When tobacco and cancer are mentioned, many people automatically assume lung cancer. But the 70-plus carcinogens identified in tobacco smoke cause at least 12 types of cancer, according to a Vital Signs report, including cancers of the stomach, kidney and renal pelvis, urinary bladder, and cervix. “Smokeless” products such as chewing tobacco carry 28 identified carcinogens.

Related: Quitting Smoking During Substance Abuse Treatment

Researchers from the CDC and National Cancer Institute analyzed data from the U.S. Cancer Statistics 2004-2013 to assess incidence and death rates for cancers caused by tobacco use. During that time, the incidence of tobacco-related cancer went down 1.3% per year, and mortality dropped 1.6% each year. Tobacco-related cancer incidence declined significantly in 44 states. Rates were lowest in the West and dropped the slowest in the Midwest.

However, the burden remains high, the researchers note, and  disparities persist among certain groups. For instance, the incidence of tobacco-related cancer rose with age: Two-fifths of deaths were among people aged ≥ 75 years. And the incidence of cancer and death rates were highest but decreased fastest among blacks.

Related: Impact of a Drop-in Group Medical Appointment on Tobacco Quit Rates

There’s no question that lung cancer remains the cancer most linked to smoking. Lung cancer accounted for about one-third of tobacco-related cancer cases and almost one-half of tobacco-related cancer deaths. Between 2009 and 2013, about 101,300 men and 65,700 women died each year of cancers attributable to cigarette smoking—most died of lung cancer. Exposure to secondhand smoke accounted for another 7,300 deaths by lung cancer among nonsmokers.

Roughly 6 million people may die prematurely of a tobacco-related cancer unless they can take advantage of more sustained, comprehensive, and evidence-based interventions, the researchers say. States that have invested in smoking prevention and control programs, they point out, have seen larger declines in youth and adult smoking, decreases in lung cancer, and reduced tobacco-related health care costs.

Related: CDC Media Campaign Helps Americans Quit Smoking

The researchers also emphasize the benefits of smoking-cessation counseling and treatment as well as screening for cervical, colorectal, and lung cancers, to help detect them at earlier more easily treatable stages. Vaccination against hepatitis B virus and human papillomavirus can prevent liver and cervix cancer,  to which tobacco can contribute.

According to Vital Signs, the CDC funds 65 comprehensive cancer control programs to prevent cancer, increase access to early detection and care for tobacco-related cancers, help cancer survivors quit using tobacco, and improve cancer outcomes, especially in communities with higher tobacco-related rates of cancer and deaths. The CDC also urges health care providers to encourage patients to quit—or not start—smoking, to be aware of screenings, and to remember that there’s no “risk-free” level of secondhand smoke.

Source:
Henley SJ, Thomas CC, Sharapova SR, et al. MMWR. 2016;65(44):1212-1218.

When tobacco and cancer are mentioned, many people automatically assume lung cancer. But the 70-plus carcinogens identified in tobacco smoke cause at least 12 types of cancer, according to a Vital Signs report, including cancers of the stomach, kidney and renal pelvis, urinary bladder, and cervix. “Smokeless” products such as chewing tobacco carry 28 identified carcinogens.

Related: Quitting Smoking During Substance Abuse Treatment

Researchers from the CDC and National Cancer Institute analyzed data from the U.S. Cancer Statistics 2004-2013 to assess incidence and death rates for cancers caused by tobacco use. During that time, the incidence of tobacco-related cancer went down 1.3% per year, and mortality dropped 1.6% each year. Tobacco-related cancer incidence declined significantly in 44 states. Rates were lowest in the West and dropped the slowest in the Midwest.

However, the burden remains high, the researchers note, and  disparities persist among certain groups. For instance, the incidence of tobacco-related cancer rose with age: Two-fifths of deaths were among people aged ≥ 75 years. And the incidence of cancer and death rates were highest but decreased fastest among blacks.

Related: Impact of a Drop-in Group Medical Appointment on Tobacco Quit Rates

There’s no question that lung cancer remains the cancer most linked to smoking. Lung cancer accounted for about one-third of tobacco-related cancer cases and almost one-half of tobacco-related cancer deaths. Between 2009 and 2013, about 101,300 men and 65,700 women died each year of cancers attributable to cigarette smoking—most died of lung cancer. Exposure to secondhand smoke accounted for another 7,300 deaths by lung cancer among nonsmokers.

Roughly 6 million people may die prematurely of a tobacco-related cancer unless they can take advantage of more sustained, comprehensive, and evidence-based interventions, the researchers say. States that have invested in smoking prevention and control programs, they point out, have seen larger declines in youth and adult smoking, decreases in lung cancer, and reduced tobacco-related health care costs.

Related: CDC Media Campaign Helps Americans Quit Smoking

The researchers also emphasize the benefits of smoking-cessation counseling and treatment as well as screening for cervical, colorectal, and lung cancers, to help detect them at earlier more easily treatable stages. Vaccination against hepatitis B virus and human papillomavirus can prevent liver and cervix cancer,  to which tobacco can contribute.

According to Vital Signs, the CDC funds 65 comprehensive cancer control programs to prevent cancer, increase access to early detection and care for tobacco-related cancers, help cancer survivors quit using tobacco, and improve cancer outcomes, especially in communities with higher tobacco-related rates of cancer and deaths. The CDC also urges health care providers to encourage patients to quit—or not start—smoking, to be aware of screenings, and to remember that there’s no “risk-free” level of secondhand smoke.

Source:
Henley SJ, Thomas CC, Sharapova SR, et al. MMWR. 2016;65(44):1212-1218.

When tobacco and cancer are mentioned, many people automatically assume lung cancer. But the 70-plus carcinogens identified in tobacco smoke cause at least 12 types of cancer, according to a Vital Signs report, including cancers of the stomach, kidney and renal pelvis, urinary bladder, and cervix. “Smokeless” products such as chewing tobacco carry 28 identified carcinogens.

Related: Quitting Smoking During Substance Abuse Treatment

Researchers from the CDC and National Cancer Institute analyzed data from the U.S. Cancer Statistics 2004-2013 to assess incidence and death rates for cancers caused by tobacco use. During that time, the incidence of tobacco-related cancer went down 1.3% per year, and mortality dropped 1.6% each year. Tobacco-related cancer incidence declined significantly in 44 states. Rates were lowest in the West and dropped the slowest in the Midwest.

However, the burden remains high, the researchers note, and  disparities persist among certain groups. For instance, the incidence of tobacco-related cancer rose with age: Two-fifths of deaths were among people aged ≥ 75 years. And the incidence of cancer and death rates were highest but decreased fastest among blacks.

Related: Impact of a Drop-in Group Medical Appointment on Tobacco Quit Rates

There’s no question that lung cancer remains the cancer most linked to smoking. Lung cancer accounted for about one-third of tobacco-related cancer cases and almost one-half of tobacco-related cancer deaths. Between 2009 and 2013, about 101,300 men and 65,700 women died each year of cancers attributable to cigarette smoking—most died of lung cancer. Exposure to secondhand smoke accounted for another 7,300 deaths by lung cancer among nonsmokers.

Roughly 6 million people may die prematurely of a tobacco-related cancer unless they can take advantage of more sustained, comprehensive, and evidence-based interventions, the researchers say. States that have invested in smoking prevention and control programs, they point out, have seen larger declines in youth and adult smoking, decreases in lung cancer, and reduced tobacco-related health care costs.

Related: CDC Media Campaign Helps Americans Quit Smoking

The researchers also emphasize the benefits of smoking-cessation counseling and treatment as well as screening for cervical, colorectal, and lung cancers, to help detect them at earlier more easily treatable stages. Vaccination against hepatitis B virus and human papillomavirus can prevent liver and cervix cancer,  to which tobacco can contribute.

According to Vital Signs, the CDC funds 65 comprehensive cancer control programs to prevent cancer, increase access to early detection and care for tobacco-related cancers, help cancer survivors quit using tobacco, and improve cancer outcomes, especially in communities with higher tobacco-related rates of cancer and deaths. The CDC also urges health care providers to encourage patients to quit—or not start—smoking, to be aware of screenings, and to remember that there’s no “risk-free” level of secondhand smoke.

Source:
Henley SJ, Thomas CC, Sharapova SR, et al. MMWR. 2016;65(44):1212-1218.

Fatal opioid overdoses have quadrupled in the U.S. from 1999 to 2013.¹ In 2013, 43,982 deaths in the U.S. were attributable to drug overdoses, and 37% of them involved opioids.¹ Data from 2005 suggested that veterans are at an increased risk with a 2-fold rise in overdose observed.² In 2013, there were 17,124 encounters at VA facilities for the treatment of opioid overdose.³ In response to this opioid epidemic, individual VA facilities began implementing Overdose Education and Naloxone Distribution (OEND) programs in 2013.⁴ In May 2014, the Under Secretary for Health mandated the implementation of OEND programs across all VA facilities, and the VA became the only health care system in the U.S. with a national OEND program.⁴

Naloxone

Naloxone is a pure opioid antagonist that competes with and displaces opioids at opioid receptors. In an overdose, opioids occupying opioid receptor sites can lead to respiratory depression, which can lead to death. Patients can experience rapid reversal of respiratory depression and opioid overdose with the first dose of naloxone 0.4 mg. Naloxone has a short half-life relative to opioids, whereas opioids can bind to opioid receptors once again after naloxone is eliminated, risking the reemergence of overdose symptoms. For this reason, a second dose of naloxone is often given. When administered appropriately with close monitoring, naloxone can provide a safe and effective way to reverse a potentially life-threatening opioid overdose.

Availability

In April 2014, Evzio, an intramuscular/subcutaneous formulation of naloxone, was FDA approved as an emergency treatment for known or suspected opioid overdose. Shortly after, in November 2015, Narcan, a nasal spray formulation of naloxone, also was approved. Each formulation has been instrumental in fulfilling an unmet medical need in the U.S. Both Evzio and Narcan have been used in opioid-overdose prevention programs to train health care professionals and lay persons to respond in the event of suspected overdose and administer naloxone.

Maxwell and colleagues implemented a naloxone distribution program in Chicago, Illinois, in January 2001 after a 4-fold increase in heroin-related overdose deaths was observed.⁵ Within a year, Chicago experienced a 20% decrease in heroin-related overdose deaths, and this trend continued with additional 10% reductions in heroin-related overdoses in 2002 and 2003. Similarly, Piper and colleagues implemented a naloxone distribution program and found that 82% of injection drug users felt “comfortable” to “very comfortable” administering naloxone in the event of an overdose, and 86% of subjects reported they would want naloxone in the event of an overdose.⁶

Naloxone is available for over-the-counter purchase in Rhode Island, which is a bordering state to VA Connecticut Healthcare System (VACT). In 2015 new legislation permitted the training and certification of Connecticut community pharmacists to prescribe naloxone. Furthermore, in May 2016, Connecticut passed legislation to permit qualified individuals to carry naloxone and administer it to another person that he or she, believes is experiencing an opioid-related drug overdose. Given the increase in naloxone availability both nationally and locally, VACT sought to implement a naloxone distribution program to offer the same access to veterans. The primary objective of this article is to describe the development, implementation, and preliminary results of this OEND program.

