When technology is mentioned in the context of health care, it is often received as an impersonal, profit- or regulatory-driven interface between a provider and patient. If designed – hopefully with a clinician involved – with the purpose of actually solving a problem, digital technology will ultimately gain favor. Examples of such tools include links and apps which provide reference information. Epocrates and doximity on the provider side and WebMD on the consumer/patient side are prime examples. There are increasingly more digital tools for patients and caregivers to help them improve self-participation in their health care as well as to navigate the system. The challenge in the health care technology space is to make people (both providers and patients) aware of them, to facilitate use, and to incorporate relevant and actionable data seamlessly into the patient’s electronic record. Technology needs to be designed in a way in which it conforms to the clinical work flow between the patient and provider. I will give examples of available tools that can improve a patient’s daunting journey. I do not have any financial or other affiliation with any companies mentioned.

1. They can help prepare for the office visit.

I don’t know why, but patients have evolved a belief that they need to present a self-diagnosed condition at the office visit. They often feel guilty not providing the diagnosis. I believe firmly (and tell patients) that their responsibility is to know when something isn’t right and to call the provider. Notwithstanding this, I encourage patients to do online research into their symptoms. Tools found at FamilyDoctor.org, the Mayo Clinic Symptom Checker, or iTriage can help frame thoughts or prompt a discussion with a caregiver prior to a visit, which can then serve as a foundation for the office encounter.

2. Patient education content.

The term “patient engagement” is used commonly today. It implies the active participation of the patient in health care and disease management. Many believe that patient engagement should be focused on medication adherence. While this is critical, it remains a reflection of a patient’s understanding of diagnosis; long-term treatment goals (which need be personalized per a discussion about them); and the components of the treatment itself, which include lifestyle changes and nontraditional pharmacologic therapies as well. Seeing disease through a patient’s eyes (empathy) is the key to good relationships that in turn promote engagement. Excellent digital patient education tools are now available for download and review by patients and caregivers. They explain diagnoses, tests, procedures, and medications. Some are proprietary and made by pharmaceutical and medical device companies, while others are produced by third-party companies that allow the provider to white label the product or even customize the content. One excellent example is Liberate Health. (Ed. note: This publication’s parent company has a relationship with Liberate Health.)

3. Social media.

This is where the patients and caregivers are. It follows then that social media is where providers should be. There are some excellent online patient communities that contain disease-specific groups. Examples are Smart Patients and Treatment Diaries. Social media is a big part of motivating patients and giving support to them and to caregivers. It allows for information exchange in a convenient, relaxing, and nonthreatening setting. While skeptics might question the validity of medical information and advice on these sites, I would say that encouraging patients to participate shows empathy. If a disclaimer is offered stating that this is not a substitute for a health care provider, it can be a significant source of support.

4. Connections to caregivers.

Caregivers are left out of many digital health tools. A good working definition of a caregiver is “an unpaid individual (a spouse, partner, family member, friend, or neighbor) involved in assisting others with activities of daily living and/or medical tasks.” About 29% of the U.S. adult population (65.7 million) provides care to someone who is ill, disabled, or aged. Other statistics about caregivers are more impressive. Health and medical apps are promising tools that can be offered to patients. The rubber has yet to fully meet the road in this arena for a few reasons, many of which are tied to the reputation, usability, and priorities of present electronic health record vendors who represent the face of digital health technology to most physicians and other health care providers. However, there is little denial that they (and other mobile health tools) will play an important role in health care’s future. Both patients and caregivers have expressed what is desired in a mobile app. As aging at home becomes a necessary goal of health care from social, financial, and societal standpoints, caregivers will assume an even greater portion of care.

5. Provide for better continuity of care.

Lack of continuity of care leading to medical errors is not a new topic of discussion. This is relevant in both the inpatient and the outpatient setting. Mobile digital technologies can reduce errors by improving communication to both providers and patients as well as among providers themselves. Use of digital tablets at the bedside by patients can improve provider-patient communication and decrease errors. Handoff of patients among providers is another opportunity for mobile health tools to decrease errors. One such app is Smart Sign Out. Ultimately, any tool that decreases errors is a patient advocate tool.

While some physicians believe that patient advocacy is distinct from patient care, I submit that patient advocacy is something any good physician does every day with every patient, including conveying empathy, providing easy to understand explanations of conditions, and offering advice to be considered in a shared decision-making process. We all enter the field of medicine because we want to contribute to the well-being of others. Let’s not lose sight of that, and let’s look to available and emerging technologies to assist us in this mission.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

When technology is mentioned in the context of health care, it is often received as an impersonal, profit- or regulatory-driven interface between a provider and patient. If designed – hopefully with a clinician involved – with the purpose of actually solving a problem, digital technology will ultimately gain favor. Examples of such tools include links and apps which provide reference information. Epocrates and doximity on the provider side and WebMD on the consumer/patient side are prime examples. There are increasingly more digital tools for patients and caregivers to help them improve self-participation in their health care as well as to navigate the system. The challenge in the health care technology space is to make people (both providers and patients) aware of them, to facilitate use, and to incorporate relevant and actionable data seamlessly into the patient’s electronic record. Technology needs to be designed in a way in which it conforms to the clinical work flow between the patient and provider. I will give examples of available tools that can improve a patient’s daunting journey. I do not have any financial or other affiliation with any companies mentioned.

1. They can help prepare for the office visit.

I don’t know why, but patients have evolved a belief that they need to present a self-diagnosed condition at the office visit. They often feel guilty not providing the diagnosis. I believe firmly (and tell patients) that their responsibility is to know when something isn’t right and to call the provider. Notwithstanding this, I encourage patients to do online research into their symptoms. Tools found at FamilyDoctor.org, the Mayo Clinic Symptom Checker, or iTriage can help frame thoughts or prompt a discussion with a caregiver prior to a visit, which can then serve as a foundation for the office encounter.

2. Patient education content.

The term “patient engagement” is used commonly today. It implies the active participation of the patient in health care and disease management. Many believe that patient engagement should be focused on medication adherence. While this is critical, it remains a reflection of a patient’s understanding of diagnosis; long-term treatment goals (which need be personalized per a discussion about them); and the components of the treatment itself, which include lifestyle changes and nontraditional pharmacologic therapies as well. Seeing disease through a patient’s eyes (empathy) is the key to good relationships that in turn promote engagement. Excellent digital patient education tools are now available for download and review by patients and caregivers. They explain diagnoses, tests, procedures, and medications. Some are proprietary and made by pharmaceutical and medical device companies, while others are produced by third-party companies that allow the provider to white label the product or even customize the content. One excellent example is Liberate Health. (Ed. note: This publication’s parent company has a relationship with Liberate Health.)

3. Social media.

This is where the patients and caregivers are. It follows then that social media is where providers should be. There are some excellent online patient communities that contain disease-specific groups. Examples are Smart Patients and Treatment Diaries. Social media is a big part of motivating patients and giving support to them and to caregivers. It allows for information exchange in a convenient, relaxing, and nonthreatening setting. While skeptics might question the validity of medical information and advice on these sites, I would say that encouraging patients to participate shows empathy. If a disclaimer is offered stating that this is not a substitute for a health care provider, it can be a significant source of support.

4. Connections to caregivers.

Caregivers are left out of many digital health tools. A good working definition of a caregiver is “an unpaid individual (a spouse, partner, family member, friend, or neighbor) involved in assisting others with activities of daily living and/or medical tasks.” About 29% of the U.S. adult population (65.7 million) provides care to someone who is ill, disabled, or aged. Other statistics about caregivers are more impressive. Health and medical apps are promising tools that can be offered to patients. The rubber has yet to fully meet the road in this arena for a few reasons, many of which are tied to the reputation, usability, and priorities of present electronic health record vendors who represent the face of digital health technology to most physicians and other health care providers. However, there is little denial that they (and other mobile health tools) will play an important role in health care’s future. Both patients and caregivers have expressed what is desired in a mobile app. As aging at home becomes a necessary goal of health care from social, financial, and societal standpoints, caregivers will assume an even greater portion of care.

5. Provide for better continuity of care.

Lack of continuity of care leading to medical errors is not a new topic of discussion. This is relevant in both the inpatient and the outpatient setting. Mobile digital technologies can reduce errors by improving communication to both providers and patients as well as among providers themselves. Use of digital tablets at the bedside by patients can improve provider-patient communication and decrease errors. Handoff of patients among providers is another opportunity for mobile health tools to decrease errors. One such app is Smart Sign Out. Ultimately, any tool that decreases errors is a patient advocate tool.

While some physicians believe that patient advocacy is distinct from patient care, I submit that patient advocacy is something any good physician does every day with every patient, including conveying empathy, providing easy to understand explanations of conditions, and offering advice to be considered in a shared decision-making process. We all enter the field of medicine because we want to contribute to the well-being of others. Let’s not lose sight of that, and let’s look to available and emerging technologies to assist us in this mission.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

When technology is mentioned in the context of health care, it is often received as an impersonal, profit- or regulatory-driven interface between a provider and patient. If designed – hopefully with a clinician involved – with the purpose of actually solving a problem, digital technology will ultimately gain favor. Examples of such tools include links and apps which provide reference information. Epocrates and doximity on the provider side and WebMD on the consumer/patient side are prime examples. There are increasingly more digital tools for patients and caregivers to help them improve self-participation in their health care as well as to navigate the system. The challenge in the health care technology space is to make people (both providers and patients) aware of them, to facilitate use, and to incorporate relevant and actionable data seamlessly into the patient’s electronic record. Technology needs to be designed in a way in which it conforms to the clinical work flow between the patient and provider. I will give examples of available tools that can improve a patient’s daunting journey. I do not have any financial or other affiliation with any companies mentioned.

1. They can help prepare for the office visit.

I don’t know why, but patients have evolved a belief that they need to present a self-diagnosed condition at the office visit. They often feel guilty not providing the diagnosis. I believe firmly (and tell patients) that their responsibility is to know when something isn’t right and to call the provider. Notwithstanding this, I encourage patients to do online research into their symptoms. Tools found at FamilyDoctor.org, the Mayo Clinic Symptom Checker, or iTriage can help frame thoughts or prompt a discussion with a caregiver prior to a visit, which can then serve as a foundation for the office encounter.

2. Patient education content.

The term “patient engagement” is used commonly today. It implies the active participation of the patient in health care and disease management. Many believe that patient engagement should be focused on medication adherence. While this is critical, it remains a reflection of a patient’s understanding of diagnosis; long-term treatment goals (which need be personalized per a discussion about them); and the components of the treatment itself, which include lifestyle changes and nontraditional pharmacologic therapies as well. Seeing disease through a patient’s eyes (empathy) is the key to good relationships that in turn promote engagement. Excellent digital patient education tools are now available for download and review by patients and caregivers. They explain diagnoses, tests, procedures, and medications. Some are proprietary and made by pharmaceutical and medical device companies, while others are produced by third-party companies that allow the provider to white label the product or even customize the content. One excellent example is Liberate Health. (Ed. note: This publication’s parent company has a relationship with Liberate Health.)

3. Social media.

This is where the patients and caregivers are. It follows then that social media is where providers should be. There are some excellent online patient communities that contain disease-specific groups. Examples are Smart Patients and Treatment Diaries. Social media is a big part of motivating patients and giving support to them and to caregivers. It allows for information exchange in a convenient, relaxing, and nonthreatening setting. While skeptics might question the validity of medical information and advice on these sites, I would say that encouraging patients to participate shows empathy. If a disclaimer is offered stating that this is not a substitute for a health care provider, it can be a significant source of support.

4. Connections to caregivers.

Caregivers are left out of many digital health tools. A good working definition of a caregiver is “an unpaid individual (a spouse, partner, family member, friend, or neighbor) involved in assisting others with activities of daily living and/or medical tasks.” About 29% of the U.S. adult population (65.7 million) provides care to someone who is ill, disabled, or aged. Other statistics about caregivers are more impressive. Health and medical apps are promising tools that can be offered to patients. The rubber has yet to fully meet the road in this arena for a few reasons, many of which are tied to the reputation, usability, and priorities of present electronic health record vendors who represent the face of digital health technology to most physicians and other health care providers. However, there is little denial that they (and other mobile health tools) will play an important role in health care’s future. Both patients and caregivers have expressed what is desired in a mobile app. As aging at home becomes a necessary goal of health care from social, financial, and societal standpoints, caregivers will assume an even greater portion of care.

5. Provide for better continuity of care.

Lack of continuity of care leading to medical errors is not a new topic of discussion. This is relevant in both the inpatient and the outpatient setting. Mobile digital technologies can reduce errors by improving communication to both providers and patients as well as among providers themselves. Use of digital tablets at the bedside by patients can improve provider-patient communication and decrease errors. Handoff of patients among providers is another opportunity for mobile health tools to decrease errors. One such app is Smart Sign Out. Ultimately, any tool that decreases errors is a patient advocate tool.

While some physicians believe that patient advocacy is distinct from patient care, I submit that patient advocacy is something any good physician does every day with every patient, including conveying empathy, providing easy to understand explanations of conditions, and offering advice to be considered in a shared decision-making process. We all enter the field of medicine because we want to contribute to the well-being of others. Let’s not lose sight of that, and let’s look to available and emerging technologies to assist us in this mission.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

SAN FRANCISCO – Use of intraoperative nerve monitoring during thyroidectomy to avoid injuring the recurrent laryngeal nerve is counterintuitively associated with a higher risk of vocal cord paralysis, in a cohort study of data from the Nationwide Inpatient Sample.

“We do caution against perhaps the broad adoption of nerve monitoring until we can really study this further,” said Dr. Thomas K. Chung, a research fellow in the department of surgery, division of otolaryngology, at the University of Alabama at Birmingham, and the study’s lead investigator.

He and his colleagues compared outcomes between 12,742 patients who had nerve monitoring and 230,433 patients who did not (the conventional practice) while undergoing thyroidectomy between 2008 and 2011.

The proportion of patients who developed vocal cord paralysis was significantly higher with monitoring than without it (1.9% vs. 1.4%), he reported at the annual clinical congress of the American College of Surgeons. The findings were essentially the same in propensity-adjusted analyses that took into account differences between groups in preoperative factors (1.8% vs. 1.3%).

There was no evidence that the difference was related to differences in the use of laryngoscopy to check for paralysis, in hospitals’ coding and billing for monitoring, or in payers’ coverage of this surgical adjunct.

Stratified analyses looking at the extent of surgery showed total thyroidectomy with neck dissection to be the exception, as patients monitored during these more complex operations were significantly less likely to develop vocal cord paralysis than were nonmonitored counterparts (2.8% vs. 4.5%).

The more often hospitals used nerve monitoring as indicated by the volume of thyroidectomy cases, the lower the rate of vocal cord paralysis – with the exception of cases of partial thyroidectomy, in which more frequent use was associated with a counterintuitive increase in the rate of this complication, according to Dr. Chung, who disclosed that he had no relevant conflicts of interest.

“Nerve monitoring demonstrates a significant benefit particularly in complex cases such as total thyroidectomy with neck dissection,” he said. “Low nerve monitoring and utilization with partial thyroidectomy appears to be associated with higher vocal cord paralysis; with respect to the partial thyroidectomies, this may be due to the fact that the burden of complication is already so low, with vocal cord paralysis rates of about 0.8%, that additional use of nerve monitoring may not confer any benefit.”

Dr. Chung offered several possible reasons as to why monitoring may be associated with a higher risk of vocal cord paralysis, including presence of a learning curve, substitution of monitoring for direct visualization of the nerve, and false-negatives whereby a lack of signal from the monitor may lead to more aggressive ablation when the nerve is in fact nearby.

The study had its limitations, he acknowledged. “Nerve monitoring may not be coded all the time,” he said. Information about prior neck radiation and surgery, which increase the risk of vocal cord paralysis, was unavailable. “In the group with thyroidectomy with neck dissection, there is no code for central neck dissection. And even if it is a partial thyroidectomy with neck dissection, the central neck dissection would put both nerves at risk and therefore certainly increase the risk of vocal cord paralysis,” he noted.

Invited discussant Julie Ann Sosa, chief of endocrine surgery at the Duke Cancer Institute in Durham, N.C., said, “I would like to congratulate you and your whole group for tackling what is perhaps one of the most highly contested and contentious issues within endocrine surgery and otolaryngology. It’s also I think a very important area for study because there is a relative paucity of data demonstrating for or against the use of this technology as an adjunct. Current guidelines basically say it’s a wash: We can’t say one way or the other whether folks should be using it. And the anticipated guidelines, those coming out from the American Thyroid Association, similarly will say that more data are needed. So I think you are filling a clear vacuum.”

Dr. Sosa questioned the generalizability of the findings, noting that nearly two-thirds of thyroid procedures are now done in the ambulatory setting. “You used the Nationwide Inpatient Sample, so I think you are looking at a minority of cases and highly complex cases, with a length of stay on the order of 2-3 days, which is really exceptional. Most of us send home patients the same day. So how generalizable do you think your conclusions are, and have you thought about potentially using some of the ambulatory surgery databases to try to ask similar questions?” she queried.

The investigators plan to repeat analyses using the Nationwide Inpatient Sample’s ambulatory data set next, according to Dr. Chung. “Being able to see whether or not this still holds true in an outpatient setting is definitely worthwhile,” he agreed.

Dr. Sosa further wondered about the roles of bilateral versus unilateral monitoring, and continuous versus intermittent monitoring, saying, “I think the approach an individual surgeon takes could definitely result in different outcomes. So I wonder, were you able to address at a more granular level the specific technologies employed?”

The Nationwide Inpatient Sample unfortunately does not capture information on these aspects of monitoring, said Dr. Chung. However, “with respect to continuous versus intermittent, we do think that that’s actually an important variable. It is possible that those who are using nerve monitoring are doing this in a continuous fashion, so when they perhaps injure the first side of the vocal cords, they may stop. So what was originally planned to be a total thyroidectomy from the get-go that had an intraoperative nerve injury may be aborted so as to not create any disastrous airway complications. That may also artificially increase the partial thyroidectomy results, thereby increasing vocal cord paralysis complications in the partial thyroidectomy group.”

SAN FRANCISCO – Use of intraoperative nerve monitoring during thyroidectomy to avoid injuring the recurrent laryngeal nerve is counterintuitively associated with a higher risk of vocal cord paralysis, in a cohort study of data from the Nationwide Inpatient Sample.

“We do caution against perhaps the broad adoption of nerve monitoring until we can really study this further,” said Dr. Thomas K. Chung, a research fellow in the department of surgery, division of otolaryngology, at the University of Alabama at Birmingham, and the study’s lead investigator.

He and his colleagues compared outcomes between 12,742 patients who had nerve monitoring and 230,433 patients who did not (the conventional practice) while undergoing thyroidectomy between 2008 and 2011.

The proportion of patients who developed vocal cord paralysis was significantly higher with monitoring than without it (1.9% vs. 1.4%), he reported at the annual clinical congress of the American College of Surgeons. The findings were essentially the same in propensity-adjusted analyses that took into account differences between groups in preoperative factors (1.8% vs. 1.3%).

There was no evidence that the difference was related to differences in the use of laryngoscopy to check for paralysis, in hospitals’ coding and billing for monitoring, or in payers’ coverage of this surgical adjunct.

Stratified analyses looking at the extent of surgery showed total thyroidectomy with neck dissection to be the exception, as patients monitored during these more complex operations were significantly less likely to develop vocal cord paralysis than were nonmonitored counterparts (2.8% vs. 4.5%).

The more often hospitals used nerve monitoring as indicated by the volume of thyroidectomy cases, the lower the rate of vocal cord paralysis – with the exception of cases of partial thyroidectomy, in which more frequent use was associated with a counterintuitive increase in the rate of this complication, according to Dr. Chung, who disclosed that he had no relevant conflicts of interest.

