In December 2014, nearly three years since its launch, the Centers for Medicare and Medicaid Services (CMS) issued the first proposed rule changes to the Shared Savings Program. The changes, if approved, would take effect in the 2016 performance year and would focus on a host of alterations impacting participating accountable care organizations (ACOs), including reduced administrative burden, improved function and transparency, and enhanced incentives to participate in risk-based models.

Experts say the changes could address some of the biggest flaws in the program but also may not go far enough to incentivize more healthcare providers to participate—or protect them from the risk of financial loss. The rules are under review following a public comment period.

“Many features about the original rules weaken the incentives to participate in ACOs,” says Michael McWilliams, MD, PhD, associate professor of healthcare policy and medicine at Harvard Medical School and a practicing primary care physician at Brigham and Women’s Hospital in Boston.

The ACO model encourages providers to realize savings under fee-for-service Medicare through better-coordinated care and improvements in metrics related to utilization and quality. Any savings relative to a benchmark year are shared between the ACO and CMS.

This year, 424 ACOs are participating in the program nationwide, and while the number of Pioneer ACOs has fallen in recent years (Pioneer ACOs wager higher savings for participants at the risk of greater financial loss), a new independent report commissioned by CMS shows the program saved more than $300 annually per beneficiary in its first two years, achieving $384 million in savings.¹ In a statement, CMS concluded this meets the criteria for expanding the Pioneer program; however, Dr. McWilliams says policy changes may still be needed to encourage participation in ACOs with downside risk.

In January, Dr. McWilliams and colleagues published a study in Health Affairs that demonstrated that existing benchmark rules may actually encourage higher Medicare spending as ACOs try to “fatten up” so they have more improvements to make and, therefore, more chance of success at realizing savings.²

Currently, providers’ performance is stacked against their performance and cost benchmarks established in the year prior to forming an ACO. As improvements are made, it becomes increasingly challenging for ACOs to do better. Dr. McWilliams says ACOs should instead be compared to other ACOs and providers.

It’s a “melting ice cube problem,” says Gregory Burke, MPA, director of innovation strategies for New York-based United Health Fund (UHF), a research and philanthropic organization focused on advancing healthcare.

“You are punishing the good, lean providers that are efficient,” he adds, “and rewarding people who are less efficient, in terms of cost of care and utilization of services.”

Burke and a colleague at UHF, health policy analyst Suzanne Brundage, recently completed qualitative and quantitative reports on ACOs in the state of New York, which currently make up 20% of Medicare fee-for-service beneficiaries.^3,4

Through their analysis, which included structured interviews with 17 Pioneer ACO leaders, Burke and Brundage found ACO rules could change in the following ways to make the program sustainable and more attractive to providers:

• Patients should be attributed to PCPs within the ACO;
• Risk adjustment should be made for ACO providers serving a sicker population of patients; and
• Benchmark rules should be altered.

Additionally, Dr. McWilliams says the shared savings rate realized by ACOs should be higher than 50%, which is especially true for hospitals within an ACO, since the goals of the program are to reduce hospital visits, extensive specialist services, and testing services.

“For a hospital system, the bulk of the money comes from inpatient care,” Burke says. “We’re saying: ‘You stomp on your own air hose today, and a year from now I’ll give you 50% oxygen—and you have to share with your buddy.’”

The 2014 State of Hospital Medicine report indicates that 36% of adult hospitalist medicine groups are in hospitals either already involved in or considering involvement in an ACO; however, respondents in that report also reflect no clear role for hospitalists in the ACO model.

This is a point disputed by Val Akopov, MD, vice president and chief of hospital medicine at WellStar Health System, a not-for-profit organization in northwestern Atlanta and a participating ACO. Dr. Akopov highlights ways in which hospitals and hospitalists could take advantage of the model.

“Five measures fall into the domain of care coordination that are directly, unequivocally related to what hospitalists do, and these metrics are part of, in my opinion, what any hospital medicine program should have as a value proposition,” Dr. Akopov says.

At WellStar, for example, hospitalists have become part of the ACO structure by serving as medical directors and attending physicians at skilled nursing facilities (SNFs). They are “solely responsible to attend to patients in SNFs, and we have seen a dramatic improvement in readmission rates and quality metrics in nursing homes, such as incidence of falls, use of antipsychotics, and 30-day unplanned readmissions to acute care hospitals,” Dr. Akopov explains.

Additionally, WellStar hospitalists work with each inpatient to ensure they have primary care follow-up scheduled before discharge, Dr. Akopov says, noting that the model is a good opportunity to explore changes to the way hospitals and providers deliver care.

“There are roughly 38,000 Medicare patients in [our] ACO; it’s much easier to work out the kinks with innovations on a limited patient population and then extrapolate findings on 1.5 million annually, rather than trying to bite too much,” he says.

Despite the challenges, experts are optimistic the ACO model can—and will—work. In their reporting, Burke and Brundage found healthcare leaders participating in ACOs remain optimistic.

“It’s a post-Copernican universe, where the world no longer revolves around the hospital, so balancing the equation is a little different,” Burke says. “But they’re staying in the game, because that’s where the puck is going to be.”

Kelly April Tyrrell is a freelance writer in Madison, Wis.

References

1. Affordable Care Act payment model saves more than $384 million in two years, meets criteria for first-ever expansion. Centers for Medicare & Medicaid Services website. Published May 4, 2015. Accessed May 11, 2015.
2. Douven R, McGuire TG, McWilliams JM. Avoiding unintended incentives in ACO payment models. Health Aff. 2015;34(1):143-149.
3. Burke, G, Brundage S. Accountable care in New York state: emerging themes and issues. United Hospital Fund. Accessed May 9, 2015.
4. Burke, G and Brundage S. New York’s Medicare ACOs: participants and performance. United Hospital Fund. Accessed May 9, 2015.

In December 2014, nearly three years since its launch, the Centers for Medicare and Medicaid Services (CMS) issued the first proposed rule changes to the Shared Savings Program. The changes, if approved, would take effect in the 2016 performance year and would focus on a host of alterations impacting participating accountable care organizations (ACOs), including reduced administrative burden, improved function and transparency, and enhanced incentives to participate in risk-based models.

Experts say the changes could address some of the biggest flaws in the program but also may not go far enough to incentivize more healthcare providers to participate—or protect them from the risk of financial loss. The rules are under review following a public comment period.

“Many features about the original rules weaken the incentives to participate in ACOs,” says Michael McWilliams, MD, PhD, associate professor of healthcare policy and medicine at Harvard Medical School and a practicing primary care physician at Brigham and Women’s Hospital in Boston.

The ACO model encourages providers to realize savings under fee-for-service Medicare through better-coordinated care and improvements in metrics related to utilization and quality. Any savings relative to a benchmark year are shared between the ACO and CMS.

This year, 424 ACOs are participating in the program nationwide, and while the number of Pioneer ACOs has fallen in recent years (Pioneer ACOs wager higher savings for participants at the risk of greater financial loss), a new independent report commissioned by CMS shows the program saved more than $300 annually per beneficiary in its first two years, achieving $384 million in savings.¹ In a statement, CMS concluded this meets the criteria for expanding the Pioneer program; however, Dr. McWilliams says policy changes may still be needed to encourage participation in ACOs with downside risk.

In January, Dr. McWilliams and colleagues published a study in Health Affairs that demonstrated that existing benchmark rules may actually encourage higher Medicare spending as ACOs try to “fatten up” so they have more improvements to make and, therefore, more chance of success at realizing savings.²

Currently, providers’ performance is stacked against their performance and cost benchmarks established in the year prior to forming an ACO. As improvements are made, it becomes increasingly challenging for ACOs to do better. Dr. McWilliams says ACOs should instead be compared to other ACOs and providers.

It’s a “melting ice cube problem,” says Gregory Burke, MPA, director of innovation strategies for New York-based United Health Fund (UHF), a research and philanthropic organization focused on advancing healthcare.

“You are punishing the good, lean providers that are efficient,” he adds, “and rewarding people who are less efficient, in terms of cost of care and utilization of services.”

Burke and a colleague at UHF, health policy analyst Suzanne Brundage, recently completed qualitative and quantitative reports on ACOs in the state of New York, which currently make up 20% of Medicare fee-for-service beneficiaries.^3,4

Through their analysis, which included structured interviews with 17 Pioneer ACO leaders, Burke and Brundage found ACO rules could change in the following ways to make the program sustainable and more attractive to providers:

• Patients should be attributed to PCPs within the ACO;
• Risk adjustment should be made for ACO providers serving a sicker population of patients; and
• Benchmark rules should be altered.

Additionally, Dr. McWilliams says the shared savings rate realized by ACOs should be higher than 50%, which is especially true for hospitals within an ACO, since the goals of the program are to reduce hospital visits, extensive specialist services, and testing services.

“For a hospital system, the bulk of the money comes from inpatient care,” Burke says. “We’re saying: ‘You stomp on your own air hose today, and a year from now I’ll give you 50% oxygen—and you have to share with your buddy.’”

The 2014 State of Hospital Medicine report indicates that 36% of adult hospitalist medicine groups are in hospitals either already involved in or considering involvement in an ACO; however, respondents in that report also reflect no clear role for hospitalists in the ACO model.

This is a point disputed by Val Akopov, MD, vice president and chief of hospital medicine at WellStar Health System, a not-for-profit organization in northwestern Atlanta and a participating ACO. Dr. Akopov highlights ways in which hospitals and hospitalists could take advantage of the model.

“Five measures fall into the domain of care coordination that are directly, unequivocally related to what hospitalists do, and these metrics are part of, in my opinion, what any hospital medicine program should have as a value proposition,” Dr. Akopov says.

At WellStar, for example, hospitalists have become part of the ACO structure by serving as medical directors and attending physicians at skilled nursing facilities (SNFs). They are “solely responsible to attend to patients in SNFs, and we have seen a dramatic improvement in readmission rates and quality metrics in nursing homes, such as incidence of falls, use of antipsychotics, and 30-day unplanned readmissions to acute care hospitals,” Dr. Akopov explains.

Additionally, WellStar hospitalists work with each inpatient to ensure they have primary care follow-up scheduled before discharge, Dr. Akopov says, noting that the model is a good opportunity to explore changes to the way hospitals and providers deliver care.

“There are roughly 38,000 Medicare patients in [our] ACO; it’s much easier to work out the kinks with innovations on a limited patient population and then extrapolate findings on 1.5 million annually, rather than trying to bite too much,” he says.

Despite the challenges, experts are optimistic the ACO model can—and will—work. In their reporting, Burke and Brundage found healthcare leaders participating in ACOs remain optimistic.

“It’s a post-Copernican universe, where the world no longer revolves around the hospital, so balancing the equation is a little different,” Burke says. “But they’re staying in the game, because that’s where the puck is going to be.”

Kelly April Tyrrell is a freelance writer in Madison, Wis.

References

1. Affordable Care Act payment model saves more than $384 million in two years, meets criteria for first-ever expansion. Centers for Medicare & Medicaid Services website. Published May 4, 2015. Accessed May 11, 2015.
2. Douven R, McGuire TG, McWilliams JM. Avoiding unintended incentives in ACO payment models. Health Aff. 2015;34(1):143-149.
3. Burke, G, Brundage S. Accountable care in New York state: emerging themes and issues. United Hospital Fund. Accessed May 9, 2015.
4. Burke, G and Brundage S. New York’s Medicare ACOs: participants and performance. United Hospital Fund. Accessed May 9, 2015.

In December 2014, nearly three years since its launch, the Centers for Medicare and Medicaid Services (CMS) issued the first proposed rule changes to the Shared Savings Program. The changes, if approved, would take effect in the 2016 performance year and would focus on a host of alterations impacting participating accountable care organizations (ACOs), including reduced administrative burden, improved function and transparency, and enhanced incentives to participate in risk-based models.

Experts say the changes could address some of the biggest flaws in the program but also may not go far enough to incentivize more healthcare providers to participate—or protect them from the risk of financial loss. The rules are under review following a public comment period.

“Many features about the original rules weaken the incentives to participate in ACOs,” says Michael McWilliams, MD, PhD, associate professor of healthcare policy and medicine at Harvard Medical School and a practicing primary care physician at Brigham and Women’s Hospital in Boston.

The ACO model encourages providers to realize savings under fee-for-service Medicare through better-coordinated care and improvements in metrics related to utilization and quality. Any savings relative to a benchmark year are shared between the ACO and CMS.

This year, 424 ACOs are participating in the program nationwide, and while the number of Pioneer ACOs has fallen in recent years (Pioneer ACOs wager higher savings for participants at the risk of greater financial loss), a new independent report commissioned by CMS shows the program saved more than $300 annually per beneficiary in its first two years, achieving $384 million in savings.¹ In a statement, CMS concluded this meets the criteria for expanding the Pioneer program; however, Dr. McWilliams says policy changes may still be needed to encourage participation in ACOs with downside risk.

In January, Dr. McWilliams and colleagues published a study in Health Affairs that demonstrated that existing benchmark rules may actually encourage higher Medicare spending as ACOs try to “fatten up” so they have more improvements to make and, therefore, more chance of success at realizing savings.²

Currently, providers’ performance is stacked against their performance and cost benchmarks established in the year prior to forming an ACO. As improvements are made, it becomes increasingly challenging for ACOs to do better. Dr. McWilliams says ACOs should instead be compared to other ACOs and providers.

It’s a “melting ice cube problem,” says Gregory Burke, MPA, director of innovation strategies for New York-based United Health Fund (UHF), a research and philanthropic organization focused on advancing healthcare.

“You are punishing the good, lean providers that are efficient,” he adds, “and rewarding people who are less efficient, in terms of cost of care and utilization of services.”

Burke and a colleague at UHF, health policy analyst Suzanne Brundage, recently completed qualitative and quantitative reports on ACOs in the state of New York, which currently make up 20% of Medicare fee-for-service beneficiaries.^3,4

Through their analysis, which included structured interviews with 17 Pioneer ACO leaders, Burke and Brundage found ACO rules could change in the following ways to make the program sustainable and more attractive to providers:

• Patients should be attributed to PCPs within the ACO;
• Risk adjustment should be made for ACO providers serving a sicker population of patients; and
• Benchmark rules should be altered.

Additionally, Dr. McWilliams says the shared savings rate realized by ACOs should be higher than 50%, which is especially true for hospitals within an ACO, since the goals of the program are to reduce hospital visits, extensive specialist services, and testing services.

“For a hospital system, the bulk of the money comes from inpatient care,” Burke says. “We’re saying: ‘You stomp on your own air hose today, and a year from now I’ll give you 50% oxygen—and you have to share with your buddy.’”

The 2014 State of Hospital Medicine report indicates that 36% of adult hospitalist medicine groups are in hospitals either already involved in or considering involvement in an ACO; however, respondents in that report also reflect no clear role for hospitalists in the ACO model.

This is a point disputed by Val Akopov, MD, vice president and chief of hospital medicine at WellStar Health System, a not-for-profit organization in northwestern Atlanta and a participating ACO. Dr. Akopov highlights ways in which hospitals and hospitalists could take advantage of the model.

“Five measures fall into the domain of care coordination that are directly, unequivocally related to what hospitalists do, and these metrics are part of, in my opinion, what any hospital medicine program should have as a value proposition,” Dr. Akopov says.

At WellStar, for example, hospitalists have become part of the ACO structure by serving as medical directors and attending physicians at skilled nursing facilities (SNFs). They are “solely responsible to attend to patients in SNFs, and we have seen a dramatic improvement in readmission rates and quality metrics in nursing homes, such as incidence of falls, use of antipsychotics, and 30-day unplanned readmissions to acute care hospitals,” Dr. Akopov explains.

Additionally, WellStar hospitalists work with each inpatient to ensure they have primary care follow-up scheduled before discharge, Dr. Akopov says, noting that the model is a good opportunity to explore changes to the way hospitals and providers deliver care.

“There are roughly 38,000 Medicare patients in [our] ACO; it’s much easier to work out the kinks with innovations on a limited patient population and then extrapolate findings on 1.5 million annually, rather than trying to bite too much,” he says.

Despite the challenges, experts are optimistic the ACO model can—and will—work. In their reporting, Burke and Brundage found healthcare leaders participating in ACOs remain optimistic.

“It’s a post-Copernican universe, where the world no longer revolves around the hospital, so balancing the equation is a little different,” Burke says. “But they’re staying in the game, because that’s where the puck is going to be.”

Kelly April Tyrrell is a freelance writer in Madison, Wis.

References

1. Affordable Care Act payment model saves more than $384 million in two years, meets criteria for first-ever expansion. Centers for Medicare & Medicaid Services website. Published May 4, 2015. Accessed May 11, 2015.
2. Douven R, McGuire TG, McWilliams JM. Avoiding unintended incentives in ACO payment models. Health Aff. 2015;34(1):143-149.
3. Burke, G, Brundage S. Accountable care in New York state: emerging themes and issues. United Hospital Fund. Accessed May 9, 2015.
4. Burke, G and Brundage S. New York’s Medicare ACOs: participants and performance. United Hospital Fund. Accessed May 9, 2015.

The estimated total amount of uncompensated costs incurred by hospitals in 2014 was $27.3 billion, which is $7.4 billion, or 21 percent, less than uncompensated hospital care would have been in 2014 at 2013 levels, before Accountable Care Act Medicaid coverage provisions took effect. Federal data reported by CNBC on March 23 indicate most of the reduction came in the 28 states and the District of Columbia that expanded their Medicare programs under the act to cover nearly all poor people in their states, while those that did not could have seen their revenues decline by an additional $1.4 billion.

The estimated total amount of uncompensated costs incurred by hospitals in 2014 was $27.3 billion, which is $7.4 billion, or 21 percent, less than uncompensated hospital care would have been in 2014 at 2013 levels, before Accountable Care Act Medicaid coverage provisions took effect. Federal data reported by CNBC on March 23 indicate most of the reduction came in the 28 states and the District of Columbia that expanded their Medicare programs under the act to cover nearly all poor people in their states, while those that did not could have seen their revenues decline by an additional $1.4 billion.

