It’s a fine line between compensated and decompensated endocrine conditions, and often, there is an underlying non–endocrine component complicating the diagnosis.

That’s according to Marilyn Tan, MD, a clinical assistant professor of medicine at Stanford (Calif.) University, where she is chief of the endocrinology clinic. She spoke about endocrinology emergencies during a case-based, rapid-fire session at HM17.

“Endocrine emergencies are usually due to an excess or a deficiency of a hormone,” Dr. Tan said, noting that these can take time to bring into balance. This is one reason Dr. Tan counseled not waiting for laboratory results before administering treatment.

To diagnose and treat diabetic ketoacidosis, combined with a hyperosmolar hyperglycemic state, Dr. Tan recommended checking hypoglycemia levels, which she said are often mild, and to check anion gap, pH, and ketones. It’s also important to be generous with IV fluids, to administer insulin only if the ketoacidosis level is greater than 3.3 mEq/L, and to not take the patient off an insulin drip too early or inappropriately. To prevent readmissions, the patient on discharge should have adequate diabetes supplies, education on their condition, and timely follow-up, Dr. Tan recommended.

For patients experiencing a thyroid storm, Dr. Tan advised that thyroid function tests are a poor surrogate for predicting who will decompensate. The clinical distinction is made by documentation of acute organ dysfunction. Reducing T3 to T4 conversion means propylthiouracil is preferred over methimazole.

Ongoing management of a myxedema coma means monitoring the clinical parameters of the patient’s mental status, cardiac and pulmonary functions, while keeping the levothyroxine dose steady and checking lab values every 1-2 days to ensure the patient is progressing.

Suspect pituitary apoplexy in cases of hypertension, major surgery, trauma, anticoagulation, pregnancy, or if there is a large sellar mass. If choosing to image a patient, Dr. Tan recommended using an MRI rather than a CT scan, which she said is less sensitive. Immediate hydrocortisone treatment must be administered, she said. About 90% of cases of acute hypercalcemia are caused by hyperparathyroidism in the outpatient setting, and malignancy in the inpatient setting, Dr. Tan said. Also, these patients tend to be volume depleted, so assessment of their ability to tolerate hydration is essential.

Regarding all endocrine emergencies, Dr. Tan said, “When in doubt, be more aggressive with treatment.”

Dr. Tan had no relevant financial disclosures.

It’s a fine line between compensated and decompensated endocrine conditions, and often, there is an underlying non–endocrine component complicating the diagnosis.

That’s according to Marilyn Tan, MD, a clinical assistant professor of medicine at Stanford (Calif.) University, where she is chief of the endocrinology clinic. She spoke about endocrinology emergencies during a case-based, rapid-fire session at HM17.

“Endocrine emergencies are usually due to an excess or a deficiency of a hormone,” Dr. Tan said, noting that these can take time to bring into balance. This is one reason Dr. Tan counseled not waiting for laboratory results before administering treatment.

To diagnose and treat diabetic ketoacidosis, combined with a hyperosmolar hyperglycemic state, Dr. Tan recommended checking hypoglycemia levels, which she said are often mild, and to check anion gap, pH, and ketones. It’s also important to be generous with IV fluids, to administer insulin only if the ketoacidosis level is greater than 3.3 mEq/L, and to not take the patient off an insulin drip too early or inappropriately. To prevent readmissions, the patient on discharge should have adequate diabetes supplies, education on their condition, and timely follow-up, Dr. Tan recommended.

For patients experiencing a thyroid storm, Dr. Tan advised that thyroid function tests are a poor surrogate for predicting who will decompensate. The clinical distinction is made by documentation of acute organ dysfunction. Reducing T3 to T4 conversion means propylthiouracil is preferred over methimazole.

Ongoing management of a myxedema coma means monitoring the clinical parameters of the patient’s mental status, cardiac and pulmonary functions, while keeping the levothyroxine dose steady and checking lab values every 1-2 days to ensure the patient is progressing.

Suspect pituitary apoplexy in cases of hypertension, major surgery, trauma, anticoagulation, pregnancy, or if there is a large sellar mass. If choosing to image a patient, Dr. Tan recommended using an MRI rather than a CT scan, which she said is less sensitive. Immediate hydrocortisone treatment must be administered, she said. About 90% of cases of acute hypercalcemia are caused by hyperparathyroidism in the outpatient setting, and malignancy in the inpatient setting, Dr. Tan said. Also, these patients tend to be volume depleted, so assessment of their ability to tolerate hydration is essential.

Regarding all endocrine emergencies, Dr. Tan said, “When in doubt, be more aggressive with treatment.”

Dr. Tan had no relevant financial disclosures.

It’s a fine line between compensated and decompensated endocrine conditions, and often, there is an underlying non–endocrine component complicating the diagnosis.

That’s according to Marilyn Tan, MD, a clinical assistant professor of medicine at Stanford (Calif.) University, where she is chief of the endocrinology clinic. She spoke about endocrinology emergencies during a case-based, rapid-fire session at HM17.

“Endocrine emergencies are usually due to an excess or a deficiency of a hormone,” Dr. Tan said, noting that these can take time to bring into balance. This is one reason Dr. Tan counseled not waiting for laboratory results before administering treatment.

To diagnose and treat diabetic ketoacidosis, combined with a hyperosmolar hyperglycemic state, Dr. Tan recommended checking hypoglycemia levels, which she said are often mild, and to check anion gap, pH, and ketones. It’s also important to be generous with IV fluids, to administer insulin only if the ketoacidosis level is greater than 3.3 mEq/L, and to not take the patient off an insulin drip too early or inappropriately. To prevent readmissions, the patient on discharge should have adequate diabetes supplies, education on their condition, and timely follow-up, Dr. Tan recommended.

For patients experiencing a thyroid storm, Dr. Tan advised that thyroid function tests are a poor surrogate for predicting who will decompensate. The clinical distinction is made by documentation of acute organ dysfunction. Reducing T3 to T4 conversion means propylthiouracil is preferred over methimazole.

Ongoing management of a myxedema coma means monitoring the clinical parameters of the patient’s mental status, cardiac and pulmonary functions, while keeping the levothyroxine dose steady and checking lab values every 1-2 days to ensure the patient is progressing.

Suspect pituitary apoplexy in cases of hypertension, major surgery, trauma, anticoagulation, pregnancy, or if there is a large sellar mass. If choosing to image a patient, Dr. Tan recommended using an MRI rather than a CT scan, which she said is less sensitive. Immediate hydrocortisone treatment must be administered, she said. About 90% of cases of acute hypercalcemia are caused by hyperparathyroidism in the outpatient setting, and malignancy in the inpatient setting, Dr. Tan said. Also, these patients tend to be volume depleted, so assessment of their ability to tolerate hydration is essential.

Regarding all endocrine emergencies, Dr. Tan said, “When in doubt, be more aggressive with treatment.”

Dr. Tan had no relevant financial disclosures.

In 2015, nearly 2.4 million Americans had an opioid use disorder. Close to 80% did not receive treatment. To help change those numbers, the Substance Abuse and Mental Health Services Administration (SAMHSA) has developed a free mobile application called MATx that supports medication-assisted treatment. The app “empowers health care practitioners to provide effective, evidence-based care for people with opioid use disorder.” Features include the following:

• Information on treatment approaches and medications approved by the FDA for use in treating opioid use disorders;
• A buprenorphine prescribing guide, including information on the Drug Addiction Treatment Act of 2000 waiver process and patient limits;
• Clinical support tools, such as treatment guidelines, ICD-10 coding, and recommendations for working with special populations;
• Access to critical helplines and SAMHSA’s treatment locators.

For more information on the app, visit http://store.samhsa.gov/apps/mat/tools/index.html?WT.ac=PEPAdSpreadWord20161018Prof.

In 2015, nearly 2.4 million Americans had an opioid use disorder. Close to 80% did not receive treatment. To help change those numbers, the Substance Abuse and Mental Health Services Administration (SAMHSA) has developed a free mobile application called MATx that supports medication-assisted treatment. The app “empowers health care practitioners to provide effective, evidence-based care for people with opioid use disorder.” Features include the following:

• Information on treatment approaches and medications approved by the FDA for use in treating opioid use disorders;
• A buprenorphine prescribing guide, including information on the Drug Addiction Treatment Act of 2000 waiver process and patient limits;
• Clinical support tools, such as treatment guidelines, ICD-10 coding, and recommendations for working with special populations;
• Access to critical helplines and SAMHSA’s treatment locators.

For more information on the app, visit http://store.samhsa.gov/apps/mat/tools/index.html?WT.ac=PEPAdSpreadWord20161018Prof.

