New, changing technologies are being incorporated into every aspect of medical care and education, and the impact cannot be overstated. While the ultimate qualitative impact (beneficial, intrusive, efficient, obstructive, or neutral) of specific individual implementations remains to be seen, there is no doubt that the faces of patient care and the financial management of healthcare delivery have been forever altered.

The amount of information now literally at our fingertips is overwhelming. Some of my patients bring the latest from www.clinicaltrials.gov to their appointments. One patient recently brought downloaded online testimony from patients who were being given an oil supplement to treat disorders including gout, neuropathy, carpal tunnel, sinusitis, headache, and postop hip and knee pain and wanted to know why I hadn’t suggested it for her. Accessing the information pipeline is like drinking from a firehose, and there is no perfect valve that can adjust the flow to every thirst.

Lest we think that only patients use sites of variable reliability in getting their online medical information, in a recent survey by Kantar Media, when 508 physicians were asked which of 49 sites they looked at most often, Wikipedia came in at number 3 (UpToDate was number 1 and Cleveland Clinic Journal of Medicine was number 25). But when asked to rate the 49 sites for “quality clinical content,” responders listed Wikipedia as 47 (UpToDate was still number 1 and CCJM was number 6).

We healthcare providers can assess the accuracy and quality of clinical content. But it is not always easy, especially when trying to access, digest, and utilize information within the real-time constraints of an office visit or inpatient consultation. The now almost universal use of electronic medical records (EMRs) in major health systems provides access to true point-of-care information to assist in clinical decision-making, but how we filter and channel this information and apply it to the patient sitting in the exam room is not always straightforward. It is naïve to think that one source can fit all of our information needs.

A “smart” EMR can reflexively direct me to diagnosis-linked clinical guidelines or care paths. But without knowing the specifics of how the guidelines were written, I can’t know if they are ideally applicable to the patient in front of me. Guidelines based solely on clinical trial data may not be ideal for a given patient due to constraints of the clinical trial design and the tested clinical populations. There are times in areas outside my clinical field that I seek clinically nuanced expertise in interpreting clinical trials rather than the actual clinical trial data. Other times, when approaching problems within my own expertise, I want to see the raw data to reach a conclusion on its applicability and likely magnitude of effect in a specific patient. Using a trusted source of predigested, summarized data (as opposed to the raw data), knowing whether an author has a relationship with a specific company, and knowing that the clinical trials of a specific therapy are not intrinsically bad or good—all of these contribute to contextual decisions that lead to my clinical recommendations. I always want to know the nature of authors’ commercial relationships, as well as the track record of my information sources.

It is in this context that the paper by Andrews et al in this issue of the Journal addresses in a very practical way some of the nuances in using several popular point-of-care information resources. This is the second of 2 papers that these authors have contributed to the CCJM in an effort to inform and direct us how to quench our thirst for information without getting bloated.

New, changing technologies are being incorporated into every aspect of medical care and education, and the impact cannot be overstated. While the ultimate qualitative impact (beneficial, intrusive, efficient, obstructive, or neutral) of specific individual implementations remains to be seen, there is no doubt that the faces of patient care and the financial management of healthcare delivery have been forever altered.

The amount of information now literally at our fingertips is overwhelming. Some of my patients bring the latest from www.clinicaltrials.gov to their appointments. One patient recently brought downloaded online testimony from patients who were being given an oil supplement to treat disorders including gout, neuropathy, carpal tunnel, sinusitis, headache, and postop hip and knee pain and wanted to know why I hadn’t suggested it for her. Accessing the information pipeline is like drinking from a firehose, and there is no perfect valve that can adjust the flow to every thirst.

Lest we think that only patients use sites of variable reliability in getting their online medical information, in a recent survey by Kantar Media, when 508 physicians were asked which of 49 sites they looked at most often, Wikipedia came in at number 3 (UpToDate was number 1 and Cleveland Clinic Journal of Medicine was number 25). But when asked to rate the 49 sites for “quality clinical content,” responders listed Wikipedia as 47 (UpToDate was still number 1 and CCJM was number 6).

We healthcare providers can assess the accuracy and quality of clinical content. But it is not always easy, especially when trying to access, digest, and utilize information within the real-time constraints of an office visit or inpatient consultation. The now almost universal use of electronic medical records (EMRs) in major health systems provides access to true point-of-care information to assist in clinical decision-making, but how we filter and channel this information and apply it to the patient sitting in the exam room is not always straightforward. It is naïve to think that one source can fit all of our information needs.

A “smart” EMR can reflexively direct me to diagnosis-linked clinical guidelines or care paths. But without knowing the specifics of how the guidelines were written, I can’t know if they are ideally applicable to the patient in front of me. Guidelines based solely on clinical trial data may not be ideal for a given patient due to constraints of the clinical trial design and the tested clinical populations. There are times in areas outside my clinical field that I seek clinically nuanced expertise in interpreting clinical trials rather than the actual clinical trial data. Other times, when approaching problems within my own expertise, I want to see the raw data to reach a conclusion on its applicability and likely magnitude of effect in a specific patient. Using a trusted source of predigested, summarized data (as opposed to the raw data), knowing whether an author has a relationship with a specific company, and knowing that the clinical trials of a specific therapy are not intrinsically bad or good—all of these contribute to contextual decisions that lead to my clinical recommendations. I always want to know the nature of authors’ commercial relationships, as well as the track record of my information sources.

It is in this context that the paper by Andrews et al in this issue of the Journal addresses in a very practical way some of the nuances in using several popular point-of-care information resources. This is the second of 2 papers that these authors have contributed to the CCJM in an effort to inform and direct us how to quench our thirst for information without getting bloated.

New, changing technologies are being incorporated into every aspect of medical care and education, and the impact cannot be overstated. While the ultimate qualitative impact (beneficial, intrusive, efficient, obstructive, or neutral) of specific individual implementations remains to be seen, there is no doubt that the faces of patient care and the financial management of healthcare delivery have been forever altered.

The amount of information now literally at our fingertips is overwhelming. Some of my patients bring the latest from www.clinicaltrials.gov to their appointments. One patient recently brought downloaded online testimony from patients who were being given an oil supplement to treat disorders including gout, neuropathy, carpal tunnel, sinusitis, headache, and postop hip and knee pain and wanted to know why I hadn’t suggested it for her. Accessing the information pipeline is like drinking from a firehose, and there is no perfect valve that can adjust the flow to every thirst.

