Background: Efforts to reduce and monitor high-risk opioid prescribing have largely focused on outpatient prescribing with less empiric evaluation of inpatient administration. Little is known about the association of inpatient opioid administration and postdischarge opioid use.

This observational study is prone to potential unmeasured confounders negating any clear causation. Rather, hospitalists should be aware of the increasing focus on inpatient opioid administration as it relates to outpatient opioid use, especially in the setting of the current opioid crisis.

Bottom line: Inpatient opioid administration and administration patterns are associated with 90-day postdischarge opioid use in opioid-­naive patients.

Citation: Donohue JM et al. Patterns of opioid administration among opioid-naive inpatients and associations with postdischarge opioid use. Ann Intern Med. 2019 Jun 18:171(2):81-90.

Dr. Ledford is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

Background: Efforts to reduce and monitor high-risk opioid prescribing have largely focused on outpatient prescribing with less empiric evaluation of inpatient administration. Little is known about the association of inpatient opioid administration and postdischarge opioid use.

This observational study is prone to potential unmeasured confounders negating any clear causation. Rather, hospitalists should be aware of the increasing focus on inpatient opioid administration as it relates to outpatient opioid use, especially in the setting of the current opioid crisis.

Bottom line: Inpatient opioid administration and administration patterns are associated with 90-day postdischarge opioid use in opioid-­naive patients.

Citation: Donohue JM et al. Patterns of opioid administration among opioid-naive inpatients and associations with postdischarge opioid use. Ann Intern Med. 2019 Jun 18:171(2):81-90.

Dr. Ledford is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

Background: Efforts to reduce and monitor high-risk opioid prescribing have largely focused on outpatient prescribing with less empiric evaluation of inpatient administration. Little is known about the association of inpatient opioid administration and postdischarge opioid use.

This observational study is prone to potential unmeasured confounders negating any clear causation. Rather, hospitalists should be aware of the increasing focus on inpatient opioid administration as it relates to outpatient opioid use, especially in the setting of the current opioid crisis.

Bottom line: Inpatient opioid administration and administration patterns are associated with 90-day postdischarge opioid use in opioid-­naive patients.

Citation: Donohue JM et al. Patterns of opioid administration among opioid-naive inpatients and associations with postdischarge opioid use. Ann Intern Med. 2019 Jun 18:171(2):81-90.

Dr. Ledford is a hospitalist at Vanderbilt University Medical Center, Nashville, Tenn.

A new algorithm on lipid management and prevention of cardiovascular disease from the American Association of Clinical Endocrinologists* (AACE) and the American College of Endocrinology (ACE) is “a nice cookbook” that many clinicians, especially those who are not lipid experts, will find useful, according to writing committee chair Yehuda Handelsman, MD.

The algorithm, published Oct. 10 in Endocrine Practice as 10 slides, or as part of a more detailed consensus statement, is a companion to the 2017 AACE/ACE guidelines for lipid management and includes more recent information about new therapies.

“What we’re trying to do here is to say, ‘focus on LDL-C, triglycerides, high-risk patients, and lifestyle. Understand all the medications available to you to reduce LDL-C and reduce triglycerides,’ ” Dr. Handelsman, of the Metabolic Institute of America, Tarzana, Calif., explained in an interview.

“We touch on lipoprotein(a), which we still don’t have medication for, but it identifies people at high risk, and we need that.”

Clinicians also need to know “that we’ve got some newer drugs in the market that can manage people who have statin intolerance,” Dr. Handelsman added.

“We introduced new therapies like icosapent ethyl” (Vascepa, Amarin) for hypertriglyceridemia, “when to use it, and how to use it. Even though it was not part of the 2017 guideline, we gave recommendations based on current data in the algorithm.”

Although there is no good evidence that lowering triglycerides reduces heart disease, he continued, many experts believe that the target triglyceride level should be less than 150 mg/dL, and the algorithm explains how to treat to this goal.

“Last, and most importantly, I cannot fail to underscore the fact that lifestyle is very important,” he emphasized.

Robert H. Eckel, MD, of the University of Colorado at Denver, Aurora, and president of medicine and science at the American Diabetes Association, who was not involved with this algorithm, said in an interview that the algorithm is important since it offers “the clinician or health care practitioner an approach, a kind of a cookbook or application of the guidelines, for how to manage lipid disorders in patients at risk ... It’s geared for the nonexperts too,” he said.

Dyslipidemia treatment summarized in 10 slides

The AACE/ACE algorithm comprises 10 slides, one each for dyslipidemic states, secondary causes of lipid disorders, screening for and assessing lipid disorders and atherosclerotic CVD (ASCVD) risk, ASCVD risk categories and treatment goals, lifestyle recommendations, treating LDL-C to goal, managing statin intolerance and safety, management of hypertriglyceridemia and the role of icosapent ethyl, assessment and management of elevated lipoprotein(a), and profiles of medications for dyslipidemia.

The algorithm defines five ASCVD risk categories and recommends increasingly lower LDL-C, non–HDL-C, and apo B target levels with increasing risk, but the same triglyceride target for all.

First, “treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids,” the consensus statement authors stress.

Next, “LDL-C has been, and remains, the main focus of efforts to improve lipid profiles in individuals at risk for ASCVD” (see table).

Statement aligns with major guidelines

In general, the 2017 AACE/ACE guidelines and algorithm are “pretty similar” to other guidelines such as the 2018 ACC/American Heart Association (AHA) guidelines for cholesterol management, the 2019 ACC/AHA guidelines for primary prevention of CVD, and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidemia, according to Dr. Eckel.

They have “all have now taken into consideration the evidence behind PCSK9 inhibitors,” he noted. “That’s important because those drugs have proven to be effective.”