“Nerve monitoring demonstrates a significant benefit particularly in complex cases such as total thyroidectomy with neck dissection,” he said. “Low nerve monitoring and utilization with partial thyroidectomy appears to be associated with higher vocal cord paralysis; with respect to the partial thyroidectomies, this may be due to the fact that the burden of complication is already so low, with vocal cord paralysis rates of about 0.8%, that additional use of nerve monitoring may not confer any benefit.”

Dr. Chung offered several possible reasons as to why monitoring may be associated with a higher risk of vocal cord paralysis, including presence of a learning curve, substitution of monitoring for direct visualization of the nerve, and false-negatives whereby a lack of signal from the monitor may lead to more aggressive ablation when the nerve is in fact nearby.

The study had its limitations, he acknowledged. “Nerve monitoring may not be coded all the time,” he said. Information about prior neck radiation and surgery, which increase the risk of vocal cord paralysis, was unavailable. “In the group with thyroidectomy with neck dissection, there is no code for central neck dissection. And even if it is a partial thyroidectomy with neck dissection, the central neck dissection would put both nerves at risk and therefore certainly increase the risk of vocal cord paralysis,” he noted.

Invited discussant Julie Ann Sosa, chief of endocrine surgery at the Duke Cancer Institute in Durham, N.C., said, “I would like to congratulate you and your whole group for tackling what is perhaps one of the most highly contested and contentious issues within endocrine surgery and otolaryngology. It’s also I think a very important area for study because there is a relative paucity of data demonstrating for or against the use of this technology as an adjunct. Current guidelines basically say it’s a wash: We can’t say one way or the other whether folks should be using it. And the anticipated guidelines, those coming out from the American Thyroid Association, similarly will say that more data are needed. So I think you are filling a clear vacuum.”

Dr. Sosa questioned the generalizability of the findings, noting that nearly two-thirds of thyroid procedures are now done in the ambulatory setting. “You used the Nationwide Inpatient Sample, so I think you are looking at a minority of cases and highly complex cases, with a length of stay on the order of 2-3 days, which is really exceptional. Most of us send home patients the same day. So how generalizable do you think your conclusions are, and have you thought about potentially using some of the ambulatory surgery databases to try to ask similar questions?” she queried.

The investigators plan to repeat analyses using the Nationwide Inpatient Sample’s ambulatory data set next, according to Dr. Chung. “Being able to see whether or not this still holds true in an outpatient setting is definitely worthwhile,” he agreed.

Dr. Sosa further wondered about the roles of bilateral versus unilateral monitoring, and continuous versus intermittent monitoring, saying, “I think the approach an individual surgeon takes could definitely result in different outcomes. So I wonder, were you able to address at a more granular level the specific technologies employed?”

The Nationwide Inpatient Sample unfortunately does not capture information on these aspects of monitoring, said Dr. Chung. However, “with respect to continuous versus intermittent, we do think that that’s actually an important variable. It is possible that those who are using nerve monitoring are doing this in a continuous fashion, so when they perhaps injure the first side of the vocal cords, they may stop. So what was originally planned to be a total thyroidectomy from the get-go that had an intraoperative nerve injury may be aborted so as to not create any disastrous airway complications. That may also artificially increase the partial thyroidectomy results, thereby increasing vocal cord paralysis complications in the partial thyroidectomy group.”

SAN FRANCISCO – Use of intraoperative nerve monitoring during thyroidectomy to avoid injuring the recurrent laryngeal nerve is counterintuitively associated with a higher risk of vocal cord paralysis, in a cohort study of data from the Nationwide Inpatient Sample.

“We do caution against perhaps the broad adoption of nerve monitoring until we can really study this further,” said Dr. Thomas K. Chung, a research fellow in the department of surgery, division of otolaryngology, at the University of Alabama at Birmingham, and the study’s lead investigator.

He and his colleagues compared outcomes between 12,742 patients who had nerve monitoring and 230,433 patients who did not (the conventional practice) while undergoing thyroidectomy between 2008 and 2011.

The proportion of patients who developed vocal cord paralysis was significantly higher with monitoring than without it (1.9% vs. 1.4%), he reported at the annual clinical congress of the American College of Surgeons. The findings were essentially the same in propensity-adjusted analyses that took into account differences between groups in preoperative factors (1.8% vs. 1.3%).

There was no evidence that the difference was related to differences in the use of laryngoscopy to check for paralysis, in hospitals’ coding and billing for monitoring, or in payers’ coverage of this surgical adjunct.

Stratified analyses looking at the extent of surgery showed total thyroidectomy with neck dissection to be the exception, as patients monitored during these more complex operations were significantly less likely to develop vocal cord paralysis than were nonmonitored counterparts (2.8% vs. 4.5%).

The more often hospitals used nerve monitoring as indicated by the volume of thyroidectomy cases, the lower the rate of vocal cord paralysis – with the exception of cases of partial thyroidectomy, in which more frequent use was associated with a counterintuitive increase in the rate of this complication, according to Dr. Chung, who disclosed that he had no relevant conflicts of interest.

“Nerve monitoring demonstrates a significant benefit particularly in complex cases such as total thyroidectomy with neck dissection,” he said. “Low nerve monitoring and utilization with partial thyroidectomy appears to be associated with higher vocal cord paralysis; with respect to the partial thyroidectomies, this may be due to the fact that the burden of complication is already so low, with vocal cord paralysis rates of about 0.8%, that additional use of nerve monitoring may not confer any benefit.”

Dr. Chung offered several possible reasons as to why monitoring may be associated with a higher risk of vocal cord paralysis, including presence of a learning curve, substitution of monitoring for direct visualization of the nerve, and false-negatives whereby a lack of signal from the monitor may lead to more aggressive ablation when the nerve is in fact nearby.

The study had its limitations, he acknowledged. “Nerve monitoring may not be coded all the time,” he said. Information about prior neck radiation and surgery, which increase the risk of vocal cord paralysis, was unavailable. “In the group with thyroidectomy with neck dissection, there is no code for central neck dissection. And even if it is a partial thyroidectomy with neck dissection, the central neck dissection would put both nerves at risk and therefore certainly increase the risk of vocal cord paralysis,” he noted.

Invited discussant Julie Ann Sosa, chief of endocrine surgery at the Duke Cancer Institute in Durham, N.C., said, “I would like to congratulate you and your whole group for tackling what is perhaps one of the most highly contested and contentious issues within endocrine surgery and otolaryngology. It’s also I think a very important area for study because there is a relative paucity of data demonstrating for or against the use of this technology as an adjunct. Current guidelines basically say it’s a wash: We can’t say one way or the other whether folks should be using it. And the anticipated guidelines, those coming out from the American Thyroid Association, similarly will say that more data are needed. So I think you are filling a clear vacuum.”

Dr. Sosa questioned the generalizability of the findings, noting that nearly two-thirds of thyroid procedures are now done in the ambulatory setting. “You used the Nationwide Inpatient Sample, so I think you are looking at a minority of cases and highly complex cases, with a length of stay on the order of 2-3 days, which is really exceptional. Most of us send home patients the same day. So how generalizable do you think your conclusions are, and have you thought about potentially using some of the ambulatory surgery databases to try to ask similar questions?” she queried.

The investigators plan to repeat analyses using the Nationwide Inpatient Sample’s ambulatory data set next, according to Dr. Chung. “Being able to see whether or not this still holds true in an outpatient setting is definitely worthwhile,” he agreed.

Dr. Sosa further wondered about the roles of bilateral versus unilateral monitoring, and continuous versus intermittent monitoring, saying, “I think the approach an individual surgeon takes could definitely result in different outcomes. So I wonder, were you able to address at a more granular level the specific technologies employed?”

The Nationwide Inpatient Sample unfortunately does not capture information on these aspects of monitoring, said Dr. Chung. However, “with respect to continuous versus intermittent, we do think that that’s actually an important variable. It is possible that those who are using nerve monitoring are doing this in a continuous fashion, so when they perhaps injure the first side of the vocal cords, they may stop. So what was originally planned to be a total thyroidectomy from the get-go that had an intraoperative nerve injury may be aborted so as to not create any disastrous airway complications. That may also artificially increase the partial thyroidectomy results, thereby increasing vocal cord paralysis complications in the partial thyroidectomy group.”

T cells

Credit: NIAID

SAN FRANCISCO—CTL019, a chimeric antigen receptor (CAR) T cell targeting CD19, is not the only CAR in the production line.

Investigators at the National Cancer Institute in Bethesda, Maryland, and Memorial Sloan Kettering Cancer Center (MSKCC) in New York City are also pursuing CAR T-cell therapy.

These groups are using a retroviral platform to transduce the T cells rather than a lentiviral one, as is the case with CTL019.

Investigators reported progress to date on these makes of CARs at the 2014 ASH Annual Meeting.

Daniel W. Lee III, MD, of the National Cancer Institute, reported on a phase 1 study of CD19 CAR T cells in children and young adults with CD19+ acute lymphoblastic leukemia or non-Hodgkin lymphoma.

And Jae H. Park, MD, of MSKCC, presented data from a trial of JCAR015—autologous T cells genetically modified to express a 19-28z CAR targeting CD19—in patients with B-cell acute lymphoblastic leukemia.

The study is sponsored by MSKCC, but JCAR015 is a product of Juno Therapeutics.

T cells

Credit: NIAID

SAN FRANCISCO—CTL019, a chimeric antigen receptor (CAR) T cell targeting CD19, is not the only CAR in the production line.

Investigators at the National Cancer Institute in Bethesda, Maryland, and Memorial Sloan Kettering Cancer Center (MSKCC) in New York City are also pursuing CAR T-cell therapy.

These groups are using a retroviral platform to transduce the T cells rather than a lentiviral one, as is the case with CTL019.

Investigators reported progress to date on these makes of CARs at the 2014 ASH Annual Meeting.

Daniel W. Lee III, MD, of the National Cancer Institute, reported on a phase 1 study of CD19 CAR T cells in children and young adults with CD19+ acute lymphoblastic leukemia or non-Hodgkin lymphoma.

And Jae H. Park, MD, of MSKCC, presented data from a trial of JCAR015—autologous T cells genetically modified to express a 19-28z CAR targeting CD19—in patients with B-cell acute lymphoblastic leukemia.

The study is sponsored by MSKCC, but JCAR015 is a product of Juno Therapeutics.

T cells

Credit: NIAID

SAN FRANCISCO—CTL019, a chimeric antigen receptor (CAR) T cell targeting CD19, is not the only CAR in the production line.

Investigators at the National Cancer Institute in Bethesda, Maryland, and Memorial Sloan Kettering Cancer Center (MSKCC) in New York City are also pursuing CAR T-cell therapy.

These groups are using a retroviral platform to transduce the T cells rather than a lentiviral one, as is the case with CTL019.

Investigators reported progress to date on these makes of CARs at the 2014 ASH Annual Meeting.

Daniel W. Lee III, MD, of the National Cancer Institute, reported on a phase 1 study of CD19 CAR T cells in children and young adults with CD19+ acute lymphoblastic leukemia or non-Hodgkin lymphoma.

And Jae H. Park, MD, of MSKCC, presented data from a trial of JCAR015—autologous T cells genetically modified to express a 19-28z CAR targeting CD19—in patients with B-cell acute lymphoblastic leukemia.

The study is sponsored by MSKCC, but JCAR015 is a product of Juno Therapeutics.

ALL patient

Credit: Bill Branson

SAN FRANCISCO—A chimeric antigen receptor (CAR) T-cell therapy is feasible in 90% of heavily pretreated or transplanted patients with acute lymphoblastic leukemia (ALL) and can serve as a bridge to transplant, according to investigators.

Daniel W. Lee III, MD, of the National Cancer Institute in Bethesda, Maryland, reported on a phase 1 study of this CD19 CAR T-cell therapy in children and young adults with CD19+ ALL or non-Hodgkin lymphoma at the 2014 ASH Annual Meeting (abstract 381*).

Twenty-one patients were enrolled on the trial. They had a preparative regimen of fludarabine and cyclophosphamide and were infused with CAR T cells 11 days after the peripheral blood mononuclear cells were collected.

Dose levels were 1 x 10⁶ CAR+ T cells/kg, 3 x 10⁶ CAR+ T cells/kg, or the maximum number of cells generated if below either one of these levels. Two patients received less than the dose assigned and were not evaluated for toxicity.

Patients were a median age of 13 years (range, 5 to 27). Fourteen were male, 20 had ALL, and 1 had diffuse large B-cell lymphoma.

All had detectable disease, and 2 were CNS2 at the time of T-cell infusion. Six had primary refractory disease, 8 had at least 1 prior stem cell transplant, and 4 had prior immunotherapy.

The investigators determined that the maximally tolerated dose was 1 x 10⁶ CAR+ T cells/kg. The dose-limiting toxicities were related to cytokine release syndrome (CRS), which was reversible if managed appropriately with tocilizumab, with or without steroids.

Grade 3 adverse events possibly related to therapy included fever (47%), febrile neutropenia (37%), electrolyte disturbance (29%), CRS (16%), hypotension (11%), transaminitis (16%), and 5% each for hypertension, prolonged QTc, dysphasia, LV systolic dysfunction, multiorgan failure, hypoxia, and pulmonary edema.

Grade 4 events possibly related to treatment included electrolyte disturbance (5%), CRS (16%), hypotension (11%), cardiac arrest (5%), and hypoxia (5%). There was no evidence of graft-vs-host disease.

The complete response (CR) rate was 67% in the intent-to-treat population and 70% in patients with ALL.

“Those patients who responded tended to have some degree of cytokine release syndrome, whereas those patients who did not respond or had stable disease did not have any CRS,” Dr Lee said. “But, also, it’s important to note that you don’t have to have severe grade 3 or grade 4 CRS in order to have significant response.”

Dr Lee also pointed out that in vivo CAR T-cell expansion significantly correlated with response (P=0.0028). And CRS severity correlated with IL-6 (P=0.0002), INF-γ (P=0.0002), C-reactive protein (P=0.0015), and CAR (P=0.0011).

At a median follow-up of 10 months, minimal residual disease-negative patients had a 79% leukemia-free survival. Overall survival was 52% for all patients enrolled. Two patients had CD19-negative relapses.

The investigators also found that CAR T cells can eliminate CNS leukemia, with 11 of 17 patients (65%) having CAR T cells detectable in their cerebrospinal fluid.

The team concluded that this therapy is feasible in 90% of heavily pretreated or transplanted ALL patients and can serve as a bridge to transplant.

*Information in the abstract differs from that presented at the meeting.

ALL patient

Credit: Bill Branson

SAN FRANCISCO—A chimeric antigen receptor (CAR) T-cell therapy is feasible in 90% of heavily pretreated or transplanted patients with acute lymphoblastic leukemia (ALL) and can serve as a bridge to transplant, according to investigators.

Daniel W. Lee III, MD, of the National Cancer Institute in Bethesda, Maryland, reported on a phase 1 study of this CD19 CAR T-cell therapy in children and young adults with CD19+ ALL or non-Hodgkin lymphoma at the 2014 ASH Annual Meeting (abstract 381*).

Twenty-one patients were enrolled on the trial. They had a preparative regimen of fludarabine and cyclophosphamide and were infused with CAR T cells 11 days after the peripheral blood mononuclear cells were collected.

Dose levels were 1 x 10⁶ CAR+ T cells/kg, 3 x 10⁶ CAR+ T cells/kg, or the maximum number of cells generated if below either one of these levels. Two patients received less than the dose assigned and were not evaluated for toxicity.

Patients were a median age of 13 years (range, 5 to 27). Fourteen were male, 20 had ALL, and 1 had diffuse large B-cell lymphoma.

All had detectable disease, and 2 were CNS2 at the time of T-cell infusion. Six had primary refractory disease, 8 had at least 1 prior stem cell transplant, and 4 had prior immunotherapy.

The investigators determined that the maximally tolerated dose was 1 x 10⁶ CAR+ T cells/kg. The dose-limiting toxicities were related to cytokine release syndrome (CRS), which was reversible if managed appropriately with tocilizumab, with or without steroids.

Grade 3 adverse events possibly related to therapy included fever (47%), febrile neutropenia (37%), electrolyte disturbance (29%), CRS (16%), hypotension (11%), transaminitis (16%), and 5% each for hypertension, prolonged QTc, dysphasia, LV systolic dysfunction, multiorgan failure, hypoxia, and pulmonary edema.

Grade 4 events possibly related to treatment included electrolyte disturbance (5%), CRS (16%), hypotension (11%), cardiac arrest (5%), and hypoxia (5%). There was no evidence of graft-vs-host disease.

The complete response (CR) rate was 67% in the intent-to-treat population and 70% in patients with ALL.

“Those patients who responded tended to have some degree of cytokine release syndrome, whereas those patients who did not respond or had stable disease did not have any CRS,” Dr Lee said. “But, also, it’s important to note that you don’t have to have severe grade 3 or grade 4 CRS in order to have significant response.”

Dr Lee also pointed out that in vivo CAR T-cell expansion significantly correlated with response (P=0.0028). And CRS severity correlated with IL-6 (P=0.0002), INF-γ (P=0.0002), C-reactive protein (P=0.0015), and CAR (P=0.0011).

At a median follow-up of 10 months, minimal residual disease-negative patients had a 79% leukemia-free survival. Overall survival was 52% for all patients enrolled. Two patients had CD19-negative relapses.

The investigators also found that CAR T cells can eliminate CNS leukemia, with 11 of 17 patients (65%) having CAR T cells detectable in their cerebrospinal fluid.

The team concluded that this therapy is feasible in 90% of heavily pretreated or transplanted ALL patients and can serve as a bridge to transplant.

*Information in the abstract differs from that presented at the meeting.

ALL patient

Credit: Bill Branson

SAN FRANCISCO—A chimeric antigen receptor (CAR) T-cell therapy is feasible in 90% of heavily pretreated or transplanted patients with acute lymphoblastic leukemia (ALL) and can serve as a bridge to transplant, according to investigators.

Daniel W. Lee III, MD, of the National Cancer Institute in Bethesda, Maryland, reported on a phase 1 study of this CD19 CAR T-cell therapy in children and young adults with CD19+ ALL or non-Hodgkin lymphoma at the 2014 ASH Annual Meeting (abstract 381*).

Twenty-one patients were enrolled on the trial. They had a preparative regimen of fludarabine and cyclophosphamide and were infused with CAR T cells 11 days after the peripheral blood mononuclear cells were collected.

Dose levels were 1 x 10⁶ CAR+ T cells/kg, 3 x 10⁶ CAR+ T cells/kg, or the maximum number of cells generated if below either one of these levels. Two patients received less than the dose assigned and were not evaluated for toxicity.

Patients were a median age of 13 years (range, 5 to 27). Fourteen were male, 20 had ALL, and 1 had diffuse large B-cell lymphoma.

All had detectable disease, and 2 were CNS2 at the time of T-cell infusion. Six had primary refractory disease, 8 had at least 1 prior stem cell transplant, and 4 had prior immunotherapy.

The investigators determined that the maximally tolerated dose was 1 x 10⁶ CAR+ T cells/kg. The dose-limiting toxicities were related to cytokine release syndrome (CRS), which was reversible if managed appropriately with tocilizumab, with or without steroids.

Grade 3 adverse events possibly related to therapy included fever (47%), febrile neutropenia (37%), electrolyte disturbance (29%), CRS (16%), hypotension (11%), transaminitis (16%), and 5% each for hypertension, prolonged QTc, dysphasia, LV systolic dysfunction, multiorgan failure, hypoxia, and pulmonary edema.

