopic procedures between January 1, 2008 and December 1, 2014. These physicians had focused their clinical practice exclusively on elective outpatient colonoscopies and accounted for 37.4% of the examinations at GWVAMC during the study period. All colonoscopy requests were triaged and assigned based on availability of open and appropriate procedure time slots without direct physician-specific referral, thus reducing the chance of skewing results. The reports were filtered through a text search to focus on examinations that listed screening or surveillance as indication. The central patient electronic health record was then reviewed to extract basic demographic data, survival status (as of August 1, 2018), and survival time in years after the index or subsequent colonoscopy. For deceased veterans, the age at the time of death, cause of death, and comorbidities were queried.

This study compared cases and control across the study. Cases were persons who clearly died early (defined as > 2 years following the index examination). They were matched with controls who lived for ≥ 5 years after their colonoscopy. These periods were selected because the USMSTF recommended that CRC screening or surveillance colonoscopy should be discontinued in persons with a life expectancy of < 5 years, and most study patients underwent their index procedure ≥ 5 years before August 2018. Cases and controls underwent a colonoscopy in the same year and were matched for age, sex, and presence of underlying inflammatory bowel disease (IBD). For cases and controls, we identified the ordering health care provider specialty, (ie, primary care, gastroenterology, or other).

In addition, we reviewed the encounter linked to the order and abstracted relevant comorbidities listed at that time, noted the use of anticoagulants, opioid analgesics, and benzodiazepines. The comorbidity burden was quantified using the Charlson Comorbidity Index.⁸ In addition, we denoted the presence of psychiatric problems (eg, anxiety, depression, bipolar disease, psychosis, substance abuse), the diagnosis of atrial fibrillation (AF) or other cardiac arrhythmias, and whether the patient had previously been treated for a malignancy that was in apparent clinical remission. Finally, we searched for routine laboratory tests at the time of this visit or, when not obtained, within 6 months of the encounter, and abstracted serum creatinine, hemoglobin (Hgb), platelet number, serum protein, and albumin. In clinical practice, cutoff values of test results are often more helpful in decision making. We, therefore, dichotomized results for Hgb (cutoff: 10 g/dL), creatinine (cutoff: 2 mg/dL), and albumin (cutoff: 3.2 mg/dL).

Descriptive and analytical statistics were obtained with Stata Version 14.1 (College Station, TX). Unless indicated otherwise, continuous data are shown as mean with 95% CIs. For dichotomous data, we used percentages with their 95% CIs. Analytic statistics were performed with the t test for continuous variables and the 2-tailed test for proportions. A P < .05 was considered a significant difference. To determine independent predictors of early death, we performed a logistic regression analysis with results being expressed as odds ratio with 95% CIs. Survival status was chosen as a dependent variable, and we entered variables that significantly correlated with survival in the bivariate analysis as independent variables.

The study was designed and conducted as a quality improvement project to assess colonoscopy performance and outcomes with the Salt Lake City Specialty Care Center of Innovation (COI), one of 5 regional COIs with an operational mission to improve health care access, utilization, and quality. Our work related to colonoscopy and access within the COI region, including Salt Lake City, has been reviewed and acknowledged by the GWVAMC Institutional Review Board as quality improvement. Andrew Gawron has an operational appointment in the GWVAMC COI, which is part of a US Department of Veterans Affairs (VA) central office initiative established in 2015. The COIs are charged with identifying best practices within the VA and applying those practices throughout the COI region. This local project to identify practice patterns and outcomes locally was sponsored by the GWVAMC COI with a focus to generate information to improve colonoscopy referral quality in patients at Salt Lake City and inform regional and national efforts in this domain.

Results

During the study period, 4,879 veterans (96.9% male) underwent at least 1 colonoscopy for screening or surveillance by 1 of the 2 providers. A total of 306 persons (6.3%) were aged > 80 years. The indication for surveillance colonoscopies included IBD in 78 (1.6%) veterans 2 of whom were women. The mean (SD) follow-up period between the index colonoscopy and study closure or death was 7.4 years (1.7). During the study time, 1,439 persons underwent a repeat examination for surveillance. The percentage of veterans with at least 1 additional colonoscopy after the index test was significantly higher in patients with known IBD compared with those without IBD (78.2% vs 28.7%; P < .01).

Between the index colonoscopy and August 2018, 974 patients (20.0%) died (Figure). The mean (SD) time between the colonoscopy and recorded year of death was 4.4 years (4.1). The fraction of women in the cohort that died (n = 18) was lower compared with 132 for the group of persons still alive (1.8% vs 3.4%; P < .05). The fraction of veterans with IBD who died by August 2018 did not differ from that of patients with IBD in the cohort of individuals who survived (19.2% vs 20.0%; P = .87). The cohort of veterans who died before study closure included 107 persons who were aged > 80 years at the time of their index colonoscopy, which is significantly more than in the cohort of persons still alive (11.0% vs 5.1%; P < .01).

Cause of Death

In 209 of the 974 (21.5%) veteran deaths a cause was recorded. Malignancies accounted for 88 of the deaths (42.1%), and CRCs were responsible for 14 (6.7%) deaths (Table 2). In 8 of these patients, the cancer had been identified at an advanced stage, not allowing for curative therapy. One patient had been asked to return for a repeat test as residual fecal matter did not allow proper visualization. He died 1 year later due to complications of sepsis after colonic perforation caused by a proximal colon cancer. Five patients underwent surgery with curative intent but suffered recurrences. In addition to malignancies, advanced diseases, such as cardiovascular, bronchopulmonary illnesses, and infections, were other commonly listed causes of death.

We also abstracted comorbidities that were known at the time of death or the most recent encounter within the VHA system. Hypertension was most commonly listed (549) followed by a current or prior diagnosis of malignancies (355) and diabetes mellitus (DM) (Table 3). Prostate cancer was the most commonly diagnosed malignancy (80), 17 of whom had a second malignancy. CRC accounted for 54 of the malignancies, 1 of which developed in a patient with long-standing ulcerative colitis, 2 were a manifestation of a known hereditary cancer syndrome (Lynch syndrome), and the remaining 51 cases were various cancers without known predisposition. The diagnosis of CRC was made during the study period in 29 veterans. In the remaining 25 patients, the colonoscopy was performed as a surveillance examination after previous surgery for CRC.

Potential Predictors of Early Death

To better define potential predictors of early death, we focused on the 258 persons (5.3%) who died within 2 years after the index procedure and paired them with matched controls. One patient underwent a colonoscopy for surveillance of previously treated cancer and was excluded due to very advanced age, as no matched control could be identified. The mean (SD) age of this male-predominant cohort was 68.2 (9.6) vs 67.9 (9.4) years for cases and controls, respectively. At the time of referral for the test, 29 persons (11.3%) were aged > 80 years, which is significantly more than seen for the overall cohort with 306 (6.3%; P < .001). While primary care providers accounted for most referrals in cases (85.2%) and controls (93.0%), the fraction of veterans referred by gastroenterologists or other specialty care providers was significantly higher in the case group compared with that in the controls (14.8% vs 7.0%; P < .05).

In our age-matched analysis, we examined other potential factors that could influence survival. The burden of comorbid conditions summarized in the Charlson Comorbidity Index significantly correlated with survival status (Table 4). As this composite index does not include psychiatric conditions, we separately examined the impact of anxiety, depression, bipolar disease, psychotic disorders, and substance abuse. The diagnoses of depression and substance use disorders (SUDs) were associated with higher rates of early death. Considering concerns about SUDs, we also assessed the association between prescription for opioids or benzodiazepines and survival status, which showed a marginal correlation. Anticoagulant use, a likely surrogate for cardiovascular disorders, were more commonly listed in the cases than they were in the controls.

Looking at specific comorbid conditions, significant problems affecting key organ systems from heart to lung, liver, kidneys, or brain (dementia) were all predictors of poor outcome. Similarly, DM with secondary complication correlated with early death after the index procedure. In contrast, a history of prior myocardial infarction, prior cancer treatment without evidence of persistent or recurrent disease, or prior peptic ulcer disease did not differ between cases and controls. Focusing on routine blood tests, we noted marginal, but statistically different results for Hgb, serum creatinine, and albumin in cases compared with controls.