Lest we think that only patients use sites of variable reliability in getting their online medical information, in a recent survey by Kantar Media, when 508 physicians were asked which of 49 sites they looked at most often, Wikipedia came in at number 3 (UpToDate was number 1 and Cleveland Clinic Journal of Medicine was number 25). But when asked to rate the 49 sites for “quality clinical content,” responders listed Wikipedia as 47 (UpToDate was still number 1 and CCJM was number 6).

We healthcare providers can assess the accuracy and quality of clinical content. But it is not always easy, especially when trying to access, digest, and utilize information within the real-time constraints of an office visit or inpatient consultation. The now almost universal use of electronic medical records (EMRs) in major health systems provides access to true point-of-care information to assist in clinical decision-making, but how we filter and channel this information and apply it to the patient sitting in the exam room is not always straightforward. It is naïve to think that one source can fit all of our information needs.

A “smart” EMR can reflexively direct me to diagnosis-linked clinical guidelines or care paths. But without knowing the specifics of how the guidelines were written, I can’t know if they are ideally applicable to the patient in front of me. Guidelines based solely on clinical trial data may not be ideal for a given patient due to constraints of the clinical trial design and the tested clinical populations. There are times in areas outside my clinical field that I seek clinically nuanced expertise in interpreting clinical trials rather than the actual clinical trial data. Other times, when approaching problems within my own expertise, I want to see the raw data to reach a conclusion on its applicability and likely magnitude of effect in a specific patient. Using a trusted source of predigested, summarized data (as opposed to the raw data), knowing whether an author has a relationship with a specific company, and knowing that the clinical trials of a specific therapy are not intrinsically bad or good—all of these contribute to contextual decisions that lead to my clinical recommendations. I always want to know the nature of authors’ commercial relationships, as well as the track record of my information sources.

It is in this context that the paper by Andrews et al in this issue of the Journal addresses in a very practical way some of the nuances in using several popular point-of-care information resources. This is the second of 2 papers that these authors have contributed to the CCJM in an effort to inform and direct us how to quench our thirst for information without getting bloated.

To the Editor: We read with great interest the article by Drs. Cawcutt and Wilson on caring for international patients.¹ They provide an overview of the challenges of delivering medical care for these patients (eg, cultural differences) and the likely benefits from such interactions (eg, gaining cultural knowledge). Having practiced medicine in 3 different continents and experienced working in various medical centers caring for international patients, we would like to offer a slightly different viewpoint.

First, gaining cultural knowledge should be regarded as a prerequisite for healthcare workers involved in the care of international patients, rather than the expected benefit and consequence of such encounters. Healthcare workers with some knowledge of an international patient’s culture are best able to serve that patient.² Indeed, unless knowledge of cultural differences is obtained before such interactions, there is a significant risk of stereotyping by amplifying the sense of “otherness,” which is unfortunately too often mistaken for cultural sensitivity. The perception of the stereotypes and prejudices during the second stage of cultural adaptation (ie, irritation, hostility) often stems from the host’s lack of cultural knowledge. Table 1 of their article clearly reflects such risk: the authors have tried to exemplify the concepts they discussed through a number of real-life scenarios. But indeed some of those cases (eg, the man from Saudi Arabia) could be interpreted more as examples of stereotyping than cultural sensitivity.

Second, the authors do not mention requests by family members of international patients for nondisclosure of serious medical diagnoses, one we have frequently received from family members from different cultural backgrounds. These requests represent another challenge of caring for these patients as they counter our obligation for full disclosure and the patients’ right to know in order to be able to make informed decisions regarding their medical care.³

To the Editor: We read with great interest the article by Drs. Cawcutt and Wilson on caring for international patients.¹ They provide an overview of the challenges of delivering medical care for these patients (eg, cultural differences) and the likely benefits from such interactions (eg, gaining cultural knowledge). Having practiced medicine in 3 different continents and experienced working in various medical centers caring for international patients, we would like to offer a slightly different viewpoint.

First, gaining cultural knowledge should be regarded as a prerequisite for healthcare workers involved in the care of international patients, rather than the expected benefit and consequence of such encounters. Healthcare workers with some knowledge of an international patient’s culture are best able to serve that patient.² Indeed, unless knowledge of cultural differences is obtained before such interactions, there is a significant risk of stereotyping by amplifying the sense of “otherness,” which is unfortunately too often mistaken for cultural sensitivity. The perception of the stereotypes and prejudices during the second stage of cultural adaptation (ie, irritation, hostility) often stems from the host’s lack of cultural knowledge. Table 1 of their article clearly reflects such risk: the authors have tried to exemplify the concepts they discussed through a number of real-life scenarios. But indeed some of those cases (eg, the man from Saudi Arabia) could be interpreted more as examples of stereotyping than cultural sensitivity.

Second, the authors do not mention requests by family members of international patients for nondisclosure of serious medical diagnoses, one we have frequently received from family members from different cultural backgrounds. These requests represent another challenge of caring for these patients as they counter our obligation for full disclosure and the patients’ right to know in order to be able to make informed decisions regarding their medical care.³

To the Editor: We read with great interest the article by Drs. Cawcutt and Wilson on caring for international patients.¹ They provide an overview of the challenges of delivering medical care for these patients (eg, cultural differences) and the likely benefits from such interactions (eg, gaining cultural knowledge). Having practiced medicine in 3 different continents and experienced working in various medical centers caring for international patients, we would like to offer a slightly different viewpoint.

First, gaining cultural knowledge should be regarded as a prerequisite for healthcare workers involved in the care of international patients, rather than the expected benefit and consequence of such encounters. Healthcare workers with some knowledge of an international patient’s culture are best able to serve that patient.² Indeed, unless knowledge of cultural differences is obtained before such interactions, there is a significant risk of stereotyping by amplifying the sense of “otherness,” which is unfortunately too often mistaken for cultural sensitivity. The perception of the stereotypes and prejudices during the second stage of cultural adaptation (ie, irritation, hostility) often stems from the host’s lack of cultural knowledge. Table 1 of their article clearly reflects such risk: the authors have tried to exemplify the concepts they discussed through a number of real-life scenarios. But indeed some of those cases (eg, the man from Saudi Arabia) could be interpreted more as examples of stereotyping than cultural sensitivity.

Second, the authors do not mention requests by family members of international patients for nondisclosure of serious medical diagnoses, one we have frequently received from family members from different cultural backgrounds. These requests represent another challenge of caring for these patients as they counter our obligation for full disclosure and the patients’ right to know in order to be able to make informed decisions regarding their medical care.³

In Reply: We appreciate the comments, and we fully agree about the dangers of blurring sensitivity and stereotyping in medicine. We also recognize that health providers working around the world have distinct backgrounds and unique perspectives, which serve to enrich the discussion.