The estimated total amount of uncompensated costs incurred by hospitals in 2014 was $27.3 billion, which is $7.4 billion, or 21 percent, less than uncompensated hospital care would have been in 2014 at 2013 levels, before Accountable Care Act Medicaid coverage provisions took effect. Federal data reported by CNBC on March 23 indicate most of the reduction came in the 28 states and the District of Columbia that expanded their Medicare programs under the act to cover nearly all poor people in their states, while those that did not could have seen their revenues decline by an additional $1.4 billion.

A best-of-research plenary presentation at HM15 in National Harbor, Md., described a project to link physicians’ schedules to the electronic health record (EHR) in order to provide real-time, individualized performance feedback on key quality improvement and value metrics.

The abstract’s lead author, Victoria Valencia, MPH, a research data and project manager at the University of California San Francisco (UCSF), explains that quality improvement priorities have driven feedback of quality metrics at the department level.

“Where I came in was to try to get the same quality metrics down to the level of the team,” she says. “We take data from our EPIC EHR, clean it up by removing outliers, merge it with our online scheduling program, and provide a robust visual presentation of individualized, real-time performance feedback to the clinical team.”

One example is counting the total number of phlebotomy “sticks” per day, per patient. Reporting this data helped to reduce the number of “sticks per day” by 20%, to 1.6 from 2.0. A similar approach is used for care transitions and the percentage of discharges with high-quality, after-visit summaries.

“The feedback is timely and actionable and allows the teams to address areas needing improvement,” Valencia says.

How have the doctors responded to this feedback?

“Our division is used to receiving quality feedback as part of an ongoing process that includes working meetings where the metrics are reviewed,” she says, adding that there hasn’t been pushback from the teams over these reports.

A best-of-research plenary presentation at HM15 in National Harbor, Md., described a project to link physicians’ schedules to the electronic health record (EHR) in order to provide real-time, individualized performance feedback on key quality improvement and value metrics.

The abstract’s lead author, Victoria Valencia, MPH, a research data and project manager at the University of California San Francisco (UCSF), explains that quality improvement priorities have driven feedback of quality metrics at the department level.

“Where I came in was to try to get the same quality metrics down to the level of the team,” she says. “We take data from our EPIC EHR, clean it up by removing outliers, merge it with our online scheduling program, and provide a robust visual presentation of individualized, real-time performance feedback to the clinical team.”

One example is counting the total number of phlebotomy “sticks” per day, per patient. Reporting this data helped to reduce the number of “sticks per day” by 20%, to 1.6 from 2.0. A similar approach is used for care transitions and the percentage of discharges with high-quality, after-visit summaries.

“The feedback is timely and actionable and allows the teams to address areas needing improvement,” Valencia says.

How have the doctors responded to this feedback?

“Our division is used to receiving quality feedback as part of an ongoing process that includes working meetings where the metrics are reviewed,” she says, adding that there hasn’t been pushback from the teams over these reports.

A best-of-research plenary presentation at HM15 in National Harbor, Md., described a project to link physicians’ schedules to the electronic health record (EHR) in order to provide real-time, individualized performance feedback on key quality improvement and value metrics.

The abstract’s lead author, Victoria Valencia, MPH, a research data and project manager at the University of California San Francisco (UCSF), explains that quality improvement priorities have driven feedback of quality metrics at the department level.

“Where I came in was to try to get the same quality metrics down to the level of the team,” she says. “We take data from our EPIC EHR, clean it up by removing outliers, merge it with our online scheduling program, and provide a robust visual presentation of individualized, real-time performance feedback to the clinical team.”

One example is counting the total number of phlebotomy “sticks” per day, per patient. Reporting this data helped to reduce the number of “sticks per day” by 20%, to 1.6 from 2.0. A similar approach is used for care transitions and the percentage of discharges with high-quality, after-visit summaries.

“The feedback is timely and actionable and allows the teams to address areas needing improvement,” Valencia says.

How have the doctors responded to this feedback?

“Our division is used to receiving quality feedback as part of an ongoing process that includes working meetings where the metrics are reviewed,” she says, adding that there hasn’t been pushback from the teams over these reports.

Research published earlier this year in the Journal of Hospital Medicine finds that rationales offered by physicians for overriding interruptive, computerized best practice alerts (BPAs) regarding whether or not to give blood transfusions vary widely, including specialty service protocolized behaviors, anticipation of surgical or procedural interventions, and imminent hospital transfers.

The electronic health record at Stanford University Medical Center in Palo Alto, Calif., has an automated alert function to check reported hemoglobin level and trigger a pop-up reminder when a doctor orders a transfusion for a patient with a hemoglobin level of 9 or above—outside of the recognized guidelines—prompting the doctor to either abort the transfusion or provide a reason for the override, explains co-author Lisa Shieh, MD, PhD, FHM, medical director of quality in the department of medicine at Stanford.

“Our study was trying to understand why providers still transfuse, even when we provide just-in-time education on transfusion recommendations,” she says. “We can’t say that all of these orders are inappropriate. But, for many reasons, blood has harms and is costly.

“We want to convey an overall understanding about why this issue is important.”

Although a substantial number of transfusions continue outside of the recommended guidelines, Stanford has reduced its numbers significantly.

“I’m a big believer in clinical decision support … if it’s designed well and doesn’t add to alert fatigue,” Dr. Shieh says. “I think this BPA was effective in education and making people stop and think why they were ordering transfusions. Our next step will be to look at the outlier practices and maybe have a conversation with them, doctor to doctor.”

Stanford is looking at sepsis treatment as a next target.

Research published earlier this year in the Journal of Hospital Medicine finds that rationales offered by physicians for overriding interruptive, computerized best practice alerts (BPAs) regarding whether or not to give blood transfusions vary widely, including specialty service protocolized behaviors, anticipation of surgical or procedural interventions, and imminent hospital transfers.

The electronic health record at Stanford University Medical Center in Palo Alto, Calif., has an automated alert function to check reported hemoglobin level and trigger a pop-up reminder when a doctor orders a transfusion for a patient with a hemoglobin level of 9 or above—outside of the recognized guidelines—prompting the doctor to either abort the transfusion or provide a reason for the override, explains co-author Lisa Shieh, MD, PhD, FHM, medical director of quality in the department of medicine at Stanford.

“Our study was trying to understand why providers still transfuse, even when we provide just-in-time education on transfusion recommendations,” she says. “We can’t say that all of these orders are inappropriate. But, for many reasons, blood has harms and is costly.

“We want to convey an overall understanding about why this issue is important.”

Although a substantial number of transfusions continue outside of the recommended guidelines, Stanford has reduced its numbers significantly.

“I’m a big believer in clinical decision support … if it’s designed well and doesn’t add to alert fatigue,” Dr. Shieh says. “I think this BPA was effective in education and making people stop and think why they were ordering transfusions. Our next step will be to look at the outlier practices and maybe have a conversation with them, doctor to doctor.”

Stanford is looking at sepsis treatment as a next target.

Research published earlier this year in the Journal of Hospital Medicine finds that rationales offered by physicians for overriding interruptive, computerized best practice alerts (BPAs) regarding whether or not to give blood transfusions vary widely, including specialty service protocolized behaviors, anticipation of surgical or procedural interventions, and imminent hospital transfers.

The electronic health record at Stanford University Medical Center in Palo Alto, Calif., has an automated alert function to check reported hemoglobin level and trigger a pop-up reminder when a doctor orders a transfusion for a patient with a hemoglobin level of 9 or above—outside of the recognized guidelines—prompting the doctor to either abort the transfusion or provide a reason for the override, explains co-author Lisa Shieh, MD, PhD, FHM, medical director of quality in the department of medicine at Stanford.

“Our study was trying to understand why providers still transfuse, even when we provide just-in-time education on transfusion recommendations,” she says. “We can’t say that all of these orders are inappropriate. But, for many reasons, blood has harms and is costly.

“We want to convey an overall understanding about why this issue is important.”

Although a substantial number of transfusions continue outside of the recommended guidelines, Stanford has reduced its numbers significantly.

“I’m a big believer in clinical decision support … if it’s designed well and doesn’t add to alert fatigue,” Dr. Shieh says. “I think this BPA was effective in education and making people stop and think why they were ordering transfusions. Our next step will be to look at the outlier practices and maybe have a conversation with them, doctor to doctor.”

Stanford is looking at sepsis treatment as a next target.

Hospital design may not contribute to patients’ satisfaction with the care given by their hospital professionals, according to new research from Johns Hopkins Hospital in Baltimore, published in the Journal of Hospital Medicine. Newly built hospitals often emphasize patient-centered features like reduced noise, natural light, visitor-friendly facilities, well-designed rooms, and hotel-like amenities, note the authors, led by Zishan Siddiqui, MD, attending physician and assistant professor of medicine at Johns Hopkins.

When Hopkins moved a number of its hospital units to the sleek new Sheikh Zayed Tower in 2012, researchers used a pre-post design experiment to compare patient satisfaction in the newer, more pleasing surroundings via Press Ganey and HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey scores. Patients responded positively to the new environment, with significant improvement in facility-related satisfaction, but were able to distinguish that satisfaction from their ratings of their doctors and nurses, which were not impacted by the new environment.

“It is more likely that provider-level interventions will have a greater impact on provider level and overall satisfaction,” the authors conclude. “Hospital administrators should not use outdated facilities as an excuse for suboptimal provider satisfaction scores.”

Hospital design may not contribute to patients’ satisfaction with the care given by their hospital professionals, according to new research from Johns Hopkins Hospital in Baltimore, published in the Journal of Hospital Medicine. Newly built hospitals often emphasize patient-centered features like reduced noise, natural light, visitor-friendly facilities, well-designed rooms, and hotel-like amenities, note the authors, led by Zishan Siddiqui, MD, attending physician and assistant professor of medicine at Johns Hopkins.

When Hopkins moved a number of its hospital units to the sleek new Sheikh Zayed Tower in 2012, researchers used a pre-post design experiment to compare patient satisfaction in the newer, more pleasing surroundings via Press Ganey and HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey scores. Patients responded positively to the new environment, with significant improvement in facility-related satisfaction, but were able to distinguish that satisfaction from their ratings of their doctors and nurses, which were not impacted by the new environment.

“It is more likely that provider-level interventions will have a greater impact on provider level and overall satisfaction,” the authors conclude. “Hospital administrators should not use outdated facilities as an excuse for suboptimal provider satisfaction scores.”

Hospital design may not contribute to patients’ satisfaction with the care given by their hospital professionals, according to new research from Johns Hopkins Hospital in Baltimore, published in the Journal of Hospital Medicine. Newly built hospitals often emphasize patient-centered features like reduced noise, natural light, visitor-friendly facilities, well-designed rooms, and hotel-like amenities, note the authors, led by Zishan Siddiqui, MD, attending physician and assistant professor of medicine at Johns Hopkins.

When Hopkins moved a number of its hospital units to the sleek new Sheikh Zayed Tower in 2012, researchers used a pre-post design experiment to compare patient satisfaction in the newer, more pleasing surroundings via Press Ganey and HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey scores. Patients responded positively to the new environment, with significant improvement in facility-related satisfaction, but were able to distinguish that satisfaction from their ratings of their doctors and nurses, which were not impacted by the new environment.

“It is more likely that provider-level interventions will have a greater impact on provider level and overall satisfaction,” the authors conclude. “Hospital administrators should not use outdated facilities as an excuse for suboptimal provider satisfaction scores.”

Each year, an estimated 25% to 30% of the US population suffers from dyspepsia.¹ Most self-treat with home remedies and over-the-counter products, but others seek medical care. Dyspepsia accounts for an estimated 2% to 5% of primary care visits annually,² mostly by patients who are found to have no organic, or structural, cause for their symptoms.^1,3

Compared with the general public, patients with functional dyspepsia have higher levels of anxiety, chronic tension, hostility, and hypochondriasis, and a tendency to be more pessimistic.

Such patients are said to have functional dyspepsia (FD), a category that applies to about two-thirds of those with dyspepsia.¹ A small number of cases are categorized as organic dyspepsia, indicating the presence of a clear structural or anatomic cause, such as an ulcer or mass. The remainder are said to have undifferentiated dyspepsia, which simply means that their signs and symptoms do not rise to the level for which further investigation is warranted and thus it is not known whether it is functional or organic.

There are many possible causes of FD, ranging from medications^3,4 to abnormal gastroduodenal motility^5,6 to Helicobacter pylori infection,⁷ and a comprehensive differential diagnosis. The first step in an investigation is to rule out red flags suggestive of gastrointestinal (GI) cancer or other serious disorders.

Patients with FD, like the vast majority of those you’ll treat in a primary care setting, suffer significant morbidity. Most have chronic symptoms, with intermittent flare-ups interspersed with periods of remission.⁸ In the text and dyspepsia treatment ALGORITHM^5,7-12 that follow, you’ll find an evidence-based patient management approach.

Symptoms and causes: What to look for

The primary symptoms of dyspepsia include bothersome postprandial fullness, early satiety, and epigastric pain and burning. To meet the Rome criteria for dyspepsia, these symptoms must have been present for the last 3 months and have had an onset ≥6 months prior to diagnosis.² Recurrent belching and nausea are also common, but are not included in the Rome diagnostic criteria.

Symptom severity is a poor predictor of the seriousness of the condition, however, and more intense symptoms are no more likely than milder cases to have an organic cause.^13,14 Indeed, anxiety is a common comorbidity in patients with FD and a risk factor for the diagnosis. Compared with the general public, patients with FD have been found to have higher levels of anxiety, chronic tension, hostility, and hypochondriasis, and a tendency to be more pessimistic.¹⁵

Possible causes of FD

While the etiology of organic dyspepsia is clear, the cause of FD is often far more difficult to determine.

Medication use should always be considered, as many types of drugs—including bisphosphonates, antibiotics, narcotics, steroids, iron, metformin, and nonsteroidal anti-inflammatory drugs (NSAIDs)—are associated with dyspepsia.^3,4

Gastroduodenal motility and accommodation, which has been found in numerous studies of patients with FD, is a proposed etiology.^5,6

Visceral hypersensitivity also appears to play a role. In one study of patients with severe dyspepsia, 87% of those with FD had a reduced or altered GI pain threshold, compared with 20% of those with organic dyspepsia.¹⁶

H pylori, commonly linked to peptic ulcer disease (PUD), is also associated with both organic dyspepsia and FD.^17,18 The gram-negative rod-shaped bacterium is present in approximately half of the population worldwide, but is more common in developing nations.⁷H pylori immunoglobulin G (IgG) is more prevalent in patients with dyspepsia, particularly in those younger than 30 years of age. The exact mechanism by which H pylori causes non-ulcerative dyspepsia is not clear, but inflammation, dysmotility, visceral hypersensitivity, and alteration of acid secretion have all been proposed.¹⁷

Dysfunctional intestinal epithelium is increasingly being considered in the pathophysiology of dyspepsia, among other conditions. Researchers theorize that certain foods, toxins, infections, and/or other stressors lead to changes in the structure and function of tight junctions, resulting in increased intestinal permeability.¹⁹ This in turn is thought to allow the outflow of antigens through the leaky epithelium and to stimulate an immune response—a process that may play a role in the increased GI inflammation or hypersensitivity associated with dyspepsia. The “leaky gut” theory may eventually lead to new ways to treat dyspepsia, but thus far, highquality evidence of the efficacy of treatments aimed at this mechanism is lacking.

A range of disorders included in the differential

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

The primary differential diagnosis for dyspepsia includes gastroesophageal reflux disease (GERD), esophagitis, chronic PUD (including both gastric and duodenal ulcers), and malignancy. The differential may also include biliary disorder, pancreatitis, hepatitis, or other liver disease; chronic abdominal wall pain, irritable bowel syndrome, motility disorders, or infiltrative diseases of the stomach (eosinophilic gastritis, Crohn’s disease, sarcoidosis); celiac disease and food sensitivities/allergies, including gluten, lactose, and other intolerances; cardiac disease, including acute coronary syndrome, myocardial infarction, and arrhythmias; intestinal angina; small intestine bacterial overgrowth; heavy metal toxicity; and hypercalcemia.⁸

Ulcers are found in approximately 10% of patients undergoing evaluation for dyspepsia.⁸ Previously, PUD was almost exclusively due to H pylori infection. In developed countries, however, chronic use of NSAIDs, including aspirin, has increased, and is now responsible for most ulcer diseases.^20,21 The combination of H pylori infection and NSAID usage appears to be synergistic, with the risk of uncomplicated PUD estimated to be 17.5 times higher among those who test positive for H pylori and take NSAIDs vs a 3- to 4-fold increase in ulcer incidence among those with either of these risk factors alone.²²

The work-up starts with a search for red flags

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

Evaluation of a patient with dyspepsia begins with a thorough history. Start by determining whether the patient has any red flags, or alarm features, that may be associated with a more serious condition—particularly an underlying malignancy. One or more of the following is an indication for an esophagogastroduodenoscopy (EGD):^5,8,12
• family and/or personal history of upper GI cancer
• unintended weight loss
• GI bleeding
• progressive dysphagia
• unexplained iron-deficiency anemia
• persistent vomiting
• palpable mass or lymphadenopathy
• jaundice.

The “leaky gut” theory may eventually lead to new ways to treat dyspepsia, but thus far, high-quality evidence of the efficacy of treatments aimed at this mechanism is lacking.

While it is important to rule out these red flags, they are poor predictors of malignancy.^23,24 With the exception of a single study, their positive predictive value was a mere 1%.⁸ Their usefulness lies in their ability to exclude malignancy, however; when none of these features is present, the negative predictive value for malignancy is >97%.⁸

Age is also a risk factor. In addition to red flags, EGD is recommended by the American Gastroenterological Association (AGA) for patients with new-onset dyspepsia who are 55 years or older—an age at which upper GI malignancy becomes more common. A repeat EGD is rarely indicated, unless Barrett’s esophagus or severe erosive esophagitis is found on the initial EGD.²⁵

Physical exam, H pylori evaluation follow

A physical examination of all patients presenting with symptoms suggestive of dyspepsia is crucial. While the exam is usually normal, it may reveal epigastric tenderness on abdominal palpation. Rebound tenderness, guarding, or evidence of other abnormalities should raise the prospect of alternative diagnoses. GERD, for example, has many symptoms in common with dyspepsia, but is a more likely diagnosis in a patient who has retrosternal burning discomfort and regurgitation and reports that symptoms worsen at night and when lying down.

