In most high-income countries, including the US, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² In the absence of a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the CDC began recommending daily use of tenofovir, disoproxil, fumarate, and emtricitabine (TDF-FTC) in high-risk individuals as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT], 46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably due to the difficulty in getting patients to take the medication daily.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ This is because, until now, no studies had demonstrated the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays study—a double-blind, multicenter study conducted in France and Canada—assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis proposed that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk for HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection—defined as having a history of unprotected anal sex with at least two partners in the past six months. Other inclusion criteria included an age of at least 18 and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance < 60 mL/min, alanine aminotransferase level more than 2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. Those who withdrew consent, were lost to follow-up, or acquired HIV-1 infection were excluded, and the remaining study participants were randomized to take TDF-FTC (n = 199) or placebo (n = 201) before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. Participants were instructed to take a loading dose of two pills of TDF-FTC or placebo with food two to 24 hours prior to intercourse, a third pill 24 hours later, and a fourth pill 24 hours after the third.

If there were multiple consecutive days of sexual intercourse, participants were to take one pill on each day of intercourse, followed by the two postexposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the PrEP; otherwise, they were to begin again with two pills two to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants four and eight weeks after enrollment, then every eight weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count, drug levels in plasma, and with an at-home, computer-assisted interview completed by participants prior to each visit.

Participants received counseling from a peer community member and were offered preventive services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took their assigned pills correctly. Participants were followed for a median of 9.3 months. Overall, 72% of participants took the study drugs (TDF-FTC or placebo), but 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. After 20 months, the study was unblinded and is now continuing as an open-label study because of the discontinuation of another PrEP study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk for HIV without PrEP. The open-label part of the study (iPrex-OLE) completed enrollment and data gathering in November 2013. The data analysis and results are pending.⁹

Eighty-six percent experienced relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with three of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group and two of the new cases were in the TDF-FTC group. This translated to an 86% relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group (NNT, 17 over 9.3 months).

The two cases in the TDF-FTC group occurred in participants found to be nonadherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain, which were seen more commonly in the treatment group than in the placebo group (14% vs 5%; number needed to harm, 11). There were also mild increases in serum creatinine level, but only two participants had a transient decrease in creatinine clearance to < 60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction nearly doubles

This is the first study to look at on-demand PrEP with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the increased benefit of on-demand PrEP is likely due to improved compliance with medication use.

CAVEATS

Can adherence be maintained?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we need to wait for the results of the open-label study to fully assess the risk for adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of the medication; the retail price of TDF-FTC is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

ACKNOWLEDGEMENT

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

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(8):556-558.

In most high-income countries, including the US, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² In the absence of a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the CDC began recommending daily use of tenofovir, disoproxil, fumarate, and emtricitabine (TDF-FTC) in high-risk individuals as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT], 46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably due to the difficulty in getting patients to take the medication daily.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ This is because, until now, no studies had demonstrated the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays study—a double-blind, multicenter study conducted in France and Canada—assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis proposed that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk for HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection—defined as having a history of unprotected anal sex with at least two partners in the past six months. Other inclusion criteria included an age of at least 18 and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance < 60 mL/min, alanine aminotransferase level more than 2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. Those who withdrew consent, were lost to follow-up, or acquired HIV-1 infection were excluded, and the remaining study participants were randomized to take TDF-FTC (n = 199) or placebo (n = 201) before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. Participants were instructed to take a loading dose of two pills of TDF-FTC or placebo with food two to 24 hours prior to intercourse, a third pill 24 hours later, and a fourth pill 24 hours after the third.

If there were multiple consecutive days of sexual intercourse, participants were to take one pill on each day of intercourse, followed by the two postexposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the PrEP; otherwise, they were to begin again with two pills two to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants four and eight weeks after enrollment, then every eight weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count, drug levels in plasma, and with an at-home, computer-assisted interview completed by participants prior to each visit.

Participants received counseling from a peer community member and were offered preventive services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took their assigned pills correctly. Participants were followed for a median of 9.3 months. Overall, 72% of participants took the study drugs (TDF-FTC or placebo), but 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. After 20 months, the study was unblinded and is now continuing as an open-label study because of the discontinuation of another PrEP study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk for HIV without PrEP. The open-label part of the study (iPrex-OLE) completed enrollment and data gathering in November 2013. The data analysis and results are pending.⁹

Eighty-six percent experienced relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with three of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group and two of the new cases were in the TDF-FTC group. This translated to an 86% relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group (NNT, 17 over 9.3 months).

The two cases in the TDF-FTC group occurred in participants found to be nonadherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain, which were seen more commonly in the treatment group than in the placebo group (14% vs 5%; number needed to harm, 11). There were also mild increases in serum creatinine level, but only two participants had a transient decrease in creatinine clearance to < 60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction nearly doubles

This is the first study to look at on-demand PrEP with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the increased benefit of on-demand PrEP is likely due to improved compliance with medication use.

CAVEATS

Can adherence be maintained?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we need to wait for the results of the open-label study to fully assess the risk for adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of the medication; the retail price of TDF-FTC is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

ACKNOWLEDGEMENT

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

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(8):556-558.

In most high-income countries, including the US, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² In the absence of a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the CDC began recommending daily use of tenofovir, disoproxil, fumarate, and emtricitabine (TDF-FTC) in high-risk individuals as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT], 46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably due to the difficulty in getting patients to take the medication daily.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ This is because, until now, no studies had demonstrated the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays study—a double-blind, multicenter study conducted in France and Canada—assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis proposed that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk for HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection—defined as having a history of unprotected anal sex with at least two partners in the past six months. Other inclusion criteria included an age of at least 18 and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance < 60 mL/min, alanine aminotransferase level more than 2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. Those who withdrew consent, were lost to follow-up, or acquired HIV-1 infection were excluded, and the remaining study participants were randomized to take TDF-FTC (n = 199) or placebo (n = 201) before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. Participants were instructed to take a loading dose of two pills of TDF-FTC or placebo with food two to 24 hours prior to intercourse, a third pill 24 hours later, and a fourth pill 24 hours after the third.

If there were multiple consecutive days of sexual intercourse, participants were to take one pill on each day of intercourse, followed by the two postexposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the PrEP; otherwise, they were to begin again with two pills two to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants four and eight weeks after enrollment, then every eight weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count, drug levels in plasma, and with an at-home, computer-assisted interview completed by participants prior to each visit.

Participants received counseling from a peer community member and were offered preventive services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took their assigned pills correctly. Participants were followed for a median of 9.3 months. Overall, 72% of participants took the study drugs (TDF-FTC or placebo), but 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. After 20 months, the study was unblinded and is now continuing as an open-label study because of the discontinuation of another PrEP study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk for HIV without PrEP. The open-label part of the study (iPrex-OLE) completed enrollment and data gathering in November 2013. The data analysis and results are pending.⁹

Eighty-six percent experienced relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with three of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group and two of the new cases were in the TDF-FTC group. This translated to an 86% relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group (NNT, 17 over 9.3 months).