We agree that gaining cultural knowledge should be a prerequisite for healthcare workers. However, healthcare providers may not uniformly have the opportunity, time, or resources for this training. Additionally, providers working in large group practices including referral and academic medical centers often do not have control over scheduling of patient appointments. Therefore, rather than prohibiting the evaluations of international patients, we advocate for the utilization of a few guiding and common principles to optimize a mutually beneficial patient care experience. Despite inherent inadequacies and potential prejudices, healthcare providers do learn through patient encounters. Within this learning environment, mistakes will be made, but there are also opportunities for further self-improvement.

We agree there is a fine line between sensitivity and stereotyping, along with common misunderstandings regarding patient labeling. Identifying the geographic homeland of a patient could be misconstrued as intent to stereotype patients. However, numerous infectious diseases and many noncommunicable syndromes are disproportionately represented within select countries. Thus, we feel the identification of a patient’s homeland along with ethnicity, age, gender, and pertinent socioeconomic details can be done respectfully and remain an important collective part of the active medical history and serve to optimize care for each patient. Within medical education, we often find ourselves generalizing patient presentations and symptom profiles. 

Yet we must recognize that the generalized concepts cannot apply to everyone. Medicine remains a profession of humility—both in our willingness to consider additional diagnoses and in our openness to care for patients of different backgrounds. With this humility, we hope to avoid the pitfalls of patient stereotyping, misjudgments, and misunderstandings.

Finally, the nondisclosure of serious medical diagnoses at the request of family members can be a tricky issue. It can be most difficult to balance unique wishes of a family with the ethics of accurate patient communication and compliance with legal statutes and medical center policies. We advocate a team approach with family members of international patients as a way to avoid breaches in medical ethics or breaks in mutual family trust. 

In Reply: We appreciate the comments, and we fully agree about the dangers of blurring sensitivity and stereotyping in medicine. We also recognize that health providers working around the world have distinct backgrounds and unique perspectives, which serve to enrich the discussion.

We agree that gaining cultural knowledge should be a prerequisite for healthcare workers. However, healthcare providers may not uniformly have the opportunity, time, or resources for this training. Additionally, providers working in large group practices including referral and academic medical centers often do not have control over scheduling of patient appointments. Therefore, rather than prohibiting the evaluations of international patients, we advocate for the utilization of a few guiding and common principles to optimize a mutually beneficial patient care experience. Despite inherent inadequacies and potential prejudices, healthcare providers do learn through patient encounters. Within this learning environment, mistakes will be made, but there are also opportunities for further self-improvement.

We agree there is a fine line between sensitivity and stereotyping, along with common misunderstandings regarding patient labeling. Identifying the geographic homeland of a patient could be misconstrued as intent to stereotype patients. However, numerous infectious diseases and many noncommunicable syndromes are disproportionately represented within select countries. Thus, we feel the identification of a patient’s homeland along with ethnicity, age, gender, and pertinent socioeconomic details can be done respectfully and remain an important collective part of the active medical history and serve to optimize care for each patient. Within medical education, we often find ourselves generalizing patient presentations and symptom profiles. 

Yet we must recognize that the generalized concepts cannot apply to everyone. Medicine remains a profession of humility—both in our willingness to consider additional diagnoses and in our openness to care for patients of different backgrounds. With this humility, we hope to avoid the pitfalls of patient stereotyping, misjudgments, and misunderstandings.

Finally, the nondisclosure of serious medical diagnoses at the request of family members can be a tricky issue. It can be most difficult to balance unique wishes of a family with the ethics of accurate patient communication and compliance with legal statutes and medical center policies. We advocate a team approach with family members of international patients as a way to avoid breaches in medical ethics or breaks in mutual family trust. 

In Reply: We appreciate the comments, and we fully agree about the dangers of blurring sensitivity and stereotyping in medicine. We also recognize that health providers working around the world have distinct backgrounds and unique perspectives, which serve to enrich the discussion.

We agree that gaining cultural knowledge should be a prerequisite for healthcare workers. However, healthcare providers may not uniformly have the opportunity, time, or resources for this training. Additionally, providers working in large group practices including referral and academic medical centers often do not have control over scheduling of patient appointments. Therefore, rather than prohibiting the evaluations of international patients, we advocate for the utilization of a few guiding and common principles to optimize a mutually beneficial patient care experience. Despite inherent inadequacies and potential prejudices, healthcare providers do learn through patient encounters. Within this learning environment, mistakes will be made, but there are also opportunities for further self-improvement.

We agree there is a fine line between sensitivity and stereotyping, along with common misunderstandings regarding patient labeling. Identifying the geographic homeland of a patient could be misconstrued as intent to stereotype patients. However, numerous infectious diseases and many noncommunicable syndromes are disproportionately represented within select countries. Thus, we feel the identification of a patient’s homeland along with ethnicity, age, gender, and pertinent socioeconomic details can be done respectfully and remain an important collective part of the active medical history and serve to optimize care for each patient. Within medical education, we often find ourselves generalizing patient presentations and symptom profiles. 

Yet we must recognize that the generalized concepts cannot apply to everyone. Medicine remains a profession of humility—both in our willingness to consider additional diagnoses and in our openness to care for patients of different backgrounds. With this humility, we hope to avoid the pitfalls of patient stereotyping, misjudgments, and misunderstandings.

Finally, the nondisclosure of serious medical diagnoses at the request of family members can be a tricky issue. It can be most difficult to balance unique wishes of a family with the ethics of accurate patient communication and compliance with legal statutes and medical center policies. We advocate a team approach with family members of international patients as a way to avoid breaches in medical ethics or breaks in mutual family trust. 

To the Editor: In their article “A patient with altered mental status and an acid-base disturbance,”¹ Drs. Shylaja Mani and Gregory W. Rutecki state that 5-oxoproline or pyroglutamic acidosis is associated with an elevated osmol gap. This is not the case. The cited reference by Tan et al² describes a patient who most likely had ketoacidosis, perhaps complicated by isopropyl alcohol ingestion.

Those disorders can certainly generate an osmol gap. Although pyroglutamic acidosis was mentioned in the differential diagnosis of that case, that condition was never documented. The accumulation of 5-oxoproline or pyroglutamic acid should not elevate the serum osmolality or generate an osmol gap.