Lab work has limited value. Although laboratory work is not specifically addressed in the AGA guidelines (except for H pylori testing), a complete blood count is a reasonable part of an initial evaluation of dyspepsia to check for anemia. Other routine blood work is not needed, but further lab testing may be warranted based on the history, exam, and differential diagnosis.

H pylori risk. Because of the association between dyspepsia and H pylori, evaluating the patient’s risk for infection with this bacterium, based primarily on his or her current and previous living conditions (TABLE 1),⁹ is the next step. Although a test for H pylori could be included in the initial work-up of all patients with dyspepsia, a better—and more cost-effective—strategy is to initially test only those at high risk. (More on testing and treating H pylori in a bit.)

Initiate acid suppression therapy for low-risk patients

First-line treatment for patients with dyspepsia who have no red flags for malignancy or other serious conditions and either are not at high risk for H pylori or are at high risk but have been tested for it and had negative results is a 4- to 8-week course of acid suppression therapy. Patients at low risk for H pylori should be tested for the bacterium only if therapy fails to alleviate their symptoms.⁹

H2RAs or PPIs? A look at the evidence

In a Cochrane review, both H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) were significantly more effective than placebo for treating FD.²⁶ However, H2RAs can lead to tachyphylaxis—an acute decrease in response to a drug—within 2 to 6 weeks, thus limiting their long-term efficacy.²⁷

Suspect gastroesophageal reflux disease, rather than dyspepsia, in a patient who has retrosternal burning and regurgitation that worsen when lying down.

PPIs appear to be more effective than H2RAs, and are the AGA’s acid suppression drug of choice.¹¹ The CADET study, a randomized controlled trial comparing PPIs (omeprazole 20 mg/d) with an H2RA (ranitidine 150 mg BID) and a prokinetic agent (cisapride 20 mg BID) as well as placebo for dyspepsia, found the PPI to be superior to the H2RA at 6 months.²⁸ In a systematic review, the number needed to treat with PPI therapy for improvement of dyspepsia symptoms was 9.²⁹

There is no specified time limit for the use of PPIs. AGA guidelines recommend that patients who respond to initial therapy stop treatment after 4 to 8 weeks.¹¹ If symptoms recur, another course of the same treatment is justified; if necessary, therapy can continue long term. However, patients should be made aware of the risk for vitamin deficiency, osteoporosis, and fracture, as well as arrhythmias, Clostridium difficile infection, and rebound upon abrupt discontinuation of PPIs.

When to test for H pylori ...

Empiric treatment for H pylori is not recommended. Thus, testing is indicated for patients who have risk factors for the bacterium or who fail to respond to acid suppression therapy. There are various ways to test for the presence of H pylori. Which test you choose depends, in part, on patient-specific factors.

Serology. IgG serology testing is extremely useful in patients who have never been diagnosed with H pylori. It is best suited for those who are currently taking proton pump inhibitors (PPIs) or who recently completed a course of antibiotics, since neither medication affects the results of the serology test.

Serology testing should not be used, however, for any patient who was previously diagnosed with or treated for H pylori, because this type of test cannot distinguish between an active or past infection. The IgG serology test has a sensitivity of 87% and a specificity of 67%.³⁰

Stool antigen. Stool tests using monoclonal antibodies to detect the presence of H pylori have a sensitivity of 87% to 92% and a specificity of 70%. Stool antigen is also an excellent post-treatment test to confirm that H pylori has been eradicated.³¹

Stool testing has some drawbacks, however. PPIs can decrease the sensitivity and should be discontinued at least 2 weeks prior to stool testing.³² In addition, a stool test for H pylori is not accurate if the patient has an acute GI bleed.

Urea breath testing. This is the most sensitive and specific test for active H pylori infection (90%-96% sensitivity and 88%-96% specificity).³³ PPIs can lower the sensitivity of the test, however, and are typically discontinued at least 2 weeks prior to testing. Urea breath testing, like stool testing, is an excellent way to confirm that H pylori has been eradicated after treatment. However, it is more expensive than other tests for H pylori and often inconvenient to obtain.¹³

An EGD is indicated for a patient who has failed to respond to acid suppression therapy and has a negative serology, stool antigen, or urea breath test for H pylori.

Biopsy-based testing for H pylori is performed with EGD and is therefore reserved for patients who have red flags or other indications of a need for invasive testing. There are 3 types of biopsy-based tests: urease (sensitivity, 70%-90%; specificity, 95%); histology (87%-92% and 70%, respectively); and culture (85%-88% and 69%, respectively). Overall, the specificity is slightly better than that of noninvasive testing, but the sensitivity can be lowered by recent use of PPIs, bismuth, or antibiotics.^12,34

... and how to treat it

H pylori infection is associated with an increased risk of noncardiac gastric adenocarcinoma, but a decreased risk of cardiac gastric adenocarcinoma and esophageal adenocarcinoma.^35,36 Thus, the potential to reduce the risk of gastric cancer is not considered an indication for H pylori treatment. The possibility of improving dyspepsia symptoms is a reason to treat H pylori infection, although eradicating it does not always do so.

IgG serology testing should not be used for any patient who was previously diagnosed with, or treated for, H pylori because this type of test can’t distinguish between an active or past infection.

In a 2006 Cochrane Review, treating H pylori had a small but statistically significant benefit for patients with FD (NNT=14).³⁷ A 2011 study on the effects of H pylori eradication on symptoms and quality of life in primary care patients with FD revealed a 12.5% improvement in quality of life and a 10.6% improvement in symptoms.³⁸

The triple therapy regimen (a PPI + amoxicillin + clarithromycin) is the most common first-line H pylori treatment in the United States, and a good initial choice in regions in which clarithromycin resistance is low (TABLE 2).^39-44 The standard duration is 7 days. A 2013 Cochrane Review showed that a longer duration (14 days) increased the rate of eradication (82% vs 73%), but this remains controversial.³⁹ The addition of bismuth subsalicylate to the triple therapy regimen has been shown to increase the eradication rate of H pylori by approximately 10%.⁴⁵ Adding probiotics (saccharomyces or lactobacillus) appears to increase eradication rates, as well.⁴⁰

Sequential therapy consists of a 5-day course of treatment in which a PPI and amoxicillin are taken twice a day, followed by another 5-day course of a PPI, clarithromycin, and metronidazole. A recent meta-analysis of sequential therapy showed that it is superior to 7-day triple therapy but equivalent to 14-day triple therapy.⁴⁰

LOAD (levofloxacin, omeprazole, nitazoxanide, and doxycycline) therapy for 7 to 10 days can be used in place of triple therapy in areas of high resistance or for persistent H pylori. In one study, the H pylori eradication rate for a 7-day course of LOAD therapy—levofloxacin and doxycycline taken once a day, omeprazole before breakfast, and nitazoxanide twice daily—was 90% vs 73.3% for a 7-day course of triple therapy.⁴¹

Quadruple therapy has 2 variations: bismuth-based and non-bismuth (concomitant) therapy. The latter uses the base triple therapy and adds either metronidazole or tinidazole for 7 to 14 days. In a multicenter randomized trial, this concomitant therapy was found to have similar efficacy to sequential therapy.⁴²

The possibility of improving dyspepsia symptoms is a reason to treat H pylori infection, although eradicating it does not always do so.

Bismuth-based quad therapy includes a PPI, bismuth, metronidazole, and tetracycline. A meta-analysis found it to have a higher rate of eradication than triple therapy for patients with antibiotic resistance.^43,44

For persistent H pylori, a PPI, levofloxacin, and amoxicillin for 10 days has been shown to be more effective and better tolerated than quadruple therapy.¹²

Confirmation is indicated when symptoms persist

If dyspepsia symptoms persist after H pylori treatment, it is reasonable to retest to confirm that the infection has in fact been eradicated. Confirmation is also indicated if the patient has an H pylori-associated ulcer or a prior history of gastric cancer.

Retesting should be performed at least 4 to 6 weeks after treatment is completed. If H pylori has not been eradicated, you can try another regimen. If retesting confirms eradication and symptoms persist, EGD with biopsy is indicated. Although EGD typically has a very low yield, even for patients with red flags, this invasive test often provides reassurance and increased satisfaction for patients with persistent symptoms.⁴⁶

More options for challenging cases

Managing FD is challenging when both initial acid suppression therapy and H pylori eradication fail. Unproven but low-risk treatments include modification of eating habits (eg, eating slower, not gulping food), reducing stress, discontinuing medications that may be related to symptoms, avoiding foods that seem to exacerbate symptoms, and cutting down or eliminating tobacco, caffeine, alcohol, and carbonated beverages.⁸ Bismuth salts have been shown to be superior to placebo for the treatment of dyspepsia.²⁵ Small studies have also demonstrated a favorable risk–benefit ratio for peppermint oil and caraway oil for the treatment of FD.⁴⁷ Prokinetics have shown efficacy compared with placebo, although a Cochrane review questioned their efficacy based on publication bias.²⁶

There is no good evidence of efficacy for over-the-counter antacids, such as TUMS, or for GI “cocktails” (antacid, antispasmotic, and lidocaine), sucralfate, psychological interventions (eg, cognitive behavioral therapy, relaxation therapy, or hypnosis), or antidepressants.^48,49 Several recent randomized controlled trials have shown the efficacy of acupuncture for the treatment of dyspepsia.^49,50 Ginger may also be helpful; it has been found to help with nausea in other GI conditions, but it’s uncertain whether it can help patients with dyspepsia.⁵¹

CORRESPONDENCE 
Michael Malone, MD, 845 Fishburn Road, Hershey, PA 17053; [email protected]

Each year, an estimated 25% to 30% of the US population suffers from dyspepsia.¹ Most self-treat with home remedies and over-the-counter products, but others seek medical care. Dyspepsia accounts for an estimated 2% to 5% of primary care visits annually,² mostly by patients who are found to have no organic, or structural, cause for their symptoms.^1,3

Compared with the general public, patients with functional dyspepsia have higher levels of anxiety, chronic tension, hostility, and hypochondriasis, and a tendency to be more pessimistic.

Such patients are said to have functional dyspepsia (FD), a category that applies to about two-thirds of those with dyspepsia.¹ A small number of cases are categorized as organic dyspepsia, indicating the presence of a clear structural or anatomic cause, such as an ulcer or mass. The remainder are said to have undifferentiated dyspepsia, which simply means that their signs and symptoms do not rise to the level for which further investigation is warranted and thus it is not known whether it is functional or organic.

There are many possible causes of FD, ranging from medications^3,4 to abnormal gastroduodenal motility^5,6 to Helicobacter pylori infection,⁷ and a comprehensive differential diagnosis. The first step in an investigation is to rule out red flags suggestive of gastrointestinal (GI) cancer or other serious disorders.

Patients with FD, like the vast majority of those you’ll treat in a primary care setting, suffer significant morbidity. Most have chronic symptoms, with intermittent flare-ups interspersed with periods of remission.⁸ In the text and dyspepsia treatment ALGORITHM^5,7-12 that follow, you’ll find an evidence-based patient management approach.

Symptoms and causes: What to look for

The primary symptoms of dyspepsia include bothersome postprandial fullness, early satiety, and epigastric pain and burning. To meet the Rome criteria for dyspepsia, these symptoms must have been present for the last 3 months and have had an onset ≥6 months prior to diagnosis.² Recurrent belching and nausea are also common, but are not included in the Rome diagnostic criteria.

Symptom severity is a poor predictor of the seriousness of the condition, however, and more intense symptoms are no more likely than milder cases to have an organic cause.^13,14 Indeed, anxiety is a common comorbidity in patients with FD and a risk factor for the diagnosis. Compared with the general public, patients with FD have been found to have higher levels of anxiety, chronic tension, hostility, and hypochondriasis, and a tendency to be more pessimistic.¹⁵

Possible causes of FD

While the etiology of organic dyspepsia is clear, the cause of FD is often far more difficult to determine.

Medication use should always be considered, as many types of drugs—including bisphosphonates, antibiotics, narcotics, steroids, iron, metformin, and nonsteroidal anti-inflammatory drugs (NSAIDs)—are associated with dyspepsia.^3,4

Gastroduodenal motility and accommodation, which has been found in numerous studies of patients with FD, is a proposed etiology.^5,6

Visceral hypersensitivity also appears to play a role. In one study of patients with severe dyspepsia, 87% of those with FD had a reduced or altered GI pain threshold, compared with 20% of those with organic dyspepsia.¹⁶

H pylori, commonly linked to peptic ulcer disease (PUD), is also associated with both organic dyspepsia and FD.^17,18 The gram-negative rod-shaped bacterium is present in approximately half of the population worldwide, but is more common in developing nations.⁷H pylori immunoglobulin G (IgG) is more prevalent in patients with dyspepsia, particularly in those younger than 30 years of age. The exact mechanism by which H pylori causes non-ulcerative dyspepsia is not clear, but inflammation, dysmotility, visceral hypersensitivity, and alteration of acid secretion have all been proposed.¹⁷

Dysfunctional intestinal epithelium is increasingly being considered in the pathophysiology of dyspepsia, among other conditions. Researchers theorize that certain foods, toxins, infections, and/or other stressors lead to changes in the structure and function of tight junctions, resulting in increased intestinal permeability.¹⁹ This in turn is thought to allow the outflow of antigens through the leaky epithelium and to stimulate an immune response—a process that may play a role in the increased GI inflammation or hypersensitivity associated with dyspepsia. The “leaky gut” theory may eventually lead to new ways to treat dyspepsia, but thus far, highquality evidence of the efficacy of treatments aimed at this mechanism is lacking.

A range of disorders included in the differential

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

The primary differential diagnosis for dyspepsia includes gastroesophageal reflux disease (GERD), esophagitis, chronic PUD (including both gastric and duodenal ulcers), and malignancy. The differential may also include biliary disorder, pancreatitis, hepatitis, or other liver disease; chronic abdominal wall pain, irritable bowel syndrome, motility disorders, or infiltrative diseases of the stomach (eosinophilic gastritis, Crohn’s disease, sarcoidosis); celiac disease and food sensitivities/allergies, including gluten, lactose, and other intolerances; cardiac disease, including acute coronary syndrome, myocardial infarction, and arrhythmias; intestinal angina; small intestine bacterial overgrowth; heavy metal toxicity; and hypercalcemia.⁸

Ulcers are found in approximately 10% of patients undergoing evaluation for dyspepsia.⁸ Previously, PUD was almost exclusively due to H pylori infection. In developed countries, however, chronic use of NSAIDs, including aspirin, has increased, and is now responsible for most ulcer diseases.^20,21 The combination of H pylori infection and NSAID usage appears to be synergistic, with the risk of uncomplicated PUD estimated to be 17.5 times higher among those who test positive for H pylori and take NSAIDs vs a 3- to 4-fold increase in ulcer incidence among those with either of these risk factors alone.²²

The work-up starts with a search for red flags

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

Evaluation of a patient with dyspepsia begins with a thorough history. Start by determining whether the patient has any red flags, or alarm features, that may be associated with a more serious condition—particularly an underlying malignancy. One or more of the following is an indication for an esophagogastroduodenoscopy (EGD):^5,8,12
• family and/or personal history of upper GI cancer
• unintended weight loss
• GI bleeding
• progressive dysphagia
• unexplained iron-deficiency anemia
• persistent vomiting
• palpable mass or lymphadenopathy
• jaundice.

The “leaky gut” theory may eventually lead to new ways to treat dyspepsia, but thus far, high-quality evidence of the efficacy of treatments aimed at this mechanism is lacking.

While it is important to rule out these red flags, they are poor predictors of malignancy.^23,24 With the exception of a single study, their positive predictive value was a mere 1%.⁸ Their usefulness lies in their ability to exclude malignancy, however; when none of these features is present, the negative predictive value for malignancy is >97%.⁸

Age is also a risk factor. In addition to red flags, EGD is recommended by the American Gastroenterological Association (AGA) for patients with new-onset dyspepsia who are 55 years or older—an age at which upper GI malignancy becomes more common. A repeat EGD is rarely indicated, unless Barrett’s esophagus or severe erosive esophagitis is found on the initial EGD.²⁵

Physical exam, H pylori evaluation follow

A physical examination of all patients presenting with symptoms suggestive of dyspepsia is crucial. While the exam is usually normal, it may reveal epigastric tenderness on abdominal palpation. Rebound tenderness, guarding, or evidence of other abnormalities should raise the prospect of alternative diagnoses. GERD, for example, has many symptoms in common with dyspepsia, but is a more likely diagnosis in a patient who has retrosternal burning discomfort and regurgitation and reports that symptoms worsen at night and when lying down.

Lab work has limited value. Although laboratory work is not specifically addressed in the AGA guidelines (except for H pylori testing), a complete blood count is a reasonable part of an initial evaluation of dyspepsia to check for anemia. Other routine blood work is not needed, but further lab testing may be warranted based on the history, exam, and differential diagnosis.

H pylori risk. Because of the association between dyspepsia and H pylori, evaluating the patient’s risk for infection with this bacterium, based primarily on his or her current and previous living conditions (TABLE 1),⁹ is the next step. Although a test for H pylori could be included in the initial work-up of all patients with dyspepsia, a better—and more cost-effective—strategy is to initially test only those at high risk. (More on testing and treating H pylori in a bit.)

Initiate acid suppression therapy for low-risk patients

First-line treatment for patients with dyspepsia who have no red flags for malignancy or other serious conditions and either are not at high risk for H pylori or are at high risk but have been tested for it and had negative results is a 4- to 8-week course of acid suppression therapy. Patients at low risk for H pylori should be tested for the bacterium only if therapy fails to alleviate their symptoms.⁹

H2RAs or PPIs? A look at the evidence

In a Cochrane review, both H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) were significantly more effective than placebo for treating FD.²⁶ However, H2RAs can lead to tachyphylaxis—an acute decrease in response to a drug—within 2 to 6 weeks, thus limiting their long-term efficacy.²⁷

Suspect gastroesophageal reflux disease, rather than dyspepsia, in a patient who has retrosternal burning and regurgitation that worsen when lying down.