Grade 4 events possibly related to treatment included electrolyte disturbance (5%), CRS (16%), hypotension (11%), cardiac arrest (5%), and hypoxia (5%). There was no evidence of graft-vs-host disease.

The complete response (CR) rate was 67% in the intent-to-treat population and 70% in patients with ALL.

“Those patients who responded tended to have some degree of cytokine release syndrome, whereas those patients who did not respond or had stable disease did not have any CRS,” Dr Lee said. “But, also, it’s important to note that you don’t have to have severe grade 3 or grade 4 CRS in order to have significant response.”

Dr Lee also pointed out that in vivo CAR T-cell expansion significantly correlated with response (P=0.0028). And CRS severity correlated with IL-6 (P=0.0002), INF-γ (P=0.0002), C-reactive protein (P=0.0015), and CAR (P=0.0011).

At a median follow-up of 10 months, minimal residual disease-negative patients had a 79% leukemia-free survival. Overall survival was 52% for all patients enrolled. Two patients had CD19-negative relapses.

The investigators also found that CAR T cells can eliminate CNS leukemia, with 11 of 17 patients (65%) having CAR T cells detectable in their cerebrospinal fluid.

The team concluded that this therapy is feasible in 90% of heavily pretreated or transplanted ALL patients and can serve as a bridge to transplant.

*Information in the abstract differs from that presented at the meeting.

CHICAGO – Implementation of preoperative venous thromboembolism prophylaxis requires a highly individualized approach and a little boost from information technology, one expert suggested.

“What may not be appreciated by some vascular surgeons is that for certain procedures we do, our patients actually have a high VTE [venous thromboembolism] risk. I know people think, ‘We use heparin, so our patients aren’t at high risk,’ but they actually are,” Dr. Melina Kibbe said at a symposium on vascular surgery sponsored by Northwestern University.

The VTE risk is 4.2% for open thoracoabdominal aortic aneurysm repair and 2.2% for thoracic endovascular aortic repair in the American College of Surgeons National Surgical Quality Improvement Program database. That may be an underestimation, however, because the NSQIP database captures only symptomatic events documented by imaging and those events occurring in the first 30 days after surgery.

Patrice Wendling/Frontline Medical News

Smaller studies looking at the problem prospectively suggest the VTE risk is closer to 2%-12% after open aortic surgery and 5.3% after endovascular aortic repair, she said.

Add to that the U.S. Surgeon General’s 2008 call to action to prevent VTE and the Institute of Medicine’s stance that failure to provide VTE prophylaxis qualifies as a medical error, and it would be tempting for vascular surgeons to prescribe pharmacologic prophylaxis for all of their patients, or at least do so based on the type of procedure.

“But VTE formation is really secondary to patient-specific and procedure-related factors,” said Dr. Kibbe, a professor of vascular surgery at Northwestern University in Chicago.

She highlighted five current VTE risk assessment models (RAMs) and the potential returns when RAMs are incorporated into clinical decision support systems.

• Kucher model. One of the earlier and most straightforward RAMs is the Kucher model. It assessed eight weighted risk factors (advanced age, obesity, bed rest, hormone replacement therapy/oral contraceptives, major surgery, cancer, prior VTE, and hypercoagulability) and provided surgeons with electronic alerts regarding prophylaxis.

VTE rates dropped from 8.2% to 4.9% in the high-risk category (score ≥ 4) with the use of the simple physician reminders (N. Engl. J. Med. 2005;352:969-77). Prospective validation showed that VTE increased proportionally with higher scores, Dr. Kibbe said. On the other hand, the model lacked sensitivity at low VTE risk, because 20% of patients with a score of 4 or less actually had VTEs.

“So, while it was simple, it only works well for the high-risk category,” she said.

• Rogers model. One of the most vigorously studied and developed RAMs is the Rogers model (J. Am. Coll. Surg. 2007;204:1211-21). It identified 15 variables (including lab values, patient characteristics, disease states, work relative-value unit, and type of operation) that were independently associated with VTE formation among 183,609 patients undergoing general, vascular, or thoracic procedures at 142 Veterans Health Administration and private hospitals. Each variable is assigned a value from 0 to 9 and added together to create a Rogers score.

Validation showed that VTE risk correlates with the Rogers score, rising from 0.11% for patients with a low score (< 7) to 1.32% for those with a high score (> 10), Dr. Kibbe said. Criticisms of the model are that it is complex, VTE incidence in the entire cohort was low at just 0.63%, the type of VTE prophylaxis used was unclear, and the model lacks prospective validation in a vascular surgery cohort.

• Caprini model. The most commonly used RAM is the 2005 Caprini model (Dis. Mon. 2005;51:70-8), which assigns a weighted score based on more than 30 VTE risk factors compiled by the authors. It has been prospectively validated in numerous studies and shown to accurately stratify 30-day VTE risk at 0.5% for patients at very low risk, 1.5% for low risk, 3% for moderate risk, and 6% for high risk.

The Caprini model, however, was not developed with the same rigor as the Rogers RAM, some of the risk factors have been shown not to be a risk for VTE, and it is complex, Dr. Kibbe observed.

• Pannucci model. The Pannucci model was created specifically to counteract the complexity of the Rogers and Caprini RAMs and incorporates only seven risk factors (personal history of VTE, current cancer, age ≥ 60 years, body mass index ≥ 40 kg/m², male sex, sepsis/septic shock/systemic inflammatory response syndrome, and family history of VTE) into a weighted index for 90-day VTE risk (Chest 2014;145:567-73). The model was developed using a statewide database and a derivation cohort made up of 20% vascular surgery patients.

Both the derivation and validation cohorts identified an 18-fold variation in VTE risk from the lowest- to highest-risk surgical population, showing that the model stratifies patients correctly. Further prospective validation is needed, Dr. Kibbe said.

• Scarborough model. Finally, in an attempt to develop a RAM specific to vascular surgery patients, Dr. John Scarborough and colleagues examined 6,035 patients undergoing open AAA repair in the NSQIP database. The 30-day VTE rate was 2.4% for the entire cohort. Eight independent perioperative risk factors were identified and used to create a nonweighted scoring system (J. Am. Coll. Surg. 2012;214:620-6).

Overall, 65% of patients had 0-1 risk factor and a VTE incidence of 1.5%, while 15% had 3 or more risk factors and a VTE incidence of 6.1%. The Scarborough model has good risk stratification, Dr. Kibbe said, but it is limited by the aforementioned criticisms regarding the NSQIP database, and it also needs prospective validation.

“We all know that proper VTE prophylaxis is very important for our patients; but we need mechanisms by which the attention given to this need for prophylaxis, which is a lot, is turned into proper implementation,” she said.

For Dr. Kibbe and her colleagues, proper implementation meant developing a RAM that was incorporated into the electronic medical record system for all surgical patients at the Jesse Brown VA Medical Center in Chicago. Clinicians were prompted to complete the RAM upon placing orders for preanesthesia testing clearance, and the clinical decision support system would provide a recommended prophylaxis regimen and easily selected electronic orders that could be signed.

A pre- and postimplementation analysis involving 400 consecutive patients revealed an 82% increase in patients with preoperative VTE prophylaxis ordered (22% vs. 40%), a 75% decrease in inappropriate cancellation of orders more than 12 hours before surgery (37% vs. 9%), and a nearly sevenfold increase in the number of patients receiving pharmacologic and mechanical prophylaxis (5% vs. 32%), she said. There was an 80% and 36% decline in DVT rates at 30 and 90 days postoperative, but event rates were too low to detect a significant difference (J. Vasc. Surg. 2010;51:648-54).

Dr. Kibbe reported having no financial disclosures.

[email protected]

CHICAGO – Implementation of preoperative venous thromboembolism prophylaxis requires a highly individualized approach and a little boost from information technology, one expert suggested.

“What may not be appreciated by some vascular surgeons is that for certain procedures we do, our patients actually have a high VTE [venous thromboembolism] risk. I know people think, ‘We use heparin, so our patients aren’t at high risk,’ but they actually are,” Dr. Melina Kibbe said at a symposium on vascular surgery sponsored by Northwestern University.

The VTE risk is 4.2% for open thoracoabdominal aortic aneurysm repair and 2.2% for thoracic endovascular aortic repair in the American College of Surgeons National Surgical Quality Improvement Program database. That may be an underestimation, however, because the NSQIP database captures only symptomatic events documented by imaging and those events occurring in the first 30 days after surgery.

Patrice Wendling/Frontline Medical News

Smaller studies looking at the problem prospectively suggest the VTE risk is closer to 2%-12% after open aortic surgery and 5.3% after endovascular aortic repair, she said.

Add to that the U.S. Surgeon General’s 2008 call to action to prevent VTE and the Institute of Medicine’s stance that failure to provide VTE prophylaxis qualifies as a medical error, and it would be tempting for vascular surgeons to prescribe pharmacologic prophylaxis for all of their patients, or at least do so based on the type of procedure.

“But VTE formation is really secondary to patient-specific and procedure-related factors,” said Dr. Kibbe, a professor of vascular surgery at Northwestern University in Chicago.

She highlighted five current VTE risk assessment models (RAMs) and the potential returns when RAMs are incorporated into clinical decision support systems.

• Kucher model. One of the earlier and most straightforward RAMs is the Kucher model. It assessed eight weighted risk factors (advanced age, obesity, bed rest, hormone replacement therapy/oral contraceptives, major surgery, cancer, prior VTE, and hypercoagulability) and provided surgeons with electronic alerts regarding prophylaxis.

VTE rates dropped from 8.2% to 4.9% in the high-risk category (score ≥ 4) with the use of the simple physician reminders (N. Engl. J. Med. 2005;352:969-77). Prospective validation showed that VTE increased proportionally with higher scores, Dr. Kibbe said. On the other hand, the model lacked sensitivity at low VTE risk, because 20% of patients with a score of 4 or less actually had VTEs.

“So, while it was simple, it only works well for the high-risk category,” she said.

• Rogers model. One of the most vigorously studied and developed RAMs is the Rogers model (J. Am. Coll. Surg. 2007;204:1211-21). It identified 15 variables (including lab values, patient characteristics, disease states, work relative-value unit, and type of operation) that were independently associated with VTE formation among 183,609 patients undergoing general, vascular, or thoracic procedures at 142 Veterans Health Administration and private hospitals. Each variable is assigned a value from 0 to 9 and added together to create a Rogers score.

Validation showed that VTE risk correlates with the Rogers score, rising from 0.11% for patients with a low score (< 7) to 1.32% for those with a high score (> 10), Dr. Kibbe said. Criticisms of the model are that it is complex, VTE incidence in the entire cohort was low at just 0.63%, the type of VTE prophylaxis used was unclear, and the model lacks prospective validation in a vascular surgery cohort.

• Caprini model. The most commonly used RAM is the 2005 Caprini model (Dis. Mon. 2005;51:70-8), which assigns a weighted score based on more than 30 VTE risk factors compiled by the authors. It has been prospectively validated in numerous studies and shown to accurately stratify 30-day VTE risk at 0.5% for patients at very low risk, 1.5% for low risk, 3% for moderate risk, and 6% for high risk.

The Caprini model, however, was not developed with the same rigor as the Rogers RAM, some of the risk factors have been shown not to be a risk for VTE, and it is complex, Dr. Kibbe observed.

• Pannucci model. The Pannucci model was created specifically to counteract the complexity of the Rogers and Caprini RAMs and incorporates only seven risk factors (personal history of VTE, current cancer, age ≥ 60 years, body mass index ≥ 40 kg/m², male sex, sepsis/septic shock/systemic inflammatory response syndrome, and family history of VTE) into a weighted index for 90-day VTE risk (Chest 2014;145:567-73). The model was developed using a statewide database and a derivation cohort made up of 20% vascular surgery patients.

Both the derivation and validation cohorts identified an 18-fold variation in VTE risk from the lowest- to highest-risk surgical population, showing that the model stratifies patients correctly. Further prospective validation is needed, Dr. Kibbe said.

• Scarborough model. Finally, in an attempt to develop a RAM specific to vascular surgery patients, Dr. John Scarborough and colleagues examined 6,035 patients undergoing open AAA repair in the NSQIP database. The 30-day VTE rate was 2.4% for the entire cohort. Eight independent perioperative risk factors were identified and used to create a nonweighted scoring system (J. Am. Coll. Surg. 2012;214:620-6).

Overall, 65% of patients had 0-1 risk factor and a VTE incidence of 1.5%, while 15% had 3 or more risk factors and a VTE incidence of 6.1%. The Scarborough model has good risk stratification, Dr. Kibbe said, but it is limited by the aforementioned criticisms regarding the NSQIP database, and it also needs prospective validation.

“We all know that proper VTE prophylaxis is very important for our patients; but we need mechanisms by which the attention given to this need for prophylaxis, which is a lot, is turned into proper implementation,” she said.

For Dr. Kibbe and her colleagues, proper implementation meant developing a RAM that was incorporated into the electronic medical record system for all surgical patients at the Jesse Brown VA Medical Center in Chicago. Clinicians were prompted to complete the RAM upon placing orders for preanesthesia testing clearance, and the clinical decision support system would provide a recommended prophylaxis regimen and easily selected electronic orders that could be signed.

A pre- and postimplementation analysis involving 400 consecutive patients revealed an 82% increase in patients with preoperative VTE prophylaxis ordered (22% vs. 40%), a 75% decrease in inappropriate cancellation of orders more than 12 hours before surgery (37% vs. 9%), and a nearly sevenfold increase in the number of patients receiving pharmacologic and mechanical prophylaxis (5% vs. 32%), she said. There was an 80% and 36% decline in DVT rates at 30 and 90 days postoperative, but event rates were too low to detect a significant difference (J. Vasc. Surg. 2010;51:648-54).

Dr. Kibbe reported having no financial disclosures.

[email protected]

CHICAGO – Implementation of preoperative venous thromboembolism prophylaxis requires a highly individualized approach and a little boost from information technology, one expert suggested.

“What may not be appreciated by some vascular surgeons is that for certain procedures we do, our patients actually have a high VTE [venous thromboembolism] risk. I know people think, ‘We use heparin, so our patients aren’t at high risk,’ but they actually are,” Dr. Melina Kibbe said at a symposium on vascular surgery sponsored by Northwestern University.

The VTE risk is 4.2% for open thoracoabdominal aortic aneurysm repair and 2.2% for thoracic endovascular aortic repair in the American College of Surgeons National Surgical Quality Improvement Program database. That may be an underestimation, however, because the NSQIP database captures only symptomatic events documented by imaging and those events occurring in the first 30 days after surgery.

Patrice Wendling/Frontline Medical News

Smaller studies looking at the problem prospectively suggest the VTE risk is closer to 2%-12% after open aortic surgery and 5.3% after endovascular aortic repair, she said.

Add to that the U.S. Surgeon General’s 2008 call to action to prevent VTE and the Institute of Medicine’s stance that failure to provide VTE prophylaxis qualifies as a medical error, and it would be tempting for vascular surgeons to prescribe pharmacologic prophylaxis for all of their patients, or at least do so based on the type of procedure.

“But VTE formation is really secondary to patient-specific and procedure-related factors,” said Dr. Kibbe, a professor of vascular surgery at Northwestern University in Chicago.

She highlighted five current VTE risk assessment models (RAMs) and the potential returns when RAMs are incorporated into clinical decision support systems.

• Kucher model. One of the earlier and most straightforward RAMs is the Kucher model. It assessed eight weighted risk factors (advanced age, obesity, bed rest, hormone replacement therapy/oral contraceptives, major surgery, cancer, prior VTE, and hypercoagulability) and provided surgeons with electronic alerts regarding prophylaxis.

VTE rates dropped from 8.2% to 4.9% in the high-risk category (score ≥ 4) with the use of the simple physician reminders (N. Engl. J. Med. 2005;352:969-77). Prospective validation showed that VTE increased proportionally with higher scores, Dr. Kibbe said. On the other hand, the model lacked sensitivity at low VTE risk, because 20% of patients with a score of 4 or less actually had VTEs.

“So, while it was simple, it only works well for the high-risk category,” she said.

• Rogers model. One of the most vigorously studied and developed RAMs is the Rogers model (J. Am. Coll. Surg. 2007;204:1211-21). It identified 15 variables (including lab values, patient characteristics, disease states, work relative-value unit, and type of operation) that were independently associated with VTE formation among 183,609 patients undergoing general, vascular, or thoracic procedures at 142 Veterans Health Administration and private hospitals. Each variable is assigned a value from 0 to 9 and added together to create a Rogers score.

Validation showed that VTE risk correlates with the Rogers score, rising from 0.11% for patients with a low score (< 7) to 1.32% for those with a high score (> 10), Dr. Kibbe said. Criticisms of the model are that it is complex, VTE incidence in the entire cohort was low at just 0.63%, the type of VTE prophylaxis used was unclear, and the model lacks prospective validation in a vascular surgery cohort.

• Caprini model. The most commonly used RAM is the 2005 Caprini model (Dis. Mon. 2005;51:70-8), which assigns a weighted score based on more than 30 VTE risk factors compiled by the authors. It has been prospectively validated in numerous studies and shown to accurately stratify 30-day VTE risk at 0.5% for patients at very low risk, 1.5% for low risk, 3% for moderate risk, and 6% for high risk.

The Caprini model, however, was not developed with the same rigor as the Rogers RAM, some of the risk factors have been shown not to be a risk for VTE, and it is complex, Dr. Kibbe observed.

• Pannucci model. The Pannucci model was created specifically to counteract the complexity of the Rogers and Caprini RAMs and incorporates only seven risk factors (personal history of VTE, current cancer, age ≥ 60 years, body mass index ≥ 40 kg/m², male sex, sepsis/septic shock/systemic inflammatory response syndrome, and family history of VTE) into a weighted index for 90-day VTE risk (Chest 2014;145:567-73). The model was developed using a statewide database and a derivation cohort made up of 20% vascular surgery patients.

Both the derivation and validation cohorts identified an 18-fold variation in VTE risk from the lowest- to highest-risk surgical population, showing that the model stratifies patients correctly. Further prospective validation is needed, Dr. Kibbe said.

• Scarborough model. Finally, in an attempt to develop a RAM specific to vascular surgery patients, Dr. John Scarborough and colleagues examined 6,035 patients undergoing open AAA repair in the NSQIP database. The 30-day VTE rate was 2.4% for the entire cohort. Eight independent perioperative risk factors were identified and used to create a nonweighted scoring system (J. Am. Coll. Surg. 2012;214:620-6).

Overall, 65% of patients had 0-1 risk factor and a VTE incidence of 1.5%, while 15% had 3 or more risk factors and a VTE incidence of 6.1%. The Scarborough model has good risk stratification, Dr. Kibbe said, but it is limited by the aforementioned criticisms regarding the NSQIP database, and it also needs prospective validation.

“We all know that proper VTE prophylaxis is very important for our patients; but we need mechanisms by which the attention given to this need for prophylaxis, which is a lot, is turned into proper implementation,” she said.

For Dr. Kibbe and her colleagues, proper implementation meant developing a RAM that was incorporated into the electronic medical record system for all surgical patients at the Jesse Brown VA Medical Center in Chicago. Clinicians were prompted to complete the RAM upon placing orders for preanesthesia testing clearance, and the clinical decision support system would provide a recommended prophylaxis regimen and easily selected electronic orders that could be signed.

A pre- and postimplementation analysis involving 400 consecutive patients revealed an 82% increase in patients with preoperative VTE prophylaxis ordered (22% vs. 40%), a 75% decrease in inappropriate cancellation of orders more than 12 hours before surgery (37% vs. 9%), and a nearly sevenfold increase in the number of patients receiving pharmacologic and mechanical prophylaxis (5% vs. 32%), she said. There was an 80% and 36% decline in DVT rates at 30 and 90 days postoperative, but event rates were too low to detect a significant difference (J. Vasc. Surg. 2010;51:648-54).