Development

In accordance with VA guidance, the VACT OEND program development and implementation process included 4 steps that required program coordinators to identify target populations, garner support, train staff members, and implement the OEND program.

A multidisciplinary team of representatives from pharmacy, mental health (MH), and substance abuse (SA) departments was established to draft hospital policy. The hospital policy detailed job functions related to the OEND program for prescribing, educating, verifying, and dispensing naloxone. This policy also served as a document to identify the target population.

With resources from the National VA Pharmacy Benefits Manager, the target population for VACT listed veterans with an opioid use disorder, prescription opioid use disorder, and injection opioid use disorder. Also listed were veterans at risk of an opioid overdose, such as those encountered in medication-assisted treatment programs for opioid use disorder, recent inpatient withdrawal management for opioid use disorder, HIV education/prevention programs, syringe access programs, outpatient and residential opioid use disorder treatment programs, community meetings/support group programs for opioid use disorder, emergency departments for opioid overdose or intoxication, domiciliary care or community-based treatment for homeless veterans, and primary health care for follow-up of recent opioid overdose or intoxication. The aim of the broad description of veterans was to ensure that naloxone access remained inclusive.

The program overview and hospital policy were presented to the VACT medication management committee (MMC), which approved a small pilot project for veterans engaged in SA treatment from January 2015 to April 2015. Barriers to implementation were encountered at this time, which included a belief that only MH or SA providers should prescribe naloxone rescue kits. Reasons for this were largely related to the belief that MH and SA providers are more familiar with substance use disorders. These barriers were addressed by increasing education to providers by detailing previous success stories regarding naloxone programs to highlight that the benefits outweighed any associated risks.

Implementation

Naloxone kits were assembled in preparation for program implementation. Each kit contained 2 vials of naloxone (each vial contains 1 dose), 2 needleless luer-lock syringes, and 1 atomizer with visual instructions for product assembly. Next, a template was created for entry into the veteran’s electronic health record (EHR) each time a naloxone kit was dispensed. The template tracked diagnosis, history of naloxone kit use, and aspects of the OEND program that were discussed with the veteran. Embedded within the template is a hyperlink to the Substance Abuse and Mental Health Services Administration Opioid Overdose Prevention Toolkit booklet, which serves as an education guide and take-home material for the veteran.

Once the naloxone kits were assembled and the template created, SA providers were able to engage in OEND program training. Training required providers to attend a 60-minute, 75-slide PowerPoint seminar, highlighting risk factors and prevention strategies for opioid overdose, proper identification and management of an opioid overdose, appropriate administration of naloxone, and monitoring parameters after administration. Providers were not screened for baseline knowledge, nor was a posttraining proficiency evaluation performed. However, providers were allowed to ask questions and request further clarification about any unclear aspects of training.

Each month, data were collected on the number of providers trained and naloxone kits dispensed. Implementation began in January 2015, and veterans were either educated during individual or group sessions led by a trained OEND provider. An institutional review board-approved quality improvement (QI) process ran concurrently that sought to improve the OEND program. Phase 1 of this QI project anonymously surveyed OEND providers to evaluate knowledge, comfort, attitude, and fear of consequences regarding naloxone distribution in an attempt to understand barriers to program implementation or success.⁷ In phase 2, veterans who received a naloxone kit will be interviewed regarding knowledge retention of OEND program education and subsequent opioid abuse and naloxone use after receiving a naloxone kit.

Results

From January 2015 through preliminary data analysis in April 2015, the facility trained 19 providers and dispensed naloxone kits to 49 veterans. In the first 4 months of program implementation, there were no reports of attempted opioid overdose reversals with naloxone in the 49 veterans who had received a naloxone kit. Of note, past studies have demonstrated that 1 death is prevented for every 227 naloxone kits distributed.⁸ Therefore, it is possible that the analysis was too early to detect an impact.

As of October 2016, VACT has dispensed 538 naloxone kits to 441 veterans, as some patients have received naloxone kit refills for various reasons (ie, lost, used, confiscated, stolen, etc). The OEND program implementation team has been made aware that at least 5 of the 441 veterans have used naloxone kits, though it is unclear whether naloxone kits were used on the veteran themselves or someone else. This is likely an underestimate of naloxone kit use, as veterans could be sent to alternative hospitals in the event of an opioid overdose, or veterans may not disclose actual use of naloxone kit to VACT providers. Phase 2 of the QI project is designed to extract an estimation of actual naloxone kit use in the VACT veteran population.

Discussion

Naloxone, a pure opioid antagonist, is readily available in many communities. In order to extend the same continuity of care to veterans, VACT implemented the OEND program to increase access to naloxone kits. This program serves as an opportunity to educate veterans regarding safe practices with opioids and provides a life-saving measure in the event of an overdose.

The 4-step approach to implementation was a feasible method of quickly implementing an OEND program. Despite ongoing prescriber interest in participating in the OEND program, barriers to implementation were encountered. The largest barrier was provider concerns related to an increase in opioid use given the availability of a reversal agent. However, the medical literature suggests that opioid use tends to decrease when naloxone programs are implemented. Additionally, OEND implementation barriers were internally analyzed in an effort to foster a successful OEND program with continuous evaluation and improvement.⁷

Clark and colleagues examined 19 published studies regarding community-based naloxone programs in order to assess whether naloxone distribution reduced fatal and nonfatal overdose rates.⁹ Naloxone was used successfully across 1,949 patients, and 8 studies reported survival rates of 83% to 96% after naloxone, while 11 studies reported 100% survival rate. The authors of a study of the Chicago Recovery Alliance program found an overall decrease in heroin overdose, and the initial downward trend was seen during the year of naloxone implementation.⁹

In addition, the cost of program implementation was minimal at the local level. Given that implementation of OENDs is a national VA mandate, all naloxone kits are provided to individual VA facilities at no cost from the Consolidated Mail Outpatient Pharmacy, which is the only foreseeable tangible cost. Therefore, intangible costs may include time spent implementing the OEND program, time spent maintaining naloxone inventory, time spent discussing and educating patients on naloxone, and time spent dispensing naloxone kits to patients. However, the intangible costs of the program are predicted to be reduced or offset by the cost-savings measure of reduced emergency department visits and hospitalizations for opioid overdose.

By implementing the OEND program at VACT, veterans are able to engage in primary prophylaxis via education regarding safe practices of opioids. These veterans are also able to obtain tertiary prophylaxis by receiving a naloxone kit and associated training. It is predicted that deaths due to opioid overdose will decrease in this veteran population with the expansion of the OEND program.

Scientific Significance

The OEND programs increase naloxone access and can potentially decrease the incidence of opioid misuse and fatal opioid overdose.

Conclusion

An OEND program can be easily implemented to dispense naloxone kits and deliver education regarding safe opioid use.

Fatal opioid overdoses have quadrupled in the U.S. from 1999 to 2013.¹ In 2013, 43,982 deaths in the U.S. were attributable to drug overdoses, and 37% of them involved opioids.¹ Data from 2005 suggested that veterans are at an increased risk with a 2-fold rise in overdose observed.² In 2013, there were 17,124 encounters at VA facilities for the treatment of opioid overdose.³ In response to this opioid epidemic, individual VA facilities began implementing Overdose Education and Naloxone Distribution (OEND) programs in 2013.⁴ In May 2014, the Under Secretary for Health mandated the implementation of OEND programs across all VA facilities, and the VA became the only health care system in the U.S. with a national OEND program.⁴

Naloxone

Naloxone is a pure opioid antagonist that competes with and displaces opioids at opioid receptors. In an overdose, opioids occupying opioid receptor sites can lead to respiratory depression, which can lead to death. Patients can experience rapid reversal of respiratory depression and opioid overdose with the first dose of naloxone 0.4 mg. Naloxone has a short half-life relative to opioids, whereas opioids can bind to opioid receptors once again after naloxone is eliminated, risking the reemergence of overdose symptoms. For this reason, a second dose of naloxone is often given. When administered appropriately with close monitoring, naloxone can provide a safe and effective way to reverse a potentially life-threatening opioid overdose.

Availability

In April 2014, Evzio, an intramuscular/subcutaneous formulation of naloxone, was FDA approved as an emergency treatment for known or suspected opioid overdose. Shortly after, in November 2015, Narcan, a nasal spray formulation of naloxone, also was approved. Each formulation has been instrumental in fulfilling an unmet medical need in the U.S. Both Evzio and Narcan have been used in opioid-overdose prevention programs to train health care professionals and lay persons to respond in the event of suspected overdose and administer naloxone.

Maxwell and colleagues implemented a naloxone distribution program in Chicago, Illinois, in January 2001 after a 4-fold increase in heroin-related overdose deaths was observed.⁵ Within a year, Chicago experienced a 20% decrease in heroin-related overdose deaths, and this trend continued with additional 10% reductions in heroin-related overdoses in 2002 and 2003. Similarly, Piper and colleagues implemented a naloxone distribution program and found that 82% of injection drug users felt “comfortable” to “very comfortable” administering naloxone in the event of an overdose, and 86% of subjects reported they would want naloxone in the event of an overdose.⁶

Naloxone is available for over-the-counter purchase in Rhode Island, which is a bordering state to VA Connecticut Healthcare System (VACT). In 2015 new legislation permitted the training and certification of Connecticut community pharmacists to prescribe naloxone. Furthermore, in May 2016, Connecticut passed legislation to permit qualified individuals to carry naloxone and administer it to another person that he or she, believes is experiencing an opioid-related drug overdose. Given the increase in naloxone availability both nationally and locally, VACT sought to implement a naloxone distribution program to offer the same access to veterans. The primary objective of this article is to describe the development, implementation, and preliminary results of this OEND program.

Development

In accordance with VA guidance, the VACT OEND program development and implementation process included 4 steps that required program coordinators to identify target populations, garner support, train staff members, and implement the OEND program.

A multidisciplinary team of representatives from pharmacy, mental health (MH), and substance abuse (SA) departments was established to draft hospital policy. The hospital policy detailed job functions related to the OEND program for prescribing, educating, verifying, and dispensing naloxone. This policy also served as a document to identify the target population.

With resources from the National VA Pharmacy Benefits Manager, the target population for VACT listed veterans with an opioid use disorder, prescription opioid use disorder, and injection opioid use disorder. Also listed were veterans at risk of an opioid overdose, such as those encountered in medication-assisted treatment programs for opioid use disorder, recent inpatient withdrawal management for opioid use disorder, HIV education/prevention programs, syringe access programs, outpatient and residential opioid use disorder treatment programs, community meetings/support group programs for opioid use disorder, emergency departments for opioid overdose or intoxication, domiciliary care or community-based treatment for homeless veterans, and primary health care for follow-up of recent opioid overdose or intoxication. The aim of the broad description of veterans was to ensure that naloxone access remained inclusive.