PPIs appear to be more effective than H2RAs, and are the AGA’s acid suppression drug of choice.¹¹ The CADET study, a randomized controlled trial comparing PPIs (omeprazole 20 mg/d) with an H2RA (ranitidine 150 mg BID) and a prokinetic agent (cisapride 20 mg BID) as well as placebo for dyspepsia, found the PPI to be superior to the H2RA at 6 months.²⁸ In a systematic review, the number needed to treat with PPI therapy for improvement of dyspepsia symptoms was 9.²⁹

There is no specified time limit for the use of PPIs. AGA guidelines recommend that patients who respond to initial therapy stop treatment after 4 to 8 weeks.¹¹ If symptoms recur, another course of the same treatment is justified; if necessary, therapy can continue long term. However, patients should be made aware of the risk for vitamin deficiency, osteoporosis, and fracture, as well as arrhythmias, Clostridium difficile infection, and rebound upon abrupt discontinuation of PPIs.

When to test for H pylori ...

Empiric treatment for H pylori is not recommended. Thus, testing is indicated for patients who have risk factors for the bacterium or who fail to respond to acid suppression therapy. There are various ways to test for the presence of H pylori. Which test you choose depends, in part, on patient-specific factors.

Serology. IgG serology testing is extremely useful in patients who have never been diagnosed with H pylori. It is best suited for those who are currently taking proton pump inhibitors (PPIs) or who recently completed a course of antibiotics, since neither medication affects the results of the serology test.

Serology testing should not be used, however, for any patient who was previously diagnosed with or treated for H pylori, because this type of test cannot distinguish between an active or past infection. The IgG serology test has a sensitivity of 87% and a specificity of 67%.³⁰

Stool antigen. Stool tests using monoclonal antibodies to detect the presence of H pylori have a sensitivity of 87% to 92% and a specificity of 70%. Stool antigen is also an excellent post-treatment test to confirm that H pylori has been eradicated.³¹

Stool testing has some drawbacks, however. PPIs can decrease the sensitivity and should be discontinued at least 2 weeks prior to stool testing.³² In addition, a stool test for H pylori is not accurate if the patient has an acute GI bleed.

Urea breath testing. This is the most sensitive and specific test for active H pylori infection (90%-96% sensitivity and 88%-96% specificity).³³ PPIs can lower the sensitivity of the test, however, and are typically discontinued at least 2 weeks prior to testing. Urea breath testing, like stool testing, is an excellent way to confirm that H pylori has been eradicated after treatment. However, it is more expensive than other tests for H pylori and often inconvenient to obtain.¹³

An EGD is indicated for a patient who has failed to respond to acid suppression therapy and has a negative serology, stool antigen, or urea breath test for H pylori.

Biopsy-based testing for H pylori is performed with EGD and is therefore reserved for patients who have red flags or other indications of a need for invasive testing. There are 3 types of biopsy-based tests: urease (sensitivity, 70%-90%; specificity, 95%); histology (87%-92% and 70%, respectively); and culture (85%-88% and 69%, respectively). Overall, the specificity is slightly better than that of noninvasive testing, but the sensitivity can be lowered by recent use of PPIs, bismuth, or antibiotics.^12,34

... and how to treat it

H pylori infection is associated with an increased risk of noncardiac gastric adenocarcinoma, but a decreased risk of cardiac gastric adenocarcinoma and esophageal adenocarcinoma.^35,36 Thus, the potential to reduce the risk of gastric cancer is not considered an indication for H pylori treatment. The possibility of improving dyspepsia symptoms is a reason to treat H pylori infection, although eradicating it does not always do so.

IgG serology testing should not be used for any patient who was previously diagnosed with, or treated for, H pylori because this type of test can’t distinguish between an active or past infection.

In a 2006 Cochrane Review, treating H pylori had a small but statistically significant benefit for patients with FD (NNT=14).³⁷ A 2011 study on the effects of H pylori eradication on symptoms and quality of life in primary care patients with FD revealed a 12.5% improvement in quality of life and a 10.6% improvement in symptoms.³⁸

The triple therapy regimen (a PPI + amoxicillin + clarithromycin) is the most common first-line H pylori treatment in the United States, and a good initial choice in regions in which clarithromycin resistance is low (TABLE 2).^39-44 The standard duration is 7 days. A 2013 Cochrane Review showed that a longer duration (14 days) increased the rate of eradication (82% vs 73%), but this remains controversial.³⁹ The addition of bismuth subsalicylate to the triple therapy regimen has been shown to increase the eradication rate of H pylori by approximately 10%.⁴⁵ Adding probiotics (saccharomyces or lactobacillus) appears to increase eradication rates, as well.⁴⁰

Sequential therapy consists of a 5-day course of treatment in which a PPI and amoxicillin are taken twice a day, followed by another 5-day course of a PPI, clarithromycin, and metronidazole. A recent meta-analysis of sequential therapy showed that it is superior to 7-day triple therapy but equivalent to 14-day triple therapy.⁴⁰

LOAD (levofloxacin, omeprazole, nitazoxanide, and doxycycline) therapy for 7 to 10 days can be used in place of triple therapy in areas of high resistance or for persistent H pylori. In one study, the H pylori eradication rate for a 7-day course of LOAD therapy—levofloxacin and doxycycline taken once a day, omeprazole before breakfast, and nitazoxanide twice daily—was 90% vs 73.3% for a 7-day course of triple therapy.⁴¹

Quadruple therapy has 2 variations: bismuth-based and non-bismuth (concomitant) therapy. The latter uses the base triple therapy and adds either metronidazole or tinidazole for 7 to 14 days. In a multicenter randomized trial, this concomitant therapy was found to have similar efficacy to sequential therapy.⁴²

The possibility of improving dyspepsia symptoms is a reason to treat H pylori infection, although eradicating it does not always do so.

Bismuth-based quad therapy includes a PPI, bismuth, metronidazole, and tetracycline. A meta-analysis found it to have a higher rate of eradication than triple therapy for patients with antibiotic resistance.^43,44

For persistent H pylori, a PPI, levofloxacin, and amoxicillin for 10 days has been shown to be more effective and better tolerated than quadruple therapy.¹²

Confirmation is indicated when symptoms persist

If dyspepsia symptoms persist after H pylori treatment, it is reasonable to retest to confirm that the infection has in fact been eradicated. Confirmation is also indicated if the patient has an H pylori-associated ulcer or a prior history of gastric cancer.

Retesting should be performed at least 4 to 6 weeks after treatment is completed. If H pylori has not been eradicated, you can try another regimen. If retesting confirms eradication and symptoms persist, EGD with biopsy is indicated. Although EGD typically has a very low yield, even for patients with red flags, this invasive test often provides reassurance and increased satisfaction for patients with persistent symptoms.⁴⁶

More options for challenging cases

Managing FD is challenging when both initial acid suppression therapy and H pylori eradication fail. Unproven but low-risk treatments include modification of eating habits (eg, eating slower, not gulping food), reducing stress, discontinuing medications that may be related to symptoms, avoiding foods that seem to exacerbate symptoms, and cutting down or eliminating tobacco, caffeine, alcohol, and carbonated beverages.⁸ Bismuth salts have been shown to be superior to placebo for the treatment of dyspepsia.²⁵ Small studies have also demonstrated a favorable risk–benefit ratio for peppermint oil and caraway oil for the treatment of FD.⁴⁷ Prokinetics have shown efficacy compared with placebo, although a Cochrane review questioned their efficacy based on publication bias.²⁶

There is no good evidence of efficacy for over-the-counter antacids, such as TUMS, or for GI “cocktails” (antacid, antispasmotic, and lidocaine), sucralfate, psychological interventions (eg, cognitive behavioral therapy, relaxation therapy, or hypnosis), or antidepressants.^48,49 Several recent randomized controlled trials have shown the efficacy of acupuncture for the treatment of dyspepsia.^49,50 Ginger may also be helpful; it has been found to help with nausea in other GI conditions, but it’s uncertain whether it can help patients with dyspepsia.⁵¹

CORRESPONDENCE 
Michael Malone, MD, 845 Fishburn Road, Hershey, PA 17053; [email protected]

Each year, an estimated 25% to 30% of the US population suffers from dyspepsia.¹ Most self-treat with home remedies and over-the-counter products, but others seek medical care. Dyspepsia accounts for an estimated 2% to 5% of primary care visits annually,² mostly by patients who are found to have no organic, or structural, cause for their symptoms.^1,3

Compared with the general public, patients with functional dyspepsia have higher levels of anxiety, chronic tension, hostility, and hypochondriasis, and a tendency to be more pessimistic.

Such patients are said to have functional dyspepsia (FD), a category that applies to about two-thirds of those with dyspepsia.¹ A small number of cases are categorized as organic dyspepsia, indicating the presence of a clear structural or anatomic cause, such as an ulcer or mass. The remainder are said to have undifferentiated dyspepsia, which simply means that their signs and symptoms do not rise to the level for which further investigation is warranted and thus it is not known whether it is functional or organic.

There are many possible causes of FD, ranging from medications^3,4 to abnormal gastroduodenal motility^5,6 to Helicobacter pylori infection,⁷ and a comprehensive differential diagnosis. The first step in an investigation is to rule out red flags suggestive of gastrointestinal (GI) cancer or other serious disorders.

Patients with FD, like the vast majority of those you’ll treat in a primary care setting, suffer significant morbidity. Most have chronic symptoms, with intermittent flare-ups interspersed with periods of remission.⁸ In the text and dyspepsia treatment ALGORITHM^5,7-12 that follow, you’ll find an evidence-based patient management approach.

Symptoms and causes: What to look for

The primary symptoms of dyspepsia include bothersome postprandial fullness, early satiety, and epigastric pain and burning. To meet the Rome criteria for dyspepsia, these symptoms must have been present for the last 3 months and have had an onset ≥6 months prior to diagnosis.² Recurrent belching and nausea are also common, but are not included in the Rome diagnostic criteria.

Symptom severity is a poor predictor of the seriousness of the condition, however, and more intense symptoms are no more likely than milder cases to have an organic cause.^13,14 Indeed, anxiety is a common comorbidity in patients with FD and a risk factor for the diagnosis. Compared with the general public, patients with FD have been found to have higher levels of anxiety, chronic tension, hostility, and hypochondriasis, and a tendency to be more pessimistic.¹⁵

Possible causes of FD

While the etiology of organic dyspepsia is clear, the cause of FD is often far more difficult to determine.

Medication use should always be considered, as many types of drugs—including bisphosphonates, antibiotics, narcotics, steroids, iron, metformin, and nonsteroidal anti-inflammatory drugs (NSAIDs)—are associated with dyspepsia.^3,4

Gastroduodenal motility and accommodation, which has been found in numerous studies of patients with FD, is a proposed etiology.^5,6

Visceral hypersensitivity also appears to play a role. In one study of patients with severe dyspepsia, 87% of those with FD had a reduced or altered GI pain threshold, compared with 20% of those with organic dyspepsia.¹⁶

H pylori, commonly linked to peptic ulcer disease (PUD), is also associated with both organic dyspepsia and FD.^17,18 The gram-negative rod-shaped bacterium is present in approximately half of the population worldwide, but is more common in developing nations.⁷H pylori immunoglobulin G (IgG) is more prevalent in patients with dyspepsia, particularly in those younger than 30 years of age. The exact mechanism by which H pylori causes non-ulcerative dyspepsia is not clear, but inflammation, dysmotility, visceral hypersensitivity, and alteration of acid secretion have all been proposed.¹⁷

Dysfunctional intestinal epithelium is increasingly being considered in the pathophysiology of dyspepsia, among other conditions. Researchers theorize that certain foods, toxins, infections, and/or other stressors lead to changes in the structure and function of tight junctions, resulting in increased intestinal permeability.¹⁹ This in turn is thought to allow the outflow of antigens through the leaky epithelium and to stimulate an immune response—a process that may play a role in the increased GI inflammation or hypersensitivity associated with dyspepsia. The “leaky gut” theory may eventually lead to new ways to treat dyspepsia, but thus far, highquality evidence of the efficacy of treatments aimed at this mechanism is lacking.

A range of disorders included in the differential

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

The primary differential diagnosis for dyspepsia includes gastroesophageal reflux disease (GERD), esophagitis, chronic PUD (including both gastric and duodenal ulcers), and malignancy. The differential may also include biliary disorder, pancreatitis, hepatitis, or other liver disease; chronic abdominal wall pain, irritable bowel syndrome, motility disorders, or infiltrative diseases of the stomach (eosinophilic gastritis, Crohn’s disease, sarcoidosis); celiac disease and food sensitivities/allergies, including gluten, lactose, and other intolerances; cardiac disease, including acute coronary syndrome, myocardial infarction, and arrhythmias; intestinal angina; small intestine bacterial overgrowth; heavy metal toxicity; and hypercalcemia.⁸

Ulcers are found in approximately 10% of patients undergoing evaluation for dyspepsia.⁸ Previously, PUD was almost exclusively due to H pylori infection. In developed countries, however, chronic use of NSAIDs, including aspirin, has increased, and is now responsible for most ulcer diseases.^20,21 The combination of H pylori infection and NSAID usage appears to be synergistic, with the risk of uncomplicated PUD estimated to be 17.5 times higher among those who test positive for H pylori and take NSAIDs vs a 3- to 4-fold increase in ulcer incidence among those with either of these risk factors alone.²²

The work-up starts with a search for red flags

Symptom severity is a poor predictor of the seriousness of dyspepsia; more intense symptoms are no more likely than milder cases to have an organic cause.

Evaluation of a patient with dyspepsia begins with a thorough history. Start by determining whether the patient has any red flags, or alarm features, that may be associated with a more serious condition—particularly an underlying malignancy. One or more of the following is an indication for an esophagogastroduodenoscopy (EGD):^5,8,12
• family and/or personal history of upper GI cancer
• unintended weight loss
• GI bleeding
• progressive dysphagia
• unexplained iron-deficiency anemia
• persistent vomiting
• palpable mass or lymphadenopathy
• jaundice.

The “leaky gut” theory may eventually lead to new ways to treat dyspepsia, but thus far, high-quality evidence of the efficacy of treatments aimed at this mechanism is lacking.

While it is important to rule out these red flags, they are poor predictors of malignancy.^23,24 With the exception of a single study, their positive predictive value was a mere 1%.⁸ Their usefulness lies in their ability to exclude malignancy, however; when none of these features is present, the negative predictive value for malignancy is >97%.⁸

Age is also a risk factor. In addition to red flags, EGD is recommended by the American Gastroenterological Association (AGA) for patients with new-onset dyspepsia who are 55 years or older—an age at which upper GI malignancy becomes more common. A repeat EGD is rarely indicated, unless Barrett’s esophagus or severe erosive esophagitis is found on the initial EGD.²⁵

Physical exam, H pylori evaluation follow

A physical examination of all patients presenting with symptoms suggestive of dyspepsia is crucial. While the exam is usually normal, it may reveal epigastric tenderness on abdominal palpation. Rebound tenderness, guarding, or evidence of other abnormalities should raise the prospect of alternative diagnoses. GERD, for example, has many symptoms in common with dyspepsia, but is a more likely diagnosis in a patient who has retrosternal burning discomfort and regurgitation and reports that symptoms worsen at night and when lying down.

Lab work has limited value. Although laboratory work is not specifically addressed in the AGA guidelines (except for H pylori testing), a complete blood count is a reasonable part of an initial evaluation of dyspepsia to check for anemia. Other routine blood work is not needed, but further lab testing may be warranted based on the history, exam, and differential diagnosis.

H pylori risk. Because of the association between dyspepsia and H pylori, evaluating the patient’s risk for infection with this bacterium, based primarily on his or her current and previous living conditions (TABLE 1),⁹ is the next step. Although a test for H pylori could be included in the initial work-up of all patients with dyspepsia, a better—and more cost-effective—strategy is to initially test only those at high risk. (More on testing and treating H pylori in a bit.)

Initiate acid suppression therapy for low-risk patients

First-line treatment for patients with dyspepsia who have no red flags for malignancy or other serious conditions and either are not at high risk for H pylori or are at high risk but have been tested for it and had negative results is a 4- to 8-week course of acid suppression therapy. Patients at low risk for H pylori should be tested for the bacterium only if therapy fails to alleviate their symptoms.⁹

H2RAs or PPIs? A look at the evidence

In a Cochrane review, both H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) were significantly more effective than placebo for treating FD.²⁶ However, H2RAs can lead to tachyphylaxis—an acute decrease in response to a drug—within 2 to 6 weeks, thus limiting their long-term efficacy.²⁷

Suspect gastroesophageal reflux disease, rather than dyspepsia, in a patient who has retrosternal burning and regurgitation that worsen when lying down.

PPIs appear to be more effective than H2RAs, and are the AGA’s acid suppression drug of choice.¹¹ The CADET study, a randomized controlled trial comparing PPIs (omeprazole 20 mg/d) with an H2RA (ranitidine 150 mg BID) and a prokinetic agent (cisapride 20 mg BID) as well as placebo for dyspepsia, found the PPI to be superior to the H2RA at 6 months.²⁸ In a systematic review, the number needed to treat with PPI therapy for improvement of dyspepsia symptoms was 9.²⁹

There is no specified time limit for the use of PPIs. AGA guidelines recommend that patients who respond to initial therapy stop treatment after 4 to 8 weeks.¹¹ If symptoms recur, another course of the same treatment is justified; if necessary, therapy can continue long term. However, patients should be made aware of the risk for vitamin deficiency, osteoporosis, and fracture, as well as arrhythmias, Clostridium difficile infection, and rebound upon abrupt discontinuation of PPIs.

When to test for H pylori ...

Empiric treatment for H pylori is not recommended. Thus, testing is indicated for patients who have risk factors for the bacterium or who fail to respond to acid suppression therapy. There are various ways to test for the presence of H pylori. Which test you choose depends, in part, on patient-specific factors.

Serology. IgG serology testing is extremely useful in patients who have never been diagnosed with H pylori. It is best suited for those who are currently taking proton pump inhibitors (PPIs) or who recently completed a course of antibiotics, since neither medication affects the results of the serology test.

Serology testing should not be used, however, for any patient who was previously diagnosed with or treated for H pylori, because this type of test cannot distinguish between an active or past infection. The IgG serology test has a sensitivity of 87% and a specificity of 67%.³⁰

Stool antigen. Stool tests using monoclonal antibodies to detect the presence of H pylori have a sensitivity of 87% to 92% and a specificity of 70%. Stool antigen is also an excellent post-treatment test to confirm that H pylori has been eradicated.³¹

Stool testing has some drawbacks, however. PPIs can decrease the sensitivity and should be discontinued at least 2 weeks prior to stool testing.³² In addition, a stool test for H pylori is not accurate if the patient has an acute GI bleed.