In 2015, nearly 2.4 million Americans had an opioid use disorder. Close to 80% did not receive treatment. To help change those numbers, the Substance Abuse and Mental Health Services Administration (SAMHSA) has developed a free mobile application called MATx that supports medication-assisted treatment. The app “empowers health care practitioners to provide effective, evidence-based care for people with opioid use disorder.” Features include the following:

• Information on treatment approaches and medications approved by the FDA for use in treating opioid use disorders;
• A buprenorphine prescribing guide, including information on the Drug Addiction Treatment Act of 2000 waiver process and patient limits;
• Clinical support tools, such as treatment guidelines, ICD-10 coding, and recommendations for working with special populations;
• Access to critical helplines and SAMHSA’s treatment locators.

For more information on the app, visit http://store.samhsa.gov/apps/mat/tools/index.html?WT.ac=PEPAdSpreadWord20161018Prof.

Sometimes the final day of a convention is nothing more than the “getaway day.”

But not at HM17. Not this year.

The finale of the 2017 annual meeting is capped off, as has become tradition, by a speech from the dean of hospital medicine: Robert Wachter, MD, MHM. The last time Dr. Wachter gave his address from a Vegas stage, it ended with him in head-to-toe Elton John regalia. While there’s no guarantee of a wardrobe reprisal, the annual address from the man who helped name the specialty promises to entertain and inform, said HM17 course director Lenny Feldman, MD, SFHM.

Sometimes the final day of a convention is nothing more than the “getaway day.”

But not at HM17. Not this year.

The finale of the 2017 annual meeting is capped off, as has become tradition, by a speech from the dean of hospital medicine: Robert Wachter, MD, MHM. The last time Dr. Wachter gave his address from a Vegas stage, it ended with him in head-to-toe Elton John regalia. While there’s no guarantee of a wardrobe reprisal, the annual address from the man who helped name the specialty promises to entertain and inform, said HM17 course director Lenny Feldman, MD, SFHM.

Sometimes the final day of a convention is nothing more than the “getaway day.”

But not at HM17. Not this year.

The finale of the 2017 annual meeting is capped off, as has become tradition, by a speech from the dean of hospital medicine: Robert Wachter, MD, MHM. The last time Dr. Wachter gave his address from a Vegas stage, it ended with him in head-to-toe Elton John regalia. While there’s no guarantee of a wardrobe reprisal, the annual address from the man who helped name the specialty promises to entertain and inform, said HM17 course director Lenny Feldman, MD, SFHM.

Robert M. Wachter, MD, MHM, has given the last plenary address at every SHM annual meeting since 2007. The talks are peppered with his one-of-a-kind take on the confluence of medicine, politics, and policy. Then there was the time when he broke into an Elton John parody.

Where does that point of view come from? Well, as the dean of hospital medicine says in his ever-popular Twitter bio, he is “what happens when a poli-sci major becomes an academic physician.”

That’s a needed perspective this year, as the level of political upheaval in the United States has added to the tumult in the health care field. Questions surrounding the implementation of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) and the continued struggles that doctors face when using electronic health records (EHRs) are among the topics that he will address in his this final discussion.

The defeat of Republicans’ plan to replace the Affordable Care Act (ACA) with the American Health Care Act (AHCA) showed that the divide over health care extends even to intraparty discussions.

“The implosion of the AHCA shows how difficult health reform is and how quickly the ACA became the de facto standard,” Dr. Wachter said. “It is now that status quo that is so difficult to change.”

Dr. Wachter, who famously helped coined the term “hospitalist” in the 1996 New England Journal of Medicine paper that propelled the nascent specialty, said that one big challenge to HM is determining the future of how hospitals get paid – and how they pay their workers (335[7]:514-7).

“The business model for hospitals will be massively challenged, and it could get worse if a lot of your patients lose insurance or [if] their payments go way down,” he predicted.

What that means for the daily schedules of hospitalists remains to be seen, but Dr. Wachter doesn’t expect much in the short term.

“The job will be the same,” he said. “Take care of patients well, make them happy, satisfy your bosses and colleagues, and do it for less money. The biggest shift is likely to be that more and more people/systems – doing the same thing – will find that they don’t need as many hospital days, which means that we’ll have fewer patients and fewer hospitals. But we knew that.”

Dr. Wachter is more interested to see what will happen in postacute and other nonhospital facilities, how quickly technology continues to disrupt, and who hospitalists will work for (be it staffing companies, medical groups, or “something new”).

The veteran physician in him says not to get too distracted “by all of the zigs and zags,” he noted, while the political idealist in him says not to ever forget that the “core values and imperatives remain.”

If the past decade of wise words ending SHM’s annual meeting are any indication, Dr. Wachter’s message of trepidation and concern will end on a high note for attendees.

Robert M. Wachter, MD, MHM, has given the last plenary address at every SHM annual meeting since 2007. The talks are peppered with his one-of-a-kind take on the confluence of medicine, politics, and policy. Then there was the time when he broke into an Elton John parody.

Where does that point of view come from? Well, as the dean of hospital medicine says in his ever-popular Twitter bio, he is “what happens when a poli-sci major becomes an academic physician.”

That’s a needed perspective this year, as the level of political upheaval in the United States has added to the tumult in the health care field. Questions surrounding the implementation of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) and the continued struggles that doctors face when using electronic health records (EHRs) are among the topics that he will address in his this final discussion.

The defeat of Republicans’ plan to replace the Affordable Care Act (ACA) with the American Health Care Act (AHCA) showed that the divide over health care extends even to intraparty discussions.

“The implosion of the AHCA shows how difficult health reform is and how quickly the ACA became the de facto standard,” Dr. Wachter said. “It is now that status quo that is so difficult to change.”

Dr. Wachter, who famously helped coined the term “hospitalist” in the 1996 New England Journal of Medicine paper that propelled the nascent specialty, said that one big challenge to HM is determining the future of how hospitals get paid – and how they pay their workers (335[7]:514-7).

“The business model for hospitals will be massively challenged, and it could get worse if a lot of your patients lose insurance or [if] their payments go way down,” he predicted.

What that means for the daily schedules of hospitalists remains to be seen, but Dr. Wachter doesn’t expect much in the short term.

“The job will be the same,” he said. “Take care of patients well, make them happy, satisfy your bosses and colleagues, and do it for less money. The biggest shift is likely to be that more and more people/systems – doing the same thing – will find that they don’t need as many hospital days, which means that we’ll have fewer patients and fewer hospitals. But we knew that.”

Dr. Wachter is more interested to see what will happen in postacute and other nonhospital facilities, how quickly technology continues to disrupt, and who hospitalists will work for (be it staffing companies, medical groups, or “something new”).

The veteran physician in him says not to get too distracted “by all of the zigs and zags,” he noted, while the political idealist in him says not to ever forget that the “core values and imperatives remain.”

If the past decade of wise words ending SHM’s annual meeting are any indication, Dr. Wachter’s message of trepidation and concern will end on a high note for attendees.

Robert M. Wachter, MD, MHM, has given the last plenary address at every SHM annual meeting since 2007. The talks are peppered with his one-of-a-kind take on the confluence of medicine, politics, and policy. Then there was the time when he broke into an Elton John parody.

Where does that point of view come from? Well, as the dean of hospital medicine says in his ever-popular Twitter bio, he is “what happens when a poli-sci major becomes an academic physician.”

That’s a needed perspective this year, as the level of political upheaval in the United States has added to the tumult in the health care field. Questions surrounding the implementation of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) and the continued struggles that doctors face when using electronic health records (EHRs) are among the topics that he will address in his this final discussion.

The defeat of Republicans’ plan to replace the Affordable Care Act (ACA) with the American Health Care Act (AHCA) showed that the divide over health care extends even to intraparty discussions.

“The implosion of the AHCA shows how difficult health reform is and how quickly the ACA became the de facto standard,” Dr. Wachter said. “It is now that status quo that is so difficult to change.”

Dr. Wachter, who famously helped coined the term “hospitalist” in the 1996 New England Journal of Medicine paper that propelled the nascent specialty, said that one big challenge to HM is determining the future of how hospitals get paid – and how they pay their workers (335[7]:514-7).

“The business model for hospitals will be massively challenged, and it could get worse if a lot of your patients lose insurance or [if] their payments go way down,” he predicted.

What that means for the daily schedules of hospitalists remains to be seen, but Dr. Wachter doesn’t expect much in the short term.