The two cases in the TDF-FTC group occurred in participants found to be nonadherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain, which were seen more commonly in the treatment group than in the placebo group (14% vs 5%; number needed to harm, 11). There were also mild increases in serum creatinine level, but only two participants had a transient decrease in creatinine clearance to < 60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction nearly doubles

This is the first study to look at on-demand PrEP with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the increased benefit of on-demand PrEP is likely due to improved compliance with medication use.

CAVEATS

Can adherence be maintained?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we need to wait for the results of the open-label study to fully assess the risk for adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of the medication; the retail price of TDF-FTC is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

ACKNOWLEDGEMENT

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

Copyright © 2016. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2016;65(8):556-558.

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

[email protected]

On Twitter @jessnicolecraig

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

[email protected]

On Twitter @jessnicolecraig

Obese patients who underwent Roux-en-Y gastric bypass had higher percentages of weight loss at long-term follow-up, compared with obese patients who underwent other surgical procedures or who did not undergo surgery, according to a large, cohort study published in JAMA Surgery.

While prior research has clearly demonstrated that bariatric surgery is the most effective intervention for inducing weight loss among obese patients, the majority of those studies were short term; therefore, there is little known about the durability of weight loss following bariatric surgery, wrote Matthew Maciejewski, PhD, of Duke University, Durham, N.C., and Durham Veterans Affairs Medical Center and his associates.

This study compared the 10-year weight change in patients who underwent Roux-en-Y gastric bypass to patients who did not receive bariatric surgical intervention of any kind. A total of 1,787 patients who had undergone Roux-en-Y gastric bypass surgery were identified and matched by investigators to one or more patients with similar demographic characteristics (age, sex, race, body mass index, diabetes diagnosis). A total of 5,305 nonsurgical matches were selected for analysis. For the Roux-en-Y gastric bypass group, mean age was 52.1 years, and for the nonsurgical matches mean age was 52.2 years. Both groups were predominantly male (73.1% and 73.7%, respectively) and had high 10-year follow-up rates of 81.9% for surgical patients and 67.4% for nonsurgical matches (JAMA Surgery. 2016. doi: 10.1001/jamasurg.2016.2317).

The study’s primary outcome of percentage change in weight at 10-year follow-up, compared with baseline strongly favored Roux-en-Y gastric bypass over no surgical intervention. At the 10-year time point, patients who underwent Roux-en-Y gastric bypass had lost 21.3% more of their baseline weight than nonsurgical matches.

Remarkably, only 3.4% of patients who underwent Roux-en-Y gastric bypass were within 5% of their original baseline weight at 10 years while 55.5% of those who did not receive surgical intervention had regained most of their weight.

Additionally, investigators compared percentage change in weight at 4-year follow-up for obese patients who underwent either Roux-en-Y gastric bypass (n = 1,785), sleeve gastrectomy (n = 379), or adjustable gastric banding (n = 246). At this time point, patients who underwent Roux-en-Y gastric bypass had lost an average of 28% of their baseline weight while patients who underwent sleeve gastrectomy or adjustable gastric banding only lost 18% and 11% of their baseline weights, respectively.

“These results provide further evidence for the beneficial association between surgery and long-term weight loss that has been demonstrated in shorter-term studies of younger, predominantly female populations,” the investigators concluded.

This study was funded by the Department of Veterans Affairs. Dr. Maciejewski and four of his associates reported receiving financial compensation from or holding stock in various companies and institutions including the Department of Veterans Affairs.

[email protected]

On Twitter @jessnicolecraig

Going to medical school at Universidad Autónoma de Guadalajara in Guadalajara, Mexico, could have been too much for Benjamin Frizner, MD, FHM.

Medicine is its own new language, as any first-year can tell you. Throw in learning Spanish? And a new culture? One could be forgiven for not excelling.

Dr. Frizner isn’t one of those people.

“The experience changed my life,” he says. “After I survived the first year, I knew I loved medicine.”

After medical school, Dr. Frizner had to complete a Fifth Pathway program, which formerly allowed students who completed four years at a foreign medical school to finish supervised clinical work at a U.S. medical school and become eligible as a U.S. resident.

He learned of hospital medicine during his residency at York Hospital in York, Pa., and, despite others suggesting hospital medicine was “something to do before you really figure out your career,” he enjoyed both working within the hospital walls and having a schedule that allowed 15 shifts a month and commensurate time off.

But as with his shift from undergraduate school in suburban Maryland to medical school in Mexico, Dr. Frizner likes a new challenge. So after a four-year stint as director of the hospitalist program at Saint Agnes Hospital in Baltimore, he took a job in August 2015 as director of the Ventilator Unit at FutureCare Irvington, a post-acute-care center in Baltimore staffed by CEP America.

“Post-acute care has become a new passion and chapter in my career,” he says, adding, “Skilled nursing facilities are extensions of the acute-care hospital and are just as challenging and fulfilling as hospitalist work.”

It’s a perspective Dr. Frizner will bring as one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Why did you choose a career in medicine?

Answer: I enjoyed math and biology in college. I started out thinking I would be an engineer but fell in love with anatomy. I like solving problems and working with people. Internal medicine/hospital medicine is a perfect match, working to solve a patient’s diagnosis and helping families make difficult decisions about placement and palliative care.

Q: What do you like most about working as a hospitalist?

A: Interacting with all the different specialties, social work, case management, residents, ED docs. I really enjoy the camaraderie.

Q: What do you dislike most?

A: Hospital groups contribute immensely to patient flow, care, quality, process improvement, throughput, but hospitals always advertise the new specialist and never the excellent hospitalist group.

Q: What’s the best advice you ever received?

A: No matter what, do what is best for the patient. Everything else will take care of itself.

Q: What’s the worst advice you ever received?

A: Don’t worry about the contract; you don’t need to really look it over.

Q: What’s the biggest change you’ve seen in HM in your career?

A: The pace of medicine continues to speed up. Residents have to hit the ground running with baseline case-management knowledge.

Q: What’s the biggest change you would like to see in HM?

A: I would like to see more hospitalists ascend into senior leadership in hospitals and healthcare systems.

Q: Why should group leaders continue to see patients?

A: It is important to maintain trust and respect with docs you are leading and managing. When I was a hospitalist director, I made sure I worked nights and weekends so I could understand the workload during those shifts and my team felt I was not just dumping on them.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Establishing trust with the patient and their family. But it has become second nature to me at this point. The secret is to introduce yourself, tell the patient and family you will take care of them in the hospital, communicate with their outpatient physician and that you are part of a 24-7 team of docs there to take care of the patient.

Q: What aspect of patient care is most rewarding?

A: Helping families navigate end-of-life decisions. It is the most stressful time in a family’s life, and I think it is the most rewarding and honorable part of practicing medicine.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I lead teaching rounds a few months a year when I was a hospitalist director, and I think the most difficult part is getting the residents to understand the workload will be a lot tougher when they get out into the real world. During their third year, residents need to practice efficiency and gauge their work ethic—not the kind of work ethic needed to pass the boards but the kind needed to stay in the ED and help your teammate out until the admissions are caught up or round on a few extra patients when there is a surge in the census.

Q: What is your biggest professional challenge?

A: [Getting others to] stop underestimating my skills and experience as a hospitalist and physician leader. I will complete an MBA through ACPE UMass this December. Learning basic accounting, business law, and finance has helped round out blind spots and build my confidence.