The program overview and hospital policy were presented to the VACT medication management committee (MMC), which approved a small pilot project for veterans engaged in SA treatment from January 2015 to April 2015. Barriers to implementation were encountered at this time, which included a belief that only MH or SA providers should prescribe naloxone rescue kits. Reasons for this were largely related to the belief that MH and SA providers are more familiar with substance use disorders. These barriers were addressed by increasing education to providers by detailing previous success stories regarding naloxone programs to highlight that the benefits outweighed any associated risks.

Implementation

Naloxone kits were assembled in preparation for program implementation. Each kit contained 2 vials of naloxone (each vial contains 1 dose), 2 needleless luer-lock syringes, and 1 atomizer with visual instructions for product assembly. Next, a template was created for entry into the veteran’s electronic health record (EHR) each time a naloxone kit was dispensed. The template tracked diagnosis, history of naloxone kit use, and aspects of the OEND program that were discussed with the veteran. Embedded within the template is a hyperlink to the Substance Abuse and Mental Health Services Administration Opioid Overdose Prevention Toolkit booklet, which serves as an education guide and take-home material for the veteran.

Once the naloxone kits were assembled and the template created, SA providers were able to engage in OEND program training. Training required providers to attend a 60-minute, 75-slide PowerPoint seminar, highlighting risk factors and prevention strategies for opioid overdose, proper identification and management of an opioid overdose, appropriate administration of naloxone, and monitoring parameters after administration. Providers were not screened for baseline knowledge, nor was a posttraining proficiency evaluation performed. However, providers were allowed to ask questions and request further clarification about any unclear aspects of training.

Each month, data were collected on the number of providers trained and naloxone kits dispensed. Implementation began in January 2015, and veterans were either educated during individual or group sessions led by a trained OEND provider. An institutional review board-approved quality improvement (QI) process ran concurrently that sought to improve the OEND program. Phase 1 of this QI project anonymously surveyed OEND providers to evaluate knowledge, comfort, attitude, and fear of consequences regarding naloxone distribution in an attempt to understand barriers to program implementation or success.⁷ In phase 2, veterans who received a naloxone kit will be interviewed regarding knowledge retention of OEND program education and subsequent opioid abuse and naloxone use after receiving a naloxone kit.

Results

From January 2015 through preliminary data analysis in April 2015, the facility trained 19 providers and dispensed naloxone kits to 49 veterans. In the first 4 months of program implementation, there were no reports of attempted opioid overdose reversals with naloxone in the 49 veterans who had received a naloxone kit. Of note, past studies have demonstrated that 1 death is prevented for every 227 naloxone kits distributed.⁸ Therefore, it is possible that the analysis was too early to detect an impact.

As of October 2016, VACT has dispensed 538 naloxone kits to 441 veterans, as some patients have received naloxone kit refills for various reasons (ie, lost, used, confiscated, stolen, etc). The OEND program implementation team has been made aware that at least 5 of the 441 veterans have used naloxone kits, though it is unclear whether naloxone kits were used on the veteran themselves or someone else. This is likely an underestimate of naloxone kit use, as veterans could be sent to alternative hospitals in the event of an opioid overdose, or veterans may not disclose actual use of naloxone kit to VACT providers. Phase 2 of the QI project is designed to extract an estimation of actual naloxone kit use in the VACT veteran population.

Discussion

Naloxone, a pure opioid antagonist, is readily available in many communities. In order to extend the same continuity of care to veterans, VACT implemented the OEND program to increase access to naloxone kits. This program serves as an opportunity to educate veterans regarding safe practices with opioids and provides a life-saving measure in the event of an overdose.

The 4-step approach to implementation was a feasible method of quickly implementing an OEND program. Despite ongoing prescriber interest in participating in the OEND program, barriers to implementation were encountered. The largest barrier was provider concerns related to an increase in opioid use given the availability of a reversal agent. However, the medical literature suggests that opioid use tends to decrease when naloxone programs are implemented. Additionally, OEND implementation barriers were internally analyzed in an effort to foster a successful OEND program with continuous evaluation and improvement.⁷

Clark and colleagues examined 19 published studies regarding community-based naloxone programs in order to assess whether naloxone distribution reduced fatal and nonfatal overdose rates.⁹ Naloxone was used successfully across 1,949 patients, and 8 studies reported survival rates of 83% to 96% after naloxone, while 11 studies reported 100% survival rate. The authors of a study of the Chicago Recovery Alliance program found an overall decrease in heroin overdose, and the initial downward trend was seen during the year of naloxone implementation.⁹

In addition, the cost of program implementation was minimal at the local level. Given that implementation of OENDs is a national VA mandate, all naloxone kits are provided to individual VA facilities at no cost from the Consolidated Mail Outpatient Pharmacy, which is the only foreseeable tangible cost. Therefore, intangible costs may include time spent implementing the OEND program, time spent maintaining naloxone inventory, time spent discussing and educating patients on naloxone, and time spent dispensing naloxone kits to patients. However, the intangible costs of the program are predicted to be reduced or offset by the cost-savings measure of reduced emergency department visits and hospitalizations for opioid overdose.

By implementing the OEND program at VACT, veterans are able to engage in primary prophylaxis via education regarding safe practices of opioids. These veterans are also able to obtain tertiary prophylaxis by receiving a naloxone kit and associated training. It is predicted that deaths due to opioid overdose will decrease in this veteran population with the expansion of the OEND program.

Scientific Significance

The OEND programs increase naloxone access and can potentially decrease the incidence of opioid misuse and fatal opioid overdose.

Conclusion

An OEND program can be easily implemented to dispense naloxone kits and deliver education regarding safe opioid use.

Fatal opioid overdoses have quadrupled in the U.S. from 1999 to 2013.¹ In 2013, 43,982 deaths in the U.S. were attributable to drug overdoses, and 37% of them involved opioids.¹ Data from 2005 suggested that veterans are at an increased risk with a 2-fold rise in overdose observed.² In 2013, there were 17,124 encounters at VA facilities for the treatment of opioid overdose.³ In response to this opioid epidemic, individual VA facilities began implementing Overdose Education and Naloxone Distribution (OEND) programs in 2013.⁴ In May 2014, the Under Secretary for Health mandated the implementation of OEND programs across all VA facilities, and the VA became the only health care system in the U.S. with a national OEND program.⁴

Naloxone

Naloxone is a pure opioid antagonist that competes with and displaces opioids at opioid receptors. In an overdose, opioids occupying opioid receptor sites can lead to respiratory depression, which can lead to death. Patients can experience rapid reversal of respiratory depression and opioid overdose with the first dose of naloxone 0.4 mg. Naloxone has a short half-life relative to opioids, whereas opioids can bind to opioid receptors once again after naloxone is eliminated, risking the reemergence of overdose symptoms. For this reason, a second dose of naloxone is often given. When administered appropriately with close monitoring, naloxone can provide a safe and effective way to reverse a potentially life-threatening opioid overdose.

Availability

In April 2014, Evzio, an intramuscular/subcutaneous formulation of naloxone, was FDA approved as an emergency treatment for known or suspected opioid overdose. Shortly after, in November 2015, Narcan, a nasal spray formulation of naloxone, also was approved. Each formulation has been instrumental in fulfilling an unmet medical need in the U.S. Both Evzio and Narcan have been used in opioid-overdose prevention programs to train health care professionals and lay persons to respond in the event of suspected overdose and administer naloxone.

Maxwell and colleagues implemented a naloxone distribution program in Chicago, Illinois, in January 2001 after a 4-fold increase in heroin-related overdose deaths was observed.⁵ Within a year, Chicago experienced a 20% decrease in heroin-related overdose deaths, and this trend continued with additional 10% reductions in heroin-related overdoses in 2002 and 2003. Similarly, Piper and colleagues implemented a naloxone distribution program and found that 82% of injection drug users felt “comfortable” to “very comfortable” administering naloxone in the event of an overdose, and 86% of subjects reported they would want naloxone in the event of an overdose.⁶

Naloxone is available for over-the-counter purchase in Rhode Island, which is a bordering state to VA Connecticut Healthcare System (VACT). In 2015 new legislation permitted the training and certification of Connecticut community pharmacists to prescribe naloxone. Furthermore, in May 2016, Connecticut passed legislation to permit qualified individuals to carry naloxone and administer it to another person that he or she, believes is experiencing an opioid-related drug overdose. Given the increase in naloxone availability both nationally and locally, VACT sought to implement a naloxone distribution program to offer the same access to veterans. The primary objective of this article is to describe the development, implementation, and preliminary results of this OEND program.

Development

In accordance with VA guidance, the VACT OEND program development and implementation process included 4 steps that required program coordinators to identify target populations, garner support, train staff members, and implement the OEND program.

A multidisciplinary team of representatives from pharmacy, mental health (MH), and substance abuse (SA) departments was established to draft hospital policy. The hospital policy detailed job functions related to the OEND program for prescribing, educating, verifying, and dispensing naloxone. This policy also served as a document to identify the target population.

With resources from the National VA Pharmacy Benefits Manager, the target population for VACT listed veterans with an opioid use disorder, prescription opioid use disorder, and injection opioid use disorder. Also listed were veterans at risk of an opioid overdose, such as those encountered in medication-assisted treatment programs for opioid use disorder, recent inpatient withdrawal management for opioid use disorder, HIV education/prevention programs, syringe access programs, outpatient and residential opioid use disorder treatment programs, community meetings/support group programs for opioid use disorder, emergency departments for opioid overdose or intoxication, domiciliary care or community-based treatment for homeless veterans, and primary health care for follow-up of recent opioid overdose or intoxication. The aim of the broad description of veterans was to ensure that naloxone access remained inclusive.

The program overview and hospital policy were presented to the VACT medication management committee (MMC), which approved a small pilot project for veterans engaged in SA treatment from January 2015 to April 2015. Barriers to implementation were encountered at this time, which included a belief that only MH or SA providers should prescribe naloxone rescue kits. Reasons for this were largely related to the belief that MH and SA providers are more familiar with substance use disorders. These barriers were addressed by increasing education to providers by detailing previous success stories regarding naloxone programs to highlight that the benefits outweighed any associated risks.

Implementation

Naloxone kits were assembled in preparation for program implementation. Each kit contained 2 vials of naloxone (each vial contains 1 dose), 2 needleless luer-lock syringes, and 1 atomizer with visual instructions for product assembly. Next, a template was created for entry into the veteran’s electronic health record (EHR) each time a naloxone kit was dispensed. The template tracked diagnosis, history of naloxone kit use, and aspects of the OEND program that were discussed with the veteran. Embedded within the template is a hyperlink to the Substance Abuse and Mental Health Services Administration Opioid Overdose Prevention Toolkit booklet, which serves as an education guide and take-home material for the veteran.

Once the naloxone kits were assembled and the template created, SA providers were able to engage in OEND program training. Training required providers to attend a 60-minute, 75-slide PowerPoint seminar, highlighting risk factors and prevention strategies for opioid overdose, proper identification and management of an opioid overdose, appropriate administration of naloxone, and monitoring parameters after administration. Providers were not screened for baseline knowledge, nor was a posttraining proficiency evaluation performed. However, providers were allowed to ask questions and request further clarification about any unclear aspects of training.