“The job will be the same,” he said. “Take care of patients well, make them happy, satisfy your bosses and colleagues, and do it for less money. The biggest shift is likely to be that more and more people/systems – doing the same thing – will find that they don’t need as many hospital days, which means that we’ll have fewer patients and fewer hospitals. But we knew that.”

Dr. Wachter is more interested to see what will happen in postacute and other nonhospital facilities, how quickly technology continues to disrupt, and who hospitalists will work for (be it staffing companies, medical groups, or “something new”).

The veteran physician in him says not to get too distracted “by all of the zigs and zags,” he noted, while the political idealist in him says not to ever forget that the “core values and imperatives remain.”

If the past decade of wise words ending SHM’s annual meeting are any indication, Dr. Wachter’s message of trepidation and concern will end on a high note for attendees.

Welcome to the third and final day of HM17!

Although it is the shortest day of the conference, day 3 is full of quality content, starting at 7:40 a.m. with a mini-track.

If you are interested in hearing about the impact of November’s election on health care reform, join me at the Health Policy Mini-Track starting first thing in the morning. The mini-track will begin with a session called “Hot Topics in Health Policy for Hospitalists” and will be followed by a panel of visitors from our nation’s capital who will weigh in on events in D.C. that will have an impact on our careers.

Welcome to the third and final day of HM17!

Although it is the shortest day of the conference, day 3 is full of quality content, starting at 7:40 a.m. with a mini-track.

If you are interested in hearing about the impact of November’s election on health care reform, join me at the Health Policy Mini-Track starting first thing in the morning. The mini-track will begin with a session called “Hot Topics in Health Policy for Hospitalists” and will be followed by a panel of visitors from our nation’s capital who will weigh in on events in D.C. that will have an impact on our careers.

Welcome to the third and final day of HM17!

Although it is the shortest day of the conference, day 3 is full of quality content, starting at 7:40 a.m. with a mini-track.

If you are interested in hearing about the impact of November’s election on health care reform, join me at the Health Policy Mini-Track starting first thing in the morning. The mini-track will begin with a session called “Hot Topics in Health Policy for Hospitalists” and will be followed by a panel of visitors from our nation’s capital who will weigh in on events in D.C. that will have an impact on our careers.

Is ultrasonography really useful in distinguishing between benign and malignant thyroid nodules? The reality facing many physicians, say researchers from the University of Alberta, is that ultrasonography reports originate from multiple sites and are dictated by physicians of varying experience, practice volumes, and styles of documentation. The researchers say although thyroid ultrasonography provides accurate results, few ultrasound reports contain the necessary information to predict malignancy and guide management.

The Thyroid Imaging and Reporting System (TI-RADS) was developed to standardize risk stratification according to nodule characteristics: size, marked hypoechogenicity, taller-than-wide shape, microcalcifications, irregular margins, and solid component. The researchers reviewed ultrasound reports using TI-RADS criteria for 329 patients who had undergone thyroidectomy and then assessed whether individual or multiple criteria were associated with malignancy.

Related: New Treatment Options for Metastatic Thyroid Cancer

About 42% of the nodules were malignant. The most common carcinoma was papillary thyroid cancer. Benign disease was predominantly cases of multinodular goiter. The difference in size between benign and malignant neoplasms was not significant. About 11% of the specimens exhibited incidental microcarcionomas.

Nearly all the reports documented nodule size. But > 90% noted ≤ 3 of the remaining TI-RADS criteria. In fact, nearly 40% included 1 or no criterion beyond the description of size. The number of features reported did not reflect an increased risk of malignancy. The researchers found no associations among reporting criteria—for example, the presence of microcalcifications did not trigger targeted comments about any other factor—and this was true for all of the criteria, they note.

Related: Tracking a Tumor

Half of the reports with a comment noted solid or cystic nodules and echogenicity. The description of a hypoechoic nodule or a solid nodule was significantly more likely to be identified in malignant neoplasms. The presence of microcalcifications was the most sensitive marker of malignancy (90%), and documentation of irregular margins was the most specific indicator.

Overall, the researchers say, it was clear that microcalcifications, hypoechogenicity, irregular margins, and solid nodules were significantly more likely to be found in malignant neoplasms. The absence of these nodules predicted benign disease. But because so few reports consistently documented all criteria, the overall ability of thyroid ultrasonography to discriminate between lower- and higher-risk nodules is limited.

Source:
Gamme G, Parrington T, Wiebe E, et al. Can J Surg. 2017;60(2):134-139
doi:10.1503/cjs.010316

Is ultrasonography really useful in distinguishing between benign and malignant thyroid nodules? The reality facing many physicians, say researchers from the University of Alberta, is that ultrasonography reports originate from multiple sites and are dictated by physicians of varying experience, practice volumes, and styles of documentation. The researchers say although thyroid ultrasonography provides accurate results, few ultrasound reports contain the necessary information to predict malignancy and guide management.

The Thyroid Imaging and Reporting System (TI-RADS) was developed to standardize risk stratification according to nodule characteristics: size, marked hypoechogenicity, taller-than-wide shape, microcalcifications, irregular margins, and solid component. The researchers reviewed ultrasound reports using TI-RADS criteria for 329 patients who had undergone thyroidectomy and then assessed whether individual or multiple criteria were associated with malignancy.

Related: New Treatment Options for Metastatic Thyroid Cancer

About 42% of the nodules were malignant. The most common carcinoma was papillary thyroid cancer. Benign disease was predominantly cases of multinodular goiter. The difference in size between benign and malignant neoplasms was not significant. About 11% of the specimens exhibited incidental microcarcionomas.

Nearly all the reports documented nodule size. But > 90% noted ≤ 3 of the remaining TI-RADS criteria. In fact, nearly 40% included 1 or no criterion beyond the description of size. The number of features reported did not reflect an increased risk of malignancy. The researchers found no associations among reporting criteria—for example, the presence of microcalcifications did not trigger targeted comments about any other factor—and this was true for all of the criteria, they note.

Related: Tracking a Tumor

Half of the reports with a comment noted solid or cystic nodules and echogenicity. The description of a hypoechoic nodule or a solid nodule was significantly more likely to be identified in malignant neoplasms. The presence of microcalcifications was the most sensitive marker of malignancy (90%), and documentation of irregular margins was the most specific indicator.

Overall, the researchers say, it was clear that microcalcifications, hypoechogenicity, irregular margins, and solid nodules were significantly more likely to be found in malignant neoplasms. The absence of these nodules predicted benign disease. But because so few reports consistently documented all criteria, the overall ability of thyroid ultrasonography to discriminate between lower- and higher-risk nodules is limited.

Source:
Gamme G, Parrington T, Wiebe E, et al. Can J Surg. 2017;60(2):134-139
doi:10.1503/cjs.010316

Is ultrasonography really useful in distinguishing between benign and malignant thyroid nodules? The reality facing many physicians, say researchers from the University of Alberta, is that ultrasonography reports originate from multiple sites and are dictated by physicians of varying experience, practice volumes, and styles of documentation. The researchers say although thyroid ultrasonography provides accurate results, few ultrasound reports contain the necessary information to predict malignancy and guide management.

The Thyroid Imaging and Reporting System (TI-RADS) was developed to standardize risk stratification according to nodule characteristics: size, marked hypoechogenicity, taller-than-wide shape, microcalcifications, irregular margins, and solid component. The researchers reviewed ultrasound reports using TI-RADS criteria for 329 patients who had undergone thyroidectomy and then assessed whether individual or multiple criteria were associated with malignancy.

Related: New Treatment Options for Metastatic Thyroid Cancer

About 42% of the nodules were malignant. The most common carcinoma was papillary thyroid cancer. Benign disease was predominantly cases of multinodular goiter. The difference in size between benign and malignant neoplasms was not significant. About 11% of the specimens exhibited incidental microcarcionomas.

Nearly all the reports documented nodule size. But > 90% noted ≤ 3 of the remaining TI-RADS criteria. In fact, nearly 40% included 1 or no criterion beyond the description of size. The number of features reported did not reflect an increased risk of malignancy. The researchers found no associations among reporting criteria—for example, the presence of microcalcifications did not trigger targeted comments about any other factor—and this was true for all of the criteria, they note.

Related: Tracking a Tumor

Half of the reports with a comment noted solid or cystic nodules and echogenicity. The description of a hypoechoic nodule or a solid nodule was significantly more likely to be identified in malignant neoplasms. The presence of microcalcifications was the most sensitive marker of malignancy (90%), and documentation of irregular margins was the most specific indicator.