Q: What is your biggest professional reward?

A: Completing quality improvement projects such as increasing DVT prophylaxis, reducing CAUTI, and decreasing throughput times, which all help make the hospital course safer and efficient for the patient.

Q: What SHM event made the most lasting impression on you?

A: Seven years ago, I attended the Level I leadership academy at the Aria hotel in Las Vegas. The meeting opened my eyes to the world of leadership, management, and healthcare economics, which sparked my drive to eventually become a hospitalist director.

Q: What’s the best book you’ve read recently? Why?

A: David and Goliath by Malcolm Gladwell. As a foreign medical graduate, I was told there would be limits to what I could achieve in my career. Mr. Gladwell’s book is filled with stories of people who overcame difficult situations and went on to rise to the top of their fields.

Richard Quinn is a freelance writer in New Jersey.

Going to medical school at Universidad Autónoma de Guadalajara in Guadalajara, Mexico, could have been too much for Benjamin Frizner, MD, FHM.

Medicine is its own new language, as any first-year can tell you. Throw in learning Spanish? And a new culture? One could be forgiven for not excelling.

Dr. Frizner isn’t one of those people.

“The experience changed my life,” he says. “After I survived the first year, I knew I loved medicine.”

After medical school, Dr. Frizner had to complete a Fifth Pathway program, which formerly allowed students who completed four years at a foreign medical school to finish supervised clinical work at a U.S. medical school and become eligible as a U.S. resident.

He learned of hospital medicine during his residency at York Hospital in York, Pa., and, despite others suggesting hospital medicine was “something to do before you really figure out your career,” he enjoyed both working within the hospital walls and having a schedule that allowed 15 shifts a month and commensurate time off.

But as with his shift from undergraduate school in suburban Maryland to medical school in Mexico, Dr. Frizner likes a new challenge. So after a four-year stint as director of the hospitalist program at Saint Agnes Hospital in Baltimore, he took a job in August 2015 as director of the Ventilator Unit at FutureCare Irvington, a post-acute-care center in Baltimore staffed by CEP America.

“Post-acute care has become a new passion and chapter in my career,” he says, adding, “Skilled nursing facilities are extensions of the acute-care hospital and are just as challenging and fulfilling as hospitalist work.”

It’s a perspective Dr. Frizner will bring as one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Why did you choose a career in medicine?

Answer: I enjoyed math and biology in college. I started out thinking I would be an engineer but fell in love with anatomy. I like solving problems and working with people. Internal medicine/hospital medicine is a perfect match, working to solve a patient’s diagnosis and helping families make difficult decisions about placement and palliative care.

Q: What do you like most about working as a hospitalist?

A: Interacting with all the different specialties, social work, case management, residents, ED docs. I really enjoy the camaraderie.

Q: What do you dislike most?

A: Hospital groups contribute immensely to patient flow, care, quality, process improvement, throughput, but hospitals always advertise the new specialist and never the excellent hospitalist group.

Q: What’s the best advice you ever received?

A: No matter what, do what is best for the patient. Everything else will take care of itself.

Q: What’s the worst advice you ever received?

A: Don’t worry about the contract; you don’t need to really look it over.

Q: What’s the biggest change you’ve seen in HM in your career?

A: The pace of medicine continues to speed up. Residents have to hit the ground running with baseline case-management knowledge.

Q: What’s the biggest change you would like to see in HM?

A: I would like to see more hospitalists ascend into senior leadership in hospitals and healthcare systems.

Q: Why should group leaders continue to see patients?

A: It is important to maintain trust and respect with docs you are leading and managing. When I was a hospitalist director, I made sure I worked nights and weekends so I could understand the workload during those shifts and my team felt I was not just dumping on them.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Establishing trust with the patient and their family. But it has become second nature to me at this point. The secret is to introduce yourself, tell the patient and family you will take care of them in the hospital, communicate with their outpatient physician and that you are part of a 24-7 team of docs there to take care of the patient.

Q: What aspect of patient care is most rewarding?

A: Helping families navigate end-of-life decisions. It is the most stressful time in a family’s life, and I think it is the most rewarding and honorable part of practicing medicine.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I lead teaching rounds a few months a year when I was a hospitalist director, and I think the most difficult part is getting the residents to understand the workload will be a lot tougher when they get out into the real world. During their third year, residents need to practice efficiency and gauge their work ethic—not the kind of work ethic needed to pass the boards but the kind needed to stay in the ED and help your teammate out until the admissions are caught up or round on a few extra patients when there is a surge in the census.

Q: What is your biggest professional challenge?

A: [Getting others to] stop underestimating my skills and experience as a hospitalist and physician leader. I will complete an MBA through ACPE UMass this December. Learning basic accounting, business law, and finance has helped round out blind spots and build my confidence.

Q: What is your biggest professional reward?

A: Completing quality improvement projects such as increasing DVT prophylaxis, reducing CAUTI, and decreasing throughput times, which all help make the hospital course safer and efficient for the patient.

Q: What SHM event made the most lasting impression on you?

A: Seven years ago, I attended the Level I leadership academy at the Aria hotel in Las Vegas. The meeting opened my eyes to the world of leadership, management, and healthcare economics, which sparked my drive to eventually become a hospitalist director.

Q: What’s the best book you’ve read recently? Why?

A: David and Goliath by Malcolm Gladwell. As a foreign medical graduate, I was told there would be limits to what I could achieve in my career. Mr. Gladwell’s book is filled with stories of people who overcame difficult situations and went on to rise to the top of their fields.

Richard Quinn is a freelance writer in New Jersey.

Going to medical school at Universidad Autónoma de Guadalajara in Guadalajara, Mexico, could have been too much for Benjamin Frizner, MD, FHM.

Medicine is its own new language, as any first-year can tell you. Throw in learning Spanish? And a new culture? One could be forgiven for not excelling.

Dr. Frizner isn’t one of those people.

“The experience changed my life,” he says. “After I survived the first year, I knew I loved medicine.”

After medical school, Dr. Frizner had to complete a Fifth Pathway program, which formerly allowed students who completed four years at a foreign medical school to finish supervised clinical work at a U.S. medical school and become eligible as a U.S. resident.

He learned of hospital medicine during his residency at York Hospital in York, Pa., and, despite others suggesting hospital medicine was “something to do before you really figure out your career,” he enjoyed both working within the hospital walls and having a schedule that allowed 15 shifts a month and commensurate time off.

But as with his shift from undergraduate school in suburban Maryland to medical school in Mexico, Dr. Frizner likes a new challenge. So after a four-year stint as director of the hospitalist program at Saint Agnes Hospital in Baltimore, he took a job in August 2015 as director of the Ventilator Unit at FutureCare Irvington, a post-acute-care center in Baltimore staffed by CEP America.

“Post-acute care has become a new passion and chapter in my career,” he says, adding, “Skilled nursing facilities are extensions of the acute-care hospital and are just as challenging and fulfilling as hospitalist work.”

It’s a perspective Dr. Frizner will bring as one of eight new members of Team Hospitalist, The Hospitalist’s volunteer editorial advisory board.

Question: Why did you choose a career in medicine?