Two differences, he pointed out, are that the 2019 ESC/EAS guidelines suggest that lipoprotein(a) measurement be considered at least once in every adult’s lifetime, and they recommend apo B analysis in people with high triglycerides but normal LDL (or no higher than 100 mg/dL), to identify additional risk.
 

*AACE changes its name, broadens focus

Shortly after its algorithm was published, AACE announced that it has a new organization name and brand, the American Association of Clinical Endocrinology, which “more clearly defines AACE as a community of individuals who work together to elevate the practice of clinical endocrinology,” according to an Oct. 20 statement.

The change is meant to acknowledge AACE’s “more modern, inclusive approach to endocrinology that supports multidisciplinary care teams – with endocrinologists leading the way.”

Along with the name change is a new global website. The statement notes that “health care professionals and community members can access all of the valuable clinical content such as guidelines, disease state networks and important education by visiting the pro portal in the top right corner of the site, or by going directly to pro.aace.com.”

Dr. Handelsman discloses that he receives research grant support from Amgen, Applied Therapeutics, AstraZeneca, BMS, Gan & Lee, Novo Nordisk, and Sanofi, and he is a consultant and/or speaker for Amarin, BI-Lilly, and Sanofi.

Dr. Eckel has received consultant/advisory board fees from Kowa, Novo Nordisk, and Provention Bio.

A new algorithm on lipid management and prevention of cardiovascular disease from the American Association of Clinical Endocrinologists* (AACE) and the American College of Endocrinology (ACE) is “a nice cookbook” that many clinicians, especially those who are not lipid experts, will find useful, according to writing committee chair Yehuda Handelsman, MD.

The algorithm, published Oct. 10 in Endocrine Practice as 10 slides, or as part of a more detailed consensus statement, is a companion to the 2017 AACE/ACE guidelines for lipid management and includes more recent information about new therapies.

“What we’re trying to do here is to say, ‘focus on LDL-C, triglycerides, high-risk patients, and lifestyle. Understand all the medications available to you to reduce LDL-C and reduce triglycerides,’ ” Dr. Handelsman, of the Metabolic Institute of America, Tarzana, Calif., explained in an interview.

“We touch on lipoprotein(a), which we still don’t have medication for, but it identifies people at high risk, and we need that.”

Clinicians also need to know “that we’ve got some newer drugs in the market that can manage people who have statin intolerance,” Dr. Handelsman added.

“We introduced new therapies like icosapent ethyl” (Vascepa, Amarin) for hypertriglyceridemia, “when to use it, and how to use it. Even though it was not part of the 2017 guideline, we gave recommendations based on current data in the algorithm.”

Although there is no good evidence that lowering triglycerides reduces heart disease, he continued, many experts believe that the target triglyceride level should be less than 150 mg/dL, and the algorithm explains how to treat to this goal.

“Last, and most importantly, I cannot fail to underscore the fact that lifestyle is very important,” he emphasized.

Robert H. Eckel, MD, of the University of Colorado at Denver, Aurora, and president of medicine and science at the American Diabetes Association, who was not involved with this algorithm, said in an interview that the algorithm is important since it offers “the clinician or health care practitioner an approach, a kind of a cookbook or application of the guidelines, for how to manage lipid disorders in patients at risk ... It’s geared for the nonexperts too,” he said.

Dyslipidemia treatment summarized in 10 slides

The AACE/ACE algorithm comprises 10 slides, one each for dyslipidemic states, secondary causes of lipid disorders, screening for and assessing lipid disorders and atherosclerotic CVD (ASCVD) risk, ASCVD risk categories and treatment goals, lifestyle recommendations, treating LDL-C to goal, managing statin intolerance and safety, management of hypertriglyceridemia and the role of icosapent ethyl, assessment and management of elevated lipoprotein(a), and profiles of medications for dyslipidemia.

The algorithm defines five ASCVD risk categories and recommends increasingly lower LDL-C, non–HDL-C, and apo B target levels with increasing risk, but the same triglyceride target for all.

First, “treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids,” the consensus statement authors stress.

Next, “LDL-C has been, and remains, the main focus of efforts to improve lipid profiles in individuals at risk for ASCVD” (see table).

Statement aligns with major guidelines

In general, the 2017 AACE/ACE guidelines and algorithm are “pretty similar” to other guidelines such as the 2018 ACC/American Heart Association (AHA) guidelines for cholesterol management, the 2019 ACC/AHA guidelines for primary prevention of CVD, and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidemia, according to Dr. Eckel.

They have “all have now taken into consideration the evidence behind PCSK9 inhibitors,” he noted. “That’s important because those drugs have proven to be effective.”

Two differences, he pointed out, are that the 2019 ESC/EAS guidelines suggest that lipoprotein(a) measurement be considered at least once in every adult’s lifetime, and they recommend apo B analysis in people with high triglycerides but normal LDL (or no higher than 100 mg/dL), to identify additional risk.
 

*AACE changes its name, broadens focus

Shortly after its algorithm was published, AACE announced that it has a new organization name and brand, the American Association of Clinical Endocrinology, which “more clearly defines AACE as a community of individuals who work together to elevate the practice of clinical endocrinology,” according to an Oct. 20 statement.

The change is meant to acknowledge AACE’s “more modern, inclusive approach to endocrinology that supports multidisciplinary care teams – with endocrinologists leading the way.”

Along with the name change is a new global website. The statement notes that “health care professionals and community members can access all of the valuable clinical content such as guidelines, disease state networks and important education by visiting the pro portal in the top right corner of the site, or by going directly to pro.aace.com.”

Dr. Handelsman discloses that he receives research grant support from Amgen, Applied Therapeutics, AstraZeneca, BMS, Gan & Lee, Novo Nordisk, and