Urea breath testing. This is the most sensitive and specific test for active H pylori infection (90%-96% sensitivity and 88%-96% specificity).³³ PPIs can lower the sensitivity of the test, however, and are typically discontinued at least 2 weeks prior to testing. Urea breath testing, like stool testing, is an excellent way to confirm that H pylori has been eradicated after treatment. However, it is more expensive than other tests for H pylori and often inconvenient to obtain.¹³

An EGD is indicated for a patient who has failed to respond to acid suppression therapy and has a negative serology, stool antigen, or urea breath test for H pylori.

Biopsy-based testing for H pylori is performed with EGD and is therefore reserved for patients who have red flags or other indications of a need for invasive testing. There are 3 types of biopsy-based tests: urease (sensitivity, 70%-90%; specificity, 95%); histology (87%-92% and 70%, respectively); and culture (85%-88% and 69%, respectively). Overall, the specificity is slightly better than that of noninvasive testing, but the sensitivity can be lowered by recent use of PPIs, bismuth, or antibiotics.^12,34

... and how to treat it

H pylori infection is associated with an increased risk of noncardiac gastric adenocarcinoma, but a decreased risk of cardiac gastric adenocarcinoma and esophageal adenocarcinoma.^35,36 Thus, the potential to reduce the risk of gastric cancer is not considered an indication for H pylori treatment. The possibility of improving dyspepsia symptoms is a reason to treat H pylori infection, although eradicating it does not always do so.

IgG serology testing should not be used for any patient who was previously diagnosed with, or treated for, H pylori because this type of test can’t distinguish between an active or past infection.

In a 2006 Cochrane Review, treating H pylori had a small but statistically significant benefit for patients with FD (NNT=14).³⁷ A 2011 study on the effects of H pylori eradication on symptoms and quality of life in primary care patients with FD revealed a 12.5% improvement in quality of life and a 10.6% improvement in symptoms.³⁸

The triple therapy regimen (a PPI + amoxicillin + clarithromycin) is the most common first-line H pylori treatment in the United States, and a good initial choice in regions in which clarithromycin resistance is low (TABLE 2).^39-44 The standard duration is 7 days. A 2013 Cochrane Review showed that a longer duration (14 days) increased the rate of eradication (82% vs 73%), but this remains controversial.³⁹ The addition of bismuth subsalicylate to the triple therapy regimen has been shown to increase the eradication rate of H pylori by approximately 10%.⁴⁵ Adding probiotics (saccharomyces or lactobacillus) appears to increase eradication rates, as well.⁴⁰

Sequential therapy consists of a 5-day course of treatment in which a PPI and amoxicillin are taken twice a day, followed by another 5-day course of a PPI, clarithromycin, and metronidazole. A recent meta-analysis of sequential therapy showed that it is superior to 7-day triple therapy but equivalent to 14-day triple therapy.⁴⁰

LOAD (levofloxacin, omeprazole, nitazoxanide, and doxycycline) therapy for 7 to 10 days can be used in place of triple therapy in areas of high resistance or for persistent H pylori. In one study, the H pylori eradication rate for a 7-day course of LOAD therapy—levofloxacin and doxycycline taken once a day, omeprazole before breakfast, and nitazoxanide twice daily—was 90% vs 73.3% for a 7-day course of triple therapy.⁴¹

Quadruple therapy has 2 variations: bismuth-based and non-bismuth (concomitant) therapy. The latter uses the base triple therapy and adds either metronidazole or tinidazole for 7 to 14 days. In a multicenter randomized trial, this concomitant therapy was found to have similar efficacy to sequential therapy.⁴²

The possibility of improving dyspepsia symptoms is a reason to treat H pylori infection, although eradicating it does not always do so.

Bismuth-based quad therapy includes a PPI, bismuth, metronidazole, and tetracycline. A meta-analysis found it to have a higher rate of eradication than triple therapy for patients with antibiotic resistance.^43,44

For persistent H pylori, a PPI, levofloxacin, and amoxicillin for 10 days has been shown to be more effective and better tolerated than quadruple therapy.¹²

Confirmation is indicated when symptoms persist

If dyspepsia symptoms persist after H pylori treatment, it is reasonable to retest to confirm that the infection has in fact been eradicated. Confirmation is also indicated if the patient has an H pylori-associated ulcer or a prior history of gastric cancer.

Retesting should be performed at least 4 to 6 weeks after treatment is completed. If H pylori has not been eradicated, you can try another regimen. If retesting confirms eradication and symptoms persist, EGD with biopsy is indicated. Although EGD typically has a very low yield, even for patients with red flags, this invasive test often provides reassurance and increased satisfaction for patients with persistent symptoms.⁴⁶

More options for challenging cases

Managing FD is challenging when both initial acid suppression therapy and H pylori eradication fail. Unproven but low-risk treatments include modification of eating habits (eg, eating slower, not gulping food), reducing stress, discontinuing medications that may be related to symptoms, avoiding foods that seem to exacerbate symptoms, and cutting down or eliminating tobacco, caffeine, alcohol, and carbonated beverages.⁸ Bismuth salts have been shown to be superior to placebo for the treatment of dyspepsia.²⁵ Small studies have also demonstrated a favorable risk–benefit ratio for peppermint oil and caraway oil for the treatment of FD.⁴⁷ Prokinetics have shown efficacy compared with placebo, although a Cochrane review questioned their efficacy based on publication bias.²⁶

There is no good evidence of efficacy for over-the-counter antacids, such as TUMS, or for GI “cocktails” (antacid, antispasmotic, and lidocaine), sucralfate, psychological interventions (eg, cognitive behavioral therapy, relaxation therapy, or hypnosis), or antidepressants.^48,49 Several recent randomized controlled trials have shown the efficacy of acupuncture for the treatment of dyspepsia.^49,50 Ginger may also be helpful; it has been found to help with nausea in other GI conditions, but it’s uncertain whether it can help patients with dyspepsia.⁵¹

CORRESPONDENCE 
Michael Malone, MD, 845 Fishburn Road, Hershey, PA 17053; [email protected]

For well over a century, the periodic health exam has been associated with the delivery of preventive services¹—a model widely accepted by physicians and patients alike. Approximately 8% of ambulatory care visits are for check-ups, and more than 20% of US residents schedule a health exam annually.²

Periodic health exams, however, do not result in optimal preventive care. Evidence suggests that important preventive services, such as dietary counseling, occur at only 8% of such visits; that just 10 seconds, on average, is devoted to smoking cessation; and that 80% of the preventive services patients receive are delivered outside of scheduled health exams.² Because physicians and patients alike understandably prioritize acute problems, any discussion of health maintenance issues during a periodic check-up is likely to occur despite the visit’s agenda, not as part of it.^3-7

Primary care physicians and practices are increasingly being held accountable for their performance on preventive measures. With that in mind, being familiar with evidence-based guidelines relating to the delivery of preventive services in ambulatory care settings, such as those developed by the US Preventive Services Task Force (USPSTF),⁸ is crucial. Identifying elements of the chronic care model that can be effectively applied to preventive care—and recognizing that the reactive acute care model is ineffective for both chronic illness and preventive services—is essential, as well.

Preventive care that's evidence-based

Good practice guidelines should have the following features, according to the Institute of Medicine:⁹
• Validity. Application would lead to the desired health and cost outcomes.
• Reliability/reproducibility. Others using the same data/interpretation would reach the same conclusion.
• Clinical applicability. Patient populations are appropriately defined.
• Clinical flexibility. Known or generally expected exceptions are identified.
• Clarity. Guideline uses unambiguous language with precise definitions.
• Multidisciplinary process. Developed with the participation of all key stakeholders.
• Scheduled review. Periodically reviewed and revised to incorporate new evidence/changing consensus.
• Documentation. Procedures used in development are well documented.

It’s estimated that a primary care physician with an average-sized patient panel would need an additional 7.4 hours per day to achieve 100% compliance with all of the USPSTF recommendations.

The USPSTF guidelines are consistent with these attributes.⁸

Some brief interventions fail

Guidelines are useful as practice standards for establishing preventive care goals, but their existence alone does not ensure the delivery of high-quality preventive services in an office setting. One key factor is time. It is estimated that a primary care physician with an average-sized patient panel would require an additional 7.4 hours per day to achieve 100% compliance with all of the USPSTF recommendations.¹⁰

Counseling, in particular, is an intervention that may be more effective in theory than in practice. Evidence suggests that even when primary care providers are trained in preventive counseling (and many are not), many brief interventions are not effective at creating sustained behavior change or health improvement.¹¹

Others are effective

That’s not to say that there’s little that can be done. Use of standing orders for influenza vaccination is one example of an effective and easily implemented preventive measure that requires little or no additional physician time. Yet some doctors are resistant, fearing loss of control or lawsuits. In fact, the National Vaccine Injury Compensation Program specifically provides protection against vaccinerelated malpractice claims.¹² A standing order for office staff to arrange a screening mammogram is another effective intervention; it has been shown to improve screening rates by as much as 30%.¹³

Lessons from chronic illness management

Chronic illness care and preventive care have much in common.¹⁴ Both acknowledge the need for proactive screening and counseling to bring about behavior change. In addition, both require ongoing care and follow-up, as well as depend on links to community resources. And finally, both are resource-intensive—too resource-intensive, some say, to be delivered in a cost-effective manner.

The Chronic Care Model has been proposed as a framework for improving preventive services (TABLE).^15,16 Evidence suggests adopting some key components of chronic care can lead to significant gains in the delivery of preventive care, with the largest improvement seen when multiple components are used simultaneously.^17-20

Self-management support. A growing body of evidence shows that self-management activities are associated with improved outcomes.²¹ Instituting a peer support group for pregnant women at a federally qualified health center, for example, led to a 7% absolute risk reduction in preterm births.²²

Not all efforts to encourage self-management are effective, however, and evaluation is crucial to determine what works. In one large-scale trial, the use of patient reminder cards to facilitate a reduction in health risk behaviors such as tobacco use, risky drinking, unhealthy dietary patterns, and physical inactivity led to fewer health risk assessments being performed, fewer individual counseling encounters, and no change in these behaviors.²³

Decision support. Clinical decision support systems, which generate patient-specific evidence-based assessments and/or recommendations that are actionable as part of the workflow at the point of care, have been found to improve care.^24,25 An example of this is a prompt that reminds the physician to discuss chemoprevention with a patient at high risk for breast cancer.

Delivery system design. The patient-centered medical home (PCMH) is a well-known example of a redesign of health care delivery.²⁶ Conversion to this model is associated with a small positive effect on preventive interventions.²⁷ However, the persistence of a fee-for-service payment system—which does not include physician reimbursement for some of the added services incorporated into the PCMH—limits the implementation of the PCMH model.²⁸

Many practices are improving health care delivery by using nonphysicians for various tasks related to preventive care. Care managers, for example, typically have smaller caseloads and focus on reducing unnecessary treatment for patients with high-risk conditions, such as congestive heart failure, while patient navigators generally have less clinical expertise but more knowledge of community services.

In one study, practice-initiated phone conversations with nonphysicians increased colorectal cancer screening by up to 40%.²⁹ And in one pilot program, the use of ancillary providers led to an increase in colorectal cancer screening by as much as 123%.³⁰ The human touch seems to be key to the success of these interventions. Passive reminders, such as videos being shown on waiting room televisions, have not proven to be effective.³¹ 

Clinical information systems. Early on, the power of electronic health records (EHRs) to improve practices’ delivery of preventive services was recognized. As early as 1995, the use of a reminder system to highlight such services during acute care visits was linked to improvements in counseling about smoking cessation and higher rates of cervical cancer screening, among other preventive measures.^32,33 Overall, the use of EHRs alone has been shown to improve rates of preventive services by as much as 66%, with most practices reporting improvements of at least 20%.³⁴

Use of standing orders for influenza vaccination is one example of an effective and easily implemented preventive measure that requires little or no additional physician time.

Today, EHRs that are Meaningful Use Stage 2-compliant have the tools needed to improve care. Requirements include the ability to generate patient registries of all those with a given disease and to identify patients on the registry who have not received needed care.³⁵ To improve preventive care, registries should focus on the mitigation of risk factors, such as identifying—and contacting—patients with diabetes who are in need of, or overdue for, an annual eye exam.

Trials using the registry function, in combination with automated messaging to deliver targeted information to various patient groups (identified by the demographic information available from the EHR), are ongoing.

Community resources. Many clinicians have informal referral relationships with community organizations, such as the YMCA. Physician practices that establish links to community resources have the potential to have a large effect on unhealthy behaviors. (See “Putting theory into practice: 2 cases”.) However, a systematic review found that, while evidence to support such connections is mainly positive, research is limited and further evaluation is needed.³⁶

The Practical Playbook (practicalplaybook.org)³⁷ developed by the deBeaumont Foundation, Duke Department of Community and Family Medicine, and the Centers for Disease Control and Prevention, offers concrete examples of how physician practices are linking with community resources to improve the health of the population. For example, Duke University’s “Just for Us” program provides in-home chronic illness care to 350 high-risk elderly individuals. The LATCH program connects thousands of Latino immigrants to health care services and culturally and linguistically appropriate health education classes.³⁷

Growing emphasis on quality

Systemic changes in the US health care system are occurring rapidly, with an emphasis on quality and improved outcomes. Many physicians are now required to submit data to external agencies for payment, and much of the data is grounded in preventive standards. Medicare’s Physicians Quality Reporting System requires that all Medicare providers provide data on preventive and chronic illness care. Rates of vaccination, obesity screening, and tobacco use screening are examples of preventive services that will be reported publicly on the Centers for Medicare & Medicaid Services’ Physician Compare Web site.³⁸

Physicians who work in accountable care organizations are required to meet quality standards on the delivery of certain preventive services, including breast cancer screening, colorectal cancer screening, influenza and pneumonia immunization, body mass index screening and follow-up, tobacco use screening and cessation intervention, screening for high blood pressure and followup, and screening for clinical depression and follow-up.³⁹ As patients discover that the Affordable Care Act mandates that preventive services be covered with no cost sharing, they are likely to become more receptive to physician attempts to provide them.^40,41

CORRESPONDENCE
Gerald Liu, MD, 1504 Springhill Avenue, Suite 3414, Mobile, AL 36604-3207; [email protected]

For well over a century, the periodic health exam has been associated with the delivery of preventive services¹—a model widely accepted by physicians and patients alike. Approximately 8% of ambulatory care visits are for check-ups, and more than 20% of US residents schedule a health exam annually.²

Periodic health exams, however, do not result in optimal preventive care. Evidence suggests that important preventive services, such as dietary counseling, occur at only 8% of such visits; that just 10 seconds, on average, is devoted to smoking cessation; and that 80% of the preventive services patients receive are delivered outside of scheduled health exams.² Because physicians and patients alike understandably prioritize acute problems, any discussion of health maintenance issues during a periodic check-up is likely to occur despite the visit’s agenda, not as part of it.^3-7

Primary care physicians and practices are increasingly being held accountable for their performance on preventive measures. With that in mind, being familiar with evidence-based guidelines relating to the delivery of preventive services in ambulatory care settings, such as those developed by the US Preventive Services Task Force (USPSTF),⁸ is crucial. Identifying elements of the chronic care model that can be effectively applied to preventive care—and recognizing that the reactive acute care model is ineffective for both chronic illness and preventive services—is essential, as well.

Preventive care that's evidence-based

Good practice guidelines should have the following features, according to the Institute of Medicine:⁹
• Validity. Application would lead to the desired health and cost outcomes.
• Reliability/reproducibility. Others using the same data/interpretation would reach the same conclusion.
• Clinical applicability. Patient populations are appropriately defined.
• Clinical flexibility. Known or generally expected exceptions are identified.
• Clarity. Guideline uses unambiguous language with precise definitions.
• Multidisciplinary process. Developed with the participation of all key stakeholders.
• Scheduled review. Periodically reviewed and revised to incorporate new evidence/changing consensus.
• Documentation. Procedures used in development are well documented.

It’s estimated that a primary care physician with an average-sized patient panel would need an additional 7.4 hours per day to achieve 100% compliance with all of the USPSTF recommendations.

The USPSTF guidelines are consistent with these attributes.⁸

Some brief interventions fail

Guidelines are useful as practice standards for establishing preventive care goals, but their existence alone does not ensure the delivery of high-quality preventive services in an office setting. One key factor is time. It is estimated that a primary care physician with an average-sized patient panel would require an additional 7.4 hours per day to achieve 100% compliance with all of the USPSTF recommendations.¹⁰

Counseling, in particular, is an intervention that may be more effective in theory than in practice. Evidence suggests that even when primary care providers are trained in preventive counseling (and many are not), many brief interventions are not effective at creating sustained behavior change or health improvement.¹¹

Others are effective

That’s not to say that there’s little that can be done. Use of standing orders for influenza vaccination is one example of an effective and easily implemented preventive measure that requires little or no additional physician time. Yet some doctors are resistant, fearing loss of control or lawsuits. In fact, the National Vaccine Injury Compensation Program specifically provides protection against vaccinerelated malpractice claims.¹² A standing order for office staff to arrange a screening mammogram is another effective intervention; it has been shown to improve screening rates by as much as 30%.¹³

Lessons from chronic illness management

Chronic illness care and preventive care have much in common.¹⁴ Both acknowledge the need for proactive screening and counseling to bring about behavior change. In addition, both require ongoing care and follow-up, as well as depend on links to community resources. And finally, both are resource-intensive—too resource-intensive, some say, to be delivered in a cost-effective manner.

The Chronic Care Model has been proposed as a framework for improving preventive services (TABLE).^15,16 Evidence suggests adopting some key components of chronic care can lead to significant gains in the delivery of preventive care, with the largest improvement seen when multiple components are used simultaneously.^17-20

Self-management support. A growing body of evidence shows that self-management activities are associated with improved outcomes.²¹ Instituting a peer support group for pregnant women at a federally qualified health center, for example, led to a 7% absolute risk reduction in preterm births.²²

Not all efforts to encourage self-management are effective, however, and evaluation is crucial to determine what works. In one large-scale trial, the use of patient reminder cards to facilitate a reduction in health risk behaviors such as tobacco use, risky drinking, unhealthy dietary patterns, and physical inactivity led to fewer health risk assessments being performed, fewer individual counseling encounters, and no change in these behaviors.²³

Decision support. Clinical decision support systems, which generate patient-specific evidence-based assessments and/or recommendations that are actionable as part of the workflow at the point of care, have been found to improve care.^24,25 An example of this is a prompt that reminds the physician to discuss chemoprevention with a patient at high risk for breast cancer.