Next we performed a logistic regression to identify independent predictors of survival status. The referring provider specialty, Charlson Comorbidity Index, the diagnosis of a SUD, current benzodiazepine use, and significant anemia or hypoalbuminemia independently predicted death within 2 years of the index examination (Table 5). Considering the composite nature of the Charlson Comorbidity Index, we separately examined the relative importance of different comorbid conditions using a logistic regression analysis. Consistent with the univariate analyses, a known malignancy; severe liver, lung, or kidney disease; and DM with secondary complications were associated with poor outcome. Only arrhythmias other than AF were independent marginal predictors of early death, whereas other variables related to cardiac performance did not reach the level of significance (Table 6). As was true for our analysis examining the composite comorbidity index, the diagnosis of a SUD remained significant as a predictor of death within 2 years of the index colonoscopy.

Discussion

This retrospective analysis followed patients for a mean time of 7 years after a colonoscopy for CRC screening or polyp surveillance. We noted a high rate of all-cause mortality, with 20% of the cohort dying within the period studied. Malignancies, cardiovascular diseases, and advanced lung diseases were most commonly listed causes of death. As expected, CRC was among the 3 most common malignancies and was the cause of death in 6.7% of the group with sufficiently detailed information. While these results fall within the expected range for the mortality related to CRC,⁹ the results do not allow us to assess the impact of screening, which has been shown to decrease cancer-related mortality in veterans.⁶ This was limited because the sample size was too small to assess the impact of screening and the cause of death was ascertained for a small percentage of the sample.

Although our findings are limited to a subset of patients seen in a single center, they suggest the importance of appropriate eligibility criteria for screening tests, as also defined in national guidelines.¹ As a key anchoring point that describes the target population, age contributed to the rate of relatively early death after the index procedure. Consistent with previously published data, we saw a significant impact of comorbid diseases.^10,11 However, our findings go beyond prior reports and show the important impact of psychiatric disease burden, most important the role of SUDs. The predictive value of a summary score, such as the Charlson Comorbidity Index, supports the idea of a cumulative impact, with an increasing disease burden decreasing life expectancy.^10-14 It is important to consider the ongoing impact of such coexisting illnesses. Our analysis shows, the mere history of prior problems did not independently predict survival status in our cohort.

Although age is the key anchoring point that defines the target population for CRC screening programs, the benefit of earlier cancer detection or, in the context of colonoscopy with polypectomy, cancer prevention comes with a delay. Thus, cancer risk, procedural risk, and life expectancy should all be weighed when discussing and deciding on the appropriateness of CRC screening. When we disregard inherited cancer syndromes, CRC is clearly a disease of the second half of life with the incidence increasing with age.¹⁵ However, other disease burdens rise, which may affects the risk of screening and treatment should cancer be found.

Using our understanding of disease development, researchers have introduced the concept of time to benefit or lag time to help decisions about screening strategies. The period defines the likely time for a precursor or early form of cancer potentially detected by screening to manifest as a clinically relevant lesion. This lag time becomes an especially important consideration in screening of older and/or chronically ill adults with life expectancies that may be close to or even less than the time to benefit.¹⁶ Modeling studies suggest that 1,000 flexible sigmoidoscopy screenings are needed to prevent 1 cancer that would manifest about 10 years after the index examination.^17,18 The mean life expectancy of a healthy person aged 75 years exceeds 10 years but drops with comorbidity burden. Consistent with these considerations, an analysis of Medicare claims data concluded that individuals with ≥ 3 significant comorbidities do not derive any benefit from screening colonoscopy.¹⁴ Looking at the impact of comorbidities, mathematical models concluded that colorectal cancer screening should not be continued in persons with moderate or severe comorbid conditions aged 66 years and 72 years, respectively.¹⁹ In contrast, modeling results suggest a benefit of continued screening up to and even above the age of 80 years if persons have an increased cancer risk and if there are no confounding comorbidities.⁴

Life expectancy and time to benefit describe probabilities. Although such probabilities are relevant in public policy decision, providers and patients may struggle with probabilistic thinking when faced with decisions that involve probabilities of individual health care vs population health care. Both are concerned about the seemingly gloomy or pessimistic undertone of discussing life expectancy and the inherent uncertainty of prognostic tools.^20,21 Prior research indicates that this reluctance translates into clinical practice. When faced with vignettes, most clinicians would offer CRC screening to healthy persons aged 80 years with rates falling when the description included a significant comorbid burden; however, more than 40% would still consider screening in octogenarians with poor health.²²

Consistent with these responses to theoretical scenarios, CRC screening of veterans dropped with age but was still continued in persons with significant comorbidity.²³ Large studies of the veteran population suggest that about 10% of veterans aged > 70 years have chronic medical problems that limit their life expectancy to < 5 years; nonetheless, more than 40% of this cohort underwent colonoscopies for CRC screening.^24,25 Interestingly, more illness burden and more clinical encounters translated into more screening examinations in older sick veterans compared with that of the cohort of healthier older persons, suggesting an impact of clinical reminders and the key role of age as the main anchoring variable.²³

Ongoing screening despite limited or even no benefit is not unique to CRC. Using validated tools, Pollock and colleagues showed comparable screening rates for breast and prostate cancer when they examined cohorts at either high or low risk of early mortality.²⁶ Similar results have been reported in veterans with about one-third of elderly males with poor life expectancy still undergoing prostate cancer screening.²⁷ Interestingly, inappropriate screening is more common in nonacademic centers and influenced by provider characteristics: nurse practitioner, physician assistants, older attending physicians and male physicians were more likely to order such tests.^27,28

Limitations

In this study, we examined a cohort of veterans enrolled in CRC screening within a single institution and obtained survival data for a mean follow-up of > 7 years. We also restricted our study to patients undergoing examinations that explicitly listed screening as indication or polyp surveillance for the test. However, inclusion was based on the indication listed in the report, which may differ from the intent of the ordering provider. Reporting systems often come with default settings, which may skew data. Comorbidities for the entire cohort of veterans who died within the time frame of the study were extracted from the chart without controlling for time-dependent changes, which may more appropriately describe the comorbidity burden at the time of the test. Using a case-control design, we addressed this potential caveat and included only illnesses recorded in the encounter linked to the colonoscopy order. Despite these limitations, our results highlight the importance to more effectively define and target appropriate candidates for CRC screening.

Conclusion

This study shows that age is a simple but not sufficiently accurate criterion to define potential candidates for CRC screening. As automated reminders often prompt discussions about and referral to screening examinations, we should develop algorithms that estimate the individual cancer risk and/or integrate an automatically calculated comorbidity index with these alerts or insert such a tool into order-sets. In addition, providers and patients need to be educated about the rationale and need for a more comprehensive approach to CRC screening that considers anticipated life expectancy. On an individual and health system level, our goal should be to reduce overall mortality rather than only cancer-specific death rates.

Colorectal cancer (CRC) ranks among the most common causes of cancer and cancer-related death in the US. The US Multi-Society Task Force (USMSTF) on Colorectal Cancer thus strongly endorsed using several available screening options.¹ The published guidelines largely rely on age to define the target population (Table 1). For average-risk individuals, national and Veterans Health Administration (VHA) guidelines currently recommend CRC screening in individuals aged between 50 and 75 years with a life expectancy of > 5 years.¹

Although case-control studies also point to a potential benefit in persons aged > 75 years,^2,3 the USMSTF cited less convincing evidence and suggested an individualized approach that should consider relative cancer risk and comorbidity burden. Such an approach is supported by modeling studies, which suggest reduced benefit and increased risk of screening with increasing age. The reduced benefit also is significantly affected by comorbidity and relative cancer risk.⁴ The VHA has successfully implemented CRC screening, capturing the majority of eligible patients based on age criteria. A recent survey showed that more than three-quarters of veterans between age 50 and 75 years had undergone some screening test for CRC as part of routine preventive care. Colonoscopy clearly emerged as the dominant modality chosen for CRC screening and accounted for nearly 84% of these screening tests.⁵ Consistent with these data, a case-control study confirmed that the widespread implementation of colonoscopy as CRC screening method reduced cancer-related mortality in veterans for cases of left but not right-sided colon cancer.⁶

With calls to expand the age range of CRC screening beyond aged 75 years, we decided to assess survival rates of a cohort of veterans who underwent a screening or surveillance colonoscopy between 2008 and 2014.⁷ The goals were to characterize the portion of the cohort that had died, the time between a screening colonoscopy and death, the portion of deaths that were aged ≥ 80 years, and the causes of the deaths. In addition, we focused on a subgroup of the cohort, defined by death within 2 years after the index colonoscopy, to identify predictors of early death that were independent of age.