Overall, the researchers say, it was clear that microcalcifications, hypoechogenicity, irregular margins, and solid nodules were significantly more likely to be found in malignant neoplasms. The absence of these nodules predicted benign disease. But because so few reports consistently documented all criteria, the overall ability of thyroid ultrasonography to discriminate between lower- and higher-risk nodules is limited.

Source:
Gamme G, Parrington T, Wiebe E, et al. Can J Surg. 2017;60(2):134-139
doi:10.1503/cjs.010316

During his testimony before the House Committee on Veterans Affairs on March 7, 2017, Secretary of Veterans Affairs David J. Shulkin, MD, expressed his intent to remove the administrative barrier prohibiting other-than-honorably (OTH) discharged service members from receiving VHA mental health care. This is the first time in VA history to integrate those veterans whose OTH discharge status had previously disenfranchised them.

In his comments to Congress, Dr. Shulkin voiced his gratitude to Rep. Mike Coffman (R-CO) for helping him to “better understand the urgency of getting this right.” In March 2016, Rep. Coffman introduced the

Veterans Fairness Act, which would permit OTH discharged combat veterans to obtain emergency mental health services. Rep. Coffman cited that 22,000 U.S. Army veterans were discharged for misconduct since 2009, most with a traumatic brain injury (TBI) or mental illness.¹ Veterans often refer to OTH discharges as having “bad paper.” In 2013, National Public Radio produced a series on OTH discharged service members that underscored their struggles.² Those reports estimated that more than 100,000 veterans left the service with OTH discharges in the decade before the story.²

These individuals, many of whom have already lost a great deal as a result of their military service, lose much more when they are OTH discharged. They are unable to apply for the GI Bill, which enables them to further their education and livelihood; they cannot get a VA home loan to help them house their families; and they are ineligible for disability even for combat-related conditions like posttraumatic stress disorder (PTSD) and TBI. Most damaging of all, until Dr. Shulkin’s historic announcement, they also could not get VA health care. In effect, OTH discharge status creates a second class of service men and women, even though the discharge may have been the result of injury and illness related to their time in uniform. That consequence makes Dr. Shulkin’s proposal not only an administrative change, but also an ethical decision regarding the civil and human rights of service members, which is the reason most major veterans service and advocacy organizations have long endorsed it.

Although research on OTH discharged veterans has been limited, studies have found a high rate of mental health problems. The OTH discharged service members are significantly represented in the cohorts who face some of the most serious public health problems that the VA has tried to address through new programs that were initiated during the prior administration and continued by the current one, such as ending homelessness and preventing suicide.

A 2017 study compared rates of mental illness and substance use among veterans with routine discharges with those who had nonroutine separations from the military.³ The results showed that there was a higher rate of almost every psychiatric diagnosis in the nonroutine discharges; the rates were particularly high for those discharged for misconduct.³ Because of the established correlation of multiple deployments to Afghanistan and Iraq and incidence of TBI, PTSD, and substance use and the association of these disorders with behaviors that contribute to OTH discharge status, a clear duty to care for these men and women emerges.

Similarly, the ethical principle of nonmalfeasance provides persuasive justification for Dr. Shulkin’s proposed change in VA eligibility for mental health care. The study also found that even if not previously entitled to VA services, these veterans share the increased risk of suicide found in all those who have worn a uniform for their country and similarly need compassionate, competent veteran-centered care.³

Recent research showed that patients who receive mental health care within the VA have lower rates of suicide than that of those who receive care in the community.⁴ The results of this study contribute to the ethical imperative to grant these former service members access to potentially life-saving mental health treatment more urgent.

The elevated suicide risk of those veterans who do not have VA mental health services makes this extension of care clinically and ethically imperative and urgent. In his testimony at the hearing, Dr. Shulkin underscored this rationale, “The President and I have made it clear that suicide prevention is one of our top priorities,” Shulkin added. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care. This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even one veteran suicide is one too many, we mean it.

The downstream consequences of OTH discharge status are the most detrimental to the veteran and have negative effects on the veteran’s family and community. Nonroutinely discharged veterans are more likely to be homeless. The new initiative would open a variety of VA mental health services to OTH discharged service members, including those available in VA emergency departments, Vet Centers, and the Veterans Crisis Line. In developing the plan to expand coverage to OTH discharged veterans, Dr. Shulkin indicated that he would consult with Veterans Service Organizations and the DoD.

We can hope that additional services will be opened to OTH discharged service members, such as case management and housing assistance, which have proven so successful in reintegrating those service members with routine discharges.

During his testimony before the House Committee on Veterans Affairs on March 7, 2017, Secretary of Veterans Affairs David J. Shulkin, MD, expressed his intent to remove the administrative barrier prohibiting other-than-honorably (OTH) discharged service members from receiving VHA mental health care. This is the first time in VA history to integrate those veterans whose OTH discharge status had previously disenfranchised them.

In his comments to Congress, Dr. Shulkin voiced his gratitude to Rep. Mike Coffman (R-CO) for helping him to “better understand the urgency of getting this right.” In March 2016, Rep. Coffman introduced the

Veterans Fairness Act, which would permit OTH discharged combat veterans to obtain emergency mental health services. Rep. Coffman cited that 22,000 U.S. Army veterans were discharged for misconduct since 2009, most with a traumatic brain injury (TBI) or mental illness.¹ Veterans often refer to OTH discharges as having “bad paper.” In 2013, National Public Radio produced a series on OTH discharged service members that underscored their struggles.² Those reports estimated that more than 100,000 veterans left the service with OTH discharges in the decade before the story.²

These individuals, many of whom have already lost a great deal as a result of their military service, lose much more when they are OTH discharged. They are unable to apply for the GI Bill, which enables them to further their education and livelihood; they cannot get a VA home loan to help them house their families; and they are ineligible for disability even for combat-related conditions like posttraumatic stress disorder (PTSD) and TBI. Most damaging of all, until Dr. Shulkin’s historic announcement, they also could not get VA health care. In effect, OTH discharge status creates a second class of service men and women, even though the discharge may have been the result of injury and illness related to their time in uniform. That consequence makes Dr. Shulkin’s proposal not only an administrative change, but also an ethical decision regarding the civil and human rights of service members, which is the reason most major veterans service and advocacy organizations have long endorsed it.

Although research on OTH discharged veterans has been limited, studies have found a high rate of mental health problems. The OTH discharged service members are significantly represented in the cohorts who face some of the most serious public health problems that the VA has tried to address through new programs that were initiated during the prior administration and continued by the current one, such as ending homelessness and preventing suicide.

A 2017 study compared rates of mental illness and substance use among veterans with routine discharges with those who had nonroutine separations from the military.³ The results showed that there was a higher rate of almost every psychiatric diagnosis in the nonroutine discharges; the rates were particularly high for those discharged for misconduct.³ Because of the established correlation of multiple deployments to Afghanistan and Iraq and incidence of TBI, PTSD, and substance use and the association of these disorders with behaviors that contribute to OTH discharge status, a clear duty to care for these men and women emerges.

Similarly, the ethical principle of nonmalfeasance provides persuasive justification for Dr. Shulkin’s proposed change in VA eligibility for mental health care. The study also found that even if not previously entitled to VA services, these veterans share the increased risk of suicide found in all those who have worn a uniform for their country and similarly need compassionate, competent veteran-centered care.³

Recent research showed that patients who receive mental health care within the VA have lower rates of suicide than that of those who receive care in the community.⁴ The results of this study contribute to the ethical imperative to grant these former service members access to potentially life-saving mental health treatment more urgent.

The elevated suicide risk of those veterans who do not have VA mental health services makes this extension of care clinically and ethically imperative and urgent. In his testimony at the hearing, Dr. Shulkin underscored this rationale, “The President and I have made it clear that suicide prevention is one of our top priorities,” Shulkin added. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care. This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even one veteran suicide is one too many, we mean it.

The downstream consequences of OTH discharge status are the most detrimental to the veteran and have negative effects on the veteran’s family and community. Nonroutinely discharged veterans are more likely to be homeless. The new initiative would open a variety of VA mental health services to OTH discharged service members, including those available in VA emergency departments, Vet Centers, and the Veterans Crisis Line. In developing the plan to expand coverage to OTH discharged veterans, Dr. Shulkin indicated that he would consult with Veterans Service Organizations and the DoD.

We can hope that additional services will be opened to OTH discharged service members, such as case management and housing assistance, which have proven so successful in reintegrating those service members with routine discharges.

During his testimony before the House Committee on Veterans Affairs on March 7, 2017, Secretary of Veterans Affairs David J. Shulkin, MD, expressed his intent to remove the administrative barrier prohibiting other-than-honorably (OTH) discharged service members from receiving VHA mental health care. This is the first time in VA history to integrate those veterans whose OTH discharge status had previously disenfranchised them.