Dr. Kibbe reported having no financial disclosures.

[email protected]

Blood collection

Credit: Charles Haymond

SAN FRANCISCO—JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, can produce durable responses in patients with B-cell acute lymphoblastic leukemia (ALL) who do not undergo subsequent hematopoietic stem cell transplant (HSCT), new research suggests.

JCAR015 consists of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (19-28z CAR) targeting CD19.

Jae H. Park, MD, of Memorial Sloan Kettering Cancer Center in New York, presented data on JCAR015 at the 2014 ASH Annual Meeting (abstract 382).* The study is sponsored by Memorial Sloan Kettering, but funding has also been provided by Juno Therapeutics, the company developing JCAR015.

JCAR015 was tested at a dose of 1 - 3 x 10⁶ CAR cells/kg in 33 adults with relapsed/refractory B-cell ALL. Twenty-eight patients were evaluable for toxicity, 27 for response, and 5 patients were too early in their treatment to evaluate at the time of data cutoff.

Twenty-one patients were male, and the median age was 55 (range, 23 to 74).

Thirteen patients (46%) had minimal disease (<5% blasts) immediately prior to T-cell infusion, and 15 patients (54%) had morphologic disease of 5% to 100% blasts (median 63%).

Eighteen patients (64%) had received 2 prior lines of therapy, and 5 (18%) each had 3 or more prior lines.

Eight patients (29%) underwent prior allogeneic HSCT, 9 patients (32%) were Philadelphia chromosome positive (Ph+), and 3 (11%) had the T315I mutation.

The overall complete response (CR) rate was 89%, and the minimal residual disease-negative CR rate was 88%. The median time to CR was 22.5 days (range, 9 to 33).

The investigators performed a subgroup analysis and found that 100% of the 13 patients with minimal disease before therapy achieved a CR, compared to 79% of patients with morphologic disease.

Eighty-six percent (6/7) of patients who had a prior HSCT and 90% (18/20) without a prior HSCT achieved a CR. Eighty-nine percent (8/9) of Ph+ patients achieved a CR, and 89% (16/18) of Philadelphia-negative patients (89%) achieved a CR.

At a median follow-up of 6 months (range, 1 to 38 months), 12 patients remained disease-free, including 7 patients who had more than a year of follow-up. Seven patients are disease-free without a subsequent HSCT.

Nine patients relapsed during a follow-up of 3 to 8 months, and 10 patients proceeded to HSCT. Two relapses occurred after HSCT, one in a patient who had CD19-negative blasts, and 7 relapses occurred without HSCT.

The overall survival rate at 6 months was 57%, and the median survival was 8.5 months.

For those patients who had a transplant after CAR therapy, the median survival was 10.8 months, and the survival rate at 6 months was 68%.

Dr Park pointed out that maximum T-cell expansion occurred between days 7 and 14 and correlated with the occurrence of cytokine release syndrome (CRS). The T cells persisted for 1 to 3 months following infusion.

The main adverse events were those associated with CRS and neurologic changes. Severe CRS requiring vasopressors or mechanical ventilation occurred in 5 patients (18%) overall and in 5 patients (33%) with morphologic disease before therapy. Severe CRS did not occur in any patient with minimal disease before therapy.

Grade 3 or 4 neurotoxicity occurred in 7 patients (25%) overall, in 6 patients (40%) with morphologic disease, and in 1 with minimal disease (8%) before therapy.

The investigators observed no graft-vs-host disease exacerbation, and CRS was managed with an IL-6R inhibitor, steroids, or both.

Dr Park noted that the neurologic symptoms are reversible and can occur independently of CRS.

He also pointed out that CR rates were similar regardless of different disease risk factors, and that durable responses have been achieved in patients who did not have a subsequent HSCT.

*Information in the abstract differs from that presented at the meeting.

Blood collection

Credit: Charles Haymond

SAN FRANCISCO—JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, can produce durable responses in patients with B-cell acute lymphoblastic leukemia (ALL) who do not undergo subsequent hematopoietic stem cell transplant (HSCT), new research suggests.

JCAR015 consists of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (19-28z CAR) targeting CD19.

Jae H. Park, MD, of Memorial Sloan Kettering Cancer Center in New York, presented data on JCAR015 at the 2014 ASH Annual Meeting (abstract 382).* The study is sponsored by Memorial Sloan Kettering, but funding has also been provided by Juno Therapeutics, the company developing JCAR015.

JCAR015 was tested at a dose of 1 - 3 x 10⁶ CAR cells/kg in 33 adults with relapsed/refractory B-cell ALL. Twenty-eight patients were evaluable for toxicity, 27 for response, and 5 patients were too early in their treatment to evaluate at the time of data cutoff.

Twenty-one patients were male, and the median age was 55 (range, 23 to 74).

Thirteen patients (46%) had minimal disease (<5% blasts) immediately prior to T-cell infusion, and 15 patients (54%) had morphologic disease of 5% to 100% blasts (median 63%).

Eighteen patients (64%) had received 2 prior lines of therapy, and 5 (18%) each had 3 or more prior lines.

Eight patients (29%) underwent prior allogeneic HSCT, 9 patients (32%) were Philadelphia chromosome positive (Ph+), and 3 (11%) had the T315I mutation.

The overall complete response (CR) rate was 89%, and the minimal residual disease-negative CR rate was 88%. The median time to CR was 22.5 days (range, 9 to 33).

The investigators performed a subgroup analysis and found that 100% of the 13 patients with minimal disease before therapy achieved a CR, compared to 79% of patients with morphologic disease.

Eighty-six percent (6/7) of patients who had a prior HSCT and 90% (18/20) without a prior HSCT achieved a CR. Eighty-nine percent (8/9) of Ph+ patients achieved a CR, and 89% (16/18) of Philadelphia-negative patients (89%) achieved a CR.

At a median follow-up of 6 months (range, 1 to 38 months), 12 patients remained disease-free, including 7 patients who had more than a year of follow-up. Seven patients are disease-free without a subsequent HSCT.

Nine patients relapsed during a follow-up of 3 to 8 months, and 10 patients proceeded to HSCT. Two relapses occurred after HSCT, one in a patient who had CD19-negative blasts, and 7 relapses occurred without HSCT.

The overall survival rate at 6 months was 57%, and the median survival was 8.5 months.

For those patients who had a transplant after CAR therapy, the median survival was 10.8 months, and the survival rate at 6 months was 68%.

Dr Park pointed out that maximum T-cell expansion occurred between days 7 and 14 and correlated with the occurrence of cytokine release syndrome (CRS). The T cells persisted for 1 to 3 months following infusion.

The main adverse events were those associated with CRS and neurologic changes. Severe CRS requiring vasopressors or mechanical ventilation occurred in 5 patients (18%) overall and in 5 patients (33%) with morphologic disease before therapy. Severe CRS did not occur in any patient with minimal disease before therapy.

Grade 3 or 4 neurotoxicity occurred in 7 patients (25%) overall, in 6 patients (40%) with morphologic disease, and in 1 with minimal disease (8%) before therapy.

The investigators observed no graft-vs-host disease exacerbation, and CRS was managed with an IL-6R inhibitor, steroids, or both.

Dr Park noted that the neurologic symptoms are reversible and can occur independently of CRS.

He also pointed out that CR rates were similar regardless of different disease risk factors, and that durable responses have been achieved in patients who did not have a subsequent HSCT.

*Information in the abstract differs from that presented at the meeting.

Blood collection

Credit: Charles Haymond

SAN FRANCISCO—JCAR015, a chimeric antigen receptor (CAR) T-cell therapy, can produce durable responses in patients with B-cell acute lymphoblastic leukemia (ALL) who do not undergo subsequent hematopoietic stem cell transplant (HSCT), new research suggests.

JCAR015 consists of autologous T cells genetically modified to express 19-28z chimeric antigen receptor (19-28z CAR) targeting CD19.

Jae H. Park, MD, of Memorial Sloan Kettering Cancer Center in New York, presented data on JCAR015 at the 2014 ASH Annual Meeting (abstract 382).* The study is sponsored by Memorial Sloan Kettering, but funding has also been provided by Juno Therapeutics, the company developing JCAR015.

JCAR015 was tested at a dose of 1 - 3 x 10⁶ CAR cells/kg in 33 adults with relapsed/refractory B-cell ALL. Twenty-eight patients were evaluable for toxicity, 27 for response, and 5 patients were too early in their treatment to evaluate at the time of data cutoff.

Twenty-one patients were male, and the median age was 55 (range, 23 to 74).

Thirteen patients (46%) had minimal disease (<5% blasts) immediately prior to T-cell infusion, and 15 patients (54%) had morphologic disease of 5% to 100% blasts (median 63%).

Eighteen patients (64%) had received 2 prior lines of therapy, and 5 (18%) each had 3 or more prior lines.

Eight patients (29%) underwent prior allogeneic HSCT, 9 patients (32%) were Philadelphia chromosome positive (Ph+), and 3 (11%) had the T315I mutation.

The overall complete response (CR) rate was 89%, and the minimal residual disease-negative CR rate was 88%. The median time to CR was 22.5 days (range, 9 to 33).

The investigators performed a subgroup analysis and found that 100% of the 13 patients with minimal disease before therapy achieved a CR, compared to 79% of patients with morphologic disease.

Eighty-six percent (6/7) of patients who had a prior HSCT and 90% (18/20) without a prior HSCT achieved a CR. Eighty-nine percent (8/9) of Ph+ patients achieved a CR, and 89% (16/18) of Philadelphia-negative patients (89%) achieved a CR.

At a median follow-up of 6 months (range, 1 to 38 months), 12 patients remained disease-free, including 7 patients who had more than a year of follow-up. Seven patients are disease-free without a subsequent HSCT.

Nine patients relapsed during a follow-up of 3 to 8 months, and 10 patients proceeded to HSCT. Two relapses occurred after HSCT, one in a patient who had CD19-negative blasts, and 7 relapses occurred without HSCT.

The overall survival rate at 6 months was 57%, and the median survival was 8.5 months.

For those patients who had a transplant after CAR therapy, the median survival was 10.8 months, and the survival rate at 6 months was 68%.

Dr Park pointed out that maximum T-cell expansion occurred between days 7 and 14 and correlated with the occurrence of cytokine release syndrome (CRS). The T cells persisted for 1 to 3 months following infusion.

The main adverse events were those associated with CRS and neurologic changes. Severe CRS requiring vasopressors or mechanical ventilation occurred in 5 patients (18%) overall and in 5 patients (33%) with morphologic disease before therapy. Severe CRS did not occur in any patient with minimal disease before therapy.

Grade 3 or 4 neurotoxicity occurred in 7 patients (25%) overall, in 6 patients (40%) with morphologic disease, and in 1 with minimal disease (8%) before therapy.

The investigators observed no graft-vs-host disease exacerbation, and CRS was managed with an IL-6R inhibitor, steroids, or both.

Dr Park noted that the neurologic symptoms are reversible and can occur independently of CRS.

He also pointed out that CR rates were similar regardless of different disease risk factors, and that durable responses have been achieved in patients who did not have a subsequent HSCT.

*Information in the abstract differs from that presented at the meeting.

Inadequate evaluation of a mole has costly consequences

A 53-year-old woman went to her physician for treatment of a mole on her upper right arm, which she stated had grown and changed color. The physician burned it off without conducting a biopsy or follow-up. Fifteen months later, the patient returned to her physician because the scar was raised with small bumps. He referred her to a surgeon, who diagnosed malignant melanoma (Clark’s level V), with a satellite lesion but negative lymph nodes. The patient underwent surgery and adjuvant interferon-alpha therapy, which caused significant adverse effects.

The patient now has anxiety related to fears of recurrence or death, and must undergo regular positron emission tomography and computed tomography scans to evaluate her for recurrence.

PLAINTIFF’S CLAIM The melanoma should have been diagnosed at the patient’s initial presentation. If it had been diagnosed at that time, the patient would have had an 85% to 90% chance of survival, but because it wasn’t, her survival rate dropped to 60%.

THE DEFENSE No information about the defense is available.

VERDICT $750,000 Virginia settlement.

COMMENT When there is any doubt—by patient or physician—cut it out and send it out (for biopsy).

A higher index of suspicion for PE could have been lifesaving

A 37-year-old morbidly obese man was recovering in a rehabilitation facility from spinal surgery performed 2 weeks earlier. On the day he was to be discharged, he was transported by ambulance to the emergency department (ED) complaining of “a syncopal episode” with weakness, lightheadedness, dizziness, and sweatiness. This was followed by a second episode with similar symptoms. The patient had no wheezes or rales and his heart rhythm was normal, with no murmurs or gallop. In the ED his pulse rose from 94 to 116 and his blood pressure (BP) rose from 106/82 to 145/102. An electrocardiogram (EKG) was abnormal.

The ED physician felt the likelihood of PE was low, despite the fact that the patient was obese and had recent back surgery and an abnormal EKG. The ED physician felt that the likelihood of pulmonary embolism (PE) was low; he suspected, instead, that it was “likely vagal syncope.” The patient returned to the rehab facility, stayed overnight, and was discharged the next day. Two days later, he became short of breath, passed out, and was taken by ambulance to the hospital, where resuscitation efforts were unsuccessful. Autopsy revealed the cause of death was pulmonary thromboemboli from deep vein thrombosis.

PLAINTIFF’S CLAIM The ED physician failed to rule out PE, which should have been considered because of the patient’s obesity, recent back surgery, immobilization, syncope, tachycardia, elevated BP, and abnormal EKG.

THE DEFENSE No information about the defense is available.

VERDICT $1.25 million Massachusetts settlement.

COMMENT Why the physician decided that this patient, who died of a PE, was at low risk for one is puzzling. I count at least 4 risk factors for PE: obesity, postoperative status, abnormal EKG, and tachycardia.

Inadequate evaluation of a mole has costly consequences

A 53-year-old woman went to her physician for treatment of a mole on her upper right arm, which she stated had grown and changed color. The physician burned it off without conducting a biopsy or follow-up. Fifteen months later, the patient returned to her physician because the scar was raised with small bumps. He referred her to a surgeon, who diagnosed malignant melanoma (Clark’s level V), with a satellite lesion but negative lymph nodes. The patient underwent surgery and adjuvant interferon-alpha therapy, which caused significant adverse effects.

The patient now has anxiety related to fears of recurrence or death, and must undergo regular positron emission tomography and computed tomography scans to evaluate her for recurrence.

PLAINTIFF’S CLAIM The melanoma should have been diagnosed at the patient’s initial presentation. If it had been diagnosed at that time, the patient would have had an 85% to 90% chance of survival, but because it wasn’t, her survival rate dropped to 60%.

THE DEFENSE No information about the defense is available.

VERDICT $750,000 Virginia settlement.

COMMENT When there is any doubt—by patient or physician—cut it out and send it out (for biopsy).

A higher index of suspicion for PE could have been lifesaving

A 37-year-old morbidly obese man was recovering in a rehabilitation facility from spinal surgery performed 2 weeks earlier. On the day he was to be discharged, he was transported by ambulance to the emergency department (ED) complaining of “a syncopal episode” with weakness, lightheadedness, dizziness, and sweatiness. This was followed by a second episode with similar symptoms. The patient had no wheezes or rales and his heart rhythm was normal, with no murmurs or gallop. In the ED his pulse rose from 94 to 116 and his blood pressure (BP) rose from 106/82 to 145/102. An electrocardiogram (EKG) was abnormal.

The ED physician felt the likelihood of PE was low, despite the fact that the patient was obese and had recent back surgery and an abnormal EKG. The ED physician felt that the likelihood of pulmonary embolism (PE) was low; he suspected, instead, that it was “likely vagal syncope.” The patient returned to the rehab facility, stayed overnight, and was discharged the next day. Two days later, he became short of breath, passed out, and was taken by ambulance to the hospital, where resuscitation efforts were unsuccessful. Autopsy revealed the cause of death was pulmonary thromboemboli from deep vein thrombosis.

PLAINTIFF’S CLAIM The ED physician failed to rule out PE, which should have been considered because of the patient’s obesity, recent back surgery, immobilization, syncope, tachycardia, elevated BP, and abnormal EKG.

THE DEFENSE No information about the defense is available.

VERDICT $1.25 million Massachusetts settlement.

COMMENT Why the physician decided that this patient, who died of a PE, was at low risk for one is puzzling. I count at least 4 risk factors for PE: obesity, postoperative status, abnormal EKG, and tachycardia.

Inadequate evaluation of a mole has costly consequences

A 53-year-old woman went to her physician for treatment of a mole on her upper right arm, which she stated had grown and changed color. The physician burned it off without conducting a biopsy or follow-up. Fifteen months later, the patient returned to her physician because the scar was raised with small bumps. He referred her to a surgeon, who diagnosed malignant melanoma (Clark’s level V), with a satellite lesion but negative lymph nodes. The patient underwent surgery and adjuvant interferon-alpha therapy, which caused significant adverse effects.

The patient now has anxiety related to fears of recurrence or death, and must undergo regular positron emission tomography and computed tomography scans to evaluate her for recurrence.

PLAINTIFF’S CLAIM The melanoma should have been diagnosed at the patient’s initial presentation. If it had been diagnosed at that time, the patient would have had an 85% to 90% chance of survival, but because it wasn’t, her survival rate dropped to 60%.

THE DEFENSE No information about the defense is available.

VERDICT $750,000 Virginia settlement.

COMMENT When there is any doubt—by patient or physician—cut it out and send it out (for biopsy).

A higher index of suspicion for PE could have been lifesaving

A 37-year-old morbidly obese man was recovering in a rehabilitation facility from spinal surgery performed 2 weeks earlier. On the day he was to be discharged, he was transported by ambulance to the emergency department (ED) complaining of “a syncopal episode” with weakness, lightheadedness, dizziness, and sweatiness. This was followed by a second episode with similar symptoms. The patient had no wheezes or rales and his heart rhythm was normal, with no murmurs or gallop. In the ED his pulse rose from 94 to 116 and his blood pressure (BP) rose from 106/82 to 145/102. An electrocardiogram (EKG) was abnormal.

The ED physician felt the likelihood of PE was low, despite the fact that the patient was obese and had recent back surgery and an abnormal EKG. The ED physician felt that the likelihood of pulmonary embolism (PE) was low; he suspected, instead, that it was “likely vagal syncope.” The patient returned to the rehab facility, stayed overnight, and was discharged the next day. Two days later, he became short of breath, passed out, and was taken by ambulance to the hospital, where resuscitation efforts were unsuccessful. Autopsy revealed the cause of death was pulmonary thromboemboli from deep vein thrombosis.

PLAINTIFF’S CLAIM The ED physician failed to rule out PE, which should have been considered because of the patient’s obesity, recent back surgery, immobilization, syncope, tachycardia, elevated BP, and abnormal EKG.

THE DEFENSE No information about the defense is available.

VERDICT $1.25 million Massachusetts settlement.

COMMENT Why the physician decided that this patient, who died of a PE, was at low risk for one is puzzling. I count at least 4 risk factors for PE: obesity, postoperative status, abnormal EKG, and tachycardia.

Illustrative case

The parents of a 6-month-old girl with moderate plagiocephaly bring their daughter in for a well child visit. Previously, you had recommended that the parents increase “tummy time” when the baby is awake, change her position in bed, and monitor the progression of the condition. They do not feel these interventions have made a difference in the shape of their daughter’s skull, and ask about using a helmet to help correct the deformity. How would you counsel them?