To the Editor: In their article “A patient with altered mental status and an acid-base disturbance,”¹ Drs. Shylaja Mani and Gregory W. Rutecki state that 5-oxoproline or pyroglutamic acidosis is associated with an elevated osmol gap. This is not the case. The cited reference by Tan et al² describes a patient who most likely had ketoacidosis, perhaps complicated by isopropyl alcohol ingestion.

Those disorders can certainly generate an osmol gap. Although pyroglutamic acidosis was mentioned in the differential diagnosis of that case, that condition was never documented. The accumulation of 5-oxoproline or pyroglutamic acid should not elevate the serum osmolality or generate an osmol gap.

To the Editor: In their article “A patient with altered mental status and an acid-base disturbance,”¹ Drs. Shylaja Mani and Gregory W. Rutecki state that 5-oxoproline or pyroglutamic acidosis is associated with an elevated osmol gap. This is not the case. The cited reference by Tan et al² describes a patient who most likely had ketoacidosis, perhaps complicated by isopropyl alcohol ingestion.

Those disorders can certainly generate an osmol gap. Although pyroglutamic acidosis was mentioned in the differential diagnosis of that case, that condition was never documented. The accumulation of 5-oxoproline or pyroglutamic acid should not elevate the serum osmolality or generate an osmol gap.

In Reply: We thank Dr. Emmett for his insightful comment. He is correct that in the case reported by Tan et al the elevated osmol gap was not a direct result of the patient’s presumed acetaminophen ingestion but more likely another unidentified toxic ingestion. The online version of our article has been modified accordingly (also see page 214 of this issue).

In Reply: We thank Dr. Emmett for his insightful comment. He is correct that in the case reported by Tan et al the elevated osmol gap was not a direct result of the patient’s presumed acetaminophen ingestion but more likely another unidentified toxic ingestion. The online version of our article has been modified accordingly (also see page 214 of this issue).

In Reply: We thank Dr. Emmett for his insightful comment. He is correct that in the case reported by Tan et al the elevated osmol gap was not a direct result of the patient’s presumed acetaminophen ingestion but more likely another unidentified toxic ingestion. The online version of our article has been modified accordingly (also see page 214 of this issue).

In the article “A patient with altered mental status and an acid-base disturbance” (Mani S, Rutecki GW, Cleve Clin J Med 2017; 84:27–34), 2 errors occurred in Table 2. The corrected table appears with corrections shown in red:

In addition, two sentences in the text regarding the osmol gap should be revised as follows:

On page 31, the last 3 lines should read as follows: “When the anion gap metabolic acidosis is multifactorial, as it was suspected to be in a case reported by Tan et al,²³ the osmol gap may be elevated as a consequence of additional toxic ingestions, as it was in the reported patient.”

And on page 33, the last sentence should read as follows: “As reflected in the revisions to MUD PILES and in the newer GOLD MARK acronym, the osmol gap has become more valuable in differential diagnosis of metabolic acidosis with an elevated anion gap consequent to an expanding array of toxic ingestions (methanol, propylene glycol, ethylene glycol, and diethylene glycol), which may accompany pyroglutamic acid-oxoproline.”

In the article “A patient with altered mental status and an acid-base disturbance” (Mani S, Rutecki GW, Cleve Clin J Med 2017; 84:27–34), 2 errors occurred in Table 2. The corrected table appears with corrections shown in red:

In addition, two sentences in the text regarding the osmol gap should be revised as follows:

On page 31, the last 3 lines should read as follows: “When the anion gap metabolic acidosis is multifactorial, as it was suspected to be in a case reported by Tan et al,²³ the osmol gap may be elevated as a consequence of additional toxic ingestions, as it was in the reported patient.”

And on page 33, the last sentence should read as follows: “As reflected in the revisions to MUD PILES and in the newer GOLD MARK acronym, the osmol gap has become more valuable in differential diagnosis of metabolic acidosis with an elevated anion gap consequent to an expanding array of toxic ingestions (methanol, propylene glycol, ethylene glycol, and diethylene glycol), which may accompany pyroglutamic acid-oxoproline.”

In the article “A patient with altered mental status and an acid-base disturbance” (Mani S, Rutecki GW, Cleve Clin J Med 2017; 84:27–34), 2 errors occurred in Table 2. The corrected table appears with corrections shown in red:

In addition, two sentences in the text regarding the osmol gap should be revised as follows:

On page 31, the last 3 lines should read as follows: “When the anion gap metabolic acidosis is multifactorial, as it was suspected to be in a case reported by Tan et al,²³ the osmol gap may be elevated as a consequence of additional toxic ingestions, as it was in the reported patient.”

And on page 33, the last sentence should read as follows: “As reflected in the revisions to MUD PILES and in the newer GOLD MARK acronym, the osmol gap has become more valuable in differential diagnosis of metabolic acidosis with an elevated anion gap consequent to an expanding array of toxic ingestions (methanol, propylene glycol, ethylene glycol, and diethylene glycol), which may accompany pyroglutamic acid-oxoproline.”

In the article, “Cardiopulmonary exercise testing: A contemporary and versatile clinical tool” (Leclerc K, Cleve Clin J Med 2017; 84:161–168), an error occurred in Table 1. Heart rate reserve was defined as maximum heart rate minus resting heart rate. It should be defined as (maximum heart rate minus resting heart rate) divided by (predicted maximum heart rate minus resting heart rate).

In the article, “Cardiopulmonary exercise testing: A contemporary and versatile clinical tool” (Leclerc K, Cleve Clin J Med 2017; 84:161–168), an error occurred in Table 1. Heart rate reserve was defined as maximum heart rate minus resting heart rate. It should be defined as (maximum heart rate minus resting heart rate) divided by (predicted maximum heart rate minus resting heart rate).

In the article, “Cardiopulmonary exercise testing: A contemporary and versatile clinical tool” (Leclerc K, Cleve Clin J Med 2017; 84:161–168), an error occurred in Table 1. Heart rate reserve was defined as maximum heart rate minus resting heart rate. It should be defined as (maximum heart rate minus resting heart rate) divided by (predicted maximum heart rate minus resting heart rate).

Flexibility and choice were key themes in the health care reform vision President Trump outlined in his first speech to a joint session of Congress on Feb. 28.

Specifically, Americans should be able to “purchase their own coverage through the use of tax credits and expanded health savings accounts, but it must be the plan they want, not the plan forced on them by our government,” Mr. Trump said. They also should be able to purchase insurance across state lines, which “will create a truly competitive national marketplace that will bring costs way down and provide far better care.”