Delivery system design. The patient-centered medical home (PCMH) is a well-known example of a redesign of health care delivery.²⁶ Conversion to this model is associated with a small positive effect on preventive interventions.²⁷ However, the persistence of a fee-for-service payment system—which does not include physician reimbursement for some of the added services incorporated into the PCMH—limits the implementation of the PCMH model.²⁸

Many practices are improving health care delivery by using nonphysicians for various tasks related to preventive care. Care managers, for example, typically have smaller caseloads and focus on reducing unnecessary treatment for patients with high-risk conditions, such as congestive heart failure, while patient navigators generally have less clinical expertise but more knowledge of community services.

In one study, practice-initiated phone conversations with nonphysicians increased colorectal cancer screening by up to 40%.²⁹ And in one pilot program, the use of ancillary providers led to an increase in colorectal cancer screening by as much as 123%.³⁰ The human touch seems to be key to the success of these interventions. Passive reminders, such as videos being shown on waiting room televisions, have not proven to be effective.³¹ 

Clinical information systems. Early on, the power of electronic health records (EHRs) to improve practices’ delivery of preventive services was recognized. As early as 1995, the use of a reminder system to highlight such services during acute care visits was linked to improvements in counseling about smoking cessation and higher rates of cervical cancer screening, among other preventive measures.^32,33 Overall, the use of EHRs alone has been shown to improve rates of preventive services by as much as 66%, with most practices reporting improvements of at least 20%.³⁴

Use of standing orders for influenza vaccination is one example of an effective and easily implemented preventive measure that requires little or no additional physician time.

Today, EHRs that are Meaningful Use Stage 2-compliant have the tools needed to improve care. Requirements include the ability to generate patient registries of all those with a given disease and to identify patients on the registry who have not received needed care.³⁵ To improve preventive care, registries should focus on the mitigation of risk factors, such as identifying—and contacting—patients with diabetes who are in need of, or overdue for, an annual eye exam.

Trials using the registry function, in combination with automated messaging to deliver targeted information to various patient groups (identified by the demographic information available from the EHR), are ongoing.

Community resources. Many clinicians have informal referral relationships with community organizations, such as the YMCA. Physician practices that establish links to community resources have the potential to have a large effect on unhealthy behaviors. (See “Putting theory into practice: 2 cases”.) However, a systematic review found that, while evidence to support such connections is mainly positive, research is limited and further evaluation is needed.³⁶

The Practical Playbook (practicalplaybook.org)³⁷ developed by the deBeaumont Foundation, Duke Department of Community and Family Medicine, and the Centers for Disease Control and Prevention, offers concrete examples of how physician practices are linking with community resources to improve the health of the population. For example, Duke University’s “Just for Us” program provides in-home chronic illness care to 350 high-risk elderly individuals. The LATCH program connects thousands of Latino immigrants to health care services and culturally and linguistically appropriate health education classes.³⁷

Growing emphasis on quality

Systemic changes in the US health care system are occurring rapidly, with an emphasis on quality and improved outcomes. Many physicians are now required to submit data to external agencies for payment, and much of the data is grounded in preventive standards. Medicare’s Physicians Quality Reporting System requires that all Medicare providers provide data on preventive and chronic illness care. Rates of vaccination, obesity screening, and tobacco use screening are examples of preventive services that will be reported publicly on the Centers for Medicare & Medicaid Services’ Physician Compare Web site.³⁸

Physicians who work in accountable care organizations are required to meet quality standards on the delivery of certain preventive services, including breast cancer screening, colorectal cancer screening, influenza and pneumonia immunization, body mass index screening and follow-up, tobacco use screening and cessation intervention, screening for high blood pressure and followup, and screening for clinical depression and follow-up.³⁹ As patients discover that the Affordable Care Act mandates that preventive services be covered with no cost sharing, they are likely to become more receptive to physician attempts to provide them.^40,41

CORRESPONDENCE
Gerald Liu, MD, 1504 Springhill Avenue, Suite 3414, Mobile, AL 36604-3207; [email protected]

For well over a century, the periodic health exam has been associated with the delivery of preventive services¹—a model widely accepted by physicians and patients alike. Approximately 8% of ambulatory care visits are for check-ups, and more than 20% of US residents schedule a health exam annually.²

Periodic health exams, however, do not result in optimal preventive care. Evidence suggests that important preventive services, such as dietary counseling, occur at only 8% of such visits; that just 10 seconds, on average, is devoted to smoking cessation; and that 80% of the preventive services patients receive are delivered outside of scheduled health exams.² Because physicians and patients alike understandably prioritize acute problems, any discussion of health maintenance issues during a periodic check-up is likely to occur despite the visit’s agenda, not as part of it.^3-7

Primary care physicians and practices are increasingly being held accountable for their performance on preventive measures. With that in mind, being familiar with evidence-based guidelines relating to the delivery of preventive services in ambulatory care settings, such as those developed by the US Preventive Services Task Force (USPSTF),⁸ is crucial. Identifying elements of the chronic care model that can be effectively applied to preventive care—and recognizing that the reactive acute care model is ineffective for both chronic illness and preventive services—is essential, as well.

Preventive care that's evidence-based

Good practice guidelines should have the following features, according to the Institute of Medicine:⁹
• Validity. Application would lead to the desired health and cost outcomes.
• Reliability/reproducibility. Others using the same data/interpretation would reach the same conclusion.
• Clinical applicability. Patient populations are appropriately defined.
• Clinical flexibility. Known or generally expected exceptions are identified.
• Clarity. Guideline uses unambiguous language with precise definitions.
• Multidisciplinary process. Developed with the participation of all key stakeholders.
• Scheduled review. Periodically reviewed and revised to incorporate new evidence/changing consensus.
• Documentation. Procedures used in development are well documented.

It’s estimated that a primary care physician with an average-sized patient panel would need an additional 7.4 hours per day to achieve 100% compliance with all of the USPSTF recommendations.

The USPSTF guidelines are consistent with these attributes.⁸

Some brief interventions fail

Guidelines are useful as practice standards for establishing preventive care goals, but their existence alone does not ensure the delivery of high-quality preventive services in an office setting. One key factor is time. It is estimated that a primary care physician with an average-sized patient panel would require an additional 7.4 hours per day to achieve 100% compliance with all of the USPSTF recommendations.¹⁰

Counseling, in particular, is an intervention that may be more effective in theory than in practice. Evidence suggests that even when primary care providers are trained in preventive counseling (and many are not), many brief interventions are not effective at creating sustained behavior change or health improvement.¹¹

Others are effective

That’s not to say that there’s little that can be done. Use of standing orders for influenza vaccination is one example of an effective and easily implemented preventive measure that requires little or no additional physician time. Yet some doctors are resistant, fearing loss of control or lawsuits. In fact, the National Vaccine Injury Compensation Program specifically provides protection against vaccinerelated malpractice claims.¹² A standing order for office staff to arrange a screening mammogram is another effective intervention; it has been shown to improve screening rates by as much as 30%.¹³

Lessons from chronic illness management

Chronic illness care and preventive care have much in common.¹⁴ Both acknowledge the need for proactive screening and counseling to bring about behavior change. In addition, both require ongoing care and follow-up, as well as depend on links to community resources. And finally, both are resource-intensive—too resource-intensive, some say, to be delivered in a cost-effective manner.

The Chronic Care Model has been proposed as a framework for improving preventive services (TABLE).^15,16 Evidence suggests adopting some key components of chronic care can lead to significant gains in the delivery of preventive care, with the largest improvement seen when multiple components are used simultaneously.^17-20

Self-management support. A growing body of evidence shows that self-management activities are associated with improved outcomes.²¹ Instituting a peer support group for pregnant women at a federally qualified health center, for example, led to a 7% absolute risk reduction in preterm births.²²

Not all efforts to encourage self-management are effective, however, and evaluation is crucial to determine what works. In one large-scale trial, the use of patient reminder cards to facilitate a reduction in health risk behaviors such as tobacco use, risky drinking, unhealthy dietary patterns, and physical inactivity led to fewer health risk assessments being performed, fewer individual counseling encounters, and no change in these behaviors.²³

Decision support. Clinical decision support systems, which generate patient-specific evidence-based assessments and/or recommendations that are actionable as part of the workflow at the point of care, have been found to improve care.^24,25 An example of this is a prompt that reminds the physician to discuss chemoprevention with a patient at high risk for breast cancer.

Delivery system design. The patient-centered medical home (PCMH) is a well-known example of a redesign of health care delivery.²⁶ Conversion to this model is associated with a small positive effect on preventive interventions.²⁷ However, the persistence of a fee-for-service payment system—which does not include physician reimbursement for some of the added services incorporated into the PCMH—limits the implementation of the PCMH model.²⁸

Many practices are improving health care delivery by using nonphysicians for various tasks related to preventive care. Care managers, for example, typically have smaller caseloads and focus on reducing unnecessary treatment for patients with high-risk conditions, such as congestive heart failure, while patient navigators generally have less clinical expertise but more knowledge of community services.

In one study, practice-initiated phone conversations with nonphysicians increased colorectal cancer screening by up to 40%.²⁹ And in one pilot program, the use of ancillary providers led to an increase in colorectal cancer screening by as much as 123%.³⁰ The human touch seems to be key to the success of these interventions. Passive reminders, such as videos being shown on waiting room televisions, have not proven to be effective.³¹ 

Clinical information systems. Early on, the power of electronic health records (EHRs) to improve practices’ delivery of preventive services was recognized. As early as 1995, the use of a reminder system to highlight such services during acute care visits was linked to improvements in counseling about smoking cessation and higher rates of cervical cancer screening, among other preventive measures.^32,33 Overall, the use of EHRs alone has been shown to improve rates of preventive services by as much as 66%, with most practices reporting improvements of at least 20%.³⁴

Use of standing orders for influenza vaccination is one example of an effective and easily implemented preventive measure that requires little or no additional physician time.

Today, EHRs that are Meaningful Use Stage 2-compliant have the tools needed to improve care. Requirements include the ability to generate patient registries of all those with a given disease and to identify patients on the registry who have not received needed care.³⁵ To improve preventive care, registries should focus on the mitigation of risk factors, such as identifying—and contacting—patients with diabetes who are in need of, or overdue for, an annual eye exam.

Trials using the registry function, in combination with automated messaging to deliver targeted information to various patient groups (identified by the demographic information available from the EHR), are ongoing.

Community resources. Many clinicians have informal referral relationships with community organizations, such as the YMCA. Physician practices that establish links to community resources have the potential to have a large effect on unhealthy behaviors. (See “Putting theory into practice: 2 cases”.) However, a systematic review found that, while evidence to support such connections is mainly positive, research is limited and further evaluation is needed.³⁶

The Practical Playbook (practicalplaybook.org)³⁷ developed by the deBeaumont Foundation, Duke Department of Community and Family Medicine, and the Centers for Disease Control and Prevention, offers concrete examples of how physician practices are linking with community resources to improve the health of the population. For example, Duke University’s “Just for Us” program provides in-home chronic illness care to 350 high-risk elderly individuals. The LATCH program connects thousands of Latino immigrants to health care services and culturally and linguistically appropriate health education classes.³⁷

Growing emphasis on quality

Systemic changes in the US health care system are occurring rapidly, with an emphasis on quality and improved outcomes. Many physicians are now required to submit data to external agencies for payment, and much of the data is grounded in preventive standards. Medicare’s Physicians Quality Reporting System requires that all Medicare providers provide data on preventive and chronic illness care. Rates of vaccination, obesity screening, and tobacco use screening are examples of preventive services that will be reported publicly on the Centers for Medicare & Medicaid Services’ Physician Compare Web site.³⁸

Physicians who work in accountable care organizations are required to meet quality standards on the delivery of certain preventive services, including breast cancer screening, colorectal cancer screening, influenza and pneumonia immunization, body mass index screening and follow-up, tobacco use screening and cessation intervention, screening for high blood pressure and followup, and screening for clinical depression and follow-up.³⁹ As patients discover that the Affordable Care Act mandates that preventive services be covered with no cost sharing, they are likely to become more receptive to physician attempts to provide them.^40,41

CORRESPONDENCE
Gerald Liu, MD, 1504 Springhill Avenue, Suite 3414, Mobile, AL 36604-3207; [email protected]

Concerns about tantrums come up a lot in pediatric care. We all know about telling parents to ignore tantrums in toddlers and not to give in. But what about when this advice does not work?

I like to think of tantrums as emotions that go beyond the child’s control. This reframing helps families consider that not all tantrums are an attempt by the child to manipulate them. That is an important first step in avoiding a solely punitive response and instead encouraging parents to look for the source of the imbalance.

Temper tantrums are most common when a child is making developmental spurts in abilities or thinking that are typically unevenly matched with self-control. There is a lot of unevenness in children’s ability to do, say, or tolerate feelings between the early tantrums of the 9-month-old until the greater coping of the 6-year-old. For example, 87% of 18- to 24-month-olds have tantrums just as they acquire autonomy and some language, yet can’t really speak their feelings, while 91% of 30- to 36-month-olds have tantrums because they can imagine big things, but are only capable of or allowed small ones. Even at 42-48 months, more than half have tantrums, which often are associated with the stress and fatigue from dropping their nap.

Life is frustrating for kids. Young children want to try to use their new skills such as climbing, opening things, or scribbling, but parents – at first delighted – suddenly want them to stop! At first, every new word is celebrated, but then toddler talk gets routine, and toddlers may be ignored or even shushed. When the child has a strong desire, the words may not be there, or emotions may make it hard to talk at all, leading to frustration.

With the development of a sense of self, the song is “I want,” “mine,” and “no!” Sharing is not in the child’s repertoire until age 3 years or older. Temperamentally more intense children give up less easily or are not readily distracted.

The threshold for frustration depends on the child’s overall state. Is the child hungry? Tired? Stressed? In pain? Here is where the differential diagnosis of excessive tantrums needs to also include pain from a medical condition such as celiac disease, arthritis, migraine, or sickle cell disease. Children under age 7 years commonly have a low tolerance for sensations as simple as loud noises and elastic waistbands, but those with sensory integration disorder are at the extreme in what sounds, feelings, or motions they cannot bear at any age and may need specific intervention by occupational or physical therapists. Mental health conditions such as attention-deficit/hyperactivity disorder, depression, anxiety, and bipolar disorder also predispose to irritable responses to even normal stresses, often in combination with lagging skills and poor sleep. Consider these when tantrums are extreme.

Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical Communications.

Concerns about tantrums come up a lot in pediatric care. We all know about telling parents to ignore tantrums in toddlers and not to give in. But what about when this advice does not work?

I like to think of tantrums as emotions that go beyond the child’s control. This reframing helps families consider that not all tantrums are an attempt by the child to manipulate them. That is an important first step in avoiding a solely punitive response and instead encouraging parents to look for the source of the imbalance.

Temper tantrums are most common when a child is making developmental spurts in abilities or thinking that are typically unevenly matched with self-control. There is a lot of unevenness in children’s ability to do, say, or tolerate feelings between the early tantrums of the 9-month-old until the greater coping of the 6-year-old. For example, 87% of 18- to 24-month-olds have tantrums just as they acquire autonomy and some language, yet can’t really speak their feelings, while 91% of 30- to 36-month-olds have tantrums because they can imagine big things, but are only capable of or allowed small ones. Even at 42-48 months, more than half have tantrums, which often are associated with the stress and fatigue from dropping their nap.

Life is frustrating for kids. Young children want to try to use their new skills such as climbing, opening things, or scribbling, but parents – at first delighted – suddenly want them to stop! At first, every new word is celebrated, but then toddler talk gets routine, and toddlers may be ignored or even shushed. When the child has a strong desire, the words may not be there, or emotions may make it hard to talk at all, leading to frustration.

With the development of a sense of self, the song is “I want,” “mine,” and “no!” Sharing is not in the child’s repertoire until age 3 years or older. Temperamentally more intense children give up less easily or are not readily distracted.

The threshold for frustration depends on the child’s overall state. Is the child hungry? Tired? Stressed? In pain? Here is where the differential diagnosis of excessive tantrums needs to also include pain from a medical condition such as celiac disease, arthritis, migraine, or sickle cell disease. Children under age 7 years commonly have a low tolerance for sensations as simple as loud noises and elastic waistbands, but those with sensory integration disorder are at the extreme in what sounds, feelings, or motions they cannot bear at any age and may need specific intervention by occupational or physical therapists. Mental health conditions such as attention-deficit/hyperactivity disorder, depression, anxiety, and bipolar disorder also predispose to irritable responses to even normal stresses, often in combination with lagging skills and poor sleep. Consider these when tantrums are extreme.

Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical Communications.

Concerns about tantrums come up a lot in pediatric care. We all know about telling parents to ignore tantrums in toddlers and not to give in. But what about when this advice does not work?

I like to think of tantrums as emotions that go beyond the child’s control. This reframing helps families consider that not all tantrums are an attempt by the child to manipulate them. That is an important first step in avoiding a solely punitive response and instead encouraging parents to look for the source of the imbalance.

Temper tantrums are most common when a child is making developmental spurts in abilities or thinking that are typically unevenly matched with self-control. There is a lot of unevenness in children’s ability to do, say, or tolerate feelings between the early tantrums of the 9-month-old until the greater coping of the 6-year-old. For example, 87% of 18- to 24-month-olds have tantrums just as they acquire autonomy and some language, yet can’t really speak their feelings, while 91% of 30- to 36-month-olds have tantrums because they can imagine big things, but are only capable of or allowed small ones. Even at 42-48 months, more than half have tantrums, which often are associated with the stress and fatigue from dropping their nap.

Life is frustrating for kids. Young children want to try to use their new skills such as climbing, opening things, or scribbling, but parents – at first delighted – suddenly want them to stop! At first, every new word is celebrated, but then toddler talk gets routine, and toddlers may be ignored or even shushed. When the child has a strong desire, the words may not be there, or emotions may make it hard to talk at all, leading to frustration.