Positional skull deformity (PSD) is a common problem of infancy. Approximately 45% of infants ages 7 to 12 weeks are estimated to have PSD, although three-quarters of them have mild cases.² The incidence of PSD began to increase in 1992 after the American Academy of Pediatrics (AAP) introduced its “Back to Sleep” campaign, which encouraged parents to place their infants on their back at bedtime to reduce sudden infant death syndrome.³

There are 2 common forms of PSD: plagiocephaly, and brachycephaly.¹ Plagiocephaly is unilateral occipital flattening, which may be accompanied by ipsilateral forehead prominence and asymmetrical ears. Brachycephaly is symmetric flattening of the back of the head, which can lead to prominence of the temporal areas, making the head appear wide. Children with severe plagiocephaly have a misshapen, asymmetric skull, while children with brachycephaly have a flattened skull. The cranial sutures remain open in both kinds of PSD.

Evaluating infants for PSD is part of the routine physical exam, and when the condition is noted, the exam should also differentiate PSD from other causes of skull deformity, such as craniosynostosis. Infants and preschool-aged children with PSD may score lower on developmental testing than children without skull deformity.⁴ However, these differences are small and inconsistent (2-3 points on a 100-point scale).⁴ Skull deformity persists into adolescence in only 1% to 2% of patients.⁵

Neither the AAP nor the American Academy of Family Physicians has a guideline or consensus statement on PSD. Helmets are intended to correct PSD by fitting closely to an infant’s head but allowing room for the skill to grow at the flattened area.¹ A 2011 clinical report by Laughlin et al⁶ recommended against using helmets for infants with mild to moderate deformities, but stated that there was little evidence of harm. Earlier studies have suggested that physical therapy might be effective for plagiocephaly caught early (7 and 8 weeks of age).^7,8 Biggs⁹ suggested considering helmet therapy for infants whose cranial sutures remain open and who do not respond to 4 to 8 weeks of physical therapy for PSD. van Wijk et al¹ conducted an RCT to explore the risks and benefits of helmet therapy for children with PSD.

STUDY SUMMARY: Helmets for infants: No help and some harm

This single-blind RCT of 84 infants ages 5 or 6 months with moderate or severe PSD compared helmet therapy (n=42) to no intervention (allowing natural growth, n=42). Infants were excluded if they had very severe PSD or skull deformity from another cause, such as torticollis or craniosynostosis.

Infants in the helmet therapy group received a custom-made helmet that they wore 23 hours a day until they were a year old, with regular evaluation by an orthotist and modification of the helmet as necessary to allow skull growth. The control group had usual care and no helmet.

At the end of the study, improvement in skull shape was almost the same in the helmet therapy and control groups. The primary outcome was improvement in skull shape at age 24 months as measured by the oblique diameter difference index (ODDI), a unitless measurement of plagiocephaly calculated by taking the ratio of measures of 2 dimensions of cranial diameter, and the cranioproportional index (CPI), a similar measurement of brachycephaly. Infants were considered fully recovered if they achieved an ODDI score of <104% and a CPI score of <90%. These scores indicate a normal head shape; higher scores indicate worse PSD.

At the end of the study, the reduction in ODDI and CPI scores was almost the same in both  the helmet therapy and the control groups. Ten children in the helmet group (26%) and 9 in the control group (23%) experienced complete resolution of their PSD (P=.74).

Secondary outcomes included infant motor development, infant quality of life, parental satisfaction with the shape of their infant’s head, and parental anxiety. Both groups were similar in infant motor development, infant quality of life, and parental satisfaction. Parental anxiety was assessed using the Spielberger State-Trait Anxiety Inventory (scores range from 20-80; a higher score indicates greater anxiety). There was less parental anxiety in the helmet therapy group: (-3.9; 95% confidence interval, -7.5 to -0.2; P=.04).

All parents of infants in the helmet therapy group reported at least one adverse effect from the intervention. These effects included skin irritation (96%), bad helmet odor (76%), pain associated with the helmet (33%), and feeling hindered from cuddling their child (77%).

WHAT’S NEW: RCT provides stronger evidence that helmets are not effective

This is the first RCT that assessed helmet therapy for PSD in children.¹ Before this, the evidence on helmets for PSD had been obtained mainly from observational or poorly designed studies with significant flaws.⁶ This study by van Wijk et al¹ included objective measurement of skull deformity, along with clinically meaningful outcomes of parental satisfaction, motor development, and parental anxiety. It also found that helmet therapy was significantly more expensive than care that focused on waiting for PSD to resolve on its own ($1935 vs $196, respectively).¹

CAVEATS: Results may not apply to all infants with skull deformity

These findings do not apply to infants with very severe cases of PSD or those with skull deformity due to secondary causes, such as craniosynostosis, who were excluded from this study.¹ In addition, this is the only RCT to date that has assessed helmet use in PSD, so it is possible that future studies will find helmets are effective.

CHALLENGES TO IMPLEMENTATION: Parents may find this evidence hard to accept

To appropriately implement this recommendation, a family physician must be comfortable making the assessment of mild, moderate, severe, or very severe PSD. Referral to physical therapy might be appropriate for infants with very severe PSD.

If another physician or physical therapist recommends helmet therapy—or if a parent requests it—explaining the findings of this study may be challenging. We believe that the reduction in parental anxiety in the helmet group likely occurred because the parents believed that the helmet would accelerate the normal reshaping of the skull shape that occurs spontaneously in almost all infants with PSD. Since this study shows that helmets don’t help correct skull deformities, parents can be assured that a helmet is unnecessary, costly, and causes adverse effects.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

The parents of a 6-month-old girl with moderate plagiocephaly bring their daughter in for a well child visit. Previously, you had recommended that the parents increase “tummy time” when the baby is awake, change her position in bed, and monitor the progression of the condition. They do not feel these interventions have made a difference in the shape of their daughter’s skull, and ask about using a helmet to help correct the deformity. How would you counsel them?

Positional skull deformity (PSD) is a common problem of infancy. Approximately 45% of infants ages 7 to 12 weeks are estimated to have PSD, although three-quarters of them have mild cases.² The incidence of PSD began to increase in 1992 after the American Academy of Pediatrics (AAP) introduced its “Back to Sleep” campaign, which encouraged parents to place their infants on their back at bedtime to reduce sudden infant death syndrome.³

There are 2 common forms of PSD: plagiocephaly, and brachycephaly.¹ Plagiocephaly is unilateral occipital flattening, which may be accompanied by ipsilateral forehead prominence and asymmetrical ears. Brachycephaly is symmetric flattening of the back of the head, which can lead to prominence of the temporal areas, making the head appear wide. Children with severe plagiocephaly have a misshapen, asymmetric skull, while children with brachycephaly have a flattened skull. The cranial sutures remain open in both kinds of PSD.

Evaluating infants for PSD is part of the routine physical exam, and when the condition is noted, the exam should also differentiate PSD from other causes of skull deformity, such as craniosynostosis. Infants and preschool-aged children with PSD may score lower on developmental testing than children without skull deformity.⁴ However, these differences are small and inconsistent (2-3 points on a 100-point scale).⁴ Skull deformity persists into adolescence in only 1% to 2% of patients.⁵

Neither the AAP nor the American Academy of Family Physicians has a guideline or consensus statement on PSD. Helmets are intended to correct PSD by fitting closely to an infant’s head but allowing room for the skill to grow at the flattened area.¹ A 2011 clinical report by Laughlin et al⁶ recommended against using helmets for infants with mild to moderate deformities, but stated that there was little evidence of harm. Earlier studies have suggested that physical therapy might be effective for plagiocephaly caught early (7 and 8 weeks of age).^7,8 Biggs⁹ suggested considering helmet therapy for infants whose cranial sutures remain open and who do not respond to 4 to 8 weeks of physical therapy for PSD. van Wijk et al¹ conducted an RCT to explore the risks and benefits of helmet therapy for children with PSD.

STUDY SUMMARY: Helmets for infants: No help and some harm

This single-blind RCT of 84 infants ages 5 or 6 months with moderate or severe PSD compared helmet therapy (n=42) to no intervention (allowing natural growth, n=42). Infants were excluded if they had very severe PSD or skull deformity from another cause, such as torticollis or craniosynostosis.

Infants in the helmet therapy group received a custom-made helmet that they wore 23 hours a day until they were a year old, with regular evaluation by an orthotist and modification of the helmet as necessary to allow skull growth. The control group had usual care and no helmet.

At the end of the study, improvement in skull shape was almost the same in the helmet therapy and control groups. The primary outcome was improvement in skull shape at age 24 months as measured by the oblique diameter difference index (ODDI), a unitless measurement of plagiocephaly calculated by taking the ratio of measures of 2 dimensions of cranial diameter, and the cranioproportional index (CPI), a similar measurement of brachycephaly. Infants were considered fully recovered if they achieved an ODDI score of <104% and a CPI score of <90%. These scores indicate a normal head shape; higher scores indicate worse PSD.

At the end of the study, the reduction in ODDI and CPI scores was almost the same in both  the helmet therapy and the control groups. Ten children in the helmet group (26%) and 9 in the control group (23%) experienced complete resolution of their PSD (P=.74).

Secondary outcomes included infant motor development, infant quality of life, parental satisfaction with the shape of their infant’s head, and parental anxiety. Both groups were similar in infant motor development, infant quality of life, and parental satisfaction. Parental anxiety was assessed using the Spielberger State-Trait Anxiety Inventory (scores range from 20-80; a higher score indicates greater anxiety). There was less parental anxiety in the helmet therapy group: (-3.9; 95% confidence interval, -7.5 to -0.2; P=.04).

All parents of infants in the helmet therapy group reported at least one adverse effect from the intervention. These effects included skin irritation (96%), bad helmet odor (76%), pain associated with the helmet (33%), and feeling hindered from cuddling their child (77%).

WHAT’S NEW: RCT provides stronger evidence that helmets are not effective

This is the first RCT that assessed helmet therapy for PSD in children.¹ Before this, the evidence on helmets for PSD had been obtained mainly from observational or poorly designed studies with significant flaws.⁶ This study by van Wijk et al¹ included objective measurement of skull deformity, along with clinically meaningful outcomes of parental satisfaction, motor development, and parental anxiety. It also found that helmet therapy was significantly more expensive than care that focused on waiting for PSD to resolve on its own ($1935 vs $196, respectively).¹

CAVEATS: Results may not apply to all infants with skull deformity

These findings do not apply to infants with very severe cases of PSD or those with skull deformity due to secondary causes, such as craniosynostosis, who were excluded from this study.¹ In addition, this is the only RCT to date that has assessed helmet use in PSD, so it is possible that future studies will find helmets are effective.

CHALLENGES TO IMPLEMENTATION: Parents may find this evidence hard to accept

To appropriately implement this recommendation, a family physician must be comfortable making the assessment of mild, moderate, severe, or very severe PSD. Referral to physical therapy might be appropriate for infants with very severe PSD.

If another physician or physical therapist recommends helmet therapy—or if a parent requests it—explaining the findings of this study may be challenging. We believe that the reduction in parental anxiety in the helmet group likely occurred because the parents believed that the helmet would accelerate the normal reshaping of the skull shape that occurs spontaneously in almost all infants with PSD. Since this study shows that helmets don’t help correct skull deformities, parents can be assured that a helmet is unnecessary, costly, and causes adverse effects.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Illustrative case

The parents of a 6-month-old girl with moderate plagiocephaly bring their daughter in for a well child visit. Previously, you had recommended that the parents increase “tummy time” when the baby is awake, change her position in bed, and monitor the progression of the condition. They do not feel these interventions have made a difference in the shape of their daughter’s skull, and ask about using a helmet to help correct the deformity. How would you counsel them?

Positional skull deformity (PSD) is a common problem of infancy. Approximately 45% of infants ages 7 to 12 weeks are estimated to have PSD, although three-quarters of them have mild cases.² The incidence of PSD began to increase in 1992 after the American Academy of Pediatrics (AAP) introduced its “Back to Sleep” campaign, which encouraged parents to place their infants on their back at bedtime to reduce sudden infant death syndrome.³

There are 2 common forms of PSD: plagiocephaly, and brachycephaly.¹ Plagiocephaly is unilateral occipital flattening, which may be accompanied by ipsilateral forehead prominence and asymmetrical ears. Brachycephaly is symmetric flattening of the back of the head, which can lead to prominence of the temporal areas, making the head appear wide. Children with severe plagiocephaly have a misshapen, asymmetric skull, while children with brachycephaly have a flattened skull. The cranial sutures remain open in both kinds of PSD.

Evaluating infants for PSD is part of the routine physical exam, and when the condition is noted, the exam should also differentiate PSD from other causes of skull deformity, such as craniosynostosis. Infants and preschool-aged children with PSD may score lower on developmental testing than children without skull deformity.⁴ However, these differences are small and inconsistent (2-3 points on a 100-point scale).⁴ Skull deformity persists into adolescence in only 1% to 2% of patients.⁵

Neither the AAP nor the American Academy of Family Physicians has a guideline or consensus statement on PSD. Helmets are intended to correct PSD by fitting closely to an infant’s head but allowing room for the skill to grow at the flattened area.¹ A 2011 clinical report by Laughlin et al⁶ recommended against using helmets for infants with mild to moderate deformities, but stated that there was little evidence of harm. Earlier studies have suggested that physical therapy might be effective for plagiocephaly caught early (7 and 8 weeks of age).^7,8 Biggs⁹ suggested considering helmet therapy for infants whose cranial sutures remain open and who do not respond to 4 to 8 weeks of physical therapy for PSD. van Wijk et al¹ conducted an RCT to explore the risks and benefits of helmet therapy for children with PSD.

STUDY SUMMARY: Helmets for infants: No help and some harm

This single-blind RCT of 84 infants ages 5 or 6 months with moderate or severe PSD compared helmet therapy (n=42) to no intervention (allowing natural growth, n=42). Infants were excluded if they had very severe PSD or skull deformity from another cause, such as torticollis or craniosynostosis.

Infants in the helmet therapy group received a custom-made helmet that they wore 23 hours a day until they were a year old, with regular evaluation by an orthotist and modification of the helmet as necessary to allow skull growth. The control group had usual care and no helmet.

At the end of the study, improvement in skull shape was almost the same in the helmet therapy and control groups. The primary outcome was improvement in skull shape at age 24 months as measured by the oblique diameter difference index (ODDI), a unitless measurement of plagiocephaly calculated by taking the ratio of measures of 2 dimensions of cranial diameter, and the cranioproportional index (CPI), a similar measurement of brachycephaly. Infants were considered fully recovered if they achieved an ODDI score of <104% and a CPI score of <90%. These scores indicate a normal head shape; higher scores indicate worse PSD.

At the end of the study, the reduction in ODDI and CPI scores was almost the same in both  the helmet therapy and the control groups. Ten children in the helmet group (26%) and 9 in the control group (23%) experienced complete resolution of their PSD (P=.74).

Secondary outcomes included infant motor development, infant quality of life, parental satisfaction with the shape of their infant’s head, and parental anxiety. Both groups were similar in infant motor development, infant quality of life, and parental satisfaction. Parental anxiety was assessed using the Spielberger State-Trait Anxiety Inventory (scores range from 20-80; a higher score indicates greater anxiety). There was less parental anxiety in the helmet therapy group: (-3.9; 95% confidence interval, -7.5 to -0.2; P=.04).

All parents of infants in the helmet therapy group reported at least one adverse effect from the intervention. These effects included skin irritation (96%), bad helmet odor (76%), pain associated with the helmet (33%), and feeling hindered from cuddling their child (77%).

WHAT’S NEW: RCT provides stronger evidence that helmets are not effective

This is the first RCT that assessed helmet therapy for PSD in children.¹ Before this, the evidence on helmets for PSD had been obtained mainly from observational or poorly designed studies with significant flaws.⁶ This study by van Wijk et al¹ included objective measurement of skull deformity, along with clinically meaningful outcomes of parental satisfaction, motor development, and parental anxiety. It also found that helmet therapy was significantly more expensive than care that focused on waiting for PSD to resolve on its own ($1935 vs $196, respectively).¹

CAVEATS: Results may not apply to all infants with skull deformity

These findings do not apply to infants with very severe cases of PSD or those with skull deformity due to secondary causes, such as craniosynostosis, who were excluded from this study.¹ In addition, this is the only RCT to date that has assessed helmet use in PSD, so it is possible that future studies will find helmets are effective.

CHALLENGES TO IMPLEMENTATION: Parents may find this evidence hard to accept

To appropriately implement this recommendation, a family physician must be comfortable making the assessment of mild, moderate, severe, or very severe PSD. Referral to physical therapy might be appropriate for infants with very severe PSD.

If another physician or physical therapist recommends helmet therapy—or if a parent requests it—explaining the findings of this study may be challenging. We believe that the reduction in parental anxiety in the helmet group likely occurred because the parents believed that the helmet would accelerate the normal reshaping of the skull shape that occurs spontaneously in almost all infants with PSD. Since this study shows that helmets don’t help correct skull deformities, parents can be assured that a helmet is unnecessary, costly, and causes adverse effects.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Alzheimer’s disease (AD), the most common form of dementia, affects more than 5 million Americans.¹ Estimates suggest that by 2050, the prevalence could triple, reaching 13 to 16 million.¹ To effectively care for patients with AD and their families, family physicians need to be familiar with the latest evidence on all facets of care, from initial detection to patient management and end-of-life care.

This evidence-based review will help you toward that end by answering common questions regarding Alzheimer’s care, including whether routine screening is advisable, what tests should be ordered, which interventions (including nonpharmacologic options) are worth considering, and how best to counsel patients and families about end-of-life care.

Routine screening? Still subject to debate

In considering routine dementia screening in primary care, the key question is whether screening improves outcomes. Advocates note that individuals with dementia may appear unimpaired during office visits and may not report symptoms due to lack of insight; they point out, too, that waiting for an event that makes cognitive impairment obvious, such as a driving mishap, is risky.² Those who advocate routine screening also note that only about half of those who have dementia are ever diagnosed.³

Others, including the US Preventive Services Task Force (USPSTF), disagree. In its 2014 evidence review, the USPSTF indicated that there is “insufficient evidence to assess the balance of benefits and harms of screening for cognitive impairment in older adults.”⁴

Mixed messages

The dearth of evidence is also reflected in the conflicting recommendations of the Affordable Care Act (ACA) and the Centers for Medicare and Medicaid Services (CMS). The ACA requires physicians to assess the cognitive function of Medicare patients during their annual wellness visits. CMS, however, instructs providers to screen for dementia only if observation or concerns raised by the patient or family suggest the possibility of impairment, and does not recommend any particular test.⁵

Cost-effectiveness analyses raise questions about the value of routine screening, as well. Evidence suggests that if a primary care physician screens 300 older patients, 39 will have a positive screen. But only about half of those 39 will agree to a diagnostic evaluation, and no more than 9 will ultimately be diagnosed with dementia. The estimated cost of identifying 9 cases is nearly $40,000—all in the absence of a treatment to cure or stop the progression of the disorder.⁶

The bottom line: Evidence does not support routine dementia screening of older adults. When cognitive impairment is suspected, however, physicians should conduct a diagnostic evaluation—and consider educating patients and families about the Alzheimer’s Association (AA)’s 10 warning signs of AD.⁷ (See “Is it Alzheimer’s? 10 warning signs”⁷ below.) A longer version, available at http://www.alz.org/national/documents/checklist_10signs.pdf, outlines the cognitive changes that are characteristic of healthy aging and compares them to changes suggestive of early dementia.⁷

How to proceed when you suspect AD

Step 1: Screening instrument. The first step in the diagnostic evaluation of a patient with suspected AD is to determine if, in fact, cognitive impairment is present. This can be done by screening with in-office screening instruments, such as the Mini-Cog (available at alz.org/documents_custom/minicog.pdf) or Mini-Mental State Examination (MMSE; health.gov.bc.ca/pharmacare/adti/clinician/pdf/ADTI%20SMMSE-GDS%20Reference%20Card.pdf), among others.⁸

Step 2: Clinical evaluation. If observation and test results suggest cognitive impairment, the next step is to determine whether clinical findings are consistent with the diagnostic criteria for AD (TABLE 1)⁹ developed by workgroups from the National Institute on Aging (NIA)/AA in 2011. A work-up is necessary to identify conditions that can mimic dementia (eg, depression) and behaviors that suggest another type of dementia, such as frontotemporal or Lewy body dementia.¹⁰ Lab testing should be included to rule out potentially reversible causes of cognitive dysfunction (eg, hypothyroidism, vitamin D deficiency).