In his comments to Congress, Dr. Shulkin voiced his gratitude to Rep. Mike Coffman (R-CO) for helping him to “better understand the urgency of getting this right.” In March 2016, Rep. Coffman introduced the

Veterans Fairness Act, which would permit OTH discharged combat veterans to obtain emergency mental health services. Rep. Coffman cited that 22,000 U.S. Army veterans were discharged for misconduct since 2009, most with a traumatic brain injury (TBI) or mental illness.¹ Veterans often refer to OTH discharges as having “bad paper.” In 2013, National Public Radio produced a series on OTH discharged service members that underscored their struggles.² Those reports estimated that more than 100,000 veterans left the service with OTH discharges in the decade before the story.²

These individuals, many of whom have already lost a great deal as a result of their military service, lose much more when they are OTH discharged. They are unable to apply for the GI Bill, which enables them to further their education and livelihood; they cannot get a VA home loan to help them house their families; and they are ineligible for disability even for combat-related conditions like posttraumatic stress disorder (PTSD) and TBI. Most damaging of all, until Dr. Shulkin’s historic announcement, they also could not get VA health care. In effect, OTH discharge status creates a second class of service men and women, even though the discharge may have been the result of injury and illness related to their time in uniform. That consequence makes Dr. Shulkin’s proposal not only an administrative change, but also an ethical decision regarding the civil and human rights of service members, which is the reason most major veterans service and advocacy organizations have long endorsed it.

Although research on OTH discharged veterans has been limited, studies have found a high rate of mental health problems. The OTH discharged service members are significantly represented in the cohorts who face some of the most serious public health problems that the VA has tried to address through new programs that were initiated during the prior administration and continued by the current one, such as ending homelessness and preventing suicide.

A 2017 study compared rates of mental illness and substance use among veterans with routine discharges with those who had nonroutine separations from the military.³ The results showed that there was a higher rate of almost every psychiatric diagnosis in the nonroutine discharges; the rates were particularly high for those discharged for misconduct.³ Because of the established correlation of multiple deployments to Afghanistan and Iraq and incidence of TBI, PTSD, and substance use and the association of these disorders with behaviors that contribute to OTH discharge status, a clear duty to care for these men and women emerges.

Similarly, the ethical principle of nonmalfeasance provides persuasive justification for Dr. Shulkin’s proposed change in VA eligibility for mental health care. The study also found that even if not previously entitled to VA services, these veterans share the increased risk of suicide found in all those who have worn a uniform for their country and similarly need compassionate, competent veteran-centered care.³

Recent research showed that patients who receive mental health care within the VA have lower rates of suicide than that of those who receive care in the community.⁴ The results of this study contribute to the ethical imperative to grant these former service members access to potentially life-saving mental health treatment more urgent.

The elevated suicide risk of those veterans who do not have VA mental health services makes this extension of care clinically and ethically imperative and urgent. In his testimony at the hearing, Dr. Shulkin underscored this rationale, “The President and I have made it clear that suicide prevention is one of our top priorities,” Shulkin added. “We know the rate of death by suicide among veterans who do not use VA care is increasing at a greater rate than veterans who use VA care. This is a national emergency that requires bold action. We must and we will do all that we can to help former service members who may be at risk. When we say even one veteran suicide is one too many, we mean it.

The downstream consequences of OTH discharge status are the most detrimental to the veteran and have negative effects on the veteran’s family and community. Nonroutinely discharged veterans are more likely to be homeless. The new initiative would open a variety of VA mental health services to OTH discharged service members, including those available in VA emergency departments, Vet Centers, and the Veterans Crisis Line. In developing the plan to expand coverage to OTH discharged veterans, Dr. Shulkin indicated that he would consult with Veterans Service Organizations and the DoD.

We can hope that additional services will be opened to OTH discharged service members, such as case management and housing assistance, which have proven so successful in reintegrating those service members with routine discharges.

Several months ago, this 8-year-old boy began losing hair from his scalp. Other than mild itching, there are no associated symptoms. The patient has no pets at home, but he spends his after-school hours with his cousin, who does.

The child is allergy prone but otherwise healthy. No one else in the family (ie, his two younger siblings) has been similarly affected.

EXAMINATION
About three-quarters of the hair is missing from a 6-cm oval patch on the parietal scalp. A few short hairs remain. The skin in this area is slightly edematous, with focal areas of broken, scaly skin.

Palpation of the head and neck reveals adenopathy in the nuchal area of the affected side. A KOH prep is performed with a #10 blade; the sample includes hairs as well as skin.

What is the diagnosis?

T tonsurans is the most common culprit in tinea captitis cases in the United States. This dermatophytic infection of the scalp is a common diagnosis in children, who typically contract it from other children. (Some causative species—such as Microsporum audouinii—spread via contact with animals, but these organisms are generally rare in the US.) Tinea capitis is seen more frequently in boys than in girls, and African-American patients are especially at risk.

Tinea capitis infects the deep hair shaft but spares the skin. Diagnosis requires a combination of clinical signs and identification of the organism in the hair shaft; the latter will also help to guide treatment. In contrast, tinea corporis is diagnosed by clinical features and KOH examination of external scales where the organism resides. Traditionally, infected hairs have needed to be removed for KOH exam—but practical experience has shown that a vigorous scrape that captures infected hairs can accomplish the same thing.

The results of fungal culture may take a month or more to finalize; in the interim, patients such as this one may be treated with griseofulvin (10 mg/kg/d) and application of topical ciclopirox cream bid to reduce infectivity. Total clearance will take at least two months.

Tinea capitis has several forms including inflammatory (which manifests with a large, swollen, inflamed mass) and black dot (named for the tips of broken hair shafts that remain in the affected areas). The differential includes psoriasis, alopecia areata, and seborrhea.

TAKE-HOME LEARNING POINTS

• Tinea capitis is a dermatophytic infection of the scalp usually caused by the dermatophytes Trychophyton tonsurans or T rubrum.
• These infections involve the hair shaft below the skin line, rather than the surface of the skin.
• The organisms that commonly cause tinea capitis in the US typically spread through contact with another person.
• Diagnosis can be made from clinical findings only, including reactive adenopathy. KOH and culture can be necessary in questionable cases, and because of the length of treatment.

Several months ago, this 8-year-old boy began losing hair from his scalp. Other than mild itching, there are no associated symptoms. The patient has no pets at home, but he spends his after-school hours with his cousin, who does.

The child is allergy prone but otherwise healthy. No one else in the family (ie, his two younger siblings) has been similarly affected.

EXAMINATION
About three-quarters of the hair is missing from a 6-cm oval patch on the parietal scalp. A few short hairs remain. The skin in this area is slightly edematous, with focal areas of broken, scaly skin.

Palpation of the head and neck reveals adenopathy in the nuchal area of the affected side. A KOH prep is performed with a #10 blade; the sample includes hairs as well as skin.

What is the diagnosis?

T tonsurans is the most common culprit in tinea captitis cases in the United States. This dermatophytic infection of the scalp is a common diagnosis in children, who typically contract it from other children. (Some causative species—such as Microsporum audouinii—spread via contact with animals, but these organisms are generally rare in the US.) Tinea capitis is seen more frequently in boys than in girls, and African-American patients are especially at risk.

Tinea capitis infects the deep hair shaft but spares the skin. Diagnosis requires a combination of clinical signs and identification of the organism in the hair shaft; the latter will also help to guide treatment. In contrast, tinea corporis is diagnosed by clinical features and KOH examination of external scales where the organism resides. Traditionally, infected hairs have needed to be removed for KOH exam—but practical experience has shown that a vigorous scrape that captures infected hairs can accomplish the same thing.

The results of fungal culture may take a month or more to finalize; in the interim, patients such as this one may be treated with griseofulvin (10 mg/kg/d) and application of topical ciclopirox cream bid to reduce infectivity. Total clearance will take at least two months.

Tinea capitis has several forms including inflammatory (which manifests with a large, swollen, inflamed mass) and black dot (named for the tips of broken hair shafts that remain in the affected areas). The differential includes psoriasis, alopecia areata, and seborrhea.

TAKE-HOME LEARNING POINTS

• Tinea capitis is a dermatophytic infection of the scalp usually caused by the dermatophytes Trychophyton tonsurans or T rubrum.
• These infections involve the hair shaft below the skin line, rather than the surface of the skin.
• The organisms that commonly cause tinea capitis in the US typically spread through contact with another person.
• Diagnosis can be made from clinical findings only, including reactive adenopathy. KOH and culture can be necessary in questionable cases, and because of the length of treatment.