Each month, data were collected on the number of providers trained and naloxone kits dispensed. Implementation began in January 2015, and veterans were either educated during individual or group sessions led by a trained OEND provider. An institutional review board-approved quality improvement (QI) process ran concurrently that sought to improve the OEND program. Phase 1 of this QI project anonymously surveyed OEND providers to evaluate knowledge, comfort, attitude, and fear of consequences regarding naloxone distribution in an attempt to understand barriers to program implementation or success.⁷ In phase 2, veterans who received a naloxone kit will be interviewed regarding knowledge retention of OEND program education and subsequent opioid abuse and naloxone use after receiving a naloxone kit.

Results

From January 2015 through preliminary data analysis in April 2015, the facility trained 19 providers and dispensed naloxone kits to 49 veterans. In the first 4 months of program implementation, there were no reports of attempted opioid overdose reversals with naloxone in the 49 veterans who had received a naloxone kit. Of note, past studies have demonstrated that 1 death is prevented for every 227 naloxone kits distributed.⁸ Therefore, it is possible that the analysis was too early to detect an impact.

As of October 2016, VACT has dispensed 538 naloxone kits to 441 veterans, as some patients have received naloxone kit refills for various reasons (ie, lost, used, confiscated, stolen, etc). The OEND program implementation team has been made aware that at least 5 of the 441 veterans have used naloxone kits, though it is unclear whether naloxone kits were used on the veteran themselves or someone else. This is likely an underestimate of naloxone kit use, as veterans could be sent to alternative hospitals in the event of an opioid overdose, or veterans may not disclose actual use of naloxone kit to VACT providers. Phase 2 of the QI project is designed to extract an estimation of actual naloxone kit use in the VACT veteran population.

Discussion

Naloxone, a pure opioid antagonist, is readily available in many communities. In order to extend the same continuity of care to veterans, VACT implemented the OEND program to increase access to naloxone kits. This program serves as an opportunity to educate veterans regarding safe practices with opioids and provides a life-saving measure in the event of an overdose.

The 4-step approach to implementation was a feasible method of quickly implementing an OEND program. Despite ongoing prescriber interest in participating in the OEND program, barriers to implementation were encountered. The largest barrier was provider concerns related to an increase in opioid use given the availability of a reversal agent. However, the medical literature suggests that opioid use tends to decrease when naloxone programs are implemented. Additionally, OEND implementation barriers were internally analyzed in an effort to foster a successful OEND program with continuous evaluation and improvement.⁷

Clark and colleagues examined 19 published studies regarding community-based naloxone programs in order to assess whether naloxone distribution reduced fatal and nonfatal overdose rates.⁹ Naloxone was used successfully across 1,949 patients, and 8 studies reported survival rates of 83% to 96% after naloxone, while 11 studies reported 100% survival rate. The authors of a study of the Chicago Recovery Alliance program found an overall decrease in heroin overdose, and the initial downward trend was seen during the year of naloxone implementation.⁹

In addition, the cost of program implementation was minimal at the local level. Given that implementation of OENDs is a national VA mandate, all naloxone kits are provided to individual VA facilities at no cost from the Consolidated Mail Outpatient Pharmacy, which is the only foreseeable tangible cost. Therefore, intangible costs may include time spent implementing the OEND program, time spent maintaining naloxone inventory, time spent discussing and educating patients on naloxone, and time spent dispensing naloxone kits to patients. However, the intangible costs of the program are predicted to be reduced or offset by the cost-savings measure of reduced emergency department visits and hospitalizations for opioid overdose.

By implementing the OEND program at VACT, veterans are able to engage in primary prophylaxis via education regarding safe practices of opioids. These veterans are also able to obtain tertiary prophylaxis by receiving a naloxone kit and associated training. It is predicted that deaths due to opioid overdose will decrease in this veteran population with the expansion of the OEND program.

Scientific Significance

The OEND programs increase naloxone access and can potentially decrease the incidence of opioid misuse and fatal opioid overdose.

Conclusion

An OEND program can be easily implemented to dispense naloxone kits and deliver education regarding safe opioid use.

Tony Antoniou, PhD

Photo courtesy of

St. Michael’s Hospital

Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.

“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”

Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.

The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.

In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.

Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.

In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.

Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack

relative to other statins. The adjusted odds ratio was 1.33.

However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.

Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.

The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.

The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.

On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.

Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.

Tony Antoniou, PhD

Photo courtesy of

St. Michael’s Hospital

Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.

“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”

Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.

The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.

In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.

Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.

In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.

Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack

relative to other statins. The adjusted odds ratio was 1.33.

However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.

Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.

The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.

The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.

On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.

Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.

Tony Antoniou, PhD

Photo courtesy of

St. Michael’s Hospital

Two commonly used statins, lovastatin and simvastatin, can increase the risk of major hemorrhage in patients receiving the anticoagulant dabigatran etexilate, according to research published in the Canadian Medical Association Journal.

“We found no difference in the risk of stroke in patients receiving dabigatran who were prescribed lovastatin or simvastatin versus other statins,” said study author Tony Antoniou, PhD, of St. Michael’s Hospital in Toronto, Ontario, Canada.

“However, an increase in the risk of bleeding requiring hospital admission or emergency department visits was seen with lovastatin and simvastatin compared with the other statins.”

Dr Antoniou and his colleagues made these discoveries by conducting 2 population-based, nested case-control studies.

The studies included patients older than 65 years of age who started treatment with dabigatran etexilate between 2012 and 2014. All patients had nonvalvular atrial fibrillation and were receiving dabigatran etexilate for the prevention of stroke and systemic embolism.

In the first study, the cases were patients with ischemic stroke. In the second study, the cases were patients with major hemorrhage. Each case had up to 4 age- and sex-matched controls.

Both cases and controls received a statin. And the researchers set out to determine the association between each outcome and the use of simvastatin or lovastatin compared to other statins.

In the 45,991 patients studied, there were 397 cases of ischemic stroke and 1117 cases of major hemorrhage.

Multivariable analysis suggested that use of simvastatin or lovastatin was not associated with an increased risk of stroke or transient ischemic attack

relative to other statins. The adjusted odds ratio was 1.33.

However, the use of simvastatin and lovastatin was associated with an increased risk of major hemorrhage. The adjusted odds ratio was 1.46.

Dr Antoniou and his colleagues believe simvastatin and lovastatin increase the risk of bleeding by increasing the amount of dabigatran absorbed by the body.

The team noted that dabigatran etexilate is metabolized to dabigatran by carboxylesterase enzymes, intestinal absorption of the prodrug is opposed by P-glycoprotein, and simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase.

The researchers said the fact that the statins inhibit P-glycoprotein appears to explain the increased risk of bleeding they observed. And the fact that simvastatin and lovastatin were not associated with an increased risk of stroke suggests carboxylesterase inhibition is of little clinical relevance in this setting.

On the other hand, the researchers also noted that the number of cases receiving lovastatin and simvastatin was small. This may have influenced the team’s power to detect an association between these drugs and stroke.

Regardless, the researchers said the results of these studies suggest there is a clinically important drug interaction between dabigatran etexilate and both simvastatin and lovastatin. Therefore, other statins should be considered in patients receiving dabigatran etexilate.

Micrograph showing APL

Image courtesy of the Armed

Forces Institute of Pathology

The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).

The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 10³/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.

Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.

“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.

“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”

Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.

Phase 3 study results

The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.

Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

Micrograph showing APL

Image courtesy of the Armed

Forces Institute of Pathology

The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).

The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 10³/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.

Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.

“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.

“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”

Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.

Phase 3 study results

The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.

Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

Micrograph showing APL

Image courtesy of the Armed

Forces Institute of Pathology

The European Commission (EC) has extended the approved indication for arsenic trioxide (Trisenox®) in patients with acute promyelocytic leukemia (APL).

The drug is now approved for use in combination with all-trans-retinoic acid (ATRA) to induce remission and for consolidation in adults with newly diagnosed low- to intermediate-risk APL (white blood cell count, ≤ 10 x 10³/μL) characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene.

Arsenic trioxide was previously approved by the EC to induce remission and as consolidation in adults with relapsed/refractory APL, which is characterized by the presence of the t(15;17) translocation and/or the presence of the PML/RARα gene, whose previous treatment included a retinoid and chemotherapy.

“This [expanded] approval by the European Commission is good news for APL patients, as we now have access to a cure for an acute leukemia without using chemotherapy,” said Francesco Lo-Coco, MD, of University of Rome Tor Vergata in Italy.

“Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies.”

Arsenic trioxide is marketed by Teva Pharmaceutical Industries Ltd.

Phase 3 study results

The EC’s expanded approval of arsenic trioxide is based on results from the APL0406 Intergroup GIMEMA-AMLSG-SAL study. Previous results from this phase 3 study were published in NEJM in 2013.

Updated results include 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.

A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).

After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).

At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).

After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.

In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.

Just what someone with diabetes who’s successfully losing weight doesn’t want to hear: Losing weight may boost appetite significantly.

NIH researchers analyzed data from a year-long study of 242 people, of whom 153 were taking canagliflozin, a drug that increases the amount of glucose excreted in urine. That calorie loss led to a gradual weight loss that averaged 8 pounds. The patients were not “directly aware” of the calorie loss, the researchers say.

Related: A VA-Based, Multidisciplinary Weight Management Program

The participants could eat and drink without restriction. Using a math model, the researchers calculated the changes in the amount of calories consumed during the study. They found no long-term calorie intake changes in the 89 people on placebo. By contrast, for every pound of lost weight, the canagliflozin patients consumed about 50 calories more per day than they were eating before the study. After about 6 months, the extra appetite-fueled calories led to a plateau in weight loss.

The findings didn’t entirely surprise the researchers. In an earlier study of participants in a weight loss program not involving canagliflozin, something similar happened. Despite the dieters’ consistent efforts, increased appetite led to a calorie intake 3 times stronger than the changes in caloric expenditure that typically accompany weight loss, the researchers say—and a plateau.

Related: Keeping Diabetes at Bay

The study provides the “first quantification of the homeostatic control of energy intake in free-living humans,” the researchers say. While energy expenditure adaptations often are thought to be the main reasons for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult, the researchers say.

The conclusion? “Persistent effort is required to avoid weight gain,” the NIH report notes. Unfortunately, “weight regain is typical in the absence of heroic and vigilant efforts to maintain behavior changes in the face of an omnipresent obesogenic environment.”

Related: A Call to Action: Intensive Lifestyle Intervention Against Diabesity

Just what someone with diabetes who’s successfully losing weight doesn’t want to hear: Losing weight may boost appetite significantly.

NIH researchers analyzed data from a year-long study of 242 people, of whom 153 were taking canagliflozin, a drug that increases the amount of glucose excreted in urine. That calorie loss led to a gradual weight loss that averaged 8 pounds. The patients were not “directly aware” of the calorie loss, the researchers say.