Step 3: Neuropsychological evaluation. The NIA/AA recommends neuropsychological testing when the brief cognitive tests, history, and clinical work-up are not sufficient for a definitive diagnosis of dementia.⁹When brief cognitive tests, history, and clinical work-up are inconclusive, refer patients for neuropsychological testing.This generally involves a referral to a neuropsychologist, who conducts a battery of standardized tests to evaluate attention, memory, language, visual-spatial abilities, and executive functions, among others. Neuropsychological testing can confirm the presence of cognitive impairment and aid in the differential diagnosis by comparing the patient’s performance in these domains with characteristic features of different dementia syndromes.

Step 4: Brain imaging with either computed tomography or magnetic resonance imaging can be included in the work-up for patients with suspected AD to rule out abnormalities—eg, metastatic cancer, hydrocephalus, or occult chronic subdural hematoma—that could be causing cognitive impairment.^9,10 Clinical features that generally warrant brain imaging include onset of cognitive impairment before age 60; unexplained focal neurologic signs or symptoms; abrupt onset or rapid decline; and/or predisposing conditions, such as cancer or anticoagulant treatment.¹⁰

The role of biomarkers and advanced brain imaging

Biomarkers that might provide confirmation of AD in patients who exhibit early symptoms of dementia have been studied extensively.¹¹ The NIA/AA identified 2 categories of AD biomarkers:

• tests for β-amyloid deposition in the brain, including spinal fluid assays for β-amyloid (Aβ₄₂) and positron emission tomography (PET) scans after intravenous injection of florbetapir or flutemetamol, which bind to amyloid in the brain; and
• tests for neuronal degeneration, which would include spinal fluid assays for tau protein and PET scans after injection of fluorodeoxyglucose (FDG), which shows decreased uptake in patients with AD.⁹

Research reveals the promise of these biomarkers as diagnostic tools, particularly in patients with an atypical presentation of dementia or mild cognitive impairment (MCI) that may be associated with early AD.¹² (More on MCI in a moment.) However, the NIA/AA concluded that additional research is needed to validate these tests for routine diagnostic purposes. Medicare covers PET scans with FDG only for the differential diagnosis of AD vs frontotemporal dementia.¹³

Mild cognitive impairment: How likely that it will progress?

Along with diagnostic criteria for AD, the NIA/AA developed criteria for a symptomatic predementia phase of AD—often referred to as MCI.¹⁴ According to the workgroup, MCI is diagnosed when:

Progression: Less likely than you might think

Patients with MCI are at risk for progression to overt dementia, with an overall annual conversion rate from MCI to dementia estimated at 10% to 15%.^15,16 This estimate must be interpreted with caution, however, because most studies were conducted prior to the 2011 guidelines, when different diagnostic criteria were used. Observers have noted, too, that the numbers largely reflect data collected in specialty clinics and that community-based studies reveal substantially lower conversion rates (3%-6% per year).¹⁶ In addition, evidence suggests that many patients with MCI demonstrate long-term stability or even reversal of deficits.¹⁷

While there is some consideration of the use of biomarkers and amyloid imaging tests to help determine which patients with MCI will progress to AD, practice guidelines do not currently recommend such testing and it is not covered by Medicare.

When evidence indicates an AD diagnosis

When faced with the need to communicate an AD diagnosis, follow the general recommendations for delivering any bad news or discouraging prognosis:

Prioritize and limit the information you provide, determining not only what the patient and family want to hear, but also how much they are able to comprehend.

Confirm that the patient and family understand the information you’ve provided.

Offer emotional support and recommend additional resources¹⁸ (TABLE 2).

Given the progressive cognitive decline that characterizes AD, it is important to address the primary caregiver’s understanding of, and ability to cope with, the disease. It is also important to explore beliefs and attitudes regarding AD. Keep in mind that different cultural groups tend to differ in their beliefs about the nature, cause, and appropriate management of AD, as well as the role of spirituality, help-seeking, and stigma.^19,20

When communicating an Alzheimer's disease diagnosis, prioritize information and offer emotional support. The progressive and ultimately fatal nature of AD also makes planning for the future a priority. Ideally, patients should be engaged in discussions regarding end-of-life care as early as possible, while they are still able to make informed decisions and express their preferences. Discussing end-of-life care can be overwhelming for newly diagnosed patients and their families, however, so it is important that you address issues—medical, financial, and legal planning, for example—that families should be considering.

TABLE 2

Drugs address cognitive and behavioral function

No current treatments
 can cure 
or significantly alter the progression of AD, but 2 classes of medications are used to improve cognitive function. No currently available treatments can cure or significantly alter the progression of AD, but 2 classes of medications are used in an attempt to improve cognitive function. One is cholinesterase inhibitors (ChEIs), which potentiate acetylcholine synaptic transmission. The other is N-methyl-D-aspartate (NMDA) glutamate receptor blockers. Other classes of drugs are sometimes used to treat behavioral symptoms of dementia, such as agitation, aggression, mood disorders, and psychosis (eg, delusions and hallucinations).

Cognitive function. Results from studies of pharmacologic management of MCI vary widely, but recent reviews have found no convincing evidence that either ChEIs or NMDA receptor blockers have an effect on progression from MCI to dementia.^21,22 Neither class is FDA-approved for treating MCI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and often of questionable clinical relevance.²³ Nonetheless, among ChEIs, donepezil is approved by the US Food and Drug Administration (FDA) for mild, moderate, and severe dementia and galantamine and rivastigmine are approved for mild and moderate dementia. There is no evidence that any one ChEI is more effective than any other,²⁴ and the choice of drugs is often guided by cost, adverse effects, and health plan formularies. Memantine, the only FDA-approved NMDA receptor blocker, is approved for moderate to severe dementia and can be used alone or in combination with a ChEI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and are often of questionable clinical relevance. If these drugs are used in an attempt to improve cognition in AD, guidelines recommend the following approach for initial therapy: Prescribe a ChEI for the mild stage, a ChEI plus memantine for the moderate stage, and memantine (with or without a ChEI) for the severe stage.²⁵ The recommendations also include monitoring every 6 months.

There is no consensus about when to discontinue medication. Various published recommendations call for continuing treatment until the patient has “lost all cognitive and functional abilities;”²² until the patient’s MMSE score falls below 10 and there is no indication that the drug is having a “worthwhile effect;”²¹ or until he or she has reached stage 7 on the Reisberg Functional Assessment Staging scale, indicating nonambulatory status with speech limited to one to 5 words a day.¹⁰

Behavioral function. A variety of drugs are used to treat behavioral symptoms in AD. While not FDA-approved for this use, the most widely prescribed agents are second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone). The main effect of these drugs is often nothing more than sedation, and one large multi­site clinical trial concluded that the adverse effects offset the benefits for patients with AD.²⁶ Indeed, the FDA has issued an advisory on the use of second-generation antipsychotics in AD patients, stating that they are associated with an increased risk of death.²⁷ The recently updated Beers Criteria strongly recommend avoiding these drugs for treating behavioral disturbances in AD unless nonpharmacologic options have failed and the patient is a threat to self or others.²⁸

The FDA has issued an advisory on the use of second-generation antipsychotics in Alzheimer’s patients, stating that they are associated with an increased risk of death. Because of the black-box warning that antipsychotics increase the risk of death, some physicians have advocated obtaining informed consent prior to prescribing such medications.²⁹ At the very least, when family or guardians are involved, a conversation about risks vs benefits should take place and be documented in the medical record.

Other drug classes are also sometimes used in an attempt to improve behavioral function, including anti-seizure medications (valproic acid, carbamazepine), antidepressants (trazodone and selective serotonin reuptake inhibitors), and anxiolytics (benzodiazepines and buspirone). Other than their sedating effects, there is no strong evidence that these drugs are effective for treating dementia-related behavioral disorders. If used, caution is required due to potential adverse effects.

Nonpharmacologic management is “promising”

A recent systematic review of nonpharmacologic interventions for MCI evaluated exercise, training in compensatory strategies, and engagement in cognitively stimulating activities and found “promising but inconclusive” results. The researchers found that studies show mostly positive effects on cognition but have significant methodologic limitations.³⁰ Importantly, there is no evidence of delayed or reduced conversion to dementia.

For patients who already have mild-to-moderate dementia, cognitive stimulation seems to help in the short term.³¹ There is also some evidence that exercise and occupational therapy may slow functional decline,³² but the effects are small to modest and their actual clinical significance (eg, the ability to delay institutionalization) is unclear. There is promising but preliminary evidence that cognitive rehabilitation (helping patients devise strategies to complete daily activities) may improve functioning in everyday life.³³

While behavioral symptoms are often due to the dementia itself, it is important to identify and treat medical and environmental causes that may be contributing, such as infection, pain, and loud or unsafe environments.Interventions such as massage therapy, aromatherapy, exercise, and music therapy may be effective in the short term for agitated behavior. As noted before, nonpharmacologic treatments are generally preferred for behavioral problems and should be considered prior to drug therapy. Approaches that identify and modify both the antecedents and consequences of problem behaviors and increase pleasant events have empirical support for the management of behavioral symptoms.³⁴ Interventions including massage therapy, aromatherapy, exercise, and music therapy may also be effective in the short term for agitated behavior.³⁵

Caregivers should be encouraged to receive training in these strategies through organizations like AA. Caregiver education and support can reduce caregivers’ distress and increase their self-efficacy and coping skills.³⁶

End-of-life care must be addressed

Perhaps the most important aspect of end-of-life care in AD is assuring that families (or health care proxies) understand that AD is a fatal illness, with most patients dying within 4 to 8 years of diagnosis.¹ Evidence indicates that patients whose proxies have a clear recognition of this are less likely to experience “burdensome” interventions such as parenteral therapy, emergency department visits, hospital admissions, and tube feedings in their last 3 months of life.³⁷

Overall, decisions regarding discontinuing medical treatments in advanced AD should be made by balancing the likelihood of benefit with the potential for adverse effects.³⁸The progressive and ultimately fatal nature of Alzheimer's disease makes planning for the future a priority. For example, the American Geriatrics Society recently recommended against feeding tubes because they often result in discomfort due to agitation, use of restraints, and worsening pressure ulcers.³⁹

Unfortunately, only a minority of families receives straightforward information on the course and prognosis of AD, including the fact that patients eventually stop eating and that the natural cause of death is often an acute infection. Studies also show that patients with dementia are at risk for inadequate treatment of pain.⁴⁰ Assuring adequate pain control is an essential component of end-of-life care.

Hospice. End-of-life care can often be improved with hospice care. This service is underused by patients with dementia, even though hospice care is available at no cost through Medicare. Hospice eligibility criteria for patients with AD are shown in
TABLE 3.^41,42

Finally, a word about prevention

Numerous risk factors have been associated with an increased risk of AD (TABLE 4)^2,3. Some, like age and genetics, are nonmodifiable, while others—particularly cardiovascular risk factors—can be modified.¹ There are also factors associated with decreased risk, most notably, physical exercise and participating in cognitively stimulating activities.³ Identification of these factors has led to the hope that addressing them can prevent AD.

But association does not equal causation. In 2010, a report from the National Institutes of Health concluded that, although there are modifiable factors associated with AD, there is insufficient evidence that addressing any of them will actually prevent AD.⁴³ In fact, there is good evidence that some of these factors (eg, statin therapy) are not effective in reducing the incidence of dementia, and that others (eg, vitamin E and estrogen therapy) are potentially harmful.⁴⁴

The absence of empirically supported preventive interventions does not mean, however, that we should disregard these risks and protective factors. Encouraging social engagement, for example, may improve both emotional health and quality of life. Addressing cardiovascular risk factors can reduce the rate of coronary and cerebrovascular disease, potentially including vascular dementia, even if it does not reduce the rate of AD.

Studies are evaluating the use of monoclonal antibodies with anti-amyloid properties for preventing AD in individuals who have APOE ε4 genotypes or high amyloid loads on neuroimaging.⁴⁵ It will be several years before results are available, however, and the outcome of these studies is uncertain as the use of anti-amyloid agents for treating established dementia has not been effective.^46,47

CORRESPONDENCE
Marisa Menchola, PhD, Department of Psychiatry, University of Arizona College of Medicine, 1501 N. Campbell Ave., 7OPC. Tucson, AZ 85724; [email protected]

Alzheimer’s disease (AD), the most common form of dementia, affects more than 5 million Americans.¹ Estimates suggest that by 2050, the prevalence could triple, reaching 13 to 16 million.¹ To effectively care for patients with AD and their families, family physicians need to be familiar with the latest evidence on all facets of care, from initial detection to patient management and end-of-life care.

This evidence-based review will help you toward that end by answering common questions regarding Alzheimer’s care, including whether routine screening is advisable, what tests should be ordered, which interventions (including nonpharmacologic options) are worth considering, and how best to counsel patients and families about end-of-life care.

Routine screening? Still subject to debate

In considering routine dementia screening in primary care, the key question is whether screening improves outcomes. Advocates note that individuals with dementia may appear unimpaired during office visits and may not report symptoms due to lack of insight; they point out, too, that waiting for an event that makes cognitive impairment obvious, such as a driving mishap, is risky.² Those who advocate routine screening also note that only about half of those who have dementia are ever diagnosed.³

Others, including the US Preventive Services Task Force (USPSTF), disagree. In its 2014 evidence review, the USPSTF indicated that there is “insufficient evidence to assess the balance of benefits and harms of screening for cognitive impairment in older adults.”⁴

Mixed messages

The dearth of evidence is also reflected in the conflicting recommendations of the Affordable Care Act (ACA) and the Centers for Medicare and Medicaid Services (CMS). The ACA requires physicians to assess the cognitive function of Medicare patients during their annual wellness visits. CMS, however, instructs providers to screen for dementia only if observation or concerns raised by the patient or family suggest the possibility of impairment, and does not recommend any particular test.⁵

Cost-effectiveness analyses raise questions about the value of routine screening, as well. Evidence suggests that if a primary care physician screens 300 older patients, 39 will have a positive screen. But only about half of those 39 will agree to a diagnostic evaluation, and no more than 9 will ultimately be diagnosed with dementia. The estimated cost of identifying 9 cases is nearly $40,000—all in the absence of a treatment to cure or stop the progression of the disorder.⁶

The bottom line: Evidence does not support routine dementia screening of older adults. When cognitive impairment is suspected, however, physicians should conduct a diagnostic evaluation—and consider educating patients and families about the Alzheimer’s Association (AA)’s 10 warning signs of AD.⁷ (See “Is it Alzheimer’s? 10 warning signs”⁷ below.) A longer version, available at http://www.alz.org/national/documents/checklist_10signs.pdf, outlines the cognitive changes that are characteristic of healthy aging and compares them to changes suggestive of early dementia.⁷

How to proceed when you suspect AD

Step 1: Screening instrument. The first step in the diagnostic evaluation of a patient with suspected AD is to determine if, in fact, cognitive impairment is present. This can be done by screening with in-office screening instruments, such as the Mini-Cog (available at alz.org/documents_custom/minicog.pdf) or Mini-Mental State Examination (MMSE; health.gov.bc.ca/pharmacare/adti/clinician/pdf/ADTI%20SMMSE-GDS%20Reference%20Card.pdf), among others.⁸

Step 2: Clinical evaluation. If observation and test results suggest cognitive impairment, the next step is to determine whether clinical findings are consistent with the diagnostic criteria for AD (TABLE 1)⁹ developed by workgroups from the National Institute on Aging (NIA)/AA in 2011. A work-up is necessary to identify conditions that can mimic dementia (eg, depression) and behaviors that suggest another type of dementia, such as frontotemporal or Lewy body dementia.¹⁰ Lab testing should be included to rule out potentially reversible causes of cognitive dysfunction (eg, hypothyroidism, vitamin D deficiency).

Step 3: Neuropsychological evaluation. The NIA/AA recommends neuropsychological testing when the brief cognitive tests, history, and clinical work-up are not sufficient for a definitive diagnosis of dementia.⁹When brief cognitive tests, history, and clinical work-up are inconclusive, refer patients for neuropsychological testing.This generally involves a referral to a neuropsychologist, who conducts a battery of standardized tests to evaluate attention, memory, language, visual-spatial abilities, and executive functions, among others. Neuropsychological testing can confirm the presence of cognitive impairment and aid in the differential diagnosis by comparing the patient’s performance in these domains with characteristic features of different dementia syndromes.

Step 4: Brain imaging with either computed tomography or magnetic resonance imaging can be included in the work-up for patients with suspected AD to rule out abnormalities—eg, metastatic cancer, hydrocephalus, or occult chronic subdural hematoma—that could be causing cognitive impairment.^9,10 Clinical features that generally warrant brain imaging include onset of cognitive impairment before age 60; unexplained focal neurologic signs or symptoms; abrupt onset or rapid decline; and/or predisposing conditions, such as cancer or anticoagulant treatment.¹⁰

The role of biomarkers and advanced brain imaging

Biomarkers that might provide confirmation of AD in patients who exhibit early symptoms of dementia have been studied extensively.¹¹ The NIA/AA identified 2 categories of AD biomarkers:

• tests for β-amyloid deposition in the brain, including spinal fluid assays for β-amyloid (Aβ₄₂) and positron emission tomography (PET) scans after intravenous injection of florbetapir or flutemetamol, which bind to amyloid in the brain; and
• tests for neuronal degeneration, which would include spinal fluid assays for tau protein and PET scans after injection of fluorodeoxyglucose (FDG), which shows decreased uptake in patients with AD.⁹

Research reveals the promise of these biomarkers as diagnostic tools, particularly in patients with an atypical presentation of dementia or mild cognitive impairment (MCI) that may be associated with early AD.¹² (More on MCI in a moment.) However, the NIA/AA concluded that additional research is needed to validate these tests for routine diagnostic purposes. Medicare covers PET scans with FDG only for the differential diagnosis of AD vs frontotemporal dementia.¹³

Mild cognitive impairment: How likely that it will progress?

Along with diagnostic criteria for AD, the NIA/AA developed criteria for a symptomatic predementia phase of AD—often referred to as MCI.¹⁴ According to the workgroup, MCI is diagnosed when:

Progression: Less likely than you might think

Patients with MCI are at risk for progression to overt dementia, with an overall annual conversion rate from MCI to dementia estimated at 10% to 15%.^15,16 This estimate must be interpreted with caution, however, because most studies were conducted prior to the 2011 guidelines, when different diagnostic criteria were used. Observers have noted, too, that the numbers largely reflect data collected in specialty clinics and that community-based studies reveal substantially lower conversion rates (3%-6% per year).¹⁶ In addition, evidence suggests that many patients with MCI demonstrate long-term stability or even reversal of deficits.¹⁷

While there is some consideration of the use of biomarkers and amyloid imaging tests to help determine which patients with MCI will progress to AD, practice guidelines do not currently recommend such testing and it is not covered by Medicare.