Methods

We queried the endoscopy reporting system (EndoWorks; Olympus America, Center Valley, PA) for all colonoscopies performed by 2 of 14 physicians at the George Wahlen VA Medical Center (GWVAMC) in Salt Lake City, Utah, who performed endoscopic procedures between January 1, 2008 and December 1, 2014. These physicians had focused their clinical practice exclusively on elective outpatient colonoscopies and accounted for 37.4% of the examinations at GWVAMC during the study period. All colonoscopy requests were triaged and assigned based on availability of open and appropriate procedure time slots without direct physician-specific referral, thus reducing the chance of skewing results. The reports were filtered through a text search to focus on examinations that listed screening or surveillance as indication. The central patient electronic health record was then reviewed to extract basic demographic data, survival status (as of August 1, 2018), and survival time in years after the index or subsequent colonoscopy. For deceased veterans, the age at the time of death, cause of death, and comorbidities were queried.

This study compared cases and control across the study. Cases were persons who clearly died early (defined as > 2 years following the index examination). They were matched with controls who lived for ≥ 5 years after their colonoscopy. These periods were selected because the USMSTF recommended that CRC screening or surveillance colonoscopy should be discontinued in persons with a life expectancy of < 5 years, and most study patients underwent their index procedure ≥ 5 years before August 2018. Cases and controls underwent a colonoscopy in the same year and were matched for age, sex, and presence of underlying inflammatory bowel disease (IBD). For cases and controls, we identified the ordering health care provider specialty, (ie, primary care, gastroenterology, or other).

In addition, we reviewed the encounter linked to the order and abstracted relevant comorbidities listed at that time, noted the use of anticoagulants, opioid analgesics, and benzodiazepines. The comorbidity burden was quantified using the Charlson Comorbidity Index.⁸ In addition, we denoted the presence of psychiatric problems (eg, anxiety, depression, bipolar disease, psychosis, substance abuse), the diagnosis of atrial fibrillation (AF) or other cardiac arrhythmias, and whether the patient had previously been treated for a malignancy that was in apparent clinical remission. Finally, we searched for routine laboratory tests at the time of this visit or, when not obtained, within 6 months of the encounter, and abstracted serum creatinine, hemoglobin (Hgb), platelet number, serum protein, and albumin. In clinical practice, cutoff values of test results are often more helpful in decision making. We, therefore, dichotomized results for Hgb (cutoff: 10 g/dL), creatinine (cutoff: 2 mg/dL), and albumin (cutoff: 3.2 mg/dL).

Descriptive and analytical statistics were obtained with Stata Version 14.1 (College Station, TX). Unless indicated otherwise, continuous data are shown as mean with 95% CIs. For dichotomous data, we used percentages with their 95% CIs. Analytic statistics were performed with the t test for continuous variables and the 2-tailed test for proportions. A P < .05 was considered a significant difference. To determine independent predictors of early death, we performed a logistic regression analysis with results being expressed as odds ratio with 95% CIs. Survival status was chosen as a dependent variable, and we entered variables that significantly correlated with survival in the bivariate analysis as independent variables.

The study was designed and conducted as a quality improvement project to assess colonoscopy performance and outcomes with the Salt Lake City Specialty Care Center of Innovation (COI), one of 5 regional COIs with an operational mission to improve health care access, utilization, and quality. Our work related to colonoscopy and access within the COI region, including Salt Lake City, has been reviewed and acknowledged by the GWVAMC Institutional Review Board as quality improvement. Andrew Gawron has an operational appointment in the GWVAMC COI, which is part of a US Department of Veterans Affairs (VA) central office initiative established in 2015. The COIs are charged with identifying best practices within the VA and applying those practices throughout the COI region. This local project to identify practice patterns and outcomes locally was sponsored by the GWVAMC COI with a focus to generate information to improve colonoscopy referral quality in patients at Salt Lake City and inform regional and national efforts in this domain.

Results

During the study period, 4,879 veterans (96.9% male) underwent at least 1 colonoscopy for screening or surveillance by 1 of the 2 providers. A total of 306 persons (6.3%) were aged > 80 years. The indication for surveillance colonoscopies included IBD in 78 (1.6%) veterans 2 of whom were women. The mean (SD) follow-up period between the index colonoscopy and study closure or death was 7.4 years (1.7). During the study time, 1,439 persons underwent a repeat examination for surveillance. The percentage of veterans with at least 1 additional colonoscopy after the index test was significantly higher in patients with known IBD compared with those without IBD (78.2% vs 28.7%; P < .01).

Between the index colonoscopy and August 2018, 974 patients (20.0%) died (Figure). The mean (SD) time between the colonoscopy and recorded year of death was 4.4 years (4.1). The fraction of women in the cohort that died (n = 18) was lower compared with 132 for the group of persons still alive (1.8% vs 3.4%; P < .05). The fraction of veterans with IBD who died by August 2018 did not differ from that of patients with IBD in the cohort of individuals who survived (19.2% vs 20.0%; P = .87). The cohort of veterans who died before study closure included 107 persons who were aged > 80 years at the time of their index colonoscopy, which is significantly more than in the cohort of persons still alive (11.0% vs 5.1%; P < .01).

Cause of Death

In 209 of the 974 (21.5%) veteran deaths a cause was recorded. Malignancies accounted for 88 of the deaths (42.1%), and CRCs were responsible for 14 (6.7%) deaths (Table 2). In 8 of these patients, the cancer had been identified at an advanced stage, not allowing for curative therapy. One patient had been asked to return for a repeat test as residual fecal matter did not allow proper visualization. He died 1 year later due to complications of sepsis after colonic perforation caused by a proximal colon cancer. Five patients underwent surgery with curative intent but suffered recurrences. In addition to malignancies, advanced diseases, such as cardiovascular, bronchopulmonary illnesses, and infections, were other commonly listed causes of death.

We also abstracted comorbidities that were known at the time of death or the most recent encounter within the VHA system. Hypertension was most commonly listed (549) followed by a current or prior diagnosis of malignancies (355) and diabetes mellitus (DM) (Table 3). Prostate cancer was the most commonly diagnosed malignancy (80), 17 of whom had a second malignancy. CRC accounted for 54 of the malignancies, 1 of which developed in a patient with long-standing ulcerative colitis, 2 were a manifestation of a known hereditary cancer syndrome (Lynch syndrome), and the remaining 51 cases were various cancers without known predisposition. The diagnosis of CRC was made during the study period in 29 veterans. In the remaining 25 patients, the colonoscopy was performed as a surveillance examination after previous surgery for CRC.

Potential Predictors of Early Death

To better define potential predictors of early death, we focused on the 258 persons (5.3%) who died within 2 years after the index procedure and paired them with matched controls. One patient underwent a colonoscopy for surveillance of previously treated cancer and was excluded due to very advanced age, as no matched control could be identified. The mean (SD) age of this male-predominant cohort was 68.2 (9.6) vs 67.9 (9.4) years for cases and controls, respectively. At the time of referral for the test, 29 persons (11.3%) were aged > 80 years, which is significantly more than seen for the overall cohort with 306 (6.3%; P < .001). While primary care providers accounted for most referrals in cases (85.2%) and controls (93.0%), the fraction of veterans referred by gastroenterologists or other specialty care providers was significantly higher in the case group compared with that in the controls (14.8% vs 7.0%; P < .05).