Answer: I enjoyed math and biology in college. I started out thinking I would be an engineer but fell in love with anatomy. I like solving problems and working with people. Internal medicine/hospital medicine is a perfect match, working to solve a patient’s diagnosis and helping families make difficult decisions about placement and palliative care.

Q: What do you like most about working as a hospitalist?

A: Interacting with all the different specialties, social work, case management, residents, ED docs. I really enjoy the camaraderie.

Q: What do you dislike most?

A: Hospital groups contribute immensely to patient flow, care, quality, process improvement, throughput, but hospitals always advertise the new specialist and never the excellent hospitalist group.

Q: What’s the best advice you ever received?

A: No matter what, do what is best for the patient. Everything else will take care of itself.

Q: What’s the worst advice you ever received?

A: Don’t worry about the contract; you don’t need to really look it over.

Q: What’s the biggest change you’ve seen in HM in your career?

A: The pace of medicine continues to speed up. Residents have to hit the ground running with baseline case-management knowledge.

Q: What’s the biggest change you would like to see in HM?

A: I would like to see more hospitalists ascend into senior leadership in hospitals and healthcare systems.

Q: Why should group leaders continue to see patients?

A: It is important to maintain trust and respect with docs you are leading and managing. When I was a hospitalist director, I made sure I worked nights and weekends so I could understand the workload during those shifts and my team felt I was not just dumping on them.

Q: As a hospitalist, seeing most of your patients for the very first time, what aspect of patient care is most challenging?

A: Establishing trust with the patient and their family. But it has become second nature to me at this point. The secret is to introduce yourself, tell the patient and family you will take care of them in the hospital, communicate with their outpatient physician and that you are part of a 24-7 team of docs there to take care of the patient.

Q: What aspect of patient care is most rewarding?

A: Helping families navigate end-of-life decisions. It is the most stressful time in a family’s life, and I think it is the most rewarding and honorable part of practicing medicine.

Q: Are you on teaching service? If so, what aspect of teaching in the 21st century is most difficult? And what is most enjoyable?

A: I lead teaching rounds a few months a year when I was a hospitalist director, and I think the most difficult part is getting the residents to understand the workload will be a lot tougher when they get out into the real world. During their third year, residents need to practice efficiency and gauge their work ethic—not the kind of work ethic needed to pass the boards but the kind needed to stay in the ED and help your teammate out until the admissions are caught up or round on a few extra patients when there is a surge in the census.

Q: What is your biggest professional challenge?

A: [Getting others to] stop underestimating my skills and experience as a hospitalist and physician leader. I will complete an MBA through ACPE UMass this December. Learning basic accounting, business law, and finance has helped round out blind spots and build my confidence.

Q: What is your biggest professional reward?

A: Completing quality improvement projects such as increasing DVT prophylaxis, reducing CAUTI, and decreasing throughput times, which all help make the hospital course safer and efficient for the patient.

Q: What SHM event made the most lasting impression on you?

A: Seven years ago, I attended the Level I leadership academy at the Aria hotel in Las Vegas. The meeting opened my eyes to the world of leadership, management, and healthcare economics, which sparked my drive to eventually become a hospitalist director.

Q: What’s the best book you’ve read recently? Why?

A: David and Goliath by Malcolm Gladwell. As a foreign medical graduate, I was told there would be limits to what I could achieve in my career. Mr. Gladwell’s book is filled with stories of people who overcame difficult situations and went on to rise to the top of their fields.

Richard Quinn is a freelance writer in New Jersey.

Three generations

of women in a family

ROME—According to researchers, a clinical decision rule can identify women who, after their first unprovoked venous thromboembolism (VTE), have a low risk of VTE recurrence and might safely discontinue anticoagulant therapy.

The researchers evaluated the HERDOO2 rule, which is named after the risk factors the rule employs to determine the likelihood of VTE recurrence, in the REVERSE II trial.

Results from the trial were presented at ESC Congress 2016 (abstract 5721).

According to the HERDOO2 rule, the following risk factors must be considered to determine a patient’s risk of VTE recurrence:

1. Hyperpigmentation, Edema, or Redness in either leg
2. D-dimer >250 μg/mL on anticoagulants
3. Obesity with body mass index >30 kg/m²
4. Older than age 65.

Women (but not men) are considered at low risk of VTE recurrence if they have 0 to 1 of these risk factors.

In the REVERSE II trial, researchers tested the HERDOO2 rule in 2779 male and female patients with a first unprovoked VTE who had completed 5 to 12 months of anticoagulant therapy.

After drop-outs and exclusions, 622 women were considered low-risk, based on HERDOO2 criteria, and the majority of these women (n=591) discontinued anticoagulant therapy.

Thirty-one low-risk women continued anticoagulant therapy, as did 1802 men and high-risk women (with 2 or more HERDOO2 criteria). Three hundred and twenty-three men and high-risk women discontinued anticoagulant therapy.

After a year of follow-up, low-risk women who had discontinued anticoagulants had a 3% rate of recurrent VTE per patient year, and low-risk women who continued anticoagulant therapy had no VTEs.

Among the men and high-risk women, the rate of recurrent VTE per patient year was 8.1% in patients who discontinued therapy and 1.6% in patients who continued to receive anticoagulant therapy.

“This is an important finding as, using our rule, over half of women with unprovoked VTE can safely discontinue anticoagulants and be spared the burdens, costs, and risks of life-long anticoagulation,” said study investigator Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.

“Since current consensus guidelines suggest anticoagulants should be continued indefinitely in all patients with unprovoked VTE and non-high bleeding risk, our results are potentially practice-changing.”

Dr Rodger noted, however, that questions remain regarding anticoagulation duration after a first unprovoked VTE.

“One is whether indefinite anticoagulation is required for men and high-risk women, [which] was not the primary focus of our study,” he said. “The second is in the subgroup of post-menopausal women aged 50 and above.”

“In this group, even those who were considered low-risk according to the HERDOO2 rule had a higher than expected rate of recurrent VTE (5.7%) when they discontinued anticoagulants. As such, further validation of HERDOO2 is required in this subset of post-menopausal women.”

Three generations

of women in a family

ROME—According to researchers, a clinical decision rule can identify women who, after their first unprovoked venous thromboembolism (VTE), have a low risk of VTE recurrence and might safely discontinue anticoagulant therapy.

The researchers evaluated the HERDOO2 rule, which is named after the risk factors the rule employs to determine the likelihood of VTE recurrence, in the REVERSE II trial.

Results from the trial were presented at ESC Congress 2016 (abstract 5721).

According to the HERDOO2 rule, the following risk factors must be considered to determine a patient’s risk of VTE recurrence:

1. Hyperpigmentation, Edema, or Redness in either leg
2. D-dimer >250 μg/mL on anticoagulants
3. Obesity with body mass index >30 kg/m²
4. Older than age 65.

Women (but not men) are considered at low risk of VTE recurrence if they have 0 to 1 of these risk factors.

In the REVERSE II trial, researchers tested the HERDOO2 rule in 2779 male and female patients with a first unprovoked VTE who had completed 5 to 12 months of anticoagulant therapy.

After drop-outs and exclusions, 622 women were considered low-risk, based on HERDOO2 criteria, and the majority of these women (n=591) discontinued anticoagulant therapy.