Courtesy whitehouse.gov

Finally, Mr. Trump called for “legal reforms that protect patients and doctors from unnecessary costs that drive up the price of insurance and work to bring down the artificially high price of drugs and bring them down immediately,” he said, adding that the Food and Drug Administration needs to slash the time to approval for drugs and other medical treatments.

Some of these concepts were mirrored in a talking-points memo from the House Republican leadership earlier in February.

According to the memo, Republican efforts to repeal and replace the ACA will focus on the following areas:

• Repealing the ACA’s Medicaid expansion and allowing states to choose between block grands or per capita grants for Medicaid funding. States could choose to use those grants and per capita grants to keep expansion.

• Rebranding high-risk pools as “state innovation grants” to provide states with flexibility to design coverage that meets the needs of their populations. States could use the innovation grants to reduce patient out-of-pocket costs, lower the cost of providing care, stabilize the individual and small-group markets, provide access to preventive care, and promote participation in private health care plans.

• Promoting health savings accounts tied to high-deductible plans through increasing maximum contribution limits and other administrative fixes to allow for greater flexibility in their use.

• Replacing ACA premium subsides with refundable flat tax credits. Credit would be age-based, with younger recipients receiving smaller credits and older taxpayers being eligible for more. Tax credits would be available to those who are not eligible to receive coverage through other sources, such as an employer or government program.

Many of these provisions were included in a health reform plan known as A Better Way, which was announced in June 2016 by House Speaker Paul Ryan (R-Wis.).

Like Mr. Trump’s outline to Congress, the GOP talking-points memo was light on specifics, including how the bill will be paid for, how much money will be distributed to states for Medicaid, and how these provisions would alter current insurance coverage rates, which government actuaries project would reach 91.5% by 2025 under current law.

The GOP talking-points memo followed a Feb. 10 discussion draft that included the legislative language required to implement these concepts and allowed insurers to charge higher premiums to people with coverage lapses; repealed a number of taxes imposed on insurers, pharmaceutical companies, and device manufacturers; eliminated many of the ACA’s essential benefits; and ended tax penalties on companies that do not provide coverage to their employees.

This proposal, however, is already running into opposition from House Republicans, with reports stating that blocks of Republicans would not approve of the provisions.

It also could run aground in the Senate, where Sen. Lamar Alexander (R-Tenn.), chairman of the Committee on Health, Education, Labor, and Pensions, has expressed his intent to tackle heath care reform in pieces (public programs, the individual market, and employer market) to avoid getting bogged down in one overarching piece of legislation.

Getting Republicans on the same page is going to be a huge hurdle to get any legislation passed long before it comes down to trying to secure any Democratic votes to help pass any replacement legislation.

As former House Speaker John Boehner told physicians and health care IT leaders at the HIMSS annual conference on Feb. 23, “In the 25 years that I served in the Unites States Congress, Republicans never ever one time agreed on what a health care proposal should look like. Not once. … If you repeal without replace, anything that happens is your fault. You broke it. … If you pass repeal without replace, you’ll never pass replace because they will never ever agree on what the [replacement] bill should be.”

[email protected]
 

Flexibility and choice were key themes in the health care reform vision President Trump outlined in his first speech to a joint session of Congress on Feb. 28.

Specifically, Americans should be able to “purchase their own coverage through the use of tax credits and expanded health savings accounts, but it must be the plan they want, not the plan forced on them by our government,” Mr. Trump said. They also should be able to purchase insurance across state lines, which “will create a truly competitive national marketplace that will bring costs way down and provide far better care.”

Courtesy whitehouse.gov

Finally, Mr. Trump called for “legal reforms that protect patients and doctors from unnecessary costs that drive up the price of insurance and work to bring down the artificially high price of drugs and bring them down immediately,” he said, adding that the Food and Drug Administration needs to slash the time to approval for drugs and other medical treatments.

Some of these concepts were mirrored in a talking-points memo from the House Republican leadership earlier in February.

According to the memo, Republican efforts to repeal and replace the ACA will focus on the following areas:

• Repealing the ACA’s Medicaid expansion and allowing states to choose between block grands or per capita grants for Medicaid funding. States could choose to use those grants and per capita grants to keep expansion.

• Rebranding high-risk pools as “state innovation grants” to provide states with flexibility to design coverage that meets the needs of their populations. States could use the innovation grants to reduce patient out-of-pocket costs, lower the cost of providing care, stabilize the individual and small-group markets, provide access to preventive care, and promote participation in private health care plans.

• Promoting health savings accounts tied to high-deductible plans through increasing maximum contribution limits and other administrative fixes to allow for greater flexibility in their use.

• Replacing ACA premium subsides with refundable flat tax credits. Credit would be age-based, with younger recipients receiving smaller credits and older taxpayers being eligible for more. Tax credits would be available to those who are not eligible to receive coverage through other sources, such as an employer or government program.

Many of these provisions were included in a health reform plan known as A Better Way, which was announced in June 2016 by House Speaker Paul Ryan (R-Wis.).

Like Mr. Trump’s outline to Congress, the GOP talking-points memo was light on specifics, including how the bill will be paid for, how much money will be distributed to states for Medicaid, and how these provisions would alter current insurance coverage rates, which government actuaries project would reach 91.5% by 2025 under current law.

The GOP talking-points memo followed a Feb. 10 discussion draft that included the legislative language required to implement these concepts and allowed insurers to charge higher premiums to people with coverage lapses; repealed a number of taxes imposed on insurers, pharmaceutical companies, and device manufacturers; eliminated many of the ACA’s essential benefits; and ended tax penalties on companies that do not provide coverage to their employees.

This proposal, however, is already running into opposition from House Republicans, with reports stating that blocks of Republicans would not approve of the provisions.

It also could run aground in the Senate, where Sen. Lamar Alexander (R-Tenn.), chairman of the Committee on Health, Education, Labor, and Pensions, has expressed his intent to tackle heath care reform in pieces (public programs, the individual market, and employer market) to avoid getting bogged down in one overarching piece of legislation.

Getting Republicans on the same page is going to be a huge hurdle to get any legislation passed long before it comes down to trying to secure any Democratic votes to help pass any replacement legislation.

As former House Speaker John Boehner told physicians and health care IT leaders at the HIMSS annual conference on Feb. 23, “In the 25 years that I served in the Unites States Congress, Republicans never ever one time agreed on what a health care proposal should look like. Not once. … If you repeal without replace, anything that happens is your fault. You broke it. … If you pass repeal without replace, you’ll never pass replace because they will never ever agree on what the [replacement] bill should be.”