In our age-matched analysis, we examined other potential factors that could influence survival. The burden of comorbid conditions summarized in the Charlson Comorbidity Index significantly correlated with survival status (Table 4). As this composite index does not include psychiatric conditions, we separately examined the impact of anxiety, depression, bipolar disease, psychotic disorders, and substance abuse. The diagnoses of depression and substance use disorders (SUDs) were associated with higher rates of early death. Considering concerns about SUDs, we also assessed the association between prescription for opioids or benzodiazepines and survival status, which showed a marginal correlation. Anticoagulant use, a likely surrogate for cardiovascular disorders, were more commonly listed in the cases than they were in the controls.

Looking at specific comorbid conditions, significant problems affecting key organ systems from heart to lung, liver, kidneys, or brain (dementia) were all predictors of poor outcome. Similarly, DM with secondary complication correlated with early death after the index procedure. In contrast, a history of prior myocardial infarction, prior cancer treatment without evidence of persistent or recurrent disease, or prior peptic ulcer disease did not differ between cases and controls. Focusing on routine blood tests, we noted marginal, but statistically different results for Hgb, serum creatinine, and albumin in cases compared with controls.

Next we performed a logistic regression to identify independent predictors of survival status. The referring provider specialty, Charlson Comorbidity Index, the diagnosis of a SUD, current benzodiazepine use, and significant anemia or hypoalbuminemia independently predicted death within 2 years of the index examination (Table 5). Considering the composite nature of the Charlson Comorbidity Index, we separately examined the relative importance of different comorbid conditions using a logistic regression analysis. Consistent with the univariate analyses, a known malignancy; severe liver, lung, or kidney disease; and DM with secondary complications were associated with poor outcome. Only arrhythmias other than AF were independent marginal predictors of early death, whereas other variables related to cardiac performance did not reach the level of significance (Table 6). As was true for our analysis examining the composite comorbidity index, the diagnosis of a SUD remained significant as a predictor of death within 2 years of the index colonoscopy.

Discussion

This retrospective analysis followed patients for a mean time of 7 years after a colonoscopy for CRC screening or polyp surveillance. We noted a high rate of all-cause mortality, with 20% of the cohort dying within the period studied. Malignancies, cardiovascular diseases, and advanced lung diseases were most commonly listed causes of death. As expected, CRC was among the 3 most common malignancies and was the cause of death in 6.7% of the group with sufficiently detailed information. While these results fall within the expected range for the mortality related to CRC,⁹ the results do not allow us to assess the impact of screening, which has been shown to decrease cancer-related mortality in veterans.⁶ This was limited because the sample size was too small to assess the impact of screening and the cause of death was ascertained for a small percentage of the sample.

Although our findings are limited to a subset of patients seen in a single center, they suggest the importance of appropriate eligibility criteria for screening tests, as also defined in national guidelines.¹ As a key anchoring point that describes the target population, age contributed to the rate of relatively early death after the index procedure. Consistent with previously published data, we saw a significant impact of comorbid diseases.^10,11 However, our findings go beyond prior reports and show the important impact of psychiatric disease burden, most important the role of SUDs. The predictive value of a summary score, such as the Charlson Comorbidity Index, supports the idea of a cumulative impact, with an increasing disease burden decreasing life expectancy.^10-14 It is important to consider the ongoing impact of such coexisting illnesses. Our analysis shows, the mere history of prior problems did not independently predict survival status in our cohort.

Although age is the key anchoring point that defines the target population for CRC screening programs, the benefit of earlier cancer detection or, in the context of colonoscopy with polypectomy, cancer prevention comes with a delay. Thus, cancer risk, procedural risk, and life expectancy should all be weighed when discussing and deciding on the appropriateness of CRC screening. When we disregard inherited cancer syndromes, CRC is clearly a disease of the second half of life with the incidence increasing with age.¹⁵ However, other disease burdens rise, which may affects the risk of screening and treatment should cancer be found.

Using our understanding of disease development, researchers have introduced the concept of time to benefit or lag time to help decisions about screening strategies. The period defines the likely time for a precursor or early form of cancer potentially detected by screening to manifest as a clinically relevant lesion. This lag time becomes an especially important consideration in screening of older and/or chronically ill adults with life expectancies that may be close to or even less than the time to benefit.¹⁶ Modeling studies suggest that 1,000 flexible sigmoidoscopy screenings are needed to prevent 1 cancer that would manifest about 10 years after the index examination.^17,18 The mean life expectancy of a healthy person aged 75 years exceeds 10 years but drops with comorbidity burden. Consistent with these considerations, an analysis of Medicare claims data concluded that individuals with ≥ 3 significant comorbidities do not derive any benefit from screening colonoscopy.¹⁴ Looking at the impact of comorbidities, mathematical models concluded that colorectal cancer screening should not be continued in persons with moderate or severe comorbid conditions aged 66 years and 72 years, respectively.¹⁹ In contrast, modeling results suggest a benefit of continued screening up to and even above the age of 80 years if persons have an increased cancer risk and if there are no confounding comorbidities.⁴

Life expectancy and time to benefit describe probabilities. Although such probabilities are relevant in public policy decision, providers and patients may struggle with probabilistic thinking when faced with decisions that involve probabilities of individual health care vs population health care. Both are concerned about the seemingly gloomy or pessimistic undertone of discussing life expectancy and the inherent uncertainty of prognostic tools.^20,21 Prior research indicates that this reluctance translates into clinical practice. When faced with vignettes, most clinicians would offer CRC screening to healthy persons aged 80 years with rates falling when the description included a significant comorbid burden; however, more than 40% would still consider screening in octogenarians with poor health.²²

Consistent with these responses to theoretical scenarios, CRC screening of veterans dropped with age but was still continued in persons with significant comorbidity.²³ Large studies of the veteran population suggest that about 10% of veterans aged > 70 years have chronic medical problems that limit their life expectancy to < 5 years; nonetheless, more than 40% of this cohort underwent colonoscopies for CRC screening.^24,25 Interestingly, more illness burden and more clinical encounters translated into more screening examinations in older sick veterans compared with that of the cohort of healthier older persons, suggesting an impact of clinical reminders and the key role of age as the main anchoring variable.²³

Ongoing screening despite limited or even no benefit is not unique to CRC. Using validated tools, Pollock and colleagues showed comparable screening rates for breast and prostate cancer when they examined cohorts at either high or low risk of early mortality.²⁶ Similar results have been reported in veterans with about one-third of elderly males with poor life expectancy still undergoing prostate cancer screening.²⁷ Interestingly, inappropriate screening is more common in nonacademic centers and influenced by provider characteristics: nurse practitioner, physician assistants, older attending physicians and male physicians were more likely to order such tests.^27,28

Limitations

In this study, we examined a cohort of veterans enrolled in CRC screening within a single institution and obtained survival data for a mean follow-up of > 7 years. We also restricted our study to patients undergoing examinations that explicitly listed screening as indication or polyp surveillance for the test. However, inclusion was based on the indication listed in the report, which may differ from the intent of the ordering provider. Reporting systems often come with default settings, which may skew data. Comorbidities for the entire cohort of veterans who died within the time frame of the study were extracted from the chart without controlling for time-dependent changes, which may more appropriately describe the comorbidity burden at the time of the test. Using a case-control design, we addressed this potential caveat and included only illnesses recorded in the encounter linked to the colonoscopy order. Despite these limitations, our results highlight the importance to more effectively define and target appropriate candidates for CRC screening.

Conclusion

This study shows that age is a simple but not sufficiently accurate criterion to define potential candidates for CRC screening. As automated reminders often prompt discussions about and referral to screening examinations, we should develop algorithms that estimate the individual cancer risk and/or integrate an automatically calculated comorbidity index with these alerts or insert such a tool into order-sets. In addition, providers and patients need to be educated about the rationale and need for a more comprehensive approach to CRC screening that considers anticipated life expectancy. On an individual and health system level, our goal should be to reduce overall mortality rather than only cancer-specific death rates.