Thirty-one low-risk women continued anticoagulant therapy, as did 1802 men and high-risk women (with 2 or more HERDOO2 criteria). Three hundred and twenty-three men and high-risk women discontinued anticoagulant therapy.

After a year of follow-up, low-risk women who had discontinued anticoagulants had a 3% rate of recurrent VTE per patient year, and low-risk women who continued anticoagulant therapy had no VTEs.

Among the men and high-risk women, the rate of recurrent VTE per patient year was 8.1% in patients who discontinued therapy and 1.6% in patients who continued to receive anticoagulant therapy.

“This is an important finding as, using our rule, over half of women with unprovoked VTE can safely discontinue anticoagulants and be spared the burdens, costs, and risks of life-long anticoagulation,” said study investigator Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.

“Since current consensus guidelines suggest anticoagulants should be continued indefinitely in all patients with unprovoked VTE and non-high bleeding risk, our results are potentially practice-changing.”

Dr Rodger noted, however, that questions remain regarding anticoagulation duration after a first unprovoked VTE.

“One is whether indefinite anticoagulation is required for men and high-risk women, [which] was not the primary focus of our study,” he said. “The second is in the subgroup of post-menopausal women aged 50 and above.”

“In this group, even those who were considered low-risk according to the HERDOO2 rule had a higher than expected rate of recurrent VTE (5.7%) when they discontinued anticoagulants. As such, further validation of HERDOO2 is required in this subset of post-menopausal women.”

Three generations

of women in a family

ROME—According to researchers, a clinical decision rule can identify women who, after their first unprovoked venous thromboembolism (VTE), have a low risk of VTE recurrence and might safely discontinue anticoagulant therapy.

The researchers evaluated the HERDOO2 rule, which is named after the risk factors the rule employs to determine the likelihood of VTE recurrence, in the REVERSE II trial.

Results from the trial were presented at ESC Congress 2016 (abstract 5721).

According to the HERDOO2 rule, the following risk factors must be considered to determine a patient’s risk of VTE recurrence:

1. Hyperpigmentation, Edema, or Redness in either leg
2. D-dimer >250 μg/mL on anticoagulants
3. Obesity with body mass index >30 kg/m²
4. Older than age 65.

Women (but not men) are considered at low risk of VTE recurrence if they have 0 to 1 of these risk factors.

In the REVERSE II trial, researchers tested the HERDOO2 rule in 2779 male and female patients with a first unprovoked VTE who had completed 5 to 12 months of anticoagulant therapy.

After drop-outs and exclusions, 622 women were considered low-risk, based on HERDOO2 criteria, and the majority of these women (n=591) discontinued anticoagulant therapy.

Thirty-one low-risk women continued anticoagulant therapy, as did 1802 men and high-risk women (with 2 or more HERDOO2 criteria). Three hundred and twenty-three men and high-risk women discontinued anticoagulant therapy.

After a year of follow-up, low-risk women who had discontinued anticoagulants had a 3% rate of recurrent VTE per patient year, and low-risk women who continued anticoagulant therapy had no VTEs.

Among the men and high-risk women, the rate of recurrent VTE per patient year was 8.1% in patients who discontinued therapy and 1.6% in patients who continued to receive anticoagulant therapy.

“This is an important finding as, using our rule, over half of women with unprovoked VTE can safely discontinue anticoagulants and be spared the burdens, costs, and risks of life-long anticoagulation,” said study investigator Marc Rodger, MD, of Ottawa Hospital and University of Ottawa in Ontario, Canada.

“Since current consensus guidelines suggest anticoagulants should be continued indefinitely in all patients with unprovoked VTE and non-high bleeding risk, our results are potentially practice-changing.”

Dr Rodger noted, however, that questions remain regarding anticoagulation duration after a first unprovoked VTE.

“One is whether indefinite anticoagulation is required for men and high-risk women, [which] was not the primary focus of our study,” he said. “The second is in the subgroup of post-menopausal women aged 50 and above.”

“In this group, even those who were considered low-risk according to the HERDOO2 rule had a higher than expected rate of recurrent VTE (5.7%) when they discontinued anticoagulants. As such, further validation of HERDOO2 is required in this subset of post-menopausal women.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Red blood cell culture showing

Staphylococcus infection

Photo by Bill Branson

Ambulatory bloodstream infections (BSIs) can be costly in young cancer patients and recipients of hematopoietic stem cell transplants, according to research published in Pediatric Blood & Cancer.

Among the 61 patients studied, the median cost for an ambulatory BSI was $40,852, and the median length of hospital stay was 7 days.

For patients who were hospitalized for BSI and other medical issues, the cost and length of stay were much higher.

“This issue has resonance beyond the pediatric stem cell transplant and oncology patient population,” said study author Amy Billett, MD, of the Dana–Farber Cancer Institute and Boston Children’s Hospital in Massachusetts.

“At a time when many aspects of care are being shifted to the home and of heightened attention to safety and cost, this is the new frontier. What we learn about preventing outpatient bloodstream infections in these patients could have broad relevance.”

To determine the economic and hospitalization impact of ambulatory BSIs, Dr Billet and her colleagues retrospectively analyzed data on outpatient BSIs at Dana-Farber/Boston Children’s that occurred between January 1, 2012, and December 31, 2013, and resulted in hospitalization.

The team identified 74 BSIs in 61 patients. Sixty-nine percent of these infections were classified as central-line-associated bloodstream infections.

In 43% of BSIs, the patient’s central line had to be surgically removed. In 15% of cases, the child was transferred to the intensive care unit. Four patients died during hospitalization, and 3 of these deaths were associated with the infections.

Most of the hospitalizations analyzed—62—were due solely to BSIs. The remainder involved at least 1 other medical issue.

The median total cost of BSIs was $40,852, and the median length of hospital stay was 7 days.

The median cost was $36,611 among patients who were hospitalized for BSIs alone (n=62) and $89,935 for patients who were hospitalized for other medical issues as well. The median lengths of hospital stay were 6 days and 15 days, respectively.

The top 3 drivers of cost for all BSIs were room and board (43%), non-chemotherapy medications (22%), and procedures (11%).

Room and board accounted for 42% of charges among patients who were hospitalized for BSIs alone and 44% among the other patients. Non-chemotherapy medications accounted for 20% and 25%, respectively. And procedures accounted for 11% and 10%, respectively.

“Behind these metrics are real and serious risks to patients’ health,” said study author Chris Wong, MD, of Dana-Farber/Boston Children’s.

“The bottom line is that the dollar cost and lengthy hospital stays signal complications that could become life-threatening or delay treatment of the children’s cancer. Reducing these infections is important both for cost containment and quality of care.”

Red blood cell culture showing

Staphylococcus infection

Photo by Bill Branson

Ambulatory bloodstream infections (BSIs) can be costly in young cancer patients and recipients of hematopoietic stem cell transplants, according to research published in Pediatric Blood & Cancer.

Among the 61 patients studied, the median cost for an ambulatory BSI was $40,852, and the median length of hospital stay was 7 days.

For patients who were hospitalized for BSI and other medical issues, the cost and length of stay were much higher.

“This issue has resonance beyond the pediatric stem cell transplant and oncology patient population,” said study author Amy Billett, MD, of the Dana–Farber Cancer Institute and Boston Children’s Hospital in Massachusetts.