Related: A VA-Based, Multidisciplinary Weight Management Program

The participants could eat and drink without restriction. Using a math model, the researchers calculated the changes in the amount of calories consumed during the study. They found no long-term calorie intake changes in the 89 people on placebo. By contrast, for every pound of lost weight, the canagliflozin patients consumed about 50 calories more per day than they were eating before the study. After about 6 months, the extra appetite-fueled calories led to a plateau in weight loss.

The findings didn’t entirely surprise the researchers. In an earlier study of participants in a weight loss program not involving canagliflozin, something similar happened. Despite the dieters’ consistent efforts, increased appetite led to a calorie intake 3 times stronger than the changes in caloric expenditure that typically accompany weight loss, the researchers say—and a plateau.

Related: Keeping Diabetes at Bay

The study provides the “first quantification of the homeostatic control of energy intake in free-living humans,” the researchers say. While energy expenditure adaptations often are thought to be the main reasons for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult, the researchers say.

The conclusion? “Persistent effort is required to avoid weight gain,” the NIH report notes. Unfortunately, “weight regain is typical in the absence of heroic and vigilant efforts to maintain behavior changes in the face of an omnipresent obesogenic environment.”

Related: A Call to Action: Intensive Lifestyle Intervention Against Diabesity

Just what someone with diabetes who’s successfully losing weight doesn’t want to hear: Losing weight may boost appetite significantly.

NIH researchers analyzed data from a year-long study of 242 people, of whom 153 were taking canagliflozin, a drug that increases the amount of glucose excreted in urine. That calorie loss led to a gradual weight loss that averaged 8 pounds. The patients were not “directly aware” of the calorie loss, the researchers say.

Related: A VA-Based, Multidisciplinary Weight Management Program

The participants could eat and drink without restriction. Using a math model, the researchers calculated the changes in the amount of calories consumed during the study. They found no long-term calorie intake changes in the 89 people on placebo. By contrast, for every pound of lost weight, the canagliflozin patients consumed about 50 calories more per day than they were eating before the study. After about 6 months, the extra appetite-fueled calories led to a plateau in weight loss.

The findings didn’t entirely surprise the researchers. In an earlier study of participants in a weight loss program not involving canagliflozin, something similar happened. Despite the dieters’ consistent efforts, increased appetite led to a calorie intake 3 times stronger than the changes in caloric expenditure that typically accompany weight loss, the researchers say—and a plateau.

Related: Keeping Diabetes at Bay

The study provides the “first quantification of the homeostatic control of energy intake in free-living humans,” the researchers say. While energy expenditure adaptations often are thought to be the main reasons for slowing of weight loss and subsequent regain, feedback control of energy intake plays an even larger role and helps explain why long-term maintenance of a reduced body weight is so difficult, the researchers say.

The conclusion? “Persistent effort is required to avoid weight gain,” the NIH report notes. Unfortunately, “weight regain is typical in the absence of heroic and vigilant efforts to maintain behavior changes in the face of an omnipresent obesogenic environment.”

Related: A Call to Action: Intensive Lifestyle Intervention Against Diabesity

Three-quarters of premature infants who receive gastroesophageal reflux medications get those drugs after being discharged from neonatal intensive care units, despite questions about the safety and efficacy of the medications in premature infants.

In a retrospective study of 2,217 premature infants treated within the Children’s Hospital of Philadelphia primary care network from 2005 to 2009, 812 were treated with gastroesophageal reflux (GER) medications. Of this group, 77% were started on GER medication after neonatal intensive care unit (NICU) discharge, according to Jo Ann D’Agostino, DNP, CRNP, and her associates (Pediatrics. 2016 Nov 23. doi: 10.1542/peds.2016-1977).

Histamine-2 receptor antagonists were the most commonly prescribed GER medication, received by 90% of infants. Proton pump inhibitors were prescribed to 37% of infants, 22% received prokinetics, and 2% received cholinergics. During the first year of life, 40% of treated infants received multiple GER medications, with 73% of these infants receiving at least two medications simultaneously.

Risk factors associated with the use of multiple GER medications include a gestation period less than 32 weeks, feeding difficulty, tube feeding, a need for supplemental oxygen, and asthma.

“Because premature infants are a medically fragile group, the need for 1 acid suppression medication, let alone 2 or more in combination, should be given careful consideration. The potential impact of acid suppression on community-acquired illnesses has yet to be explored for this vulnerable population,” said Dr. D’Agostino of the department of pediatrics at the Children’s Hospital of Philadelphia, and her coauthors.

Infants who received GER treatment after NICU discharge were started on medication at a mean chronological age of 95 days and received medication for a mean of 294 days. Infants who started GER treatment while in the NICU received medication for a mean of 375 days.

A total of 743 infants were started on GER medications before the age of 6 months, and of this group, 43% were still being treated at the age of 1 year. Extended medication usage was associated with a gestational age under 32 weeks, chronic lung disease, airway malacia, and reactive airways disease.

A gestation period of less than 32 weeks was associated with a 31% increase in GER medication duration, compared with infants with a gestation period of 34-35 weeks, and a gestation period of less than 28 weeks was associated with a 50% increase in medication duration.

“Physiologic reflux symptoms are reported to peak at 4 months of age. Feeding issues are also common for premature infants. Whether this combination of issues is influencing the decision to start treatment, as opposed to actual GER disease, is an important distinction for providers to consider before starting medication,” Dr. D’Agostino and her associates noted.

“With uncertain evidence of efficacy, the rationale for using these medications in this high-risk population should be carefully evaluated,” they concluded.

The study was funded by the National Institutes of Health. The authors had no relevant financial disclosures.

[email protected]

Three-quarters of premature infants who receive gastroesophageal reflux medications get those drugs after being discharged from neonatal intensive care units, despite questions about the safety and efficacy of the medications in premature infants.

In a retrospective study of 2,217 premature infants treated within the Children’s Hospital of Philadelphia primary care network from 2005 to 2009, 812 were treated with gastroesophageal reflux (GER) medications. Of this group, 77% were started on GER medication after neonatal intensive care unit (NICU) discharge, according to Jo Ann D’Agostino, DNP, CRNP, and her associates (Pediatrics. 2016 Nov 23. doi: 10.1542/peds.2016-1977).

Histamine-2 receptor antagonists were the most commonly prescribed GER medication, received by 90% of infants. Proton pump inhibitors were prescribed to 37% of infants, 22% received prokinetics, and 2% received cholinergics. During the first year of life, 40% of treated infants received multiple GER medications, with 73% of these infants receiving at least two medications simultaneously.

Risk factors associated with the use of multiple GER medications include a gestation period less than 32 weeks, feeding difficulty, tube feeding, a need for supplemental oxygen, and asthma.

“Because premature infants are a medically fragile group, the need for 1 acid suppression medication, let alone 2 or more in combination, should be given careful consideration. The potential impact of acid suppression on community-acquired illnesses has yet to be explored for this vulnerable population,” said Dr. D’Agostino of the department of pediatrics at the Children’s Hospital of Philadelphia, and her coauthors.

Infants who received GER treatment after NICU discharge were started on medication at a mean chronological age of 95 days and received medication for a mean of 294 days. Infants who started GER treatment while in the NICU received medication for a mean of 375 days.

A total of 743 infants were started on GER medications before the age of 6 months, and of this group, 43% were still being treated at the age of 1 year. Extended medication usage was associated with a gestational age under 32 weeks, chronic lung disease, airway malacia, and reactive airways disease.

A gestation period of less than 32 weeks was associated with a 31% increase in GER medication duration, compared with infants with a gestation period of 34-35 weeks, and a gestation period of less than 28 weeks was associated with a 50% increase in medication duration.

“Physiologic reflux symptoms are reported to peak at 4 months of age. Feeding issues are also common for premature infants. Whether this combination of issues is influencing the decision to start treatment, as opposed to actual GER disease, is an important distinction for providers to consider before starting medication,” Dr. D’Agostino and her associates noted.

“With uncertain evidence of efficacy, the rationale for using these medications in this high-risk population should be carefully evaluated,” they concluded.

The study was funded by the National Institutes of Health. The authors had no relevant financial disclosures.

[email protected]

Three-quarters of premature infants who receive gastroesophageal reflux medications get those drugs after being discharged from neonatal intensive care units, despite questions about the safety and efficacy of the medications in premature infants.

In a retrospective study of 2,217 premature infants treated within the Children’s Hospital of Philadelphia primary care network from 2005 to 2009, 812 were treated with gastroesophageal reflux (GER) medications. Of this group, 77% were started on GER medication after neonatal intensive care unit (NICU) discharge, according to Jo Ann D’Agostino, DNP, CRNP, and her associates (Pediatrics. 2016 Nov 23. doi: 10.1542/peds.2016-1977).

Histamine-2 receptor antagonists were the most commonly prescribed GER medication, received by 90% of infants. Proton pump inhibitors were prescribed to 37% of infants, 22% received prokinetics, and 2% received cholinergics. During the first year of life, 40% of treated infants received multiple GER medications, with 73% of these infants receiving at least two medications simultaneously.

Risk factors associated with the use of multiple GER medications include a gestation period less than 32 weeks, feeding difficulty, tube feeding, a need for supplemental oxygen, and asthma.

“Because premature infants are a medically fragile group, the need for 1 acid suppression medication, let alone 2 or more in combination, should be given careful consideration. The potential impact of acid suppression on community-acquired illnesses has yet to be explored for this vulnerable population,” said Dr. D’Agostino of the department of pediatrics at the Children’s Hospital of Philadelphia, and her coauthors.

Infants who received GER treatment after NICU discharge were started on medication at a mean chronological age of 95 days and received medication for a mean of 294 days. Infants who started GER treatment while in the NICU received medication for a mean of 375 days.

A total of 743 infants were started on GER medications before the age of 6 months, and of this group, 43% were still being treated at the age of 1 year. Extended medication usage was associated with a gestational age under 32 weeks, chronic lung disease, airway malacia, and reactive airways disease.

A gestation period of less than 32 weeks was associated with a 31% increase in GER medication duration, compared with infants with a gestation period of 34-35 weeks, and a gestation period of less than 28 weeks was associated with a 50% increase in medication duration.

“Physiologic reflux symptoms are reported to peak at 4 months of age. Feeding issues are also common for premature infants. Whether this combination of issues is influencing the decision to start treatment, as opposed to actual GER disease, is an important distinction for providers to consider before starting medication,” Dr. D’Agostino and her associates noted.

“With uncertain evidence of efficacy, the rationale for using these medications in this high-risk population should be carefully evaluated,” they concluded.

The study was funded by the National Institutes of Health. The authors had no relevant financial disclosures.

[email protected]

The FP examined the rash closely and considered a diagnosis of inverse psoriasis. He looked at the patient’s nails for further clues and found that the patient had nail pitting and some onycholysis, which are both found in psoriasis. There were also some psoriatic plaques over the dorsum of his fingers. The remainder of the patient’s skin was clear.