[email protected]
 

Flexibility and choice were key themes in the health care reform vision President Trump outlined in his first speech to a joint session of Congress on Feb. 28.

Specifically, Americans should be able to “purchase their own coverage through the use of tax credits and expanded health savings accounts, but it must be the plan they want, not the plan forced on them by our government,” Mr. Trump said. They also should be able to purchase insurance across state lines, which “will create a truly competitive national marketplace that will bring costs way down and provide far better care.”

Courtesy whitehouse.gov

Finally, Mr. Trump called for “legal reforms that protect patients and doctors from unnecessary costs that drive up the price of insurance and work to bring down the artificially high price of drugs and bring them down immediately,” he said, adding that the Food and Drug Administration needs to slash the time to approval for drugs and other medical treatments.

Some of these concepts were mirrored in a talking-points memo from the House Republican leadership earlier in February.

According to the memo, Republican efforts to repeal and replace the ACA will focus on the following areas:

• Repealing the ACA’s Medicaid expansion and allowing states to choose between block grands or per capita grants for Medicaid funding. States could choose to use those grants and per capita grants to keep expansion.

• Rebranding high-risk pools as “state innovation grants” to provide states with flexibility to design coverage that meets the needs of their populations. States could use the innovation grants to reduce patient out-of-pocket costs, lower the cost of providing care, stabilize the individual and small-group markets, provide access to preventive care, and promote participation in private health care plans.

• Promoting health savings accounts tied to high-deductible plans through increasing maximum contribution limits and other administrative fixes to allow for greater flexibility in their use.

• Replacing ACA premium subsides with refundable flat tax credits. Credit would be age-based, with younger recipients receiving smaller credits and older taxpayers being eligible for more. Tax credits would be available to those who are not eligible to receive coverage through other sources, such as an employer or government program.

Many of these provisions were included in a health reform plan known as A Better Way, which was announced in June 2016 by House Speaker Paul Ryan (R-Wis.).

Like Mr. Trump’s outline to Congress, the GOP talking-points memo was light on specifics, including how the bill will be paid for, how much money will be distributed to states for Medicaid, and how these provisions would alter current insurance coverage rates, which government actuaries project would reach 91.5% by 2025 under current law.

The GOP talking-points memo followed a Feb. 10 discussion draft that included the legislative language required to implement these concepts and allowed insurers to charge higher premiums to people with coverage lapses; repealed a number of taxes imposed on insurers, pharmaceutical companies, and device manufacturers; eliminated many of the ACA’s essential benefits; and ended tax penalties on companies that do not provide coverage to their employees.

This proposal, however, is already running into opposition from House Republicans, with reports stating that blocks of Republicans would not approve of the provisions.

It also could run aground in the Senate, where Sen. Lamar Alexander (R-Tenn.), chairman of the Committee on Health, Education, Labor, and Pensions, has expressed his intent to tackle heath care reform in pieces (public programs, the individual market, and employer market) to avoid getting bogged down in one overarching piece of legislation.

Getting Republicans on the same page is going to be a huge hurdle to get any legislation passed long before it comes down to trying to secure any Democratic votes to help pass any replacement legislation.

As former House Speaker John Boehner told physicians and health care IT leaders at the HIMSS annual conference on Feb. 23, “In the 25 years that I served in the Unites States Congress, Republicans never ever one time agreed on what a health care proposal should look like. Not once. … If you repeal without replace, anything that happens is your fault. You broke it. … If you pass repeal without replace, you’ll never pass replace because they will never ever agree on what the [replacement] bill should be.”

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Because of a spate of mumps outbreaks over the last decade, adding a third dose of the mumps vaccine to the currently standard two-dose series was debated during a meeting of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

“Data [on recent outbreaks] were presented to ACIP in 2012, and ACIP determined that the data were insufficient to recommend for or against the use of a third dose of MMR vaccine for mumps outbreak control,” explained Mona Marin, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. “Subsequently, CDC issued guidance for consideration for use of a third dose in specifically identified target populations, along with criteria for public health departments to consider for decision-making. That includes settings with high two-dose coverage, intense exposure, and ongoing transmission.”

Steve Mann/thinkstock

[email protected]

Because of a spate of mumps outbreaks over the last decade, adding a third dose of the mumps vaccine to the currently standard two-dose series was debated during a meeting of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

“Data [on recent outbreaks] were presented to ACIP in 2012, and ACIP determined that the data were insufficient to recommend for or against the use of a third dose of MMR vaccine for mumps outbreak control,” explained Mona Marin, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. “Subsequently, CDC issued guidance for consideration for use of a third dose in specifically identified target populations, along with criteria for public health departments to consider for decision-making. That includes settings with high two-dose coverage, intense exposure, and ongoing transmission.”

Steve Mann/thinkstock

[email protected]

Because of a spate of mumps outbreaks over the last decade, adding a third dose of the mumps vaccine to the currently standard two-dose series was debated during a meeting of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP).

“Data [on recent outbreaks] were presented to ACIP in 2012, and ACIP determined that the data were insufficient to recommend for or against the use of a third dose of MMR vaccine for mumps outbreak control,” explained Mona Marin, MD, of the CDC’s National Center for Immunization and Respiratory Diseases. “Subsequently, CDC issued guidance for consideration for use of a third dose in specifically identified target populations, along with criteria for public health departments to consider for decision-making. That includes settings with high two-dose coverage, intense exposure, and ongoing transmission.”

Steve Mann/thinkstock

[email protected]

Photo by Steven Fruitsmaak

ORLANDO, FL—A single, 4 mg-dose of the bisphosphonate zoledronic acid (ZA) prior to allogeneic hematopoietic stem cell transplant (HSCT) prevents femoral neck (FN) bone loss at day 100 in patients with lymphoid or myeloid malignancies, according to new research.

The study also suggests that patients who receive risk-adapted ZA therapy after transplant can experience significant reductions in bone loss between days 100 and 365.

However, patients with acute and chronic graft-versus-host disease (GVHD) continue to be at risk of bone loss.

Eric Wong, of the Royal Melbourne Hospital in Parkville, Australia, presented these findings at the 2017 BMT Tandem Meetings (abstract 53) on behalf of the Australasian Leukaemia and Lymphoma Group.

“Previous studies have demonstrated that efforts to prevent bone loss through calcium and vitamin D supplementation as well as hormone-replacement therapy alone have been ineffective in preventing bone loss,” Wong explained.