“At a time when many aspects of care are being shifted to the home and of heightened attention to safety and cost, this is the new frontier. What we learn about preventing outpatient bloodstream infections in these patients could have broad relevance.”

To determine the economic and hospitalization impact of ambulatory BSIs, Dr Billet and her colleagues retrospectively analyzed data on outpatient BSIs at Dana-Farber/Boston Children’s that occurred between January 1, 2012, and December 31, 2013, and resulted in hospitalization.

The team identified 74 BSIs in 61 patients. Sixty-nine percent of these infections were classified as central-line-associated bloodstream infections.

In 43% of BSIs, the patient’s central line had to be surgically removed. In 15% of cases, the child was transferred to the intensive care unit. Four patients died during hospitalization, and 3 of these deaths were associated with the infections.

Most of the hospitalizations analyzed—62—were due solely to BSIs. The remainder involved at least 1 other medical issue.

The median total cost of BSIs was $40,852, and the median length of hospital stay was 7 days.

The median cost was $36,611 among patients who were hospitalized for BSIs alone (n=62) and $89,935 for patients who were hospitalized for other medical issues as well. The median lengths of hospital stay were 6 days and 15 days, respectively.

The top 3 drivers of cost for all BSIs were room and board (43%), non-chemotherapy medications (22%), and procedures (11%).

Room and board accounted for 42% of charges among patients who were hospitalized for BSIs alone and 44% among the other patients. Non-chemotherapy medications accounted for 20% and 25%, respectively. And procedures accounted for 11% and 10%, respectively.

“Behind these metrics are real and serious risks to patients’ health,” said study author Chris Wong, MD, of Dana-Farber/Boston Children’s.

“The bottom line is that the dollar cost and lengthy hospital stays signal complications that could become life-threatening or delay treatment of the children’s cancer. Reducing these infections is important both for cost containment and quality of care.”

Red blood cell culture showing

Staphylococcus infection

Photo by Bill Branson

Ambulatory bloodstream infections (BSIs) can be costly in young cancer patients and recipients of hematopoietic stem cell transplants, according to research published in Pediatric Blood & Cancer.

Among the 61 patients studied, the median cost for an ambulatory BSI was $40,852, and the median length of hospital stay was 7 days.

For patients who were hospitalized for BSI and other medical issues, the cost and length of stay were much higher.

“This issue has resonance beyond the pediatric stem cell transplant and oncology patient population,” said study author Amy Billett, MD, of the Dana–Farber Cancer Institute and Boston Children’s Hospital in Massachusetts.

“At a time when many aspects of care are being shifted to the home and of heightened attention to safety and cost, this is the new frontier. What we learn about preventing outpatient bloodstream infections in these patients could have broad relevance.”

To determine the economic and hospitalization impact of ambulatory BSIs, Dr Billet and her colleagues retrospectively analyzed data on outpatient BSIs at Dana-Farber/Boston Children’s that occurred between January 1, 2012, and December 31, 2013, and resulted in hospitalization.

The team identified 74 BSIs in 61 patients. Sixty-nine percent of these infections were classified as central-line-associated bloodstream infections.

In 43% of BSIs, the patient’s central line had to be surgically removed. In 15% of cases, the child was transferred to the intensive care unit. Four patients died during hospitalization, and 3 of these deaths were associated with the infections.

Most of the hospitalizations analyzed—62—were due solely to BSIs. The remainder involved at least 1 other medical issue.

The median total cost of BSIs was $40,852, and the median length of hospital stay was 7 days.

The median cost was $36,611 among patients who were hospitalized for BSIs alone (n=62) and $89,935 for patients who were hospitalized for other medical issues as well. The median lengths of hospital stay were 6 days and 15 days, respectively.

The top 3 drivers of cost for all BSIs were room and board (43%), non-chemotherapy medications (22%), and procedures (11%).

Room and board accounted for 42% of charges among patients who were hospitalized for BSIs alone and 44% among the other patients. Non-chemotherapy medications accounted for 20% and 25%, respectively. And procedures accounted for 11% and 10%, respectively.

“Behind these metrics are real and serious risks to patients’ health,” said study author Chris Wong, MD, of Dana-Farber/Boston Children’s.

“The bottom line is that the dollar cost and lengthy hospital stays signal complications that could become life-threatening or delay treatment of the children’s cancer. Reducing these infections is important both for cost containment and quality of care.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

Researchers say they have identified compounds that might be used to inhibit Zika virus replication and reduce the ability of the virus to kill brain cells.

The compounds include emricasan (a drug being investigated as a treatment to reduce liver damage from hepatitis C virus), niclosamide (a drug approved in the US to combat parasitic infections), and an investigational cyclin-dependent kinase inhibitor known as PHA-690509.

The researchers described the anti-Zika activity of these compounds in Nature Medicine.

About the virus

The Zika virus has been reported in 60 countries and territories worldwide. Currently, there are no vaccines or effective treatments for the virus.

Research and anecdotal evidence have suggested infection with the Zika virus is related to fetal microcephaly, an abnormally small head resulting from an underdeveloped and/or damaged brain. The virus has also been linked with neurological diseases such as Guillain-Barré syndrome in infected adults.

The Zika virus is spread primarily through bites from infected Aedes aegypti mosquitoes, but it can also be transmitted from mother to child, through sexual contact, via blood transfusion, and possibly through other methods.

“The Zika virus poses a global health threat,” said study author Anton Simeonov, PhD, of the National Center for Advancing Translational Sciences in Bethesda, Maryland.

“While we await the development of effective vaccines, which can take a significant amount of time, our identification of repurposed small-molecule compounds may accelerate the translational process of finding a potential therapy.”

“It takes years, if not decades, to develop a new drug,” noted study author Hongjun Song, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland. “In this sort of global health emergency, we don’t have that kind of time.”

“So instead of using new drugs, we chose to screen existing drugs,” added Guo-li Ming, MD, PhD, also of Johns Hopkins. “In this way, we hope to create a therapy much more quickly.”

Identifying potential treatments

The researchers screened 6000 compounds, both investigational and approved (in the US), looking for drugs that might be effective against the Zika virus.

The team first exposed cell cultures to 3 strains of the virus—Ugandan, Cambodian, and Puerto Rican. Then, they introduced the various compounds and looked for indicators of cell death.

The researchers identified more than 100 promising compounds. The 3 lead compounds were emricasan, niclosamide, and PHA-690509.

These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. Emricasan prevents cell death, while niclosamide and PHA-690509 stop virus replication.

The researchers found that combining emricasan and PHA-690509 prevented both cell death and virus replication.

Dr Song cautioned that the 3 drugs “are very effective against Zika in the dish, but we don’t know if they can work in humans in the same way.”

For example, he noted that, although niclosamide can safely treat parasites in the human gastrointestinal tract, researchers have not yet determined if the drug can penetrate the central nervous system of adults or a fetus inside a carrier’s womb to treat the brain cells targeted by Zika.

Furthermore, it’s not clear if the drugs would address the wide range of effects of Zika infection.

“To address these questions, additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,” Dr Ming said. “So we could still be years away from finding a treatment that works.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

Researchers say they have identified compounds that might be used to inhibit Zika virus replication and reduce the ability of the virus to kill brain cells.