Clostridium difficile (C difficile) is a gram-positive, toxin-producing bacterium that is of increasing concern among health care providers and patients. Infection with C difficile can have manifestations ranging from mild diarrhea to severe toxic megacolon and can result in prolonged hospitalization with severe cases requiring admission to an intensive care unit.¹ In 2014, the US was estimated to have more than 600,000 cases of C difficile infection (CDI), previously known as C difficile–associated diarrhea, and more than 44,000 associated deaths. The annual economic cost of CDI is thought to exceed $5 billion.¹ According to studies of health care–associated illness, CDI rates are comparable to or have surpassed rates of methicillin-resistant Staphylococcus aureus infection within the US, including at US Department of Veterans Affairs (VA) acute care centers nationwide.^2,3

C difficile has been shown to be the causative agent in 10% to 20% of antibiotic-associated diarrhea episodes.⁴ Colonization of C difficile is uncommon in healthy adults, but colonization rates are as high as 21% in hospitalized patients, with increasing rates proportional to increasing hospital length of stay.^5,6 Although not all colonized patients develop clinically significant CDI, those who do may require multiple treatment courses, over months to years, because of the high risk of disease recurrence. An estimated 25% of patients have a single recurrent episode of CDI within 30 days after treatment completion, and 45% of those patients have additional recurrent infections.^7,8 Although probiotics do not have an approved US Food and Drug Administration (FDA) indication, these supplements are often used to try to prevent CDI from developing during concomitant antibiotic use. Probiotics are microorganisms with potential health benefits, but the mechanisms of these benefits are not fully understood. Proposed mechanisms include reduced growth of pathogenic bacteria, modulation of the immune system, and support of the intestinal wall barrier.⁹ The many probiotic formulations currently marketed include Lactobacillus acidophilus (L acidophilus) capsules and various combinations of L acidophilus, Lactobacillus casei, Bifidobacterium lactis, Bifidobacterium longum, Streptococcus thermophilus, and other bacterial strains.

Dosing and Guidelines

Manufacturers’ suggested dosing for their Lactobacillus capsules, tablets, and packets varies from 1 unit daily to 4 units 4 times daily for dietary supplementation; the products’ labeling does not include any information regarding treatment duration.^10-13 In addition, there are no published recommendations or product labeling guiding the dosing of probiotics or their duration of use in the primary prevention of CDI.

In 2017, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) updated their CDI treatment guidelines.¹⁴ As these guidelines indicate that the data on probiotic use in CDI are inadequate, IDSA and SHEA make no recommendation for or against probiotic use in primary prevention of the disease. The guidelines point to several limitations in the literature, including variability in probiotic formulations studied, duration of probiotic administration, definitions of CDI, and duration of study follow-up.

Given the lack of consensus guidelines that clinicians can use when deciding which probiotic dosing and duration are appropriate for a patient for primary prevention of CDI, we evaluated the literature on the topic and summarize their findings here.

Review of Probiotoc Literature

Conflicting data exist about probiotics and their effect on CDI prevention. The literature reviewed was selected based on our assessment of its contribution to the topic and its potential utility to clinicians in determining appropriate probiotic therapies and recommendations. Included in our discussion is a large Cochrane Review of probiotic efficacy, 2 trials of probiotic dosing, the PLACIDE trial, and a systematic review of timely probiotic initiation. All of these studies attempted to determine the effect of probiotics on CDI incidence (Table).

In their 2017 Cochrane Review, Goldenberg and colleagues reviewed 39 trials that investigated the efficacy of probiotics in CDI prevention in 9,955 immunocompetent patients receiving antibiotics.¹⁵ The incidence of CDI was significantly lower in patients who received a probiotic than in patients who received placebo or no treatment (1.5% vs 4.0%; relative risk [RR], 0.40; 95% CI, 0.30-0.52; I² = 0%). It is important to note that trials with a control-group CDI incidence of 0% to 2% (baseline CDI risk) found no statistically significant difference in CDI risk between patients using and not using probiotics (RR, 0.77; 95% CI, 0.45-1.32; I² = 0%) and that the preceding statistically significant result may have been driven by the inclusion of trials with high baseline CDI risk (> 5%). Trials that enrolled patients who were at this risk level found a statistically significant 70% reduction in CDI risk in those using probiotics (vs no probiotics) while on concomitant antibiotic therapy (RR, 0.30; 95% CI, 0.21-0.42; I² = 0%).

Probiotic therapy seems to be effective in reducing CDI risk in immunocompetent patients and may be particularly beneficial in patients at higher CDI risk, though Goldenberg and colleagues did not elaborate on what constitutes higher risk and based their conclusion on their control group’s high CDI incidence (> 5%). The most common adverse events (AEs) attributable to probiotics included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. The review’s findings are limited in that the inclusion of many small trials with high baseline CDI risk likely contributed to a statistically significant result, and 17 of the review’s 39 trials were industry-sponsored or were conducted by investigators with industry associations; another 12 lacked statements about funding or sponsorship.

Two of the trials in the Cochrane Review investigated whether probiotics have a dose effect on CDI prevention. Gao and colleagues randomly assigned 255 hospitalized Asian patients to 3 groups: those receiving placebo, 1 probiotic capsule daily, and 2 probiotic capsules daily.¹⁶ Each probiotic capsule contained 50 billion colony-forming units (CFUs) of Lactobacillus. Incidence of CDI was lower in patients taking 2 probiotic capsules daily than in those taking 1 probiotic capsule daily (1.2% vs 9.4%; P = .04) or placebo (1.2% vs 23.8%; P = .002). In the other trial, Ouwehand and colleagues randomly assigned 503 hospitalized Asian patients to 3 groups as well: those receiving placebo, low-dose probiotic (4.17 billion CFUs of Lactobacillus and Bifidobacterium), and high-dose probiotic (17 billion CFUs).¹⁷ The incidence of CDI in each probiotic group (low-dose, high-dose) was 1.8%, which was significantly lower than the 4.8% in the placebo group (P = .04).

The Cochrane Review’s largest and most rigorous trial was PLACIDE, a 2013 randomized controlled study of the effect of probiotics on CDI.¹⁸ Allen and colleagues randomly assigned 2,981 inpatients (aged ≥ 65 years; exposed to antibiotics within preceding 7 days) to 2 groups: those receiving either 1 probiotic capsule daily, or 1 placebo capsule daily, for 21 days. Results showed no difference in CDI incidence between the probiotic and placebo groups (0.8% vs 1.2%; RR, 0.71; 95% CI, 0.34-1.47; P = .35). Of note, this trial is free of industry sponsorship, is the largest probiotic trial to date, has a control-group baseline CDI rate consistent with the rate in hospital and ambulatory settings in the US, and found a negative result regarding probiotic use in CDI prevention. Findings are limited in that the study allowed for initiating probiotic therapy up to 7 days after the start of antibiotics, and patients were given 1 relatively low-dose capsule daily, which may have contributed to lack of an effect on CDI prevention. No serious AEs were attributed to probiotic use.

In a 2017 systematic meta-analysis of 19 studies, Shen and colleagues investigated whether timely use of probiotics prevented CDI in 6,261 hospitalized patients receiving antibiotics.¹⁹ The incidence of CDI was significantly lower in patients receiving vs not receiving probiotics (1.6% vs 3.9%; RR, 0.42; 95% CI, 0.30-0.57; I² = 0%; P < .001).¹⁹ A subgroup analysis was performed to compare studies initiating probiotics within 2 days after the start of antibiotics with studies initiating probiotics more than 2 days after the start. CDI risk was reduced by 68% when probiotics were started within 2 days, vs 30% when started after 2 days (RR, 0.32; 95% CI, 0.22-0.48; I² = 0% vs RR, 0.70; 95% CI, 0.40-1.23; I² = 0%; P = .02). Of note, no difference was found in efficacy among the various probiotic formulations, and no significant AEs were noted in any study group.

Trials included in the Cochrane Review used many different probiotic regimens over various durations.¹⁵ All these trials continued probiotics for at least the duration of antibiotic therapy. The 2 trials that evaluated the effect of probiotic therapy over an extended period required probiotics be started within 48 hours after initiation of antibiotic therapy; one trial continued probiotics for 5 days after completion of antibiotics, and the other for 7 days after completion.^16,20 In both trials, CDI was statistically significantly reduced among adults using probiotics compared with adults receiving placebo.