Several months ago, this 8-year-old boy began losing hair from his scalp. Other than mild itching, there are no associated symptoms. The patient has no pets at home, but he spends his after-school hours with his cousin, who does.

The child is allergy prone but otherwise healthy. No one else in the family (ie, his two younger siblings) has been similarly affected.

EXAMINATION
About three-quarters of the hair is missing from a 6-cm oval patch on the parietal scalp. A few short hairs remain. The skin in this area is slightly edematous, with focal areas of broken, scaly skin.

Palpation of the head and neck reveals adenopathy in the nuchal area of the affected side. A KOH prep is performed with a #10 blade; the sample includes hairs as well as skin.

What is the diagnosis?

T tonsurans is the most common culprit in tinea captitis cases in the United States. This dermatophytic infection of the scalp is a common diagnosis in children, who typically contract it from other children. (Some causative species—such as Microsporum audouinii—spread via contact with animals, but these organisms are generally rare in the US.) Tinea capitis is seen more frequently in boys than in girls, and African-American patients are especially at risk.

Tinea capitis infects the deep hair shaft but spares the skin. Diagnosis requires a combination of clinical signs and identification of the organism in the hair shaft; the latter will also help to guide treatment. In contrast, tinea corporis is diagnosed by clinical features and KOH examination of external scales where the organism resides. Traditionally, infected hairs have needed to be removed for KOH exam—but practical experience has shown that a vigorous scrape that captures infected hairs can accomplish the same thing.

The results of fungal culture may take a month or more to finalize; in the interim, patients such as this one may be treated with griseofulvin (10 mg/kg/d) and application of topical ciclopirox cream bid to reduce infectivity. Total clearance will take at least two months.

Tinea capitis has several forms including inflammatory (which manifests with a large, swollen, inflamed mass) and black dot (named for the tips of broken hair shafts that remain in the affected areas). The differential includes psoriasis, alopecia areata, and seborrhea.

TAKE-HOME LEARNING POINTS

• Tinea capitis is a dermatophytic infection of the scalp usually caused by the dermatophytes Trychophyton tonsurans or T rubrum.
• These infections involve the hair shaft below the skin line, rather than the surface of the skin.
• The organisms that commonly cause tinea capitis in the US typically spread through contact with another person.
• Diagnosis can be made from clinical findings only, including reactive adenopathy. KOH and culture can be necessary in questionable cases, and because of the length of treatment.

multiple myeloma

The E-selectin antagonist GMI-1271 can restore sensitivity to bortezomib in resistant multiple myeloma (MM), according to preclinical research published in Leukemia.

Researchers found evidence to suggest that E-selectin ligands induce an aggressive form of MM that is resistant to treatment with bortezomib.

However, treatment with GMI-1271 was able to overcome this resistance in a mouse model of the disease.

“The results in this preclinical study demonstrate that targeting E-selectin may provide a novel approach to treatment of patients with multiple myeloma and could potentially restore sensitivity to chemotherapy and, in particular, proteasome inhibitor therapy,” said John L. Magnani, PhD, vice-president and chief scientific officer of GlycoMimetics Inc., the company developing GMI-1271.

This research was supported by GlycoMimetics, and some of the researchers involved are employees of the company.

The researchers noted that E-selectin ligands are recognized by an antibody known as HECA452. So the team screened 9 MM cell lines for E-selectin ligands using HECA452.

Most of the cell lines were negative for HECA452. However, a minority of cells in 2 of the cell lines—11.2% of RPMI8226 cells and 2.4% of MM1S cells—were positive for HECA452.

So the researchers established HECA452-enriched cell lines from the RPMI8226 and MM1S cells to investigate the biology of E-selectin ligands in MM.

The team said they found that “HECA452-enriched cells express functional E-selectin ligands and exhibit enhanced rolling and adhesion capabilities on E-selectin, which are amenable to therapeutic intervention.”

Experiments in mice

To build on their in vitro findings, the researchers compared the effects of parental MM1S cells and HECA452-enriched MM1S cells in mice.

The team found that animals transplanted with HECA452-enriched cells had significantly shorter survival than those transplanted with parental MM1S cells.

The researchers said this difference is unlikely to be due to a different proliferation rate between the 2 cell types because they demonstrated comparable proliferation and clonogenic capacity in vitro.

The team then tested treatments in a second cohort of mice transplanted with parental or HECA452-enriched MM1S cells. The mice received saline, GMI-1271 alone, bortezomib alone, or GMI-1271 plus bortezomib.

In mice with parental MM1S cells, the median survival was 33 days in the saline group, 31 days in the GMI-1271 group, 42 days in the bortezomib group (P=0.0622 vs saline), and 60 days in the GMI-1271 plus bortezomib group (P=0.0101 vs saline, P=0.0363 vs bortezomib alone).

In mice with HECA452-enriched MM1S cells, the median survival was 25.5 days in the saline group, 30 days in the GMI-1271 group, 24 days in the bortezomib group (P=0.6743 vs saline), and 56.5 days in the GMI-1271 plus bortezomib group (P=0.0028 vs saline, P=0.0123 vs bortezomib alone).

The researchers said additional experiments in mice revealed that GMI-1271 mobilizes HECA452-positive human MM cells from the bone marrow into the peripheral blood.

Investigation in patients

Finally, the researchers evaluated the role of E-selectin and its ligands in patients with MM.

The team looked for HECA452-positive plasma cells in bone marrow samples from MM patients and found these cells were more common in patients with relapsed or refractory MM (14/50) than in those with newly diagnosed MM (1/33, P=0.009).

Next, the researchers analyzed RNA sequencing data from the CoMMpass study and found that increased expression of genes involved in E-selectin ligand synthesis (ST3Gal-6 or ST3Gal-4 and FUT7) is associated with poor progression-free survival (hazard ratio=1.37, P=0.02).

The team concluded that their results “provide compelling evidence that E-selectin and its ligands play an important role in disease progression and drug resistance in MM.” And there is “a strong rationale” for targeting E-selectin and its ligands in patients with MM.

multiple myeloma

The E-selectin antagonist GMI-1271 can restore sensitivity to bortezomib in resistant multiple myeloma (MM), according to preclinical research published in Leukemia.

Researchers found evidence to suggest that E-selectin ligands induce an aggressive form of MM that is resistant to treatment with bortezomib.

However, treatment with GMI-1271 was able to overcome this resistance in a mouse model of the disease.

“The results in this preclinical study demonstrate that targeting E-selectin may provide a novel approach to treatment of patients with multiple myeloma and could potentially restore sensitivity to chemotherapy and, in particular, proteasome inhibitor therapy,” said John L. Magnani, PhD, vice-president and chief scientific officer of GlycoMimetics Inc., the company developing GMI-1271.

This research was supported by GlycoMimetics, and some of the researchers involved are employees of the company.

The researchers noted that E-selectin ligands are recognized by an antibody known as HECA452. So the team screened 9 MM cell lines for E-selectin ligands using HECA452.

Most of the cell lines were negative for HECA452. However, a minority of cells in 2 of the cell lines—11.2% of RPMI8226 cells and 2.4% of MM1S cells—were positive for HECA452.

So the researchers established HECA452-enriched cell lines from the RPMI8226 and MM1S cells to investigate the biology of E-selectin ligands in MM.

The team said they found that “HECA452-enriched cells express functional E-selectin ligands and exhibit enhanced rolling and adhesion capabilities on E-selectin, which are amenable to therapeutic intervention.”

Experiments in mice

To build on their in vitro findings, the researchers compared the effects of parental MM1S cells and HECA452-enriched MM1S cells in mice.

The team found that animals transplanted with HECA452-enriched cells had significantly shorter survival than those transplanted with parental MM1S cells.

The researchers said this difference is unlikely to be due to a different proliferation rate between the 2 cell types because they demonstrated comparable proliferation and clonogenic capacity in vitro.

The team then tested treatments in a second cohort of mice transplanted with parental or HECA452-enriched MM1S cells. The mice received saline, GMI-1271 alone, bortezomib alone, or GMI-1271 plus bortezomib.

In mice with parental MM1S cells, the median survival was 33 days in the saline group, 31 days in the GMI-1271 group, 42 days in the bortezomib group (P=0.0622 vs saline), and 60 days in the GMI-1271 plus bortezomib group (P=0.0101 vs saline, P=0.0363 vs bortezomib alone).