When evidence indicates an AD diagnosis

When faced with the need to communicate an AD diagnosis, follow the general recommendations for delivering any bad news or discouraging prognosis:

Prioritize and limit the information you provide, determining not only what the patient and family want to hear, but also how much they are able to comprehend.

Confirm that the patient and family understand the information you’ve provided.

Offer emotional support and recommend additional resources¹⁸ (TABLE 2).

Given the progressive cognitive decline that characterizes AD, it is important to address the primary caregiver’s understanding of, and ability to cope with, the disease. It is also important to explore beliefs and attitudes regarding AD. Keep in mind that different cultural groups tend to differ in their beliefs about the nature, cause, and appropriate management of AD, as well as the role of spirituality, help-seeking, and stigma.^19,20

When communicating an Alzheimer's disease diagnosis, prioritize information and offer emotional support. The progressive and ultimately fatal nature of AD also makes planning for the future a priority. Ideally, patients should be engaged in discussions regarding end-of-life care as early as possible, while they are still able to make informed decisions and express their preferences. Discussing end-of-life care can be overwhelming for newly diagnosed patients and their families, however, so it is important that you address issues—medical, financial, and legal planning, for example—that families should be considering.

TABLE 2

Drugs address cognitive and behavioral function

No current treatments
 can cure 
or significantly alter the progression of AD, but 2 classes of medications are used to improve cognitive function. No currently available treatments can cure or significantly alter the progression of AD, but 2 classes of medications are used in an attempt to improve cognitive function. One is cholinesterase inhibitors (ChEIs), which potentiate acetylcholine synaptic transmission. The other is N-methyl-D-aspartate (NMDA) glutamate receptor blockers. Other classes of drugs are sometimes used to treat behavioral symptoms of dementia, such as agitation, aggression, mood disorders, and psychosis (eg, delusions and hallucinations).

Cognitive function. Results from studies of pharmacologic management of MCI vary widely, but recent reviews have found no convincing evidence that either ChEIs or NMDA receptor blockers have an effect on progression from MCI to dementia.^21,22 Neither class is FDA-approved for treating MCI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and often of questionable clinical relevance.²³ Nonetheless, among ChEIs, donepezil is approved by the US Food and Drug Administration (FDA) for mild, moderate, and severe dementia and galantamine and rivastigmine are approved for mild and moderate dementia. There is no evidence that any one ChEI is more effective than any other,²⁴ and the choice of drugs is often guided by cost, adverse effects, and health plan formularies. Memantine, the only FDA-approved NMDA receptor blocker, is approved for moderate to severe dementia and can be used alone or in combination with a ChEI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and are often of questionable clinical relevance. If these drugs are used in an attempt to improve cognition in AD, guidelines recommend the following approach for initial therapy: Prescribe a ChEI for the mild stage, a ChEI plus memantine for the moderate stage, and memantine (with or without a ChEI) for the severe stage.²⁵ The recommendations also include monitoring every 6 months.

There is no consensus about when to discontinue medication. Various published recommendations call for continuing treatment until the patient has “lost all cognitive and functional abilities;”²² until the patient’s MMSE score falls below 10 and there is no indication that the drug is having a “worthwhile effect;”²¹ or until he or she has reached stage 7 on the Reisberg Functional Assessment Staging scale, indicating nonambulatory status with speech limited to one to 5 words a day.¹⁰

Behavioral function. A variety of drugs are used to treat behavioral symptoms in AD. While not FDA-approved for this use, the most widely prescribed agents are second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone). The main effect of these drugs is often nothing more than sedation, and one large multi­site clinical trial concluded that the adverse effects offset the benefits for patients with AD.²⁶ Indeed, the FDA has issued an advisory on the use of second-generation antipsychotics in AD patients, stating that they are associated with an increased risk of death.²⁷ The recently updated Beers Criteria strongly recommend avoiding these drugs for treating behavioral disturbances in AD unless nonpharmacologic options have failed and the patient is a threat to self or others.²⁸

The FDA has issued an advisory on the use of second-generation antipsychotics in Alzheimer’s patients, stating that they are associated with an increased risk of death. Because of the black-box warning that antipsychotics increase the risk of death, some physicians have advocated obtaining informed consent prior to prescribing such medications.²⁹ At the very least, when family or guardians are involved, a conversation about risks vs benefits should take place and be documented in the medical record.

Other drug classes are also sometimes used in an attempt to improve behavioral function, including anti-seizure medications (valproic acid, carbamazepine), antidepressants (trazodone and selective serotonin reuptake inhibitors), and anxiolytics (benzodiazepines and buspirone). Other than their sedating effects, there is no strong evidence that these drugs are effective for treating dementia-related behavioral disorders. If used, caution is required due to potential adverse effects.

Nonpharmacologic management is “promising”

A recent systematic review of nonpharmacologic interventions for MCI evaluated exercise, training in compensatory strategies, and engagement in cognitively stimulating activities and found “promising but inconclusive” results. The researchers found that studies show mostly positive effects on cognition but have significant methodologic limitations.³⁰ Importantly, there is no evidence of delayed or reduced conversion to dementia.

For patients who already have mild-to-moderate dementia, cognitive stimulation seems to help in the short term.³¹ There is also some evidence that exercise and occupational therapy may slow functional decline,³² but the effects are small to modest and their actual clinical significance (eg, the ability to delay institutionalization) is unclear. There is promising but preliminary evidence that cognitive rehabilitation (helping patients devise strategies to complete daily activities) may improve functioning in everyday life.³³

While behavioral symptoms are often due to the dementia itself, it is important to identify and treat medical and environmental causes that may be contributing, such as infection, pain, and loud or unsafe environments.Interventions such as massage therapy, aromatherapy, exercise, and music therapy may be effective in the short term for agitated behavior. As noted before, nonpharmacologic treatments are generally preferred for behavioral problems and should be considered prior to drug therapy. Approaches that identify and modify both the antecedents and consequences of problem behaviors and increase pleasant events have empirical support for the management of behavioral symptoms.³⁴ Interventions including massage therapy, aromatherapy, exercise, and music therapy may also be effective in the short term for agitated behavior.³⁵

Caregivers should be encouraged to receive training in these strategies through organizations like AA. Caregiver education and support can reduce caregivers’ distress and increase their self-efficacy and coping skills.³⁶

End-of-life care must be addressed

Perhaps the most important aspect of end-of-life care in AD is assuring that families (or health care proxies) understand that AD is a fatal illness, with most patients dying within 4 to 8 years of diagnosis.¹ Evidence indicates that patients whose proxies have a clear recognition of this are less likely to experience “burdensome” interventions such as parenteral therapy, emergency department visits, hospital admissions, and tube feedings in their last 3 months of life.³⁷

Overall, decisions regarding discontinuing medical treatments in advanced AD should be made by balancing the likelihood of benefit with the potential for adverse effects.³⁸The progressive and ultimately fatal nature of Alzheimer's disease makes planning for the future a priority. For example, the American Geriatrics Society recently recommended against feeding tubes because they often result in discomfort due to agitation, use of restraints, and worsening pressure ulcers.³⁹

Unfortunately, only a minority of families receives straightforward information on the course and prognosis of AD, including the fact that patients eventually stop eating and that the natural cause of death is often an acute infection. Studies also show that patients with dementia are at risk for inadequate treatment of pain.⁴⁰ Assuring adequate pain control is an essential component of end-of-life care.

Hospice. End-of-life care can often be improved with hospice care. This service is underused by patients with dementia, even though hospice care is available at no cost through Medicare. Hospice eligibility criteria for patients with AD are shown in
TABLE 3.^41,42

Finally, a word about prevention

Numerous risk factors have been associated with an increased risk of AD (TABLE 4)^2,3. Some, like age and genetics, are nonmodifiable, while others—particularly cardiovascular risk factors—can be modified.¹ There are also factors associated with decreased risk, most notably, physical exercise and participating in cognitively stimulating activities.³ Identification of these factors has led to the hope that addressing them can prevent AD.

But association does not equal causation. In 2010, a report from the National Institutes of Health concluded that, although there are modifiable factors associated with AD, there is insufficient evidence that addressing any of them will actually prevent AD.⁴³ In fact, there is good evidence that some of these factors (eg, statin therapy) are not effective in reducing the incidence of dementia, and that others (eg, vitamin E and estrogen therapy) are potentially harmful.⁴⁴

The absence of empirically supported preventive interventions does not mean, however, that we should disregard these risks and protective factors. Encouraging social engagement, for example, may improve both emotional health and quality of life. Addressing cardiovascular risk factors can reduce the rate of coronary and cerebrovascular disease, potentially including vascular dementia, even if it does not reduce the rate of AD.

Studies are evaluating the use of monoclonal antibodies with anti-amyloid properties for preventing AD in individuals who have APOE ε4 genotypes or high amyloid loads on neuroimaging.⁴⁵ It will be several years before results are available, however, and the outcome of these studies is uncertain as the use of anti-amyloid agents for treating established dementia has not been effective.^46,47

CORRESPONDENCE
Marisa Menchola, PhD, Department of Psychiatry, University of Arizona College of Medicine, 1501 N. Campbell Ave., 7OPC. Tucson, AZ 85724; [email protected]

Alzheimer’s disease (AD), the most common form of dementia, affects more than 5 million Americans.¹ Estimates suggest that by 2050, the prevalence could triple, reaching 13 to 16 million.¹ To effectively care for patients with AD and their families, family physicians need to be familiar with the latest evidence on all facets of care, from initial detection to patient management and end-of-life care.

This evidence-based review will help you toward that end by answering common questions regarding Alzheimer’s care, including whether routine screening is advisable, what tests should be ordered, which interventions (including nonpharmacologic options) are worth considering, and how best to counsel patients and families about end-of-life care.

Routine screening? Still subject to debate

In considering routine dementia screening in primary care, the key question is whether screening improves outcomes. Advocates note that individuals with dementia may appear unimpaired during office visits and may not report symptoms due to lack of insight; they point out, too, that waiting for an event that makes cognitive impairment obvious, such as a driving mishap, is risky.² Those who advocate routine screening also note that only about half of those who have dementia are ever diagnosed.³

Others, including the US Preventive Services Task Force (USPSTF), disagree. In its 2014 evidence review, the USPSTF indicated that there is “insufficient evidence to assess the balance of benefits and harms of screening for cognitive impairment in older adults.”⁴

Mixed messages

The dearth of evidence is also reflected in the conflicting recommendations of the Affordable Care Act (ACA) and the Centers for Medicare and Medicaid Services (CMS). The ACA requires physicians to assess the cognitive function of Medicare patients during their annual wellness visits. CMS, however, instructs providers to screen for dementia only if observation or concerns raised by the patient or family suggest the possibility of impairment, and does not recommend any particular test.⁵

Cost-effectiveness analyses raise questions about the value of routine screening, as well. Evidence suggests that if a primary care physician screens 300 older patients, 39 will have a positive screen. But only about half of those 39 will agree to a diagnostic evaluation, and no more than 9 will ultimately be diagnosed with dementia. The estimated cost of identifying 9 cases is nearly $40,000—all in the absence of a treatment to cure or stop the progression of the disorder.⁶

The bottom line: Evidence does not support routine dementia screening of older adults. When cognitive impairment is suspected, however, physicians should conduct a diagnostic evaluation—and consider educating patients and families about the Alzheimer’s Association (AA)’s 10 warning signs of AD.⁷ (See “Is it Alzheimer’s? 10 warning signs”⁷ below.) A longer version, available at http://www.alz.org/national/documents/checklist_10signs.pdf, outlines the cognitive changes that are characteristic of healthy aging and compares them to changes suggestive of early dementia.⁷

How to proceed when you suspect AD

Step 1: Screening instrument. The first step in the diagnostic evaluation of a patient with suspected AD is to determine if, in fact, cognitive impairment is present. This can be done by screening with in-office screening instruments, such as the Mini-Cog (available at alz.org/documents_custom/minicog.pdf) or Mini-Mental State Examination (MMSE; health.gov.bc.ca/pharmacare/adti/clinician/pdf/ADTI%20SMMSE-GDS%20Reference%20Card.pdf), among others.⁸

Step 2: Clinical evaluation. If observation and test results suggest cognitive impairment, the next step is to determine whether clinical findings are consistent with the diagnostic criteria for AD (TABLE 1)⁹ developed by workgroups from the National Institute on Aging (NIA)/AA in 2011. A work-up is necessary to identify conditions that can mimic dementia (eg, depression) and behaviors that suggest another type of dementia, such as frontotemporal or Lewy body dementia.¹⁰ Lab testing should be included to rule out potentially reversible causes of cognitive dysfunction (eg, hypothyroidism, vitamin D deficiency).

Step 3: Neuropsychological evaluation. The NIA/AA recommends neuropsychological testing when the brief cognitive tests, history, and clinical work-up are not sufficient for a definitive diagnosis of dementia.⁹When brief cognitive tests, history, and clinical work-up are inconclusive, refer patients for neuropsychological testing.This generally involves a referral to a neuropsychologist, who conducts a battery of standardized tests to evaluate attention, memory, language, visual-spatial abilities, and executive functions, among others. Neuropsychological testing can confirm the presence of cognitive impairment and aid in the differential diagnosis by comparing the patient’s performance in these domains with characteristic features of different dementia syndromes.

Step 4: Brain imaging with either computed tomography or magnetic resonance imaging can be included in the work-up for patients with suspected AD to rule out abnormalities—eg, metastatic cancer, hydrocephalus, or occult chronic subdural hematoma—that could be causing cognitive impairment.^9,10 Clinical features that generally warrant brain imaging include onset of cognitive impairment before age 60; unexplained focal neurologic signs or symptoms; abrupt onset or rapid decline; and/or predisposing conditions, such as cancer or anticoagulant treatment.¹⁰

The role of biomarkers and advanced brain imaging

Biomarkers that might provide confirmation of AD in patients who exhibit early symptoms of dementia have been studied extensively.¹¹ The NIA/AA identified 2 categories of AD biomarkers:

• tests for β-amyloid deposition in the brain, including spinal fluid assays for β-amyloid (Aβ₄₂) and positron emission tomography (PET) scans after intravenous injection of florbetapir or flutemetamol, which bind to amyloid in the brain; and
• tests for neuronal degeneration, which would include spinal fluid assays for tau protein and PET scans after injection of fluorodeoxyglucose (FDG), which shows decreased uptake in patients with AD.⁹

Research reveals the promise of these biomarkers as diagnostic tools, particularly in patients with an atypical presentation of dementia or mild cognitive impairment (MCI) that may be associated with early AD.¹² (More on MCI in a moment.) However, the NIA/AA concluded that additional research is needed to validate these tests for routine diagnostic purposes. Medicare covers PET scans with FDG only for the differential diagnosis of AD vs frontotemporal dementia.¹³

Mild cognitive impairment: How likely that it will progress?

Along with diagnostic criteria for AD, the NIA/AA developed criteria for a symptomatic predementia phase of AD—often referred to as MCI.¹⁴ According to the workgroup, MCI is diagnosed when:

Progression: Less likely than you might think

Patients with MCI are at risk for progression to overt dementia, with an overall annual conversion rate from MCI to dementia estimated at 10% to 15%.^15,16 This estimate must be interpreted with caution, however, because most studies were conducted prior to the 2011 guidelines, when different diagnostic criteria were used. Observers have noted, too, that the numbers largely reflect data collected in specialty clinics and that community-based studies reveal substantially lower conversion rates (3%-6% per year).¹⁶ In addition, evidence suggests that many patients with MCI demonstrate long-term stability or even reversal of deficits.¹⁷

While there is some consideration of the use of biomarkers and amyloid imaging tests to help determine which patients with MCI will progress to AD, practice guidelines do not currently recommend such testing and it is not covered by Medicare.

When evidence indicates an AD diagnosis

When faced with the need to communicate an AD diagnosis, follow the general recommendations for delivering any bad news or discouraging prognosis:

Prioritize and limit the information you provide, determining not only what the patient and family want to hear, but also how much they are able to comprehend.

Confirm that the patient and family understand the information you’ve provided.

Offer emotional support and recommend additional resources¹⁸ (TABLE 2).

Given the progressive cognitive decline that characterizes AD, it is important to address the primary caregiver’s understanding of, and ability to cope with, the disease. It is also important to explore beliefs and attitudes regarding AD. Keep in mind that different cultural groups tend to differ in their beliefs about the nature, cause, and appropriate management of AD, as well as the role of spirituality, help-seeking, and stigma.^19,20

When communicating an Alzheimer's disease diagnosis, prioritize information and offer emotional support. The progressive and ultimately fatal nature of AD also makes planning for the future a priority. Ideally, patients should be engaged in discussions regarding end-of-life care as early as possible, while they are still able to make informed decisions and express their preferences. Discussing end-of-life care can be overwhelming for newly diagnosed patients and their families, however, so it is important that you address issues—medical, financial, and legal planning, for example—that families should be considering.

TABLE 2

Drugs address cognitive and behavioral function

No current treatments
 can cure 
or significantly alter the progression of AD, but 2 classes of medications are used to improve cognitive function. No currently available treatments can cure or significantly alter the progression of AD, but 2 classes of medications are used in an attempt to improve cognitive function. One is cholinesterase inhibitors (ChEIs), which potentiate acetylcholine synaptic transmission. The other is N-methyl-D-aspartate (NMDA) glutamate receptor blockers. Other classes of drugs are sometimes used to treat behavioral symptoms of dementia, such as agitation, aggression, mood disorders, and psychosis (eg, delusions and hallucinations).

Cognitive function. Results from studies of pharmacologic management of MCI vary widely, but recent reviews have found no convincing evidence that either ChEIs or NMDA receptor blockers have an effect on progression from MCI to dementia.^21,22 Neither class is FDA-approved for treating MCI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and often of questionable clinical relevance.²³ Nonetheless, among ChEIs, donepezil is approved by the US Food and Drug Administration (FDA) for mild, moderate, and severe dementia and galantamine and rivastigmine are approved for mild and moderate dementia. There is no evidence that any one ChEI is more effective than any other,²⁴ and the choice of drugs is often guided by cost, adverse effects, and health plan formularies. Memantine, the only FDA-approved NMDA receptor blocker, is approved for moderate to severe dementia and can be used alone or in combination with a ChEI.

In patients with dementia, the effects of ChEIs and NMDA receptor blockers on cognition are statistically significant but modest, and are often of questionable clinical relevance. If these drugs are used in an attempt to improve cognition in AD, guidelines recommend the following approach for initial therapy: Prescribe a ChEI for the mild stage, a ChEI plus memantine for the moderate stage, and memantine (with or without a ChEI) for the severe stage.²⁵ The recommendations also include monitoring every 6 months.

There is no consensus about when to discontinue medication. Various published recommendations call for continuing treatment until the patient has “lost all cognitive and functional abilities;”²² until the patient’s MMSE score falls below 10 and there is no indication that the drug is having a “worthwhile effect;”²¹ or until he or she has reached stage 7 on the Reisberg Functional Assessment Staging scale, indicating nonambulatory status with speech limited to one to 5 words a day.¹⁰

Behavioral function. A variety of drugs are used to treat behavioral symptoms in AD. While not FDA-approved for this use, the most widely prescribed agents are second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone). The main effect of these drugs is often nothing more than sedation, and one large multi­site clinical trial concluded that the adverse effects offset the benefits for patients with AD.²⁶ Indeed, the FDA has issued an advisory on the use of second-generation antipsychotics in AD patients, stating that they are associated with an increased risk of death.²⁷ The recently updated Beers Criteria strongly recommend avoiding these drugs for treating behavioral disturbances in AD unless nonpharmacologic options have failed and the patient is a threat to self or others.²⁸

The FDA has issued an advisory on the use of second-generation antipsychotics in Alzheimer’s patients, stating that they are associated with an increased risk of death. Because of the black-box warning that antipsychotics increase the risk of death, some physicians have advocated obtaining informed consent prior to prescribing such medications.²⁹ At the very least, when family or guardians are involved, a conversation about risks vs benefits should take place and be documented in the medical record.