Probiotic Safety

The FDA has not approved probiotics for the prevention or treatment of any health problems. Most probiotics are FDA-regulated as dietary supplements and do not have to meet stringent drug-approval requirements. The FDA has given many strains of common probiotics the Generally Recognized as Safe designation for use in commercially available products and foods.^21-23 Probiotic use has not been associated with significant AEs in clinical trials and generally has been considered safe in immunocompetent and otherwise healthy persons.^15-19 However, clinical trials have been inadequate in reporting or investigating AEs; the alternative for evaluating the risks of probiotic therapy is case reports.^24,25 Theoretical risks associated with probiotics include sepsis, deleterious effects on normal gut digestion, excessive immune stimulation, and possible transfer of antimicrobial resistance genes among microorganisms.²⁶ Boyle and colleagues further described a handful of case reports of sepsis caused by probiotics in immunocompromised individuals; the other theoretical risks have not been reported outside animal studies.²⁶

CDI Risk Factors

Many factors can increase a patient’s CDI risk. Specific antibiotics (eg, ampicillin, amoxicillin, cephalosporins, clindamycin, fluoroquinolones) confer higher risk.^27,28 Other factors include inflammatory bowel disease, organ transplantation, chemotherapy, chronic kidney disease, and immunodeficiency. Advanced age increases CDI risk and can increase the severity of infection. The evidence regarding acid suppression and CDI risk is conflicting, though a recent meta-analysis found that use of proton pump inhibitors is associated with a 2-fold higher risk of developing CDI.²⁹ Patient-specific risk factors should be evaluated when the risk–benefit ratio for probiotic use is being considered.

Conclusion

CDIs are becoming increasingly burdensome to the health care system. More research is needed on the role of probiotics in CDI prevention in patients taking antibiotics. Given the limited risk for AEs when probiotics are used in immunocompetent patients and the relatively low cost of these supplements, the risks likely are outweighed by the postulated benefits, and probiotics may be recommended in select patient populations.

The PLACIDE trial found no benefit of probiotics in preventing CDI in a population similar to that of a typical US hospital or ambulatory setting, but its intervention allowed late initiation of relatively low doses of probiotics. Therefore, probiotics may be recommended for CDI prevention in patients taking antibiotics, especially patients at high risk for developing CDI. When clinicians recommend probiotic use in this setting, the probiotic should be initiated within 2 days after the start of antibiotics and should be continued for the duration of antibiotic therapy and for up to 7 days after that therapy is completed. Optimal probiotic dosing, likely dependent on the product used, remains unclear. PLACIDE trial results suggest that a dosage of at least 1 probiotic capsule 2 times daily may confer additional efficacy.

Clostridium difficile (C difficile) is a gram-positive, toxin-producing bacterium that is of increasing concern among health care providers and patients. Infection with C difficile can have manifestations ranging from mild diarrhea to severe toxic megacolon and can result in prolonged hospitalization with severe cases requiring admission to an intensive care unit.¹ In 2014, the US was estimated to have more than 600,000 cases of C difficile infection (CDI), previously known as C difficile–associated diarrhea, and more than 44,000 associated deaths. The annual economic cost of CDI is thought to exceed $5 billion.¹ According to studies of health care–associated illness, CDI rates are comparable to or have surpassed rates of methicillin-resistant Staphylococcus aureus infection within the US, including at US Department of Veterans Affairs (VA) acute care centers nationwide.^2,3

C difficile has been shown to be the causative agent in 10% to 20% of antibiotic-associated diarrhea episodes.⁴ Colonization of C difficile is uncommon in healthy adults, but colonization rates are as high as 21% in hospitalized patients, with increasing rates proportional to increasing hospital length of stay.^5,6 Although not all colonized patients develop clinically significant CDI, those who do may require multiple treatment courses, over months to years, because of the high risk of disease recurrence. An estimated 25% of patients have a single recurrent episode of CDI within 30 days after treatment completion, and 45% of those patients have additional recurrent infections.^7,8 Although probiotics do not have an approved US Food and Drug Administration (FDA) indication, these supplements are often used to try to prevent CDI from developing during concomitant antibiotic use. Probiotics are microorganisms with potential health benefits, but the mechanisms of these benefits are not fully understood. Proposed mechanisms include reduced growth of pathogenic bacteria, modulation of the immune system, and support of the intestinal wall barrier.⁹ The many probiotic formulations currently marketed include Lactobacillus acidophilus (L acidophilus) capsules and various combinations of L acidophilus, Lactobacillus casei, Bifidobacterium lactis, Bifidobacterium longum, Streptococcus thermophilus, and other bacterial strains.

Dosing and Guidelines

Manufacturers’ suggested dosing for their Lactobacillus capsules, tablets, and packets varies from 1 unit daily to 4 units 4 times daily for dietary supplementation; the products’ labeling does not include any information regarding treatment duration.^10-13 In addition, there are no published recommendations or product labeling guiding the dosing of probiotics or their duration of use in the primary prevention of CDI.

In 2017, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) updated their CDI treatment guidelines.¹⁴ As these guidelines indicate that the data on probiotic use in CDI are inadequate, IDSA and SHEA make no recommendation for or against probiotic use in primary prevention of the disease. The guidelines point to several limitations in the literature, including variability in probiotic formulations studied, duration of probiotic administration, definitions of CDI, and duration of study follow-up.

Given the lack of consensus guidelines that clinicians can use when deciding which probiotic dosing and duration are appropriate for a patient for primary prevention of CDI, we evaluated the literature on the topic and summarize their findings here.

Review of Probiotoc Literature

Conflicting data exist about probiotics and their effect on CDI prevention. The literature reviewed was selected based on our assessment of its contribution to the topic and its potential utility to clinicians in determining appropriate probiotic therapies and recommendations. Included in our discussion is a large Cochrane Review of probiotic efficacy, 2 trials of probiotic dosing, the PLACIDE trial, and a systematic review of timely probiotic initiation. All of these studies attempted to determine the effect of probiotics on CDI incidence (Table).

In their 2017 Cochrane Review, Goldenberg and colleagues reviewed 39 trials that investigated the efficacy of probiotics in CDI prevention in 9,955 immunocompetent patients receiving antibiotics.¹⁵ The incidence of CDI was significantly lower in patients who received a probiotic than in patients who received placebo or no treatment (1.5% vs 4.0%; relative risk [RR], 0.40; 95% CI, 0.30-0.52; I² = 0%). It is important to note that trials with a control-group CDI incidence of 0% to 2% (baseline CDI risk) found no statistically significant difference in CDI risk between patients using and not using probiotics (RR, 0.77; 95% CI, 0.45-1.32; I² = 0%) and that the preceding statistically significant result may have been driven by the inclusion of trials with high baseline CDI risk (> 5%). Trials that enrolled patients who were at this risk level found a statistically significant 70% reduction in CDI risk in those using probiotics (vs no probiotics) while on concomitant antibiotic therapy (RR, 0.30; 95% CI, 0.21-0.42; I² = 0%).

Probiotic therapy seems to be effective in reducing CDI risk in immunocompetent patients and may be particularly beneficial in patients at higher CDI risk, though Goldenberg and colleagues did not elaborate on what constitutes higher risk and based their conclusion on their control group’s high CDI incidence (> 5%). The most common adverse events (AEs) attributable to probiotics included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. The review’s findings are limited in that the inclusion of many small trials with high baseline CDI risk likely contributed to a statistically significant result, and 17 of the review’s 39 trials were industry-sponsored or were conducted by investigators with industry associations; another 12 lacked statements about funding or sponsorship.

Two of the trials in the Cochrane Review investigated whether probiotics have a dose effect on CDI prevention. Gao and colleagues randomly assigned 255 hospitalized Asian patients to 3 groups: those receiving placebo, 1 probiotic capsule daily, and 2 probiotic capsules daily.¹⁶ Each probiotic capsule contained 50 billion colony-forming units (CFUs) of Lactobacillus. Incidence of CDI was lower in patients taking 2 probiotic capsules daily than in those taking 1 probiotic capsule daily (1.2% vs 9.4%; P = .04) or placebo (1.2% vs 23.8%; P = .002). In the other trial, Ouwehand and colleagues randomly assigned 503 hospitalized Asian patients to 3 groups as well: those receiving placebo, low-dose probiotic (4.17 billion CFUs of Lactobacillus and Bifidobacterium), and high-dose probiotic (17 billion CFUs).¹⁷ The incidence of CDI in each probiotic group (low-dose, high-dose) was 1.8%, which was significantly lower than the 4.8% in the placebo group (P = .04).