In mice with HECA452-enriched MM1S cells, the median survival was 25.5 days in the saline group, 30 days in the GMI-1271 group, 24 days in the bortezomib group (P=0.6743 vs saline), and 56.5 days in the GMI-1271 plus bortezomib group (P=0.0028 vs saline, P=0.0123 vs bortezomib alone).

The researchers said additional experiments in mice revealed that GMI-1271 mobilizes HECA452-positive human MM cells from the bone marrow into the peripheral blood.

Investigation in patients

Finally, the researchers evaluated the role of E-selectin and its ligands in patients with MM.

The team looked for HECA452-positive plasma cells in bone marrow samples from MM patients and found these cells were more common in patients with relapsed or refractory MM (14/50) than in those with newly diagnosed MM (1/33, P=0.009).

Next, the researchers analyzed RNA sequencing data from the CoMMpass study and found that increased expression of genes involved in E-selectin ligand synthesis (ST3Gal-6 or ST3Gal-4 and FUT7) is associated with poor progression-free survival (hazard ratio=1.37, P=0.02).

The team concluded that their results “provide compelling evidence that E-selectin and its ligands play an important role in disease progression and drug resistance in MM.” And there is “a strong rationale” for targeting E-selectin and its ligands in patients with MM.

multiple myeloma

The E-selectin antagonist GMI-1271 can restore sensitivity to bortezomib in resistant multiple myeloma (MM), according to preclinical research published in Leukemia.

Researchers found evidence to suggest that E-selectin ligands induce an aggressive form of MM that is resistant to treatment with bortezomib.

However, treatment with GMI-1271 was able to overcome this resistance in a mouse model of the disease.

“The results in this preclinical study demonstrate that targeting E-selectin may provide a novel approach to treatment of patients with multiple myeloma and could potentially restore sensitivity to chemotherapy and, in particular, proteasome inhibitor therapy,” said John L. Magnani, PhD, vice-president and chief scientific officer of GlycoMimetics Inc., the company developing GMI-1271.

This research was supported by GlycoMimetics, and some of the researchers involved are employees of the company.

The researchers noted that E-selectin ligands are recognized by an antibody known as HECA452. So the team screened 9 MM cell lines for E-selectin ligands using HECA452.

Most of the cell lines were negative for HECA452. However, a minority of cells in 2 of the cell lines—11.2% of RPMI8226 cells and 2.4% of MM1S cells—were positive for HECA452.

So the researchers established HECA452-enriched cell lines from the RPMI8226 and MM1S cells to investigate the biology of E-selectin ligands in MM.

The team said they found that “HECA452-enriched cells express functional E-selectin ligands and exhibit enhanced rolling and adhesion capabilities on E-selectin, which are amenable to therapeutic intervention.”

Experiments in mice

To build on their in vitro findings, the researchers compared the effects of parental MM1S cells and HECA452-enriched MM1S cells in mice.

The team found that animals transplanted with HECA452-enriched cells had significantly shorter survival than those transplanted with parental MM1S cells.

The researchers said this difference is unlikely to be due to a different proliferation rate between the 2 cell types because they demonstrated comparable proliferation and clonogenic capacity in vitro.

The team then tested treatments in a second cohort of mice transplanted with parental or HECA452-enriched MM1S cells. The mice received saline, GMI-1271 alone, bortezomib alone, or GMI-1271 plus bortezomib.

In mice with parental MM1S cells, the median survival was 33 days in the saline group, 31 days in the GMI-1271 group, 42 days in the bortezomib group (P=0.0622 vs saline), and 60 days in the GMI-1271 plus bortezomib group (P=0.0101 vs saline, P=0.0363 vs bortezomib alone).

In mice with HECA452-enriched MM1S cells, the median survival was 25.5 days in the saline group, 30 days in the GMI-1271 group, 24 days in the bortezomib group (P=0.6743 vs saline), and 56.5 days in the GMI-1271 plus bortezomib group (P=0.0028 vs saline, P=0.0123 vs bortezomib alone).

The researchers said additional experiments in mice revealed that GMI-1271 mobilizes HECA452-positive human MM cells from the bone marrow into the peripheral blood.

Investigation in patients

Finally, the researchers evaluated the role of E-selectin and its ligands in patients with MM.

The team looked for HECA452-positive plasma cells in bone marrow samples from MM patients and found these cells were more common in patients with relapsed or refractory MM (14/50) than in those with newly diagnosed MM (1/33, P=0.009).

Next, the researchers analyzed RNA sequencing data from the CoMMpass study and found that increased expression of genes involved in E-selectin ligand synthesis (ST3Gal-6 or ST3Gal-4 and FUT7) is associated with poor progression-free survival (hazard ratio=1.37, P=0.02).

The team concluded that their results “provide compelling evidence that E-selectin and its ligands play an important role in disease progression and drug resistance in MM.” And there is “a strong rationale” for targeting E-selectin and its ligands in patients with MM.

Photo by Steven Harbour

New research indicates that limiting how pharmaceutical sales representatives can market their products to physicians changes the physicians’ prescribing behaviors.

Researchers examined the effects of restrictions on pharmaceutical representatives’ visits to doctors’ offices at 19 academic medical centers in 5 US states.

The team found these restrictions were associated with “modest but significant” reductions in prescribing promoted drugs.

“Social science has long demonstrated that professionals, even well-meaning ones, are powerfully influenced by conflicts of interest,” said George Loewenstein, PhD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“A large body of research also shows that simply disclosing conflicts of interests is insufficient to reduce their influence and may even exacerbate it. The results from this study underline the effectiveness of, and need for, centralized rules and regulations.”

Dr Loewenstein and his colleagues reported the results of this study in JAMA.

The researchers noted that pharmaceutical sales representatives’ visits to doctors, which are known as “detailing,” are the most common form of interaction between physicians and industry. However, little was known about how practice-level detailing restrictions affect physician prescribing.

To gain some insight, Dr Loewenstein and his colleagues looked at the prescribing behavior of doctors whose practices did and did not have restrictions on detailing.

The team assessed the prescribing behavior of 2126 doctors at 19 academic medical centers in 5 states (California, Illinois, Massachusetts, Pennsylvania, and New York) before and after the centers introduced policies restricting detailing.

The researchers compared the prescribing behavior of these doctors with the prescribing behavior of a control group of 24,593 physicians practicing in the same geographic regions who were not subject to detailing restrictions.

The data covered 262 drugs in 8 major drug classes—ranging from statins to antidepressants—representing more than $60 billion in aggregate sales in the US.

In all, there were 16,121,483 prescriptions written between January 2006 and June 2012 by both intervention and control physicians.

Overall results

The researchers found the enactment of detailing restrictions was associated with a significant decrease in the prescribing of detailed drugs (1.67 percentage points of market share) and a significant increase in the prescribing of nondetailed drugs (0.84 percentage points, P<0.001 for both).

The mean market share of detailed drugs was 19.3% prior to the enactment of restrictions, so the 1.67 percentage-point reduction represented an 8.7% relative decrease in market share.

The mean market share of nondetailed drugs was 14.2% prior to the enactment of restrictions, so the 0.84 percentage-point increase represented a 5.6% relative increase in market share.

“The study cannot definitively prove a causal link between policies that regulated detailing and changes in physician prescribing, but, absent a randomized control, this evidence is as definitive as possible,” said study author Ian Larkin, PhD, of the University of California, Los Angeles.

“We investigated 19 different policy implementations that happened over a 6-year period, included a control group of highly similar physicians not subject to detailing restrictions, and looked at effects in 8 large drug classes. The results were remarkably robust. After the introduction of policies, about 5% to 10% of physician prescribing behavior changed.”

Results by drug class, medical center

The researchers said detailing restrictions were associated with significant changes in market share for 6 of the 8 drug classes studied (lipid-lowering drugs, gastroesophageal reflux disease drugs, antihypertensive drugs, sleep aids, attention-deficit/hyperactivity disorder drugs, and antidepressants).

Looking at the medical centers individually, the researchers found that detailing restrictions were associated with significant changes in market share for detailed drugs at 9 centers and for nondetailed drugs at 8 centers.

The team noted that detailing restrictions differed among the centers.

Eleven of the centers regulated gifts to physicians, restricted sales representatives’ access to facilities, and had explicit enforcement policies. For 8 of these 11 centers, there was a significant change in prescribing practices.

The remaining 8 centers had less stringent restrictions in that they did not cover all 3 areas of restriction (regulating gifts, restricting access, and having enforcement policies). There was a significant change in prescribing practices for only 1 of these centers.

“No medical center completely barred salesperson visits,” Dr Larkin noted. “Salespeople could and did continue to visit physicians at all medical centers in the study. The most common restriction put in place was a ban on meals and other small gifts.”