With the development of a sense of self, the song is “I want,” “mine,” and “no!” Sharing is not in the child’s repertoire until age 3 years or older. Temperamentally more intense children give up less easily or are not readily distracted.

The threshold for frustration depends on the child’s overall state. Is the child hungry? Tired? Stressed? In pain? Here is where the differential diagnosis of excessive tantrums needs to also include pain from a medical condition such as celiac disease, arthritis, migraine, or sickle cell disease. Children under age 7 years commonly have a low tolerance for sensations as simple as loud noises and elastic waistbands, but those with sensory integration disorder are at the extreme in what sounds, feelings, or motions they cannot bear at any age and may need specific intervention by occupational or physical therapists. Mental health conditions such as attention-deficit/hyperactivity disorder, depression, anxiety, and bipolar disorder also predispose to irritable responses to even normal stresses, often in combination with lagging skills and poor sleep. Consider these when tantrums are extreme.

Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical Communications.

CASE › Joe M, age 59, seeks care at the local emergency department (ED) for shortness of breath. He also complains that his abdomen has been getting “bigger and bigger.” The ED physician recognizes that he is suffering from cirrhosis with secondary ascites and admits him. A paracentesis is performed and 7 L of fluid are removed. The patient is started on furosemide 40 mg/d and the health care team educates him about the relationship between his alcohol consumption and his enlarging abdomen. At discharge, he is told to follow up with his primary care physician.

Two weeks later, the patient arrives at your clinic for followup. What is the next step in managing this patient?

Cirrhosis—the end stage of chronic liver disease characterized by inflammation and fibrosis—is a relatively common and often fatal diagnosis. In the United States, an estimated 633,000 adults have cirrhosis,¹ and each year approximately 32,000 people die from the condition.² The most common causes of cirrhosis are heavy alcohol use, chronic hepatitis B or C infection, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.³ Cirrhosis typically involves degeneration and necrosis of hepatocytes, which are replaced by fibrotic tissues and regenerative nodules, leading to loss of liver function.⁴

Patients with cirrhosis can be treated as outpatients—that is, until they decompensate. Obviously, treatment specific to the underlying causes of cirrhosis, such as interferon for a patient with hepatitis and abstinence for a patient with alcohol-related liver disease, should be the first concern. However, this article focuses on the family physician’s role in identifying and treating several of the most common complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. We will also cover which patients should be referred for evaluation for liver transplantation. (For a guide to providing patient education for individuals with cirrhosis, see “Dx cirrhosis: What to teach your patient”.^3,5-10)

Sodium restriction, diuretics are first steps for ascites

The goals of ascites treatment are to prevent or relieve dyspnea and abdominal pain and to prevent life-threatening complications, such as spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome.¹¹ Patient education is key regarding weight gain; that’s why it’s important to instruct patients to contact you if they gain more than 2 lbs/d for 3 consecutive days or more than 10 lbs.¹²

Approximately 10% of patients with ascites respond well to sodium restriction alone (1500-2000 mg/d).¹¹ In addition to sodium restriction, patients with grade 2 ascites (moderate ascites with proportionate abdominal distension) should receive a low-dose diuretic, such as spironolactone (initial dose, 50-100 mg/d; increase up to 200-300 mg/d)¹³ or amiloride (5-10 mg/d).⁵

Approximately 10% of patients with ascites respond well to sodium restriction alone.

Painful gynecomastia and hyperkalemia are the most common adverse effects of spironolactone.¹³ Amiloride has fewer adverse effects than spironolactone, but is less effective.¹¹ Low-dose furosemide (20-40 mg/d) may be added, although weight loss should be monitored to watch for excessive diuresis, which can lead to renal failure, hyponatremia, or encephalopathy.^5,13 Also monitor electrolytes to watch for hypokalemia or hyponatremia.¹³

Recommended weight loss to prevent renal failure is 300 to 500 g/d (.66-1.1 lbs/d) for patients without peripheral edema, and 800 to 1000 g/d (1.7-2.2 lbs/d) for patients with peripheral edema.^5,13

Patients with grade 3 (tense) or refractory ascites should have large-volume paracentesis (LVP) plus an albumin infusion.⁵ LVP (removal of >5 L of fluid) is more effective, faster, and has less risk of adverse effects than increasing the dosage of the patient’s diuretic.^5,13 LVP can be done in an outpatient setting and is considered safe—even for patients with a prolonged prothrombin time.^13,14 Rare complications of LVP include significant bleeding at the puncture site, infection, and intestinal perforation.⁵

Diuretics should be prescribed after LVP to prevent ascites recurrence.⁵ Plasma expanders can prevent hepatorenal syndrome, ascites recurrence, and dilutional hyponatremia.^5,11 Albumin is the most efficacious of these agents;^5,14 it is administered intravenously at a dose of 8 to 10 g/L of fluid removed.^13,15

Take steps to prevent variceal bleeding

Soon after a patient is diagnosed with cirrhosis, he or she should undergo esophagogastroduodenoscopy to screen for the presence and size of varices.¹⁶ Although they can’t prevent esophagogastric varices, nonselective beta-blockers (NSBBs) are the gold standard for preventing first variceal hemorrhage in patients with small varices with red wale signs on the varices and/or Child-Pugh Class B or C cirrhosis (TABLE¹⁷), and in all patients with medium or large varices.¹⁸ Propranolol is usually started at 20 mg BID, or nadolol is started at 20 to 40 mg/d.¹⁶ The NSBB dose is adjusted to the maximum tolerated dose, which occurs when the patient's heart rate is reduced to 55 to 60 beats/min.

NSBBs are associated with poor survival in patients with refractory ascites and thus are contraindicated in these patients.¹⁹ NSBBs also should not be taken by patients with SBP because use of these medications is associated with worse outcomes compared to those not receiving NSBBs.²⁰

Endoscopic variceal ligation is an alternative to NSBBs for the primary prophylaxis of variceal hemorrhage in patients with medium to large varices.¹⁸ In particular, ligation should be considered for patients with high-risk varices in whom beta-blockers are contraindicated or must be discontinued because of adverse effects.²¹

Avoid nitrates in patients with varices because these agents do not prevent first variceal hemorrhage and have been associated with higher mortality rates in patients older than 50.¹⁶ There is no significant additional benefit or mortality reduction associated with adding a nitrate to an NSBB.²² Transjugular intrahepatic portosystemic shunt (TIPS) or surgically created shunts are reserved for patients for whom medical therapy fails.¹⁸

Mental status changes suggest hepatic encephalopathy

Hepatic encephalopathy is a reversible impairment of neuropsychiatric function that is associated with impaired hepatic function. Because a patient with encephalopathy presents with an altered mental status, he or she may need to be admitted to the hospital for evaluation, diagnosis, and treatment.

The goals of hepatic encephalopathy treatment are to identify and correct precipitating causes and lower serum ammonia concentrations to improve mental status.¹⁵ Nutritional support should be provided without protein restriction unless the patient is severely proteinintolerant.²³ The recommended initial therapy is lactulose 30 to 45 mL 2 to 4 times per day, to decrease absorption of ammonia in the gut. The dose should be titrated until patients have 2 to 3 soft stools daily.²⁴

For patients who can’t tolerate lactulose or whose mental status doesn’t improve within 48 hours, rifaximin 400 mg orally 3 times daily or 550 mg 2 times daily is recommended.²⁵ Neomycin 500 mg orally 3 times a day or 1 g twice daily is a second-line agent reserved for patients who are unable to take rifaximin; however, its efficacy is not well established, and neomycin has been associated with ototoxicity and nephrotoxicity.²⁴

Watch for signs of kidney failure

Hepatorenal syndrome is renal failure induced by severe hepatic injury and characterized by azotemia and decreased renal blood flow and glomerular filtration rate.¹⁵ It is a diagnosis of exclusion. Hepatorenal syndrome is typically caused by arterial vasodilation in the splanchnic circulation in patients with portal hypertension.^15,26,27 Type 1 hepatorenal syndrome is characterized by at least a 2-fold increase in serum creatinine to a level of >2.5 mg/dL over more than 2 weeks. Patients typically have urine output <400 to 500 mL/d. Type 2 hepatorenal syndrome is characterized by less severe renal impairment; it is associated with ascites that does not improve with diuretics.²⁸

Endoscopic variceal ligation is an alternative to nonselective beta-blockers for preventing variceal hemorrhage in patients with medium to large varices.

Patients with hepatorenal syndrome should not use any nephrotoxic agents, such as nonsteroidal anti-inflammatory drugs. Inpatient treatment is usually required and may include norepinephrine with albumin, terlipressin with midodrine, or octreotide and albumin. Patients who fail to respond to medical therapy may benefit from TIPS as a bridge until they can undergo liver transplantation.²⁹

When to consider liver transplantation

The appropriateness and timing of liver transplantation should be determined on a case-by-case basis. For some patients with cirrhosis, transplantation may be the definitive treatment. For example, in some patients with hepatocellular carcinoma (HCC), liver transplantation is an option because transplantation can cure the tumor and underlying cirrhosis. However, while transplantation is a suitable option for early HCC in patients with cirrhosis, it has been shown to have limited efficacy in patients with advanced disease who are not selected using specific criteria.³⁰

Referral for evaluation for transplantation should be considered once a patient with cirrhosis experiences a major complication (eg, ascites, variceal hemorrhage, or hepatic encephalopathy).³¹ Another criterion for timing and allocation of liver transplantation is based on the statistical model for end-stage liver disease (MELD), which is used to predict 3-month survival in patients with cirrhosis based on the relationships between serum bilirubin, serum creatinine, and international normalized ratio values.¹⁵ Liver transplantation should be considered for patients with a MELD score ≥15.^15,31 Such patients should be promptly referred to a liver transplantation specialist to allow sufficient time for the appropriate psychosocial assessments and medical evaluations, and for patients and their families to receive appropriate education on things like the risks and benefits of transplantation.¹⁵

CASE › After evaluating Mr. M, you prescribe spironolactone 100 mg/d and furosemide 40 mg twice a day to address ascites, and propranolol—which you titrate to 80 mg twice a day—to prevent variceal hemorrhage. Mr. M is maintained on these medications and returns with his daughter, as he has been doing every 2 to 3 months. He is excited that he breathes easily as long as he avoids salt and takes his medications. He continues to see his hepatologist regularly, and his last paracentesis was 4 months ago. He has not used any alcohol since he was taught about the relationship between alcohol and his breathing.

CORRESPONDENCE
Suzanne Minor, MD, FAAF P, Assistant Professor of Family Medicine, Department of Humanities, Health, & Society, Florida International University, Herbert Wertheim College of Medicine, 11200 SW 8th Street, AHC II, 554A, Miami, FL 33199; [email protected]

CASE › Joe M, age 59, seeks care at the local emergency department (ED) for shortness of breath. He also complains that his abdomen has been getting “bigger and bigger.” The ED physician recognizes that he is suffering from cirrhosis with secondary ascites and admits him. A paracentesis is performed and 7 L of fluid are removed. The patient is started on furosemide 40 mg/d and the health care team educates him about the relationship between his alcohol consumption and his enlarging abdomen. At discharge, he is told to follow up with his primary care physician.

Two weeks later, the patient arrives at your clinic for followup. What is the next step in managing this patient?

Cirrhosis—the end stage of chronic liver disease characterized by inflammation and fibrosis—is a relatively common and often fatal diagnosis. In the United States, an estimated 633,000 adults have cirrhosis,¹ and each year approximately 32,000 people die from the condition.² The most common causes of cirrhosis are heavy alcohol use, chronic hepatitis B or C infection, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.³ Cirrhosis typically involves degeneration and necrosis of hepatocytes, which are replaced by fibrotic tissues and regenerative nodules, leading to loss of liver function.⁴

Patients with cirrhosis can be treated as outpatients—that is, until they decompensate. Obviously, treatment specific to the underlying causes of cirrhosis, such as interferon for a patient with hepatitis and abstinence for a patient with alcohol-related liver disease, should be the first concern. However, this article focuses on the family physician’s role in identifying and treating several of the most common complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. We will also cover which patients should be referred for evaluation for liver transplantation. (For a guide to providing patient education for individuals with cirrhosis, see “Dx cirrhosis: What to teach your patient”.^3,5-10)

Sodium restriction, diuretics are first steps for ascites

The goals of ascites treatment are to prevent or relieve dyspnea and abdominal pain and to prevent life-threatening complications, such as spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome.¹¹ Patient education is key regarding weight gain; that’s why it’s important to instruct patients to contact you if they gain more than 2 lbs/d for 3 consecutive days or more than 10 lbs.¹²

Approximately 10% of patients with ascites respond well to sodium restriction alone (1500-2000 mg/d).¹¹ In addition to sodium restriction, patients with grade 2 ascites (moderate ascites with proportionate abdominal distension) should receive a low-dose diuretic, such as spironolactone (initial dose, 50-100 mg/d; increase up to 200-300 mg/d)¹³ or amiloride (5-10 mg/d).⁵

Approximately 10% of patients with ascites respond well to sodium restriction alone.

Painful gynecomastia and hyperkalemia are the most common adverse effects of spironolactone.¹³ Amiloride has fewer adverse effects than spironolactone, but is less effective.¹¹ Low-dose furosemide (20-40 mg/d) may be added, although weight loss should be monitored to watch for excessive diuresis, which can lead to renal failure, hyponatremia, or encephalopathy.^5,13 Also monitor electrolytes to watch for hypokalemia or hyponatremia.¹³

Recommended weight loss to prevent renal failure is 300 to 500 g/d (.66-1.1 lbs/d) for patients without peripheral edema, and 800 to 1000 g/d (1.7-2.2 lbs/d) for patients with peripheral edema.^5,13

Patients with grade 3 (tense) or refractory ascites should have large-volume paracentesis (LVP) plus an albumin infusion.⁵ LVP (removal of >5 L of fluid) is more effective, faster, and has less risk of adverse effects than increasing the dosage of the patient’s diuretic.^5,13 LVP can be done in an outpatient setting and is considered safe—even for patients with a prolonged prothrombin time.^13,14 Rare complications of LVP include significant bleeding at the puncture site, infection, and intestinal perforation.⁵

Diuretics should be prescribed after LVP to prevent ascites recurrence.⁵ Plasma expanders can prevent hepatorenal syndrome, ascites recurrence, and dilutional hyponatremia.^5,11 Albumin is the most efficacious of these agents;^5,14 it is administered intravenously at a dose of 8 to 10 g/L of fluid removed.^13,15

Take steps to prevent variceal bleeding

Soon after a patient is diagnosed with cirrhosis, he or she should undergo esophagogastroduodenoscopy to screen for the presence and size of varices.¹⁶ Although they can’t prevent esophagogastric varices, nonselective beta-blockers (NSBBs) are the gold standard for preventing first variceal hemorrhage in patients with small varices with red wale signs on the varices and/or Child-Pugh Class B or C cirrhosis (TABLE¹⁷), and in all patients with medium or large varices.¹⁸ Propranolol is usually started at 20 mg BID, or nadolol is started at 20 to 40 mg/d.¹⁶ The NSBB dose is adjusted to the maximum tolerated dose, which occurs when the patient's heart rate is reduced to 55 to 60 beats/min.

NSBBs are associated with poor survival in patients with refractory ascites and thus are contraindicated in these patients.¹⁹ NSBBs also should not be taken by patients with SBP because use of these medications is associated with worse outcomes compared to those not receiving NSBBs.²⁰

Endoscopic variceal ligation is an alternative to NSBBs for the primary prophylaxis of variceal hemorrhage in patients with medium to large varices.¹⁸ In particular, ligation should be considered for patients with high-risk varices in whom beta-blockers are contraindicated or must be discontinued because of adverse effects.²¹

Avoid nitrates in patients with varices because these agents do not prevent first variceal hemorrhage and have been associated with higher mortality rates in patients older than 50.¹⁶ There is no significant additional benefit or mortality reduction associated with adding a nitrate to an NSBB.²² Transjugular intrahepatic portosystemic shunt (TIPS) or surgically created shunts are reserved for patients for whom medical therapy fails.¹⁸

Mental status changes suggest hepatic encephalopathy

Hepatic encephalopathy is a reversible impairment of neuropsychiatric function that is associated with impaired hepatic function. Because a patient with encephalopathy presents with an altered mental status, he or she may need to be admitted to the hospital for evaluation, diagnosis, and treatment.

The goals of hepatic encephalopathy treatment are to identify and correct precipitating causes and lower serum ammonia concentrations to improve mental status.¹⁵ Nutritional support should be provided without protein restriction unless the patient is severely proteinintolerant.²³ The recommended initial therapy is lactulose 30 to 45 mL 2 to 4 times per day, to decrease absorption of ammonia in the gut. The dose should be titrated until patients have 2 to 3 soft stools daily.²⁴

For patients who can’t tolerate lactulose or whose mental status doesn’t improve within 48 hours, rifaximin 400 mg orally 3 times daily or 550 mg 2 times daily is recommended.²⁵ Neomycin 500 mg orally 3 times a day or 1 g twice daily is a second-line agent reserved for patients who are unable to take rifaximin; however, its efficacy is not well established, and neomycin has been associated with ototoxicity and nephrotoxicity.²⁴

Watch for signs of kidney failure

Hepatorenal syndrome is renal failure induced by severe hepatic injury and characterized by azotemia and decreased renal blood flow and glomerular filtration rate.¹⁵ It is a diagnosis of exclusion. Hepatorenal syndrome is typically caused by arterial vasodilation in the splanchnic circulation in patients with portal hypertension.^15,26,27 Type 1 hepatorenal syndrome is characterized by at least a 2-fold increase in serum creatinine to a level of >2.5 mg/dL over more than 2 weeks. Patients typically have urine output <400 to 500 mL/d. Type 2 hepatorenal syndrome is characterized by less severe renal impairment; it is associated with ascites that does not improve with diuretics.²⁸

Endoscopic variceal ligation is an alternative to nonselective beta-blockers for preventing variceal hemorrhage in patients with medium to large varices.