The Cochrane Review’s largest and most rigorous trial was PLACIDE, a 2013 randomized controlled study of the effect of probiotics on CDI.¹⁸ Allen and colleagues randomly assigned 2,981 inpatients (aged ≥ 65 years; exposed to antibiotics within preceding 7 days) to 2 groups: those receiving either 1 probiotic capsule daily, or 1 placebo capsule daily, for 21 days. Results showed no difference in CDI incidence between the probiotic and placebo groups (0.8% vs 1.2%; RR, 0.71; 95% CI, 0.34-1.47; P = .35). Of note, this trial is free of industry sponsorship, is the largest probiotic trial to date, has a control-group baseline CDI rate consistent with the rate in hospital and ambulatory settings in the US, and found a negative result regarding probiotic use in CDI prevention. Findings are limited in that the study allowed for initiating probiotic therapy up to 7 days after the start of antibiotics, and patients were given 1 relatively low-dose capsule daily, which may have contributed to lack of an effect on CDI prevention. No serious AEs were attributed to probiotic use.

In a 2017 systematic meta-analysis of 19 studies, Shen and colleagues investigated whether timely use of probiotics prevented CDI in 6,261 hospitalized patients receiving antibiotics.¹⁹ The incidence of CDI was significantly lower in patients receiving vs not receiving probiotics (1.6% vs 3.9%; RR, 0.42; 95% CI, 0.30-0.57; I² = 0%; P < .001).¹⁹ A subgroup analysis was performed to compare studies initiating probiotics within 2 days after the start of antibiotics with studies initiating probiotics more than 2 days after the start. CDI risk was reduced by 68% when probiotics were started within 2 days, vs 30% when started after 2 days (RR, 0.32; 95% CI, 0.22-0.48; I² = 0% vs RR, 0.70; 95% CI, 0.40-1.23; I² = 0%; P = .02). Of note, no difference was found in efficacy among the various probiotic formulations, and no significant AEs were noted in any study group.

Trials included in the Cochrane Review used many different probiotic regimens over various durations.¹⁵ All these trials continued probiotics for at least the duration of antibiotic therapy. The 2 trials that evaluated the effect of probiotic therapy over an extended period required probiotics be started within 48 hours after initiation of antibiotic therapy; one trial continued probiotics for 5 days after completion of antibiotics, and the other for 7 days after completion.^16,20 In both trials, CDI was statistically significantly reduced among adults using probiotics compared with adults receiving placebo.

Probiotic Safety

The FDA has not approved probiotics for the prevention or treatment of any health problems. Most probiotics are FDA-regulated as dietary supplements and do not have to meet stringent drug-approval requirements. The FDA has given many strains of common probiotics the Generally Recognized as Safe designation for use in commercially available products and foods.^21-23 Probiotic use has not been associated with significant AEs in clinical trials and generally has been considered safe in immunocompetent and otherwise healthy persons.^15-19 However, clinical trials have been inadequate in reporting or investigating AEs; the alternative for evaluating the risks of probiotic therapy is case reports.^24,25 Theoretical risks associated with probiotics include sepsis, deleterious effects on normal gut digestion, excessive immune stimulation, and possible transfer of antimicrobial resistance genes among microorganisms.²⁶ Boyle and colleagues further described a handful of case reports of sepsis caused by probiotics in immunocompromised individuals; the other theoretical risks have not been reported outside animal studies.²⁶

CDI Risk Factors

Many factors can increase a patient’s CDI risk. Specific antibiotics (eg, ampicillin, amoxicillin, cephalosporins, clindamycin, fluoroquinolones) confer higher risk.^27,28 Other factors include inflammatory bowel disease, organ transplantation, chemotherapy, chronic kidney disease, and immunodeficiency. Advanced age increases CDI risk and can increase the severity of infection. The evidence regarding acid suppression and CDI risk is conflicting, though a recent meta-analysis found that use of proton pump inhibitors is associated with a 2-fold higher risk of developing CDI.²⁹ Patient-specific risk factors should be evaluated when the risk–benefit ratio for probiotic use is being considered.

Conclusion

CDIs are becoming increasingly burdensome to the health care system. More research is needed on the role of probiotics in CDI prevention in patients taking antibiotics. Given the limited risk for AEs when probiotics are used in immunocompetent patients and the relatively low cost of these supplements, the risks likely are outweighed by the postulated benefits, and probiotics may be recommended in select patient populations.

The PLACIDE trial found no benefit of probiotics in preventing CDI in a population similar to that of a typical US hospital or ambulatory setting, but its intervention allowed late initiation of relatively low doses of probiotics. Therefore, probiotics may be recommended for CDI prevention in patients taking antibiotics, especially patients at high risk for developing CDI. When clinicians recommend probiotic use in this setting, the probiotic should be initiated within 2 days after the start of antibiotics and should be continued for the duration of antibiotic therapy and for up to 7 days after that therapy is completed. Optimal probiotic dosing, likely dependent on the product used, remains unclear. PLACIDE trial results suggest that a dosage of at least 1 probiotic capsule 2 times daily may confer additional efficacy.

Clostridium difficile (C difficile) is a gram-positive, toxin-producing bacterium that is of increasing concern among health care providers and patients. Infection with C difficile can have manifestations ranging from mild diarrhea to severe toxic megacolon and can result in prolonged hospitalization with severe cases requiring admission to an intensive care unit.¹ In 2014, the US was estimated to have more than 600,000 cases of C difficile infection (CDI), previously known as C difficile–associated diarrhea, and more than 44,000 associated deaths. The annual economic cost of CDI is thought to exceed $5 billion.¹ According to studies of health care–associated illness, CDI rates are comparable to or have surpassed rates of methicillin-resistant Staphylococcus aureus infection within the US, including at US Department of Veterans Affairs (VA) acute care centers nationwide.^2,3

C difficile has been shown to be the causative agent in 10% to 20% of antibiotic-associated diarrhea episodes.⁴ Colonization of C difficile is uncommon in healthy adults, but colonization rates are as high as 21% in hospitalized patients, with increasing rates proportional to increasing hospital length of stay.^5,6 Although not all colonized patients develop clinically significant CDI, those who do may require multiple treatment courses, over months to years, because of the high risk of disease recurrence. An estimated 25% of patients have a single recurrent episode of CDI within 30 days after treatment completion, and 45% of those patients have additional recurrent infections.^7,8 Although probiotics do not have an approved US Food and Drug Administration (FDA) indication, these supplements are often used to try to prevent CDI from developing during concomitant antibiotic use. Probiotics are microorganisms with potential health benefits, but the mechanisms of these benefits are not fully understood. Proposed mechanisms include reduced growth of pathogenic bacteria, modulation of the immune system, and support of the intestinal wall barrier.⁹ The many probiotic formulations currently marketed include Lactobacillus acidophilus (L acidophilus) capsules and various combinations of L acidophilus, Lactobacillus casei, Bifidobacterium lactis, Bifidobacterium longum, Streptococcus thermophilus, and other bacterial strains.

Dosing and Guidelines

Manufacturers’ suggested dosing for their Lactobacillus capsules, tablets, and packets varies from 1 unit daily to 4 units 4 times daily for dietary supplementation; the products’ labeling does not include any information regarding treatment duration.^10-13 In addition, there are no published recommendations or product labeling guiding the dosing of probiotics or their duration of use in the primary prevention of CDI.

In 2017, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) updated their CDI treatment guidelines.¹⁴ As these guidelines indicate that the data on probiotic use in CDI are inadequate, IDSA and SHEA make no recommendation for or against probiotic use in primary prevention of the disease. The guidelines point to several limitations in the literature, including variability in probiotic formulations studied, duration of probiotic administration, definitions of CDI, and duration of study follow-up.

Given the lack of consensus guidelines that clinicians can use when deciding which probiotic dosing and duration are appropriate for a patient for primary prevention of CDI, we evaluated the literature on the topic and summarize their findings here.