Between the nail findings and the fact that the rash didn’t respond to antifungal medicine, the FP realized that this was truly inverse psoriasis and decided not to perform a potassium hydroxide (KOH) preparation.

The partial response to hydrocortisone supported the psoriasis diagnosis as well, but the FP knew that hydrocortisone was rarely potent enough to treat psoriasis, so he prescribed topical triamcinolone cream. While ointments are frequently more potent, the choice of the cream was made to avoid the greasiness that the patient would feel with an ointment in the groin.

Triamcinolone was chosen to avoid issues of atrophy that could occur with a higher potency steroid in an intertriginous area. However, if the triamcinolone was not effective, the FP was prepared to prescribe a stronger potency topical steroid for a short period of time until the psoriasis cleared. Then, the moderate potency triamcinolone could be used to prevent recurrence. The patient was also told he could use the triamcinolone on his fingers.

The physician counseled the patient on quitting smoking because smoking worsens psoriasis and, of course, has many health risks. The patient was not willing to completely stop, but said he would try to cut down. The FP encouraged him to have a long-term goal of complete smoking cessation.

At a follow-up visit one month later, the rash was 90% better, but the psoriasis over the fingers was only 50% better. The FP then prescribed clobetasol ointment for the fingers and told the patient to also use it in the inguinal area for one week. Two months later, the patient had 95% clearance in both areas. The FP told the patient that this is a lifelong disease that can often be controlled, but not cured.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP examined the rash closely and considered a diagnosis of inverse psoriasis. He looked at the patient’s nails for further clues and found that the patient had nail pitting and some onycholysis, which are both found in psoriasis. There were also some psoriatic plaques over the dorsum of his fingers. The remainder of the patient’s skin was clear.

Between the nail findings and the fact that the rash didn’t respond to antifungal medicine, the FP realized that this was truly inverse psoriasis and decided not to perform a potassium hydroxide (KOH) preparation.

The partial response to hydrocortisone supported the psoriasis diagnosis as well, but the FP knew that hydrocortisone was rarely potent enough to treat psoriasis, so he prescribed topical triamcinolone cream. While ointments are frequently more potent, the choice of the cream was made to avoid the greasiness that the patient would feel with an ointment in the groin.

Triamcinolone was chosen to avoid issues of atrophy that could occur with a higher potency steroid in an intertriginous area. However, if the triamcinolone was not effective, the FP was prepared to prescribe a stronger potency topical steroid for a short period of time until the psoriasis cleared. Then, the moderate potency triamcinolone could be used to prevent recurrence. The patient was also told he could use the triamcinolone on his fingers.

The physician counseled the patient on quitting smoking because smoking worsens psoriasis and, of course, has many health risks. The patient was not willing to completely stop, but said he would try to cut down. The FP encouraged him to have a long-term goal of complete smoking cessation.

At a follow-up visit one month later, the rash was 90% better, but the psoriasis over the fingers was only 50% better. The FP then prescribed clobetasol ointment for the fingers and told the patient to also use it in the inguinal area for one week. Two months later, the patient had 95% clearance in both areas. The FP told the patient that this is a lifelong disease that can often be controlled, but not cured.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP examined the rash closely and considered a diagnosis of inverse psoriasis. He looked at the patient’s nails for further clues and found that the patient had nail pitting and some onycholysis, which are both found in psoriasis. There were also some psoriatic plaques over the dorsum of his fingers. The remainder of the patient’s skin was clear.

Between the nail findings and the fact that the rash didn’t respond to antifungal medicine, the FP realized that this was truly inverse psoriasis and decided not to perform a potassium hydroxide (KOH) preparation.

The partial response to hydrocortisone supported the psoriasis diagnosis as well, but the FP knew that hydrocortisone was rarely potent enough to treat psoriasis, so he prescribed topical triamcinolone cream. While ointments are frequently more potent, the choice of the cream was made to avoid the greasiness that the patient would feel with an ointment in the groin.

Triamcinolone was chosen to avoid issues of atrophy that could occur with a higher potency steroid in an intertriginous area. However, if the triamcinolone was not effective, the FP was prepared to prescribe a stronger potency topical steroid for a short period of time until the psoriasis cleared. Then, the moderate potency triamcinolone could be used to prevent recurrence. The patient was also told he could use the triamcinolone on his fingers.

The physician counseled the patient on quitting smoking because smoking worsens psoriasis and, of course, has many health risks. The patient was not willing to completely stop, but said he would try to cut down. The FP encouraged him to have a long-term goal of complete smoking cessation.

At a follow-up visit one month later, the rash was 90% better, but the psoriasis over the fingers was only 50% better. The FP then prescribed clobetasol ointment for the fingers and told the patient to also use it in the inguinal area for one week. Two months later, the patient had 95% clearance in both areas. The FP told the patient that this is a lifelong disease that can often be controlled, but not cured.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

LOS ANGELES – Initial outcomes measures are beginning to emerge from Pulmonary Embolism Response Teams.

Members of the Cleveland Clinic’s PERT, which was established in 2014, presented some of their preliminary data during a presentation at the CHEST annual meeting.

Frontline Medical News

The concept behind the PERT is to rapidly mobilize a team with varied expertise helpful for treating patients with pulmonary embolisms (PEs). While the PERT “can be activated by any (clinician) for any patient, even low-risk patients ... those with submassive and massive PEs [intermediate- and high-risk patients]” are the target patients, said Dr. Mahar of the Cleveland Clinic.

The first PERT was created at Massachusetts General Hospital in Boston in 2012, according to the National Consortium of Pulmonary Embolism Response Team’s website. As of May 2015, the PERT model has been adopted by physicians and health care professionals from more than 40 institutions.

Dr. Mahar reported that the Cleveland Clinic’s PERT is activated through a single pager that resides with a vascular medicine fellow during the day and a critical care fellow at night. When paged, the fellow promptly evaluates the patient and ensures a complete basic work-up, which includes an ECG, cardiac enzymes, N-terminal pro b-type natriuretic peptide, lower-extremity deep vein thrombosis scans, transthoracic echocardiogram, and confirmatory CT/PE protocol or ventilation/perfusion scan.

Based on the simplified Pulmonary Embolism Severity Index and Bova scores, the patient is risk stratified and the patient’s indications, and relative and absolute contraindications to advanced therapies are reviewed. The fellow next sends a group notification to the PERT via email and text message. The team then convenes online for a virtual meeting and case presentation that includes sharing of lab and test results and images.

The process sounds complex, but the surgeon, interventional radiologist, vascular medicine specialist, and cardiologist are on call and simultaneously get the message and respond, Dr. Mahar said. With a team approach, the decision to use advanced therapies – systemic lytics, surgery, catheter-directed lysis and extracorporeal membrane oxygenation – is expedited. “For example, over the last 2 years, four out of four patients who underwent surgical embolectomies had good outcomes without any deaths,” he said.

Based on a retrospective chart review from October 2014 through August 2016, Cleveland Clinic’s PERT had been activated for 134 patients, 112 of whom were found to have PEs, Dr. Mahar said during his presentation at the annual meeting of the American College of Chest Physicians (CHEST).

The number of low risk, submassive, and massive PEs were 14 (12%), 76 (68%), and 22 (20%), respectively. Just over half of the PE patients, 55% (60 patients), were treated with anticoagulation therapy alone. Inferior vena cava filters were placed in 32 patients (29%); 14 patients received catheter-directed thrombolysis, 3 received a suction thrombectomy, and 4 received a surgical embolectomy.

The 30-day all-cause mortality rate was 9%; the deaths occurred in six patients who had massive PEs, three patients with submassive PEs, and one patient with a low-risk PE. Six of the patients who died had been treated with anticoagulation, two had received catheter-directed thrombolysis, and one had received a full dose of systemic thrombolysis.

Bleeding complications occurred in 10 patients, 6 of whom were treated with anticoagulation alone and 4 of whom underwent catheter-directed thrombolysis.

Cleveland Clinic is a large entity with multiple resources, but the principles of PERT can be applied in smaller facilities, as well, according to Gustavo A. Heresi-Davila, MD, medical director of the Cleveland Clinic’s pulmonary thromboendarterectomy program and the lead researcher for the PERT project at the clinic. “I would emphasize the notion that a PERT has to be multidisciplinary, as people with different backgrounds and expertise bring complementary talent to the discussion of each case. I would not minimize the challenges of assembling such a team,” he said during an interview following the meeting.

The moderator of the meeting session, Robert Schilz, DO, PhD, noted, that the goal of PERT is to determine the best approach for an individual patient based on available resources. To establish a PERT, “you don’t have to be able to put a patient on ECMO [extracorporeal membrane oxygenation] in 15 minutes, and you don’t have to be able to do endarterectomies, embolectomies, and all the catheter-drive techniques emergently. But you do need to have the disposition to have efficient and standardized care, and the solutions may need to be very geographic. What hospital A may do may be very different from hospital B.”

Small hospitals can draw on their available resources, added Dr. Schilz, director of pulmonary vascular disease and lung transplantation at Case Western Reserve University, Cleveland. “Most hospitals have cardiologists on call 24/7, and many have some flavor of interventional radiology; others have clear referral and transfer schemes. Emergency department personnel at small rural hospitals can rapidly identify patients appropriate for transfer.”

Dr. Mahar added that PERTs are already being utilized in smaller hospitals and that he thinks that, in the next 5 years, having a PERT will be the standard protocol.

Dr. Mahar reported no disclosures.

[email protected]

Mary Jo Dales contributed to this report.

LOS ANGELES – Initial outcomes measures are beginning to emerge from Pulmonary Embolism Response Teams.

Members of the Cleveland Clinic’s PERT, which was established in 2014, presented some of their preliminary data during a presentation at the CHEST annual meeting.

Frontline Medical News

The concept behind the PERT is to rapidly mobilize a team with varied expertise helpful for treating patients with pulmonary embolisms (PEs). While the PERT “can be activated by any (clinician) for any patient, even low-risk patients ... those with submassive and massive PEs [intermediate- and high-risk patients]” are the target patients, said Dr. Mahar of the Cleveland Clinic.

The first PERT was created at Massachusetts General Hospital in Boston in 2012, according to the National Consortium of Pulmonary Embolism Response Team’s website. As of May 2015, the PERT model has been adopted by physicians and health care professionals from more than 40 institutions.

Dr. Mahar reported that the Cleveland Clinic’s PERT is activated through a single pager that resides with a vascular medicine fellow during the day and a critical care fellow at night. When paged, the fellow promptly evaluates the patient and ensures a complete basic work-up, which includes an ECG, cardiac enzymes, N-terminal pro b-type natriuretic peptide, lower-extremity deep vein thrombosis scans, transthoracic echocardiogram, and confirmatory CT/PE protocol or ventilation/perfusion scan.

Based on the simplified Pulmonary Embolism Severity Index and Bova scores, the patient is risk stratified and the patient’s indications, and relative and absolute contraindications to advanced therapies are reviewed. The fellow next sends a group notification to the PERT via email and text message. The team then convenes online for a virtual meeting and case presentation that includes sharing of lab and test results and images.