And monthly pamidronate begun prior to HSCT reduces, but does not prevent, FN bone density loss.

So Wong and his colleagues began a trial of ZA, which is approximately 100-fold more potent than pamidronate.

Study design

The researchers enrolled 82 patients into the phase 2 ALLG BM07 trial. All patients received a single shot of ZA prior to HSCT conditioning.

All patients also received vitamin D and calcium supplements, and pre-menopausal women received hormone replacement therapy.

Depending on their risk of bone loss, patients received individualized ZA therapy after transplant. Researchers assessed the patients’ bone density at days 100, 180, 270, and 365 post-HSCT. Patients at high risk of bone loss received additional doses of ZA.

Risks for bone loss included bone mineral density (BMD) reduction of 5% or greater compared to baseline, prednisolone exposure of 1 mg/kg/d or greater for 2 weeks, or prednisolone exposure of 10 mg/d or more for 6 weeks

The primary endpoint of the study was the change in FN BMD at days 100 and 365 after HSCT compared to baseline.

The researchers also compared patients’ FN BMD with 35 untreated historical controls assessed at the same time points.

Patient characteristics

Seventy patients were alive and had not relapsed at day 100. Most (87%) were 60 years or younger, 60% were male, 53% had myeloid disease, 43% lymphoid, and 4% other disease.

“The most common indications for transplant were acute myeloid leukemia and acute lymphoblastic leukemia,” Wong said, “which, together, formed over 50% of the entire cohort.”

Seventy percent of patients were ECOG status 0 or 1, and 30% were 2 or greater.

Most (59%) had received myeloablative conditioning, the predominant regimens being busulfan/cyclophosphamide or cyclophosphamide/total-body irradiation. And the most common reduced-intensity conditioning regimen was fludarabine/melphalan.

Fifty-six percent of patients had a sibling donor, and 43% had a matched unrelated donor.

Thirty-eight percent of patients developed acute GVHD—19% grade 1, and 19% grade 2 to 3.

“Of note,” Wong said, “no patient developed grade 4 acute GVHD.”

Patients received a median of 2 ZA doses (range, 1–4), including the pre-transplant dose.

Sixty patients received at least 1 dose of ZA between day 100 and day 365, including 33% who received multiple doses.

At day 100, 33 patients received additional ZA. At day 180, 27 patients received additional ZA, including 8 patients who did not have it at day 100. And at day 270, 18 patients had additional ZA, including 1 patient who had no additional ZA at earlier time points.

Results

At day 100, there was no statistically significant change in FN bone density compared with baseline. The mean change was -2.6% (range, -6.6% to 1.4%).

For patients with acute GVHD, however, the change in bone density was significant (P=0.03). Patients with grade 1-2 GVHD had a mean change of -1.6% ± 3.7%, and patients with grade 3-4 GVHD had a mean change of -8.5% ± 11.2%.

Sixty-five patients were available for the day 365 efficacy analysis.

Bone density did not change significantly between day 100 and 365 for the entire group.

“By day 365,” Wong noted, “there was a net loss of bone density of -2.9%.”

But by day 365, patients with extensive chronic GVHD had significantly more bone loss compared with patients who had no chronic GVHD (P=0.03).

Age, sex, duration of cyclosporine, and mean steroid dose were not associated with a change in bone density at day 100 or 365, although there was a trend for an association between high steroid exposure and increased bone loss (P=0.07).

When the researchers compared the patients to untreated historical controls, patients who received ZA had significantly less bone loss at day 100  (P=0.001) and day 365 (P<0.0001).

The researchers observed no serious adverse events with ZA.

Wong concluded that patients with extensive GVHD are a “high-risk cohort that needs augmented therapies.”

Photo by Steven Fruitsmaak

ORLANDO, FL—A single, 4 mg-dose of the bisphosphonate zoledronic acid (ZA) prior to allogeneic hematopoietic stem cell transplant (HSCT) prevents femoral neck (FN) bone loss at day 100 in patients with lymphoid or myeloid malignancies, according to new research.

The study also suggests that patients who receive risk-adapted ZA therapy after transplant can experience significant reductions in bone loss between days 100 and 365.

However, patients with acute and chronic graft-versus-host disease (GVHD) continue to be at risk of bone loss.

Eric Wong, of the Royal Melbourne Hospital in Parkville, Australia, presented these findings at the 2017 BMT Tandem Meetings (abstract 53) on behalf of the Australasian Leukaemia and Lymphoma Group.

“Previous studies have demonstrated that efforts to prevent bone loss through calcium and vitamin D supplementation as well as hormone-replacement therapy alone have been ineffective in preventing bone loss,” Wong explained.

And monthly pamidronate begun prior to HSCT reduces, but does not prevent, FN bone density loss.

So Wong and his colleagues began a trial of ZA, which is approximately 100-fold more potent than pamidronate.

Study design

The researchers enrolled 82 patients into the phase 2 ALLG BM07 trial. All patients received a single shot of ZA prior to HSCT conditioning.

All patients also received vitamin D and calcium supplements, and pre-menopausal women received hormone replacement therapy.

Depending on their risk of bone loss, patients received individualized ZA therapy after transplant. Researchers assessed the patients’ bone density at days 100, 180, 270, and 365 post-HSCT. Patients at high risk of bone loss received additional doses of ZA.

Risks for bone loss included bone mineral density (BMD) reduction of 5% or greater compared to baseline, prednisolone exposure of 1 mg/kg/d or greater for 2 weeks, or prednisolone exposure of 10 mg/d or more for 6 weeks

The primary endpoint of the study was the change in FN BMD at days 100 and 365 after HSCT compared to baseline.

The researchers also compared patients’ FN BMD with 35 untreated historical controls assessed at the same time points.

Patient characteristics

Seventy patients were alive and had not relapsed at day 100. Most (87%) were 60 years or younger, 60% were male, 53% had myeloid disease, 43% lymphoid, and 4% other disease.

“The most common indications for transplant were acute myeloid leukemia and acute lymphoblastic leukemia,” Wong said, “which, together, formed over 50% of the entire cohort.”

Seventy percent of patients were ECOG status 0 or 1, and 30% were 2 or greater.

Most (59%) had received myeloablative conditioning, the predominant regimens being busulfan/cyclophosphamide or cyclophosphamide/total-body irradiation. And the most common reduced-intensity conditioning regimen was fludarabine/melphalan.