Review of Probiotoc Literature

Conflicting data exist about probiotics and their effect on CDI prevention. The literature reviewed was selected based on our assessment of its contribution to the topic and its potential utility to clinicians in determining appropriate probiotic therapies and recommendations. Included in our discussion is a large Cochrane Review of probiotic efficacy, 2 trials of probiotic dosing, the PLACIDE trial, and a systematic review of timely probiotic initiation. All of these studies attempted to determine the effect of probiotics on CDI incidence (Table).

In their 2017 Cochrane Review, Goldenberg and colleagues reviewed 39 trials that investigated the efficacy of probiotics in CDI prevention in 9,955 immunocompetent patients receiving antibiotics.¹⁵ The incidence of CDI was significantly lower in patients who received a probiotic than in patients who received placebo or no treatment (1.5% vs 4.0%; relative risk [RR], 0.40; 95% CI, 0.30-0.52; I² = 0%). It is important to note that trials with a control-group CDI incidence of 0% to 2% (baseline CDI risk) found no statistically significant difference in CDI risk between patients using and not using probiotics (RR, 0.77; 95% CI, 0.45-1.32; I² = 0%) and that the preceding statistically significant result may have been driven by the inclusion of trials with high baseline CDI risk (> 5%). Trials that enrolled patients who were at this risk level found a statistically significant 70% reduction in CDI risk in those using probiotics (vs no probiotics) while on concomitant antibiotic therapy (RR, 0.30; 95% CI, 0.21-0.42; I² = 0%).

Probiotic therapy seems to be effective in reducing CDI risk in immunocompetent patients and may be particularly beneficial in patients at higher CDI risk, though Goldenberg and colleagues did not elaborate on what constitutes higher risk and based their conclusion on their control group’s high CDI incidence (> 5%). The most common adverse events (AEs) attributable to probiotics included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. The review’s findings are limited in that the inclusion of many small trials with high baseline CDI risk likely contributed to a statistically significant result, and 17 of the review’s 39 trials were industry-sponsored or were conducted by investigators with industry associations; another 12 lacked statements about funding or sponsorship.

Two of the trials in the Cochrane Review investigated whether probiotics have a dose effect on CDI prevention. Gao and colleagues randomly assigned 255 hospitalized Asian patients to 3 groups: those receiving placebo, 1 probiotic capsule daily, and 2 probiotic capsules daily.¹⁶ Each probiotic capsule contained 50 billion colony-forming units (CFUs) of Lactobacillus. Incidence of CDI was lower in patients taking 2 probiotic capsules daily than in those taking 1 probiotic capsule daily (1.2% vs 9.4%; P = .04) or placebo (1.2% vs 23.8%; P = .002). In the other trial, Ouwehand and colleagues randomly assigned 503 hospitalized Asian patients to 3 groups as well: those receiving placebo, low-dose probiotic (4.17 billion CFUs of Lactobacillus and Bifidobacterium), and high-dose probiotic (17 billion CFUs).¹⁷ The incidence of CDI in each probiotic group (low-dose, high-dose) was 1.8%, which was significantly lower than the 4.8% in the placebo group (P = .04).

The Cochrane Review’s largest and most rigorous trial was PLACIDE, a 2013 randomized controlled study of the effect of probiotics on CDI.¹⁸ Allen and colleagues randomly assigned 2,981 inpatients (aged ≥ 65 years; exposed to antibiotics within preceding 7 days) to 2 groups: those receiving either 1 probiotic capsule daily, or 1 placebo capsule daily, for 21 days. Results showed no difference in CDI incidence between the probiotic and placebo groups (0.8% vs 1.2%; RR, 0.71; 95% CI, 0.34-1.47; P = .35). Of note, this trial is free of industry sponsorship, is the largest probiotic trial to date, has a control-group baseline CDI rate consistent with the rate in hospital and ambulatory settings in the US, and found a negative result regarding probiotic use in CDI prevention. Findings are limited in that the study allowed for initiating probiotic therapy up to 7 days after the start of antibiotics, and patients were given 1 relatively low-dose capsule daily, which may have contributed to lack of an effect on CDI prevention. No serious AEs were attributed to probiotic use.

In a 2017 systematic meta-analysis of 19 studies, Shen and colleagues investigated whether timely use of probiotics prevented CDI in 6,261 hospitalized patients receiving antibiotics.¹⁹ The incidence of CDI was significantly lower in patients receiving vs not receiving probiotics (1.6% vs 3.9%; RR, 0.42; 95% CI, 0.30-0.57; I² = 0%; P < .001).¹⁹ A subgroup analysis was performed to compare studies initiating probiotics within 2 days after the start of antibiotics with studies initiating probiotics more than 2 days after the start. CDI risk was reduced by 68% when probiotics were started within 2 days, vs 30% when started after 2 days (RR, 0.32; 95% CI, 0.22-0.48; I² = 0% vs RR, 0.70; 95% CI, 0.40-1.23; I² = 0%; P = .02). Of note, no difference was found in efficacy among the various probiotic formulations, and no significant AEs were noted in any study group.

Trials included in the Cochrane Review used many different probiotic regimens over various durations.¹⁵ All these trials continued probiotics for at least the duration of antibiotic therapy. The 2 trials that evaluated the effect of probiotic therapy over an extended period required probiotics be started within 48 hours after initiation of antibiotic therapy; one trial continued probiotics for 5 days after completion of antibiotics, and the other for 7 days after completion.^16,20 In both trials, CDI was statistically significantly reduced among adults using probiotics compared with adults receiving placebo.

Probiotic Safety

The FDA has not approved probiotics for the prevention or treatment of any health problems. Most probiotics are FDA-regulated as dietary supplements and do not have to meet stringent drug-approval requirements. The FDA has given many strains of common probiotics the Generally Recognized as Safe designation for use in commercially available products and foods.^21-23 Probiotic use has not been associated with significant AEs in clinical trials and generally has been considered safe in immunocompetent and otherwise healthy persons.^15-19 However, clinical trials have been inadequate in reporting or investigating AEs; the alternative for evaluating the risks of probiotic therapy is case reports.^24,25 Theoretical risks associated with probiotics include sepsis, deleterious effects on normal gut digestion, excessive immune stimulation, and possible transfer of antimicrobial resistance genes among microorganisms.²⁶ Boyle and colleagues further described a handful of case reports of sepsis caused by probiotics in immunocompromised individuals; the other theoretical risks have not been reported outside animal studies.²⁶

CDI Risk Factors

Many factors can increase a patient’s CDI risk. Specific antibiotics (eg, ampicillin, amoxicillin, cephalosporins, clindamycin, fluoroquinolones) confer higher risk.^27,28 Other factors include inflammatory bowel disease, organ transplantation, chemotherapy, chronic kidney disease, and immunodeficiency. Advanced age increases CDI risk and can increase the severity of infection. The evidence regarding acid suppression and CDI risk is conflicting, though a recent meta-analysis found that use of proton pump inhibitors is associated with a 2-fold higher risk of developing CDI.²⁹ Patient-specific risk factors should be evaluated when the risk–benefit ratio for probiotic use is being considered.

Conclusion

CDIs are becoming increasingly burdensome to the health care system. More research is needed on the role of probiotics in CDI prevention in patients taking antibiotics. Given the limited risk for AEs when probiotics are used in immunocompetent patients and the relatively low cost of these supplements, the risks likely are outweighed by the postulated benefits, and probiotics may be recommended in select patient populations.

The PLACIDE trial found no benefit of probiotics in preventing CDI in a population similar to that of a typical US hospital or ambulatory setting, but its intervention allowed late initiation of relatively low doses of probiotics. Therefore, probiotics may be recommended for CDI prevention in patients taking antibiotics, especially patients at high risk for developing CDI. When clinicians recommend probiotic use in this setting, the probiotic should be initiated within 2 days after the start of antibiotics and should be continued for the duration of antibiotic therapy and for up to 7 days after that therapy is completed. Optimal probiotic dosing, likely dependent on the product used, remains unclear. PLACIDE trial results suggest that a dosage of at least 1 probiotic capsule 2 times daily may confer additional efficacy.