The process sounds complex, but the surgeon, interventional radiologist, vascular medicine specialist, and cardiologist are on call and simultaneously get the message and respond, Dr. Mahar said. With a team approach, the decision to use advanced therapies – systemic lytics, surgery, catheter-directed lysis and extracorporeal membrane oxygenation – is expedited. “For example, over the last 2 years, four out of four patients who underwent surgical embolectomies had good outcomes without any deaths,” he said.

Based on a retrospective chart review from October 2014 through August 2016, Cleveland Clinic’s PERT had been activated for 134 patients, 112 of whom were found to have PEs, Dr. Mahar said during his presentation at the annual meeting of the American College of Chest Physicians (CHEST).

The number of low risk, submassive, and massive PEs were 14 (12%), 76 (68%), and 22 (20%), respectively. Just over half of the PE patients, 55% (60 patients), were treated with anticoagulation therapy alone. Inferior vena cava filters were placed in 32 patients (29%); 14 patients received catheter-directed thrombolysis, 3 received a suction thrombectomy, and 4 received a surgical embolectomy.

The 30-day all-cause mortality rate was 9%; the deaths occurred in six patients who had massive PEs, three patients with submassive PEs, and one patient with a low-risk PE. Six of the patients who died had been treated with anticoagulation, two had received catheter-directed thrombolysis, and one had received a full dose of systemic thrombolysis.

Bleeding complications occurred in 10 patients, 6 of whom were treated with anticoagulation alone and 4 of whom underwent catheter-directed thrombolysis.

Cleveland Clinic is a large entity with multiple resources, but the principles of PERT can be applied in smaller facilities, as well, according to Gustavo A. Heresi-Davila, MD, medical director of the Cleveland Clinic’s pulmonary thromboendarterectomy program and the lead researcher for the PERT project at the clinic. “I would emphasize the notion that a PERT has to be multidisciplinary, as people with different backgrounds and expertise bring complementary talent to the discussion of each case. I would not minimize the challenges of assembling such a team,” he said during an interview following the meeting.

The moderator of the meeting session, Robert Schilz, DO, PhD, noted, that the goal of PERT is to determine the best approach for an individual patient based on available resources. To establish a PERT, “you don’t have to be able to put a patient on ECMO [extracorporeal membrane oxygenation] in 15 minutes, and you don’t have to be able to do endarterectomies, embolectomies, and all the catheter-drive techniques emergently. But you do need to have the disposition to have efficient and standardized care, and the solutions may need to be very geographic. What hospital A may do may be very different from hospital B.”

Small hospitals can draw on their available resources, added Dr. Schilz, director of pulmonary vascular disease and lung transplantation at Case Western Reserve University, Cleveland. “Most hospitals have cardiologists on call 24/7, and many have some flavor of interventional radiology; others have clear referral and transfer schemes. Emergency department personnel at small rural hospitals can rapidly identify patients appropriate for transfer.”

Dr. Mahar added that PERTs are already being utilized in smaller hospitals and that he thinks that, in the next 5 years, having a PERT will be the standard protocol.

Dr. Mahar reported no disclosures.

[email protected]

Mary Jo Dales contributed to this report.

LOS ANGELES – Initial outcomes measures are beginning to emerge from Pulmonary Embolism Response Teams.

Members of the Cleveland Clinic’s PERT, which was established in 2014, presented some of their preliminary data during a presentation at the CHEST annual meeting.

Frontline Medical News

The concept behind the PERT is to rapidly mobilize a team with varied expertise helpful for treating patients with pulmonary embolisms (PEs). While the PERT “can be activated by any (clinician) for any patient, even low-risk patients ... those with submassive and massive PEs [intermediate- and high-risk patients]” are the target patients, said Dr. Mahar of the Cleveland Clinic.

The first PERT was created at Massachusetts General Hospital in Boston in 2012, according to the National Consortium of Pulmonary Embolism Response Team’s website. As of May 2015, the PERT model has been adopted by physicians and health care professionals from more than 40 institutions.

Dr. Mahar reported that the Cleveland Clinic’s PERT is activated through a single pager that resides with a vascular medicine fellow during the day and a critical care fellow at night. When paged, the fellow promptly evaluates the patient and ensures a complete basic work-up, which includes an ECG, cardiac enzymes, N-terminal pro b-type natriuretic peptide, lower-extremity deep vein thrombosis scans, transthoracic echocardiogram, and confirmatory CT/PE protocol or ventilation/perfusion scan.

Based on the simplified Pulmonary Embolism Severity Index and Bova scores, the patient is risk stratified and the patient’s indications, and relative and absolute contraindications to advanced therapies are reviewed. The fellow next sends a group notification to the PERT via email and text message. The team then convenes online for a virtual meeting and case presentation that includes sharing of lab and test results and images.

The process sounds complex, but the surgeon, interventional radiologist, vascular medicine specialist, and cardiologist are on call and simultaneously get the message and respond, Dr. Mahar said. With a team approach, the decision to use advanced therapies – systemic lytics, surgery, catheter-directed lysis and extracorporeal membrane oxygenation – is expedited. “For example, over the last 2 years, four out of four patients who underwent surgical embolectomies had good outcomes without any deaths,” he said.

Based on a retrospective chart review from October 2014 through August 2016, Cleveland Clinic’s PERT had been activated for 134 patients, 112 of whom were found to have PEs, Dr. Mahar said during his presentation at the annual meeting of the American College of Chest Physicians (CHEST).

The number of low risk, submassive, and massive PEs were 14 (12%), 76 (68%), and 22 (20%), respectively. Just over half of the PE patients, 55% (60 patients), were treated with anticoagulation therapy alone. Inferior vena cava filters were placed in 32 patients (29%); 14 patients received catheter-directed thrombolysis, 3 received a suction thrombectomy, and 4 received a surgical embolectomy.

The 30-day all-cause mortality rate was 9%; the deaths occurred in six patients who had massive PEs, three patients with submassive PEs, and one patient with a low-risk PE. Six of the patients who died had been treated with anticoagulation, two had received catheter-directed thrombolysis, and one had received a full dose of systemic thrombolysis.

Bleeding complications occurred in 10 patients, 6 of whom were treated with anticoagulation alone and 4 of whom underwent catheter-directed thrombolysis.

Cleveland Clinic is a large entity with multiple resources, but the principles of PERT can be applied in smaller facilities, as well, according to Gustavo A. Heresi-Davila, MD, medical director of the Cleveland Clinic’s pulmonary thromboendarterectomy program and the lead researcher for the PERT project at the clinic. “I would emphasize the notion that a PERT has to be multidisciplinary, as people with different backgrounds and expertise bring complementary talent to the discussion of each case. I would not minimize the challenges of assembling such a team,” he said during an interview following the meeting.

The moderator of the meeting session, Robert Schilz, DO, PhD, noted, that the goal of PERT is to determine the best approach for an individual patient based on available resources. To establish a PERT, “you don’t have to be able to put a patient on ECMO [extracorporeal membrane oxygenation] in 15 minutes, and you don’t have to be able to do endarterectomies, embolectomies, and all the catheter-drive techniques emergently. But you do need to have the disposition to have efficient and standardized care, and the solutions may need to be very geographic. What hospital A may do may be very different from hospital B.”

Small hospitals can draw on their available resources, added Dr. Schilz, director of pulmonary vascular disease and lung transplantation at Case Western Reserve University, Cleveland. “Most hospitals have cardiologists on call 24/7, and many have some flavor of interventional radiology; others have clear referral and transfer schemes. Emergency department personnel at small rural hospitals can rapidly identify patients appropriate for transfer.”

Dr. Mahar added that PERTs are already being utilized in smaller hospitals and that he thinks that, in the next 5 years, having a PERT will be the standard protocol.

Dr. Mahar reported no disclosures.

[email protected]

Mary Jo Dales contributed to this report.

ROME—Carotid stenting was associated with a roughly 30% higher risk of cardiovascular events, compared with carotid endarterectomy, during 12 years of follow-up in a large, real-world, population-based cohort study, Mohamad A. Hussain, MD, reported at the Annual Congress of the European Society of Cardiology. “Our data raise concerns about the external validity of randomized controlled trials of carotid endarterectomy versus stenting and question the potential interchangeability of carotid endarterectomy and stenting as stated in clinical practice guidelines,” said Dr. Hussain, a vascular surgeon at the University of Toronto.

Major practice guidelines cite randomized trial evidence in suggesting that carotid endarterectomy and stenting can be used interchangeably in treating low- or average-risk patients with significant carotid artery disease. Dr. Hussain and his coinvestigators, suspecting that the generalizability of the randomized trial findings might be limited because of operator and institutional selection bias, decided to conduct a retrospective cohort study of all patients older than 40 who underwent carotid endarterectomy or carotid stenting in the province of Ontario from April 2002 through March 2013.

Using validated chart abstraction software, they identified 12,529 patients who had carotid endarterectomy and 1,935 who had carotid stenting. The two groups were similar in terms of most baseline characteristics. Notably, however, stent recipients were significantly more likely to have symptomatic carotid disease and also had more comorbid conditions, as reflected in a higher Charlson Comorbidity Index score.

The primary outcome in the study was the 12-year rate of a composite comprising ischemic stroke, transient ischemic attack (TIA), myocardial infarction, or death. The rate was 35.4% in the carotid endarterectomy group and 44.5% in the stent group. After adjustment for the baseline differences, the stent group still had a statistically significant 28% greater risk of the primary outcome.

“We found the difference remained significant in all of our subgroup analyses, regardless of age, sex, year of procedure, symptomatic or asymptomatic carotid artery disease, CAD [coronary artery disease] or no CAD, diabetes (type 1 or 2) or no diabetes. Outcomes with endarterectomy were always significantly better,” said Dr. Hussain.

“I think our study shows that in clinical practice, we’re not quite seeing the outcomes reported in the clinical trials,” he added.

A Closer Look at the Data

As for the individual components of the composite end point, the 12-year rate of ischemic stroke or TIA was 9% in the carotid endarterectomy group and 14% with stenting, for an adjusted 40% increased risk in the stent group. The 12-year all-cause mortality rate was 26% in the carotid endarterectomy group and 34% with stenting, for an adjusted 28% increased risk. The incidence of myocardial infarction was 8% in both groups.

The investigators next conducted a confirmatory propensity-matched analysis in which 1,927 of the stented patients were closely matched to 3,844 surgical patients, eliminating baseline differences in the prevalence of symptomatic carotid artery disease and other disparities. In this matched cohort, the primary outcome occurred in 37.4% of the carotid endarterectomy group and 44.3% of stent patients, for an adjusted 32% increase in risk in the stented group.

The differences in outcome were driven by sharply higher periprocedural risk in the stented group. After the periprocedural period, the outcome curves remained parallel in the two treatment groups.