Other drug classes are also sometimes used in an attempt to improve behavioral function, including anti-seizure medications (valproic acid, carbamazepine), antidepressants (trazodone and selective serotonin reuptake inhibitors), and anxiolytics (benzodiazepines and buspirone). Other than their sedating effects, there is no strong evidence that these drugs are effective for treating dementia-related behavioral disorders. If used, caution is required due to potential adverse effects.

Nonpharmacologic management is “promising”

A recent systematic review of nonpharmacologic interventions for MCI evaluated exercise, training in compensatory strategies, and engagement in cognitively stimulating activities and found “promising but inconclusive” results. The researchers found that studies show mostly positive effects on cognition but have significant methodologic limitations.³⁰ Importantly, there is no evidence of delayed or reduced conversion to dementia.

For patients who already have mild-to-moderate dementia, cognitive stimulation seems to help in the short term.³¹ There is also some evidence that exercise and occupational therapy may slow functional decline,³² but the effects are small to modest and their actual clinical significance (eg, the ability to delay institutionalization) is unclear. There is promising but preliminary evidence that cognitive rehabilitation (helping patients devise strategies to complete daily activities) may improve functioning in everyday life.³³

While behavioral symptoms are often due to the dementia itself, it is important to identify and treat medical and environmental causes that may be contributing, such as infection, pain, and loud or unsafe environments.Interventions such as massage therapy, aromatherapy, exercise, and music therapy may be effective in the short term for agitated behavior. As noted before, nonpharmacologic treatments are generally preferred for behavioral problems and should be considered prior to drug therapy. Approaches that identify and modify both the antecedents and consequences of problem behaviors and increase pleasant events have empirical support for the management of behavioral symptoms.³⁴ Interventions including massage therapy, aromatherapy, exercise, and music therapy may also be effective in the short term for agitated behavior.³⁵

Caregivers should be encouraged to receive training in these strategies through organizations like AA. Caregiver education and support can reduce caregivers’ distress and increase their self-efficacy and coping skills.³⁶

End-of-life care must be addressed

Perhaps the most important aspect of end-of-life care in AD is assuring that families (or health care proxies) understand that AD is a fatal illness, with most patients dying within 4 to 8 years of diagnosis.¹ Evidence indicates that patients whose proxies have a clear recognition of this are less likely to experience “burdensome” interventions such as parenteral therapy, emergency department visits, hospital admissions, and tube feedings in their last 3 months of life.³⁷

Overall, decisions regarding discontinuing medical treatments in advanced AD should be made by balancing the likelihood of benefit with the potential for adverse effects.³⁸The progressive and ultimately fatal nature of Alzheimer's disease makes planning for the future a priority. For example, the American Geriatrics Society recently recommended against feeding tubes because they often result in discomfort due to agitation, use of restraints, and worsening pressure ulcers.³⁹

Unfortunately, only a minority of families receives straightforward information on the course and prognosis of AD, including the fact that patients eventually stop eating and that the natural cause of death is often an acute infection. Studies also show that patients with dementia are at risk for inadequate treatment of pain.⁴⁰ Assuring adequate pain control is an essential component of end-of-life care.

Hospice. End-of-life care can often be improved with hospice care. This service is underused by patients with dementia, even though hospice care is available at no cost through Medicare. Hospice eligibility criteria for patients with AD are shown in
TABLE 3.^41,42

Finally, a word about prevention

Numerous risk factors have been associated with an increased risk of AD (TABLE 4)^2,3. Some, like age and genetics, are nonmodifiable, while others—particularly cardiovascular risk factors—can be modified.¹ There are also factors associated with decreased risk, most notably, physical exercise and participating in cognitively stimulating activities.³ Identification of these factors has led to the hope that addressing them can prevent AD.

But association does not equal causation. In 2010, a report from the National Institutes of Health concluded that, although there are modifiable factors associated with AD, there is insufficient evidence that addressing any of them will actually prevent AD.⁴³ In fact, there is good evidence that some of these factors (eg, statin therapy) are not effective in reducing the incidence of dementia, and that others (eg, vitamin E and estrogen therapy) are potentially harmful.⁴⁴

The absence of empirically supported preventive interventions does not mean, however, that we should disregard these risks and protective factors. Encouraging social engagement, for example, may improve both emotional health and quality of life. Addressing cardiovascular risk factors can reduce the rate of coronary and cerebrovascular disease, potentially including vascular dementia, even if it does not reduce the rate of AD.

Studies are evaluating the use of monoclonal antibodies with anti-amyloid properties for preventing AD in individuals who have APOE ε4 genotypes or high amyloid loads on neuroimaging.⁴⁵ It will be several years before results are available, however, and the outcome of these studies is uncertain as the use of anti-amyloid agents for treating established dementia has not been effective.^46,47

CORRESPONDENCE
Marisa Menchola, PhD, Department of Psychiatry, University of Arizona College of Medicine, 1501 N. Campbell Ave., 7OPC. Tucson, AZ 85724; [email protected]

EVIDENCE SUMMARY

A systematic review and meta-analysis included 29 studies that compared the sensitivity and specificity of nucleic acid amplification tests on specimens collected invasively from the cervix or urethra with noninvasively collected urine specimens.¹ Studies included both asymptomatic and symptomatic patients. Reference standards varied and included cervical culture, enzyme immunoassay, direct fluorescent antibody, ligase chain reaction, and positive results on 2 of 3 nucleic acid amplification assays.

The sensitivity and specificity of chlamydia and gonorrhea detection didn’t differ between urine and cervical specimens. The pooled sensitivity and specificity for polymerase chain reaction urine samples were 83.3% (95% confidence interval [CI], 77.7%-88.9%) and 99.5% (CI, 99.3%-99.8%), respectively, and for cervical samples 85.5% (CI, 80.3%-90.6%) and 99.6% (CI, 99.4%-99.8%), respectively.¹

Pelvic exams detect adnexal masses, but not reliably

A prospective cohort of 127 women undergoing pelvic surgery had preoperative bimanual exams under anesthesia to detect an adnexal mass.² The gold standard for detection was findings at surgery. The woman had a high prevalence (20%) of ovarian masses. Indications for surgery included diagnosis, sterilization, and suspected malignancy.

When the preoperative bimanual examination detected a left adnexal mass, the odds of finding one at surgery increased 2.8 times, whereas when the exam was normal the odds decreased by 0.8 (positive predictive value [PPV]=0.64; 95% CI, 0.45-0.83). Conversely, the preoperative examination failed to correctly predict a right adnexal mass regardless of the result; the likelihood ratio for both normal and abnormal right adnexal examinations was 1 (PPV=0.26; 95% CI, 0.12-0.47).

An investigation of transvaginal ultrasonography (TVUS) from November 1987 to January 1991 screened a cohort of 1300 asymptomatic postmenopausal women for an ovarian tumor.³ To be eligible for the study, subjects had to have been without menses for at least 6 months and have no history of a pelvic tumor. Each woman underwent both a pelvic exam and TVUS.

TVUS found that 33 of the women had abnormal ovarian size and morphology when compared with normal standards. Twenty-seven of the 33, who had abnormalities that persisted longer than 1 month, underwent exploratory laparotomy. Ovarian enlargement also was apparent on clinical examination in 10 patients.

Of the 27 patients who underwent surgery, 2 had primary ovarian carcinomas. Significantly, both women had documented normal pelvic examinations on screening.

Another cohort trial conducted between October 1984 and July 1987 studied 801 women ages 40 to 70 years who were at high risk for ovarian cancer.⁴ Risk factors included nulliparity; symptoms such as abdominal pain, urinary frequency, or irregular bleeding; a personal history of cancer; and a family history of ovarian, breast, or endometrial cancer.

The women underwent both pelvic examination and abdominal ultrasound scanning. Fifty-one patients had abnormal pelvic examinations but normal sonograms. None of the 51 patients, who were followed to the end of the study, developed evidence of ovarian carcinoma. Abnormal abdominal ultrasound scans in 163 patients resulted in 3 diagnoses of malignancy. The 3 patients had normal pelvic examinations.  

A pelvic exam isn’t needed before prescribing hormonal contraception

A 2001 JAMA literature review addressed pelvic exams as a prerequisite for administering hormonal contraceptives.⁵ Investigators identified consensus statements, policy statements, and reviews on the subject and contacted major health associations such as the World Health Organization for their recommendations.

Despite a lack of evidence, these expert sources concluded that a pelvic exam isn’t necessary to identify conditions in which OCPs are contraindicated (pregnancy, breast cancer, hypertension, and thromboembolic disease). Medical history and blood pressure measurement provide adequate screening.

Vulvar disease is uncommon and almost always symptomatic. The United Kingdom national cancer registry found an incidence of 3.7 per 100,000.⁶ A prospective study of 102 women presenting with squamous cell carcinoma of the vulva showed that 94% reported a history of symptomatic vulvar irritation.⁷ Eighty-eight percent had had symptoms for longer than 6 months.

RECOMMENDATIONS

Regarding screening for gonorrhea and chlamydia, the United States Preventive Services Task Force (USPSTF) states that newer tests, including nucleic acid amplification tests of urine, have improved sensitivity and comparable specificity when compared with cervical culture.^8,9

An ACOG committee recommends annual exams, even though it found no evidence to support an annual pelvic exam for asymptomatic, low-risk patients. The USPSTF recommends against screening for ovarian cancer in general, (Grade D recommendation: no net benefit or the harms outweigh the benefits). The Task Force states that the sensitivity of pelvic examination in detecting ovarian cancer is unknown based on several ultrasound studies.¹⁰

A 2012 ACOG committee opinion recommends that an annual pelvic examination remain a part of the well-woman visit even though the committee found no evidence in support of an annual exam for asymptomatic, low-risk patients.¹¹ The committee notes that patients and providers should discuss the decision to perform a pelvic exam annually.

EVIDENCE SUMMARY

A systematic review and meta-analysis included 29 studies that compared the sensitivity and specificity of nucleic acid amplification tests on specimens collected invasively from the cervix or urethra with noninvasively collected urine specimens.¹ Studies included both asymptomatic and symptomatic patients. Reference standards varied and included cervical culture, enzyme immunoassay, direct fluorescent antibody, ligase chain reaction, and positive results on 2 of 3 nucleic acid amplification assays.

The sensitivity and specificity of chlamydia and gonorrhea detection didn’t differ between urine and cervical specimens. The pooled sensitivity and specificity for polymerase chain reaction urine samples were 83.3% (95% confidence interval [CI], 77.7%-88.9%) and 99.5% (CI, 99.3%-99.8%), respectively, and for cervical samples 85.5% (CI, 80.3%-90.6%) and 99.6% (CI, 99.4%-99.8%), respectively.¹

Pelvic exams detect adnexal masses, but not reliably

A prospective cohort of 127 women undergoing pelvic surgery had preoperative bimanual exams under anesthesia to detect an adnexal mass.² The gold standard for detection was findings at surgery. The woman had a high prevalence (20%) of ovarian masses. Indications for surgery included diagnosis, sterilization, and suspected malignancy.

When the preoperative bimanual examination detected a left adnexal mass, the odds of finding one at surgery increased 2.8 times, whereas when the exam was normal the odds decreased by 0.8 (positive predictive value [PPV]=0.64; 95% CI, 0.45-0.83). Conversely, the preoperative examination failed to correctly predict a right adnexal mass regardless of the result; the likelihood ratio for both normal and abnormal right adnexal examinations was 1 (PPV=0.26; 95% CI, 0.12-0.47).

An investigation of transvaginal ultrasonography (TVUS) from November 1987 to January 1991 screened a cohort of 1300 asymptomatic postmenopausal women for an ovarian tumor.³ To be eligible for the study, subjects had to have been without menses for at least 6 months and have no history of a pelvic tumor. Each woman underwent both a pelvic exam and TVUS.

TVUS found that 33 of the women had abnormal ovarian size and morphology when compared with normal standards. Twenty-seven of the 33, who had abnormalities that persisted longer than 1 month, underwent exploratory laparotomy. Ovarian enlargement also was apparent on clinical examination in 10 patients.

Of the 27 patients who underwent surgery, 2 had primary ovarian carcinomas. Significantly, both women had documented normal pelvic examinations on screening.

Another cohort trial conducted between October 1984 and July 1987 studied 801 women ages 40 to 70 years who were at high risk for ovarian cancer.⁴ Risk factors included nulliparity; symptoms such as abdominal pain, urinary frequency, or irregular bleeding; a personal history of cancer; and a family history of ovarian, breast, or endometrial cancer.

The women underwent both pelvic examination and abdominal ultrasound scanning. Fifty-one patients had abnormal pelvic examinations but normal sonograms. None of the 51 patients, who were followed to the end of the study, developed evidence of ovarian carcinoma. Abnormal abdominal ultrasound scans in 163 patients resulted in 3 diagnoses of malignancy. The 3 patients had normal pelvic examinations.  

A pelvic exam isn’t needed before prescribing hormonal contraception

A 2001 JAMA literature review addressed pelvic exams as a prerequisite for administering hormonal contraceptives.⁵ Investigators identified consensus statements, policy statements, and reviews on the subject and contacted major health associations such as the World Health Organization for their recommendations.

Despite a lack of evidence, these expert sources concluded that a pelvic exam isn’t necessary to identify conditions in which OCPs are contraindicated (pregnancy, breast cancer, hypertension, and thromboembolic disease). Medical history and blood pressure measurement provide adequate screening.

Vulvar disease is uncommon and almost always symptomatic. The United Kingdom national cancer registry found an incidence of 3.7 per 100,000.⁶ A prospective study of 102 women presenting with squamous cell carcinoma of the vulva showed that 94% reported a history of symptomatic vulvar irritation.⁷ Eighty-eight percent had had symptoms for longer than 6 months.

RECOMMENDATIONS

Regarding screening for gonorrhea and chlamydia, the United States Preventive Services Task Force (USPSTF) states that newer tests, including nucleic acid amplification tests of urine, have improved sensitivity and comparable specificity when compared with cervical culture.^8,9

An ACOG committee recommends annual exams, even though it found no evidence to support an annual pelvic exam for asymptomatic, low-risk patients. The USPSTF recommends against screening for ovarian cancer in general, (Grade D recommendation: no net benefit or the harms outweigh the benefits). The Task Force states that the sensitivity of pelvic examination in detecting ovarian cancer is unknown based on several ultrasound studies.¹⁰

A 2012 ACOG committee opinion recommends that an annual pelvic examination remain a part of the well-woman visit even though the committee found no evidence in support of an annual exam for asymptomatic, low-risk patients.¹¹ The committee notes that patients and providers should discuss the decision to perform a pelvic exam annually.

EVIDENCE SUMMARY

A systematic review and meta-analysis included 29 studies that compared the sensitivity and specificity of nucleic acid amplification tests on specimens collected invasively from the cervix or urethra with noninvasively collected urine specimens.¹ Studies included both asymptomatic and symptomatic patients. Reference standards varied and included cervical culture, enzyme immunoassay, direct fluorescent antibody, ligase chain reaction, and positive results on 2 of 3 nucleic acid amplification assays.

The sensitivity and specificity of chlamydia and gonorrhea detection didn’t differ between urine and cervical specimens. The pooled sensitivity and specificity for polymerase chain reaction urine samples were 83.3% (95% confidence interval [CI], 77.7%-88.9%) and 99.5% (CI, 99.3%-99.8%), respectively, and for cervical samples 85.5% (CI, 80.3%-90.6%) and 99.6% (CI, 99.4%-99.8%), respectively.¹

Pelvic exams detect adnexal masses, but not reliably

A prospective cohort of 127 women undergoing pelvic surgery had preoperative bimanual exams under anesthesia to detect an adnexal mass.² The gold standard for detection was findings at surgery. The woman had a high prevalence (20%) of ovarian masses. Indications for surgery included diagnosis, sterilization, and suspected malignancy.

When the preoperative bimanual examination detected a left adnexal mass, the odds of finding one at surgery increased 2.8 times, whereas when the exam was normal the odds decreased by 0.8 (positive predictive value [PPV]=0.64; 95% CI, 0.45-0.83). Conversely, the preoperative examination failed to correctly predict a right adnexal mass regardless of the result; the likelihood ratio for both normal and abnormal right adnexal examinations was 1 (PPV=0.26; 95% CI, 0.12-0.47).

An investigation of transvaginal ultrasonography (TVUS) from November 1987 to January 1991 screened a cohort of 1300 asymptomatic postmenopausal women for an ovarian tumor.³ To be eligible for the study, subjects had to have been without menses for at least 6 months and have no history of a pelvic tumor. Each woman underwent both a pelvic exam and TVUS.

TVUS found that 33 of the women had abnormal ovarian size and morphology when compared with normal standards. Twenty-seven of the 33, who had abnormalities that persisted longer than 1 month, underwent exploratory laparotomy. Ovarian enlargement also was apparent on clinical examination in 10 patients.

Of the 27 patients who underwent surgery, 2 had primary ovarian carcinomas. Significantly, both women had documented normal pelvic examinations on screening.

Another cohort trial conducted between October 1984 and July 1987 studied 801 women ages 40 to 70 years who were at high risk for ovarian cancer.⁴ Risk factors included nulliparity; symptoms such as abdominal pain, urinary frequency, or irregular bleeding; a personal history of cancer; and a family history of ovarian, breast, or endometrial cancer.

The women underwent both pelvic examination and abdominal ultrasound scanning. Fifty-one patients had abnormal pelvic examinations but normal sonograms. None of the 51 patients, who were followed to the end of the study, developed evidence of ovarian carcinoma. Abnormal abdominal ultrasound scans in 163 patients resulted in 3 diagnoses of malignancy. The 3 patients had normal pelvic examinations.  

A pelvic exam isn’t needed before prescribing hormonal contraception

A 2001 JAMA literature review addressed pelvic exams as a prerequisite for administering hormonal contraceptives.⁵ Investigators identified consensus statements, policy statements, and reviews on the subject and contacted major health associations such as the World Health Organization for their recommendations.

Despite a lack of evidence, these expert sources concluded that a pelvic exam isn’t necessary to identify conditions in which OCPs are contraindicated (pregnancy, breast cancer, hypertension, and thromboembolic disease). Medical history and blood pressure measurement provide adequate screening.

Vulvar disease is uncommon and almost always symptomatic. The United Kingdom national cancer registry found an incidence of 3.7 per 100,000.⁶ A prospective study of 102 women presenting with squamous cell carcinoma of the vulva showed that 94% reported a history of symptomatic vulvar irritation.⁷ Eighty-eight percent had had symptoms for longer than 6 months.

RECOMMENDATIONS

Regarding screening for gonorrhea and chlamydia, the United States Preventive Services Task Force (USPSTF) states that newer tests, including nucleic acid amplification tests of urine, have improved sensitivity and comparable specificity when compared with cervical culture.^8,9

An ACOG committee recommends annual exams, even though it found no evidence to support an annual pelvic exam for asymptomatic, low-risk patients. The USPSTF recommends against screening for ovarian cancer in general, (Grade D recommendation: no net benefit or the harms outweigh the benefits). The Task Force states that the sensitivity of pelvic examination in detecting ovarian cancer is unknown based on several ultrasound studies.¹⁰

A 2012 ACOG committee opinion recommends that an annual pelvic examination remain a part of the well-woman visit even though the committee found no evidence in support of an annual exam for asymptomatic, low-risk patients.¹¹ The committee notes that patients and providers should discuss the decision to perform a pelvic exam annually.