The compounds include emricasan (a drug being investigated as a treatment to reduce liver damage from hepatitis C virus), niclosamide (a drug approved in the US to combat parasitic infections), and an investigational cyclin-dependent kinase inhibitor known as PHA-690509.

The researchers described the anti-Zika activity of these compounds in Nature Medicine.

About the virus

The Zika virus has been reported in 60 countries and territories worldwide. Currently, there are no vaccines or effective treatments for the virus.

Research and anecdotal evidence have suggested infection with the Zika virus is related to fetal microcephaly, an abnormally small head resulting from an underdeveloped and/or damaged brain. The virus has also been linked with neurological diseases such as Guillain-Barré syndrome in infected adults.

The Zika virus is spread primarily through bites from infected Aedes aegypti mosquitoes, but it can also be transmitted from mother to child, through sexual contact, via blood transfusion, and possibly through other methods.

“The Zika virus poses a global health threat,” said study author Anton Simeonov, PhD, of the National Center for Advancing Translational Sciences in Bethesda, Maryland.

“While we await the development of effective vaccines, which can take a significant amount of time, our identification of repurposed small-molecule compounds may accelerate the translational process of finding a potential therapy.”

“It takes years, if not decades, to develop a new drug,” noted study author Hongjun Song, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland. “In this sort of global health emergency, we don’t have that kind of time.”

“So instead of using new drugs, we chose to screen existing drugs,” added Guo-li Ming, MD, PhD, also of Johns Hopkins. “In this way, we hope to create a therapy much more quickly.”

Identifying potential treatments

The researchers screened 6000 compounds, both investigational and approved (in the US), looking for drugs that might be effective against the Zika virus.

The team first exposed cell cultures to 3 strains of the virus—Ugandan, Cambodian, and Puerto Rican. Then, they introduced the various compounds and looked for indicators of cell death.

The researchers identified more than 100 promising compounds. The 3 lead compounds were emricasan, niclosamide, and PHA-690509.

These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. Emricasan prevents cell death, while niclosamide and PHA-690509 stop virus replication.

The researchers found that combining emricasan and PHA-690509 prevented both cell death and virus replication.

Dr Song cautioned that the 3 drugs “are very effective against Zika in the dish, but we don’t know if they can work in humans in the same way.”

For example, he noted that, although niclosamide can safely treat parasites in the human gastrointestinal tract, researchers have not yet determined if the drug can penetrate the central nervous system of adults or a fetus inside a carrier’s womb to treat the brain cells targeted by Zika.

Furthermore, it’s not clear if the drugs would address the wide range of effects of Zika infection.

“To address these questions, additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,” Dr Ming said. “So we could still be years away from finding a treatment that works.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

Researchers say they have identified compounds that might be used to inhibit Zika virus replication and reduce the ability of the virus to kill brain cells.

The compounds include emricasan (a drug being investigated as a treatment to reduce liver damage from hepatitis C virus), niclosamide (a drug approved in the US to combat parasitic infections), and an investigational cyclin-dependent kinase inhibitor known as PHA-690509.

The researchers described the anti-Zika activity of these compounds in Nature Medicine.

About the virus

The Zika virus has been reported in 60 countries and territories worldwide. Currently, there are no vaccines or effective treatments for the virus.

Research and anecdotal evidence have suggested infection with the Zika virus is related to fetal microcephaly, an abnormally small head resulting from an underdeveloped and/or damaged brain. The virus has also been linked with neurological diseases such as Guillain-Barré syndrome in infected adults.

The Zika virus is spread primarily through bites from infected Aedes aegypti mosquitoes, but it can also be transmitted from mother to child, through sexual contact, via blood transfusion, and possibly through other methods.

“The Zika virus poses a global health threat,” said study author Anton Simeonov, PhD, of the National Center for Advancing Translational Sciences in Bethesda, Maryland.

“While we await the development of effective vaccines, which can take a significant amount of time, our identification of repurposed small-molecule compounds may accelerate the translational process of finding a potential therapy.”

“It takes years, if not decades, to develop a new drug,” noted study author Hongjun Song, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland. “In this sort of global health emergency, we don’t have that kind of time.”

“So instead of using new drugs, we chose to screen existing drugs,” added Guo-li Ming, MD, PhD, also of Johns Hopkins. “In this way, we hope to create a therapy much more quickly.”

Identifying potential treatments

The researchers screened 6000 compounds, both investigational and approved (in the US), looking for drugs that might be effective against the Zika virus.

The team first exposed cell cultures to 3 strains of the virus—Ugandan, Cambodian, and Puerto Rican. Then, they introduced the various compounds and looked for indicators of cell death.

The researchers identified more than 100 promising compounds. The 3 lead compounds were emricasan, niclosamide, and PHA-690509.

These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. Emricasan prevents cell death, while niclosamide and PHA-690509 stop virus replication.

The researchers found that combining emricasan and PHA-690509 prevented both cell death and virus replication.

Dr Song cautioned that the 3 drugs “are very effective against Zika in the dish, but we don’t know if they can work in humans in the same way.”

For example, he noted that, although niclosamide can safely treat parasites in the human gastrointestinal tract, researchers have not yet determined if the drug can penetrate the central nervous system of adults or a fetus inside a carrier’s womb to treat the brain cells targeted by Zika.

Furthermore, it’s not clear if the drugs would address the wide range of effects of Zika infection.

“To address these questions, additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,” Dr Ming said. “So we could still be years away from finding a treatment that works.”

Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist, is used in human and veterinary medicine for its anesthetic and analgesic properties.¹ NMDA receptors could trigger cellular and behavioral responses, and ketamine blocks neuronal communication pathways.

How ketamine works

Water- and lipid-soluble, ketamine is available in oral, topical, IM, and IV forms. Plasma concentrations reach maximum levels minutes after IV infusion; 5 to 15 minutes after IM administration; and 30 minutes after oral ingestion.¹ The duration of action is as long as 2 hours after IM injection, and 4 to 6 hours orally. Metabolites are eliminated in urine.

Ketamine, co-prescribed with stimulants and some antidepressant drugs, can induce unwanted effects, such as increased blood pressure. Auditory and visual hallucinations are reported occasionally, especially in patients receiving a high dosage or in those with alcohol dependence.¹ Hypertension, tachycardia, cardiac arrhythmia, and pain at injection site are the most common adverse effects.

Some advantages over ECT in treating depression

The efficacy of electroconvulsive therapy (ECT) in alleviating depression depends on seizure duration. Compared with methohexital, an anesthetic used for ECT, ketamine offers some advantages:

• increased ictal time
• augmented mid-ictal slow-wave amplitude
• shortened post-treatment re-orientation time
• less cognitive dysfunction.²

Uses for ketamine

Treatment-resistant depression. The glutamatergic system is implicated in depression.^2,3 Ketamine works in patients with treatment-resistant depression by blocking glutamate NMDA receptors and increasing the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, resulting in a rapid, sustained antidepressant effect. Response to ketamine occurs within 2 hours and lasts approximately 1 week.