In the first 30 days post procedure, the primary composite outcome occurred in 5.4% of the carotid endarterectomy group and 10% of stented patients, for an adjusted 40% increase in relative risk in percutaneously treated patients. The 30-day rate of ischemic stroke or TIA was 3.4% in the surgical group, compared with 6.4% in stented patients. Thirty-day mortality was 0.9% with carotid endarterectomy versus 3.3% with stenting.

Possible Explanations for the Disparity

Asked for his thoughts on the disparity between the results of his real-world study and the major randomized trials of carotid endarterectomy versus stenting, Dr. Hussain replied, “It may be because the trials had high-volume operators at high-volume centers who are experts in carotid stenting, while in the real world, many physicians may not be selecting the right people for carotid stenting.”

Differences in sample size may also figure in the disparity, he continued. He noted that in the recent 10-year report from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite end point of stroke, myocardial infarction, or death occurred in 9.9% of the carotid endarterectomy group, compared with 11.8% of the stenting group, but this difference in favor of carotid endarterectomy did not achieve statistical significance because of the wide confidence intervals resulting from a smaller sample size than in the Ontario study.

Looking to the future, Dr. Hussain said he thinks the ongoing CREST-2 trial is “important.” It is randomizing patients with asymptomatic high-grade carotid stenosis to uniform intensive medical management either alone or in combination with carotid endarterectomy or stenting with embolic protection. “That study might end up showing us that medical therapy is as good as or even better than stenting or carotid endarterectomy, especially in asymptomatic patients,” he said.

Dr. Hussain reported having no financial conflicts regarding his academically funded study.

—Bruce Jancin

Suggested Reading

Brott TG, Howard G, Roubin GS, et al. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med. 2016;374(11):1021-1031.

ROME—Carotid stenting was associated with a roughly 30% higher risk of cardiovascular events, compared with carotid endarterectomy, during 12 years of follow-up in a large, real-world, population-based cohort study, Mohamad A. Hussain, MD, reported at the Annual Congress of the European Society of Cardiology. “Our data raise concerns about the external validity of randomized controlled trials of carotid endarterectomy versus stenting and question the potential interchangeability of carotid endarterectomy and stenting as stated in clinical practice guidelines,” said Dr. Hussain, a vascular surgeon at the University of Toronto.

Major practice guidelines cite randomized trial evidence in suggesting that carotid endarterectomy and stenting can be used interchangeably in treating low- or average-risk patients with significant carotid artery disease. Dr. Hussain and his coinvestigators, suspecting that the generalizability of the randomized trial findings might be limited because of operator and institutional selection bias, decided to conduct a retrospective cohort study of all patients older than 40 who underwent carotid endarterectomy or carotid stenting in the province of Ontario from April 2002 through March 2013.

Using validated chart abstraction software, they identified 12,529 patients who had carotid endarterectomy and 1,935 who had carotid stenting. The two groups were similar in terms of most baseline characteristics. Notably, however, stent recipients were significantly more likely to have symptomatic carotid disease and also had more comorbid conditions, as reflected in a higher Charlson Comorbidity Index score.

The primary outcome in the study was the 12-year rate of a composite comprising ischemic stroke, transient ischemic attack (TIA), myocardial infarction, or death. The rate was 35.4% in the carotid endarterectomy group and 44.5% in the stent group. After adjustment for the baseline differences, the stent group still had a statistically significant 28% greater risk of the primary outcome.

“We found the difference remained significant in all of our subgroup analyses, regardless of age, sex, year of procedure, symptomatic or asymptomatic carotid artery disease, CAD [coronary artery disease] or no CAD, diabetes (type 1 or 2) or no diabetes. Outcomes with endarterectomy were always significantly better,” said Dr. Hussain.

“I think our study shows that in clinical practice, we’re not quite seeing the outcomes reported in the clinical trials,” he added.

A Closer Look at the Data

As for the individual components of the composite end point, the 12-year rate of ischemic stroke or TIA was 9% in the carotid endarterectomy group and 14% with stenting, for an adjusted 40% increased risk in the stent group. The 12-year all-cause mortality rate was 26% in the carotid endarterectomy group and 34% with stenting, for an adjusted 28% increased risk. The incidence of myocardial infarction was 8% in both groups.

The investigators next conducted a confirmatory propensity-matched analysis in which 1,927 of the stented patients were closely matched to 3,844 surgical patients, eliminating baseline differences in the prevalence of symptomatic carotid artery disease and other disparities. In this matched cohort, the primary outcome occurred in 37.4% of the carotid endarterectomy group and 44.3% of stent patients, for an adjusted 32% increase in risk in the stented group.

The differences in outcome were driven by sharply higher periprocedural risk in the stented group. After the periprocedural period, the outcome curves remained parallel in the two treatment groups.

In the first 30 days post procedure, the primary composite outcome occurred in 5.4% of the carotid endarterectomy group and 10% of stented patients, for an adjusted 40% increase in relative risk in percutaneously treated patients. The 30-day rate of ischemic stroke or TIA was 3.4% in the surgical group, compared with 6.4% in stented patients. Thirty-day mortality was 0.9% with carotid endarterectomy versus 3.3% with stenting.

Possible Explanations for the Disparity

Asked for his thoughts on the disparity between the results of his real-world study and the major randomized trials of carotid endarterectomy versus stenting, Dr. Hussain replied, “It may be because the trials had high-volume operators at high-volume centers who are experts in carotid stenting, while in the real world, many physicians may not be selecting the right people for carotid stenting.”

Differences in sample size may also figure in the disparity, he continued. He noted that in the recent 10-year report from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite end point of stroke, myocardial infarction, or death occurred in 9.9% of the carotid endarterectomy group, compared with 11.8% of the stenting group, but this difference in favor of carotid endarterectomy did not achieve statistical significance because of the wide confidence intervals resulting from a smaller sample size than in the Ontario study.

Looking to the future, Dr. Hussain said he thinks the ongoing CREST-2 trial is “important.” It is randomizing patients with asymptomatic high-grade carotid stenosis to uniform intensive medical management either alone or in combination with carotid endarterectomy or stenting with embolic protection. “That study might end up showing us that medical therapy is as good as or even better than stenting or carotid endarterectomy, especially in asymptomatic patients,” he said.

Dr. Hussain reported having no financial conflicts regarding his academically funded study.

—Bruce Jancin

Suggested Reading

Brott TG, Howard G, Roubin GS, et al. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med. 2016;374(11):1021-1031.

ROME—Carotid stenting was associated with a roughly 30% higher risk of cardiovascular events, compared with carotid endarterectomy, during 12 years of follow-up in a large, real-world, population-based cohort study, Mohamad A. Hussain, MD, reported at the Annual Congress of the European Society of Cardiology. “Our data raise concerns about the external validity of randomized controlled trials of carotid endarterectomy versus stenting and question the potential interchangeability of carotid endarterectomy and stenting as stated in clinical practice guidelines,” said Dr. Hussain, a vascular surgeon at the University of Toronto.

Major practice guidelines cite randomized trial evidence in suggesting that carotid endarterectomy and stenting can be used interchangeably in treating low- or average-risk patients with significant carotid artery disease. Dr. Hussain and his coinvestigators, suspecting that the generalizability of the randomized trial findings might be limited because of operator and institutional selection bias, decided to conduct a retrospective cohort study of all patients older than 40 who underwent carotid endarterectomy or carotid stenting in the province of Ontario from April 2002 through March 2013.

Using validated chart abstraction software, they identified 12,529 patients who had carotid endarterectomy and 1,935 who had carotid stenting. The two groups were similar in terms of most baseline characteristics. Notably, however, stent recipients were significantly more likely to have symptomatic carotid disease and also had more comorbid conditions, as reflected in a higher Charlson Comorbidity Index score.

The primary outcome in the study was the 12-year rate of a composite comprising ischemic stroke, transient ischemic attack (TIA), myocardial infarction, or death. The rate was 35.4% in the carotid endarterectomy group and 44.5% in the stent group. After adjustment for the baseline differences, the stent group still had a statistically significant 28% greater risk of the primary outcome.

“We found the difference remained significant in all of our subgroup analyses, regardless of age, sex, year of procedure, symptomatic or asymptomatic carotid artery disease, CAD [coronary artery disease] or no CAD, diabetes (type 1 or 2) or no diabetes. Outcomes with endarterectomy were always significantly better,” said Dr. Hussain.

“I think our study shows that in clinical practice, we’re not quite seeing the outcomes reported in the clinical trials,” he added.

A Closer Look at the Data

As for the individual components of the composite end point, the 12-year rate of ischemic stroke or TIA was 9% in the carotid endarterectomy group and 14% with stenting, for an adjusted 40% increased risk in the stent group. The 12-year all-cause mortality rate was 26% in the carotid endarterectomy group and 34% with stenting, for an adjusted 28% increased risk. The incidence of myocardial infarction was 8% in both groups.

The investigators next conducted a confirmatory propensity-matched analysis in which 1,927 of the stented patients were closely matched to 3,844 surgical patients, eliminating baseline differences in the prevalence of symptomatic carotid artery disease and other disparities. In this matched cohort, the primary outcome occurred in 37.4% of the carotid endarterectomy group and 44.3% of stent patients, for an adjusted 32% increase in risk in the stented group.

The differences in outcome were driven by sharply higher periprocedural risk in the stented group. After the periprocedural period, the outcome curves remained parallel in the two treatment groups.

In the first 30 days post procedure, the primary composite outcome occurred in 5.4% of the carotid endarterectomy group and 10% of stented patients, for an adjusted 40% increase in relative risk in percutaneously treated patients. The 30-day rate of ischemic stroke or TIA was 3.4% in the surgical group, compared with 6.4% in stented patients. Thirty-day mortality was 0.9% with carotid endarterectomy versus 3.3% with stenting.

Possible Explanations for the Disparity

Asked for his thoughts on the disparity between the results of his real-world study and the major randomized trials of carotid endarterectomy versus stenting, Dr. Hussain replied, “It may be because the trials had high-volume operators at high-volume centers who are experts in carotid stenting, while in the real world, many physicians may not be selecting the right people for carotid stenting.”

Differences in sample size may also figure in the disparity, he continued. He noted that in the recent 10-year report from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite end point of stroke, myocardial infarction, or death occurred in 9.9% of the carotid endarterectomy group, compared with 11.8% of the stenting group, but this difference in favor of carotid endarterectomy did not achieve statistical significance because of the wide confidence intervals resulting from a smaller sample size than in the Ontario study.

Looking to the future, Dr. Hussain said he thinks the ongoing CREST-2 trial is “important.” It is randomizing patients with asymptomatic high-grade carotid stenosis to uniform intensive medical management either alone or in combination with carotid endarterectomy or stenting with embolic protection. “That study might end up showing us that medical therapy is as good as or even better than stenting or carotid endarterectomy, especially in asymptomatic patients,” he said.

Dr. Hussain reported having no financial conflicts regarding his academically funded study.

—Bruce Jancin

Suggested Reading

Brott TG, Howard G, Roubin GS, et al. Long-term results of stenting versus endarterectomy for carotid-artery stenosis. N Engl J Med. 2016;374(11):1021-1031.