Patients with hepatorenal syndrome should not use any nephrotoxic agents, such as nonsteroidal anti-inflammatory drugs. Inpatient treatment is usually required and may include norepinephrine with albumin, terlipressin with midodrine, or octreotide and albumin. Patients who fail to respond to medical therapy may benefit from TIPS as a bridge until they can undergo liver transplantation.²⁹

When to consider liver transplantation

The appropriateness and timing of liver transplantation should be determined on a case-by-case basis. For some patients with cirrhosis, transplantation may be the definitive treatment. For example, in some patients with hepatocellular carcinoma (HCC), liver transplantation is an option because transplantation can cure the tumor and underlying cirrhosis. However, while transplantation is a suitable option for early HCC in patients with cirrhosis, it has been shown to have limited efficacy in patients with advanced disease who are not selected using specific criteria.³⁰

Referral for evaluation for transplantation should be considered once a patient with cirrhosis experiences a major complication (eg, ascites, variceal hemorrhage, or hepatic encephalopathy).³¹ Another criterion for timing and allocation of liver transplantation is based on the statistical model for end-stage liver disease (MELD), which is used to predict 3-month survival in patients with cirrhosis based on the relationships between serum bilirubin, serum creatinine, and international normalized ratio values.¹⁵ Liver transplantation should be considered for patients with a MELD score ≥15.^15,31 Such patients should be promptly referred to a liver transplantation specialist to allow sufficient time for the appropriate psychosocial assessments and medical evaluations, and for patients and their families to receive appropriate education on things like the risks and benefits of transplantation.¹⁵

CASE › After evaluating Mr. M, you prescribe spironolactone 100 mg/d and furosemide 40 mg twice a day to address ascites, and propranolol—which you titrate to 80 mg twice a day—to prevent variceal hemorrhage. Mr. M is maintained on these medications and returns with his daughter, as he has been doing every 2 to 3 months. He is excited that he breathes easily as long as he avoids salt and takes his medications. He continues to see his hepatologist regularly, and his last paracentesis was 4 months ago. He has not used any alcohol since he was taught about the relationship between alcohol and his breathing.

CORRESPONDENCE
Suzanne Minor, MD, FAAF P, Assistant Professor of Family Medicine, Department of Humanities, Health, & Society, Florida International University, Herbert Wertheim College of Medicine, 11200 SW 8th Street, AHC II, 554A, Miami, FL 33199; [email protected]

CASE › Joe M, age 59, seeks care at the local emergency department (ED) for shortness of breath. He also complains that his abdomen has been getting “bigger and bigger.” The ED physician recognizes that he is suffering from cirrhosis with secondary ascites and admits him. A paracentesis is performed and 7 L of fluid are removed. The patient is started on furosemide 40 mg/d and the health care team educates him about the relationship between his alcohol consumption and his enlarging abdomen. At discharge, he is told to follow up with his primary care physician.

Two weeks later, the patient arrives at your clinic for followup. What is the next step in managing this patient?

Cirrhosis—the end stage of chronic liver disease characterized by inflammation and fibrosis—is a relatively common and often fatal diagnosis. In the United States, an estimated 633,000 adults have cirrhosis,¹ and each year approximately 32,000 people die from the condition.² The most common causes of cirrhosis are heavy alcohol use, chronic hepatitis B or C infection, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.³ Cirrhosis typically involves degeneration and necrosis of hepatocytes, which are replaced by fibrotic tissues and regenerative nodules, leading to loss of liver function.⁴

Patients with cirrhosis can be treated as outpatients—that is, until they decompensate. Obviously, treatment specific to the underlying causes of cirrhosis, such as interferon for a patient with hepatitis and abstinence for a patient with alcohol-related liver disease, should be the first concern. However, this article focuses on the family physician’s role in identifying and treating several of the most common complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. We will also cover which patients should be referred for evaluation for liver transplantation. (For a guide to providing patient education for individuals with cirrhosis, see “Dx cirrhosis: What to teach your patient”.^3,5-10)

Sodium restriction, diuretics are first steps for ascites

The goals of ascites treatment are to prevent or relieve dyspnea and abdominal pain and to prevent life-threatening complications, such as spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome.¹¹ Patient education is key regarding weight gain; that’s why it’s important to instruct patients to contact you if they gain more than 2 lbs/d for 3 consecutive days or more than 10 lbs.¹²

Approximately 10% of patients with ascites respond well to sodium restriction alone (1500-2000 mg/d).¹¹ In addition to sodium restriction, patients with grade 2 ascites (moderate ascites with proportionate abdominal distension) should receive a low-dose diuretic, such as spironolactone (initial dose, 50-100 mg/d; increase up to 200-300 mg/d)¹³ or amiloride (5-10 mg/d).⁵

Approximately 10% of patients with ascites respond well to sodium restriction alone.

Painful gynecomastia and hyperkalemia are the most common adverse effects of spironolactone.¹³ Amiloride has fewer adverse effects than spironolactone, but is less effective.¹¹ Low-dose furosemide (20-40 mg/d) may be added, although weight loss should be monitored to watch for excessive diuresis, which can lead to renal failure, hyponatremia, or encephalopathy.^5,13 Also monitor electrolytes to watch for hypokalemia or hyponatremia.¹³

Recommended weight loss to prevent renal failure is 300 to 500 g/d (.66-1.1 lbs/d) for patients without peripheral edema, and 800 to 1000 g/d (1.7-2.2 lbs/d) for patients with peripheral edema.^5,13

Patients with grade 3 (tense) or refractory ascites should have large-volume paracentesis (LVP) plus an albumin infusion.⁵ LVP (removal of >5 L of fluid) is more effective, faster, and has less risk of adverse effects than increasing the dosage of the patient’s diuretic.^5,13 LVP can be done in an outpatient setting and is considered safe—even for patients with a prolonged prothrombin time.^13,14 Rare complications of LVP include significant bleeding at the puncture site, infection, and intestinal perforation.⁵

Diuretics should be prescribed after LVP to prevent ascites recurrence.⁵ Plasma expanders can prevent hepatorenal syndrome, ascites recurrence, and dilutional hyponatremia.^5,11 Albumin is the most efficacious of these agents;^5,14 it is administered intravenously at a dose of 8 to 10 g/L of fluid removed.^13,15

Take steps to prevent variceal bleeding

Soon after a patient is diagnosed with cirrhosis, he or she should undergo esophagogastroduodenoscopy to screen for the presence and size of varices.¹⁶ Although they can’t prevent esophagogastric varices, nonselective beta-blockers (NSBBs) are the gold standard for preventing first variceal hemorrhage in patients with small varices with red wale signs on the varices and/or Child-Pugh Class B or C cirrhosis (TABLE¹⁷), and in all patients with medium or large varices.¹⁸ Propranolol is usually started at 20 mg BID, or nadolol is started at 20 to 40 mg/d.¹⁶ The NSBB dose is adjusted to the maximum tolerated dose, which occurs when the patient's heart rate is reduced to 55 to 60 beats/min.

NSBBs are associated with poor survival in patients with refractory ascites and thus are contraindicated in these patients.¹⁹ NSBBs also should not be taken by patients with SBP because use of these medications is associated with worse outcomes compared to those not receiving NSBBs.²⁰

Endoscopic variceal ligation is an alternative to NSBBs for the primary prophylaxis of variceal hemorrhage in patients with medium to large varices.¹⁸ In particular, ligation should be considered for patients with high-risk varices in whom beta-blockers are contraindicated or must be discontinued because of adverse effects.²¹

Avoid nitrates in patients with varices because these agents do not prevent first variceal hemorrhage and have been associated with higher mortality rates in patients older than 50.¹⁶ There is no significant additional benefit or mortality reduction associated with adding a nitrate to an NSBB.²² Transjugular intrahepatic portosystemic shunt (TIPS) or surgically created shunts are reserved for patients for whom medical therapy fails.¹⁸

Mental status changes suggest hepatic encephalopathy

Hepatic encephalopathy is a reversible impairment of neuropsychiatric function that is associated with impaired hepatic function. Because a patient with encephalopathy presents with an altered mental status, he or she may need to be admitted to the hospital for evaluation, diagnosis, and treatment.

The goals of hepatic encephalopathy treatment are to identify and correct precipitating causes and lower serum ammonia concentrations to improve mental status.¹⁵ Nutritional support should be provided without protein restriction unless the patient is severely proteinintolerant.²³ The recommended initial therapy is lactulose 30 to 45 mL 2 to 4 times per day, to decrease absorption of ammonia in the gut. The dose should be titrated until patients have 2 to 3 soft stools daily.²⁴

For patients who can’t tolerate lactulose or whose mental status doesn’t improve within 48 hours, rifaximin 400 mg orally 3 times daily or 550 mg 2 times daily is recommended.²⁵ Neomycin 500 mg orally 3 times a day or 1 g twice daily is a second-line agent reserved for patients who are unable to take rifaximin; however, its efficacy is not well established, and neomycin has been associated with ototoxicity and nephrotoxicity.²⁴

Watch for signs of kidney failure

Hepatorenal syndrome is renal failure induced by severe hepatic injury and characterized by azotemia and decreased renal blood flow and glomerular filtration rate.¹⁵ It is a diagnosis of exclusion. Hepatorenal syndrome is typically caused by arterial vasodilation in the splanchnic circulation in patients with portal hypertension.^15,26,27 Type 1 hepatorenal syndrome is characterized by at least a 2-fold increase in serum creatinine to a level of >2.5 mg/dL over more than 2 weeks. Patients typically have urine output <400 to 500 mL/d. Type 2 hepatorenal syndrome is characterized by less severe renal impairment; it is associated with ascites that does not improve with diuretics.²⁸

Endoscopic variceal ligation is an alternative to nonselective beta-blockers for preventing variceal hemorrhage in patients with medium to large varices.

Patients with hepatorenal syndrome should not use any nephrotoxic agents, such as nonsteroidal anti-inflammatory drugs. Inpatient treatment is usually required and may include norepinephrine with albumin, terlipressin with midodrine, or octreotide and albumin. Patients who fail to respond to medical therapy may benefit from TIPS as a bridge until they can undergo liver transplantation.²⁹

When to consider liver transplantation

The appropriateness and timing of liver transplantation should be determined on a case-by-case basis. For some patients with cirrhosis, transplantation may be the definitive treatment. For example, in some patients with hepatocellular carcinoma (HCC), liver transplantation is an option because transplantation can cure the tumor and underlying cirrhosis. However, while transplantation is a suitable option for early HCC in patients with cirrhosis, it has been shown to have limited efficacy in patients with advanced disease who are not selected using specific criteria.³⁰

Referral for evaluation for transplantation should be considered once a patient with cirrhosis experiences a major complication (eg, ascites, variceal hemorrhage, or hepatic encephalopathy).³¹ Another criterion for timing and allocation of liver transplantation is based on the statistical model for end-stage liver disease (MELD), which is used to predict 3-month survival in patients with cirrhosis based on the relationships between serum bilirubin, serum creatinine, and international normalized ratio values.¹⁵ Liver transplantation should be considered for patients with a MELD score ≥15.^15,31 Such patients should be promptly referred to a liver transplantation specialist to allow sufficient time for the appropriate psychosocial assessments and medical evaluations, and for patients and their families to receive appropriate education on things like the risks and benefits of transplantation.¹⁵

CASE › After evaluating Mr. M, you prescribe spironolactone 100 mg/d and furosemide 40 mg twice a day to address ascites, and propranolol—which you titrate to 80 mg twice a day—to prevent variceal hemorrhage. Mr. M is maintained on these medications and returns with his daughter, as he has been doing every 2 to 3 months. He is excited that he breathes easily as long as he avoids salt and takes his medications. He continues to see his hepatologist regularly, and his last paracentesis was 4 months ago. He has not used any alcohol since he was taught about the relationship between alcohol and his breathing.

CORRESPONDENCE
Suzanne Minor, MD, FAAF P, Assistant Professor of Family Medicine, Department of Humanities, Health, & Society, Florida International University, Herbert Wertheim College of Medicine, 11200 SW 8th Street, AHC II, 554A, Miami, FL 33199; [email protected]

One of my favorite professional activities is teaching an evidence-based continuing medical education course each year at state Academy of Family Physicians meetings. In 12 intensive hours, 4 evidence-based medicine (EBM) experts guide family physicians, nurse practitioners, and physician assistants through nearly 400 abstracts that summarize recent studies that impact primary care practice.

In some cases, the new studies support current practice and standards of care, but for many topics, the new evidence suggests we ought to change our practice, either by stopping something we are currently doing or by starting to do something new. Who would have thought, for instance, that we should abandon the routine bimanual pelvic exam because the potential for harm is greater than the potential for benefit?

Frequently, however, we conclude a talk by describing the uncertainty surrounding particular issues and the need for more high-quality research. For example, there is scant evidence that vitamin D supplementation in healthy Americans leads to any positive outcomes compared to a decent diet and 15 minutes in the sun each day. Luckily, there are several large randomized trials currently underway that will evaluate vitamin D supplementation.

Who would have thought that we should abandon the routine bimanual pelvic exam? And yet, that is what the evidence tells us.

The strength of the scientific evidence to support screening tests and treatments is important to consider. A study examining changes in 11 American College of Cardiology/American Heart Association guidelines found that, out of 619 recommendations, 90% were unchanged in the updated version if supported by multiple randomized trials, and 74% were unchanged if supported by expert opinion.¹

In The Journal of Family Practice, we use the Strength of Recommendation Taxonomy (SORT) that was developed by family physician EBM experts² because it is an approach to grading evidence that takes into account “patient-oriented evidence that matters.” An A-level recommendation is based on consistent and good-quality patient-oriented evidence; a B-level recommendation is based on inconsistent or limited-quality patient-oriented evidence; and a C-level recommendation is based on consensus, usual practice, opinion, disease-oriented evidence, or case series.

We ask our authors to carefully select the level of evidence supporting their clinical recommendations. But your input—and the lively discussion that can often follow—is important, too. Just last month, we published a letter from 2 readers who challenged the evidence-based answer to a Clinical Inquiries question on breastfeeding.

Such ongoing dialogue is useful and enlightening. And we encourage you to write us if you disagree with any of the SORT ratings published in the journal. Let’s keep talking about what the evidence says.

One of my favorite professional activities is teaching an evidence-based continuing medical education course each year at state Academy of Family Physicians meetings. In 12 intensive hours, 4 evidence-based medicine (EBM) experts guide family physicians, nurse practitioners, and physician assistants through nearly 400 abstracts that summarize recent studies that impact primary care practice.

In some cases, the new studies support current practice and standards of care, but for many topics, the new evidence suggests we ought to change our practice, either by stopping something we are currently doing or by starting to do something new. Who would have thought, for instance, that we should abandon the routine bimanual pelvic exam because the potential for harm is greater than the potential for benefit?

Frequently, however, we conclude a talk by describing the uncertainty surrounding particular issues and the need for more high-quality research. For example, there is scant evidence that vitamin D supplementation in healthy Americans leads to any positive outcomes compared to a decent diet and 15 minutes in the sun each day. Luckily, there are several large randomized trials currently underway that will evaluate vitamin D supplementation.

Who would have thought that we should abandon the routine bimanual pelvic exam? And yet, that is what the evidence tells us.

The strength of the scientific evidence to support screening tests and treatments is important to consider. A study examining changes in 11 American College of Cardiology/American Heart Association guidelines found that, out of 619 recommendations, 90% were unchanged in the updated version if supported by multiple randomized trials, and 74% were unchanged if supported by expert opinion.¹

In The Journal of Family Practice, we use the Strength of Recommendation Taxonomy (SORT) that was developed by family physician EBM experts² because it is an approach to grading evidence that takes into account “patient-oriented evidence that matters.” An A-level recommendation is based on consistent and good-quality patient-oriented evidence; a B-level recommendation is based on inconsistent or limited-quality patient-oriented evidence; and a C-level recommendation is based on consensus, usual practice, opinion, disease-oriented evidence, or case series.

We ask our authors to carefully select the level of evidence supporting their clinical recommendations. But your input—and the lively discussion that can often follow—is important, too. Just last month, we published a letter from 2 readers who challenged the evidence-based answer to a Clinical Inquiries question on breastfeeding.

Such ongoing dialogue is useful and enlightening. And we encourage you to write us if you disagree with any of the SORT ratings published in the journal. Let’s keep talking about what the evidence says.

One of my favorite professional activities is teaching an evidence-based continuing medical education course each year at state Academy of Family Physicians meetings. In 12 intensive hours, 4 evidence-based medicine (EBM) experts guide family physicians, nurse practitioners, and physician assistants through nearly 400 abstracts that summarize recent studies that impact primary care practice.

In some cases, the new studies support current practice and standards of care, but for many topics, the new evidence suggests we ought to change our practice, either by stopping something we are currently doing or by starting to do something new. Who would have thought, for instance, that we should abandon the routine bimanual pelvic exam because the potential for harm is greater than the potential for benefit?

Frequently, however, we conclude a talk by describing the uncertainty surrounding particular issues and the need for more high-quality research. For example, there is scant evidence that vitamin D supplementation in healthy Americans leads to any positive outcomes compared to a decent diet and 15 minutes in the sun each day. Luckily, there are several large randomized trials currently underway that will evaluate vitamin D supplementation.

Who would have thought that we should abandon the routine bimanual pelvic exam? And yet, that is what the evidence tells us.

The strength of the scientific evidence to support screening tests and treatments is important to consider. A study examining changes in 11 American College of Cardiology/American Heart Association guidelines found that, out of 619 recommendations, 90% were unchanged in the updated version if supported by multiple randomized trials, and 74% were unchanged if supported by expert opinion.¹

In The Journal of Family Practice, we use the Strength of Recommendation Taxonomy (SORT) that was developed by family physician EBM experts² because it is an approach to grading evidence that takes into account “patient-oriented evidence that matters.” An A-level recommendation is based on consistent and good-quality patient-oriented evidence; a B-level recommendation is based on inconsistent or limited-quality patient-oriented evidence; and a C-level recommendation is based on consensus, usual practice, opinion, disease-oriented evidence, or case series.

We ask our authors to carefully select the level of evidence supporting their clinical recommendations. But your input—and the lively discussion that can often follow—is important, too. Just last month, we published a letter from 2 readers who challenged the evidence-based answer to a Clinical Inquiries question on breastfeeding.

Such ongoing dialogue is useful and enlightening. And we encourage you to write us if you disagree with any of the SORT ratings published in the journal. Let’s keep talking about what the evidence says.