“The fact that regulating gifts while still allowing sales calls still led to a switch to cheaper, generic drugs may suggest that gifts such as meals play an important role in influencing physicians. The correlation between meals and prescribing has been well established in the literature, but our study suggests this relationship may be causal in nature.”

Photo by Steven Harbour

New research indicates that limiting how pharmaceutical sales representatives can market their products to physicians changes the physicians’ prescribing behaviors.

Researchers examined the effects of restrictions on pharmaceutical representatives’ visits to doctors’ offices at 19 academic medical centers in 5 US states.

The team found these restrictions were associated with “modest but significant” reductions in prescribing promoted drugs.

“Social science has long demonstrated that professionals, even well-meaning ones, are powerfully influenced by conflicts of interest,” said George Loewenstein, PhD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“A large body of research also shows that simply disclosing conflicts of interests is insufficient to reduce their influence and may even exacerbate it. The results from this study underline the effectiveness of, and need for, centralized rules and regulations.”

Dr Loewenstein and his colleagues reported the results of this study in JAMA.

The researchers noted that pharmaceutical sales representatives’ visits to doctors, which are known as “detailing,” are the most common form of interaction between physicians and industry. However, little was known about how practice-level detailing restrictions affect physician prescribing.

To gain some insight, Dr Loewenstein and his colleagues looked at the prescribing behavior of doctors whose practices did and did not have restrictions on detailing.

The team assessed the prescribing behavior of 2126 doctors at 19 academic medical centers in 5 states (California, Illinois, Massachusetts, Pennsylvania, and New York) before and after the centers introduced policies restricting detailing.

The researchers compared the prescribing behavior of these doctors with the prescribing behavior of a control group of 24,593 physicians practicing in the same geographic regions who were not subject to detailing restrictions.

The data covered 262 drugs in 8 major drug classes—ranging from statins to antidepressants—representing more than $60 billion in aggregate sales in the US.

In all, there were 16,121,483 prescriptions written between January 2006 and June 2012 by both intervention and control physicians.

Overall results

The researchers found the enactment of detailing restrictions was associated with a significant decrease in the prescribing of detailed drugs (1.67 percentage points of market share) and a significant increase in the prescribing of nondetailed drugs (0.84 percentage points, P<0.001 for both).

The mean market share of detailed drugs was 19.3% prior to the enactment of restrictions, so the 1.67 percentage-point reduction represented an 8.7% relative decrease in market share.

The mean market share of nondetailed drugs was 14.2% prior to the enactment of restrictions, so the 0.84 percentage-point increase represented a 5.6% relative increase in market share.

“The study cannot definitively prove a causal link between policies that regulated detailing and changes in physician prescribing, but, absent a randomized control, this evidence is as definitive as possible,” said study author Ian Larkin, PhD, of the University of California, Los Angeles.

“We investigated 19 different policy implementations that happened over a 6-year period, included a control group of highly similar physicians not subject to detailing restrictions, and looked at effects in 8 large drug classes. The results were remarkably robust. After the introduction of policies, about 5% to 10% of physician prescribing behavior changed.”

Results by drug class, medical center

The researchers said detailing restrictions were associated with significant changes in market share for 6 of the 8 drug classes studied (lipid-lowering drugs, gastroesophageal reflux disease drugs, antihypertensive drugs, sleep aids, attention-deficit/hyperactivity disorder drugs, and antidepressants).

Looking at the medical centers individually, the researchers found that detailing restrictions were associated with significant changes in market share for detailed drugs at 9 centers and for nondetailed drugs at 8 centers.

The team noted that detailing restrictions differed among the centers.

Eleven of the centers regulated gifts to physicians, restricted sales representatives’ access to facilities, and had explicit enforcement policies. For 8 of these 11 centers, there was a significant change in prescribing practices.

The remaining 8 centers had less stringent restrictions in that they did not cover all 3 areas of restriction (regulating gifts, restricting access, and having enforcement policies). There was a significant change in prescribing practices for only 1 of these centers.

“No medical center completely barred salesperson visits,” Dr Larkin noted. “Salespeople could and did continue to visit physicians at all medical centers in the study. The most common restriction put in place was a ban on meals and other small gifts.”

“The fact that regulating gifts while still allowing sales calls still led to a switch to cheaper, generic drugs may suggest that gifts such as meals play an important role in influencing physicians. The correlation between meals and prescribing has been well established in the literature, but our study suggests this relationship may be causal in nature.”

Photo by Steven Harbour

New research indicates that limiting how pharmaceutical sales representatives can market their products to physicians changes the physicians’ prescribing behaviors.

Researchers examined the effects of restrictions on pharmaceutical representatives’ visits to doctors’ offices at 19 academic medical centers in 5 US states.

The team found these restrictions were associated with “modest but significant” reductions in prescribing promoted drugs.

“Social science has long demonstrated that professionals, even well-meaning ones, are powerfully influenced by conflicts of interest,” said George Loewenstein, PhD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“A large body of research also shows that simply disclosing conflicts of interests is insufficient to reduce their influence and may even exacerbate it. The results from this study underline the effectiveness of, and need for, centralized rules and regulations.”

Dr Loewenstein and his colleagues reported the results of this study in JAMA.

The researchers noted that pharmaceutical sales representatives’ visits to doctors, which are known as “detailing,” are the most common form of interaction between physicians and industry. However, little was known about how practice-level detailing restrictions affect physician prescribing.

To gain some insight, Dr Loewenstein and his colleagues looked at the prescribing behavior of doctors whose practices did and did not have restrictions on detailing.

The team assessed the prescribing behavior of 2126 doctors at 19 academic medical centers in 5 states (California, Illinois, Massachusetts, Pennsylvania, and New York) before and after the centers introduced policies restricting detailing.

The researchers compared the prescribing behavior of these doctors with the prescribing behavior of a control group of 24,593 physicians practicing in the same geographic regions who were not subject to detailing restrictions.

The data covered 262 drugs in 8 major drug classes—ranging from statins to antidepressants—representing more than $60 billion in aggregate sales in the US.

In all, there were 16,121,483 prescriptions written between January 2006 and June 2012 by both intervention and control physicians.

Overall results

The researchers found the enactment of detailing restrictions was associated with a significant decrease in the prescribing of detailed drugs (1.67 percentage points of market share) and a significant increase in the prescribing of nondetailed drugs (0.84 percentage points, P<0.001 for both).

The mean market share of detailed drugs was 19.3% prior to the enactment of restrictions, so the 1.67 percentage-point reduction represented an 8.7% relative decrease in market share.

The mean market share of nondetailed drugs was 14.2% prior to the enactment of restrictions, so the 0.84 percentage-point increase represented a 5.6% relative increase in market share.

“The study cannot definitively prove a causal link between policies that regulated detailing and changes in physician prescribing, but, absent a randomized control, this evidence is as definitive as possible,” said study author Ian Larkin, PhD, of the University of California, Los Angeles.

“We investigated 19 different policy implementations that happened over a 6-year period, included a control group of highly similar physicians not subject to detailing restrictions, and looked at effects in 8 large drug classes. The results were remarkably robust. After the introduction of policies, about 5% to 10% of physician prescribing behavior changed.”

Results by drug class, medical center

The researchers said detailing restrictions were associated with significant changes in market share for 6 of the 8 drug classes studied (lipid-lowering drugs, gastroesophageal reflux disease drugs, antihypertensive drugs, sleep aids, attention-deficit/hyperactivity disorder drugs, and antidepressants).

Looking at the medical centers individually, the researchers found that detailing restrictions were associated with significant changes in market share for detailed drugs at 9 centers and for nondetailed drugs at 8 centers.

The team noted that detailing restrictions differed among the centers.

Eleven of the centers regulated gifts to physicians, restricted sales representatives’ access to facilities, and had explicit enforcement policies. For 8 of these 11 centers, there was a significant change in prescribing practices.

The remaining 8 centers had less stringent restrictions in that they did not cover all 3 areas of restriction (regulating gifts, restricting access, and having enforcement policies). There was a significant change in prescribing practices for only 1 of these centers.

“No medical center completely barred salesperson visits,” Dr Larkin noted. “Salespeople could and did continue to visit physicians at all medical centers in the study. The most common restriction put in place was a ban on meals and other small gifts.”

“The fact that regulating gifts while still allowing sales calls still led to a switch to cheaper, generic drugs may suggest that gifts such as meals play an important role in influencing physicians. The correlation between meals and prescribing has been well established in the literature, but our study suggests this relationship may be causal in nature.”