Fifty-six percent of patients had a sibling donor, and 43% had a matched unrelated donor.

Thirty-eight percent of patients developed acute GVHD—19% grade 1, and 19% grade 2 to 3.

“Of note,” Wong said, “no patient developed grade 4 acute GVHD.”

Patients received a median of 2 ZA doses (range, 1–4), including the pre-transplant dose.

Sixty patients received at least 1 dose of ZA between day 100 and day 365, including 33% who received multiple doses.

At day 100, 33 patients received additional ZA. At day 180, 27 patients received additional ZA, including 8 patients who did not have it at day 100. And at day 270, 18 patients had additional ZA, including 1 patient who had no additional ZA at earlier time points.

Results

At day 100, there was no statistically significant change in FN bone density compared with baseline. The mean change was -2.6% (range, -6.6% to 1.4%).

For patients with acute GVHD, however, the change in bone density was significant (P=0.03). Patients with grade 1-2 GVHD had a mean change of -1.6% ± 3.7%, and patients with grade 3-4 GVHD had a mean change of -8.5% ± 11.2%.

Sixty-five patients were available for the day 365 efficacy analysis.

Bone density did not change significantly between day 100 and 365 for the entire group.

“By day 365,” Wong noted, “there was a net loss of bone density of -2.9%.”

But by day 365, patients with extensive chronic GVHD had significantly more bone loss compared with patients who had no chronic GVHD (P=0.03).

Age, sex, duration of cyclosporine, and mean steroid dose were not associated with a change in bone density at day 100 or 365, although there was a trend for an association between high steroid exposure and increased bone loss (P=0.07).

When the researchers compared the patients to untreated historical controls, patients who received ZA had significantly less bone loss at day 100  (P=0.001) and day 365 (P<0.0001).

The researchers observed no serious adverse events with ZA.

Wong concluded that patients with extensive GVHD are a “high-risk cohort that needs augmented therapies.”

Photo by Steven Fruitsmaak

ORLANDO, FL—A single, 4 mg-dose of the bisphosphonate zoledronic acid (ZA) prior to allogeneic hematopoietic stem cell transplant (HSCT) prevents femoral neck (FN) bone loss at day 100 in patients with lymphoid or myeloid malignancies, according to new research.

The study also suggests that patients who receive risk-adapted ZA therapy after transplant can experience significant reductions in bone loss between days 100 and 365.

However, patients with acute and chronic graft-versus-host disease (GVHD) continue to be at risk of bone loss.

Eric Wong, of the Royal Melbourne Hospital in Parkville, Australia, presented these findings at the 2017 BMT Tandem Meetings (abstract 53) on behalf of the Australasian Leukaemia and Lymphoma Group.

“Previous studies have demonstrated that efforts to prevent bone loss through calcium and vitamin D supplementation as well as hormone-replacement therapy alone have been ineffective in preventing bone loss,” Wong explained.

And monthly pamidronate begun prior to HSCT reduces, but does not prevent, FN bone density loss.

So Wong and his colleagues began a trial of ZA, which is approximately 100-fold more potent than pamidronate.

Study design

The researchers enrolled 82 patients into the phase 2 ALLG BM07 trial. All patients received a single shot of ZA prior to HSCT conditioning.

All patients also received vitamin D and calcium supplements, and pre-menopausal women received hormone replacement therapy.

Depending on their risk of bone loss, patients received individualized ZA therapy after transplant. Researchers assessed the patients’ bone density at days 100, 180, 270, and 365 post-HSCT. Patients at high risk of bone loss received additional doses of ZA.

Risks for bone loss included bone mineral density (BMD) reduction of 5% or greater compared to baseline, prednisolone exposure of 1 mg/kg/d or greater for 2 weeks, or prednisolone exposure of 10 mg/d or more for 6 weeks

The primary endpoint of the study was the change in FN BMD at days 100 and 365 after HSCT compared to baseline.

The researchers also compared patients’ FN BMD with 35 untreated historical controls assessed at the same time points.

Patient characteristics

Seventy patients were alive and had not relapsed at day 100. Most (87%) were 60 years or younger, 60% were male, 53% had myeloid disease, 43% lymphoid, and 4% other disease.

“The most common indications for transplant were acute myeloid leukemia and acute lymphoblastic leukemia,” Wong said, “which, together, formed over 50% of the entire cohort.”

Seventy percent of patients were ECOG status 0 or 1, and 30% were 2 or greater.

Most (59%) had received myeloablative conditioning, the predominant regimens being busulfan/cyclophosphamide or cyclophosphamide/total-body irradiation. And the most common reduced-intensity conditioning regimen was fludarabine/melphalan.

Fifty-six percent of patients had a sibling donor, and 43% had a matched unrelated donor.

Thirty-eight percent of patients developed acute GVHD—19% grade 1, and 19% grade 2 to 3.

“Of note,” Wong said, “no patient developed grade 4 acute GVHD.”

Patients received a median of 2 ZA doses (range, 1–4), including the pre-transplant dose.

Sixty patients received at least 1 dose of ZA between day 100 and day 365, including 33% who received multiple doses.

At day 100, 33 patients received additional ZA. At day 180, 27 patients received additional ZA, including 8 patients who did not have it at day 100. And at day 270, 18 patients had additional ZA, including 1 patient who had no additional ZA at earlier time points.

Results

At day 100, there was no statistically significant change in FN bone density compared with baseline. The mean change was -2.6% (range, -6.6% to 1.4%).

For patients with acute GVHD, however, the change in bone density was significant (P=0.03). Patients with grade 1-2 GVHD had a mean change of -1.6% ± 3.7%, and patients with grade 3-4 GVHD had a mean change of -8.5% ± 11.2%.

Sixty-five patients were available for the day 365 efficacy analysis.

Bone density did not change significantly between day 100 and 365 for the entire group.

“By day 365,” Wong noted, “there was a net loss of bone density of -2.9%.”

But by day 365, patients with extensive chronic GVHD had significantly more bone loss compared with patients who had no chronic GVHD (P=0.03).

Age, sex, duration of cyclosporine, and mean steroid dose were not associated with a change in bone density at day 100 or 365, although there was a trend for an association between high steroid exposure and increased bone loss (P=0.07).

When the researchers compared the patients to untreated historical controls, patients who received ZA had significantly less bone loss at day 100  (P=0.001) and day 365 (P<0.0001).

The researchers observed no serious adverse events with ZA.

Wong concluded that patients with extensive GVHD are a “high-risk cohort that needs augmented therapies.”