Abuse potential

There is documented risk of ketamine abuse. It may create psychedelic effects that some people find pleasurable, such as sedation, disinhibition, and altered perceptions.⁶ There also may be a component of physiological dependence.⁶

Conclusion

Ketamine’s rapid antidepressant effect results could be beneficial when used in severely depressed and suicidal patients. Given the potential risks of ketamine, safety considerations will determine whether this drug is successful as a therapy for people with a mood disorder.

Further research about ketamine usage including pain management and affective disorders is anticipated.⁷ Investigations substantiating relative safety and clinical trials are still on-going.⁸

Related Resources
• Nichols SD, Bishop J. Is the evidence compelling for using ketamine to treat resistant depression? Current Psychiatry. 2015;15(5):48-51.
• National Institute of Mental Health. Highlight: ketamine: a new (and faster) path to treating depression. www.nimh.nih.gov/about/strategic-planning-reports/highlights/highlight-ketamine-a-new-and-faster-path-to-treatingdepression.shtml.

Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist, is used in human and veterinary medicine for its anesthetic and analgesic properties.¹ NMDA receptors could trigger cellular and behavioral responses, and ketamine blocks neuronal communication pathways.

How ketamine works

Water- and lipid-soluble, ketamine is available in oral, topical, IM, and IV forms. Plasma concentrations reach maximum levels minutes after IV infusion; 5 to 15 minutes after IM administration; and 30 minutes after oral ingestion.¹ The duration of action is as long as 2 hours after IM injection, and 4 to 6 hours orally. Metabolites are eliminated in urine.

Ketamine, co-prescribed with stimulants and some antidepressant drugs, can induce unwanted effects, such as increased blood pressure. Auditory and visual hallucinations are reported occasionally, especially in patients receiving a high dosage or in those with alcohol dependence.¹ Hypertension, tachycardia, cardiac arrhythmia, and pain at injection site are the most common adverse effects.

Some advantages over ECT in treating depression

The efficacy of electroconvulsive therapy (ECT) in alleviating depression depends on seizure duration. Compared with methohexital, an anesthetic used for ECT, ketamine offers some advantages:

• increased ictal time
• augmented mid-ictal slow-wave amplitude
• shortened post-treatment re-orientation time
• less cognitive dysfunction.²

Uses for ketamine

Treatment-resistant depression. The glutamatergic system is implicated in depression.^2,3 Ketamine works in patients with treatment-resistant depression by blocking glutamate NMDA receptors and increasing the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, resulting in a rapid, sustained antidepressant effect. Response to ketamine occurs within 2 hours and lasts approximately 1 week.

Abuse potential

There is documented risk of ketamine abuse. It may create psychedelic effects that some people find pleasurable, such as sedation, disinhibition, and altered perceptions.⁶ There also may be a component of physiological dependence.⁶

Conclusion

Ketamine’s rapid antidepressant effect results could be beneficial when used in severely depressed and suicidal patients. Given the potential risks of ketamine, safety considerations will determine whether this drug is successful as a therapy for people with a mood disorder.

Further research about ketamine usage including pain management and affective disorders is anticipated.⁷ Investigations substantiating relative safety and clinical trials are still on-going.⁸

Related Resources
• Nichols SD, Bishop J. Is the evidence compelling for using ketamine to treat resistant depression? Current Psychiatry. 2015;15(5):48-51.
• National Institute of Mental Health. Highlight: ketamine: a new (and faster) path to treating depression. www.nimh.nih.gov/about/strategic-planning-reports/highlights/highlight-ketamine-a-new-and-faster-path-to-treatingdepression.shtml.

Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist, is used in human and veterinary medicine for its anesthetic and analgesic properties.¹ NMDA receptors could trigger cellular and behavioral responses, and ketamine blocks neuronal communication pathways.

How ketamine works

Water- and lipid-soluble, ketamine is available in oral, topical, IM, and IV forms. Plasma concentrations reach maximum levels minutes after IV infusion; 5 to 15 minutes after IM administration; and 30 minutes after oral ingestion.¹ The duration of action is as long as 2 hours after IM injection, and 4 to 6 hours orally. Metabolites are eliminated in urine.

Ketamine, co-prescribed with stimulants and some antidepressant drugs, can induce unwanted effects, such as increased blood pressure. Auditory and visual hallucinations are reported occasionally, especially in patients receiving a high dosage or in those with alcohol dependence.¹ Hypertension, tachycardia, cardiac arrhythmia, and pain at injection site are the most common adverse effects.

Some advantages over ECT in treating depression

The efficacy of electroconvulsive therapy (ECT) in alleviating depression depends on seizure duration. Compared with methohexital, an anesthetic used for ECT, ketamine offers some advantages:

• increased ictal time
• augmented mid-ictal slow-wave amplitude
• shortened post-treatment re-orientation time
• less cognitive dysfunction.²

Uses for ketamine

Treatment-resistant depression. The glutamatergic system is implicated in depression.^2,3 Ketamine works in patients with treatment-resistant depression by blocking glutamate NMDA receptors and increasing the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, resulting in a rapid, sustained antidepressant effect. Response to ketamine occurs within 2 hours and lasts approximately 1 week.

Abuse potential

There is documented risk of ketamine abuse. It may create psychedelic effects that some people find pleasurable, such as sedation, disinhibition, and altered perceptions.⁶ There also may be a component of physiological dependence.⁶

Conclusion

Ketamine’s rapid antidepressant effect results could be beneficial when used in severely depressed and suicidal patients. Given the potential risks of ketamine, safety considerations will determine whether this drug is successful as a therapy for people with a mood disorder.

Further research about ketamine usage including pain management and affective disorders is anticipated.⁷ Investigations substantiating relative safety and clinical trials are still on-going.⁸

Related Resources
• Nichols SD, Bishop J. Is the evidence compelling for using ketamine to treat resistant depression? Current Psychiatry. 2015;15(5):48-51.
• National Institute of Mental Health. Highlight: ketamine: a new (and faster) path to treating depression. www.nimh.nih.gov/about/strategic-planning-reports/highlights/highlight-ketamine-a-new-and-faster-path-to-treatingdepression.shtml.

Obesity meets 3 standard defining criteria of a disease: it is associated with impairment of normal bodily function, has characteristic signs and symptoms, and results in bodily harm.¹ Accordingly, authoritative organizations, including the American Medical Association, formally recognize obesity as a disease—more specifically, a chronic, relapsing, neurobehavioral disease.^1-6

Click here to read the activity. 

Click here to complete the posttest and evaluation.

Obesity meets 3 standard defining criteria of a disease: it is associated with impairment of normal bodily function, has characteristic signs and symptoms, and results in bodily harm.¹ Accordingly, authoritative organizations, including the American Medical Association, formally recognize obesity as a disease—more specifically, a chronic, relapsing, neurobehavioral disease.^1-6

Click here to read the activity. 

Click here to complete the posttest and evaluation.

Obesity meets 3 standard defining criteria of a disease: it is associated with impairment of normal bodily function, has characteristic signs and symptoms, and results in bodily harm.¹ Accordingly, authoritative organizations, including the American Medical Association, formally recognize obesity as a disease—more specifically, a chronic, relapsing, neurobehavioral disease.^1-6

Click here to read the activity. 

Click here to complete the posttest and evaluation.

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

[email protected]

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

[email protected]

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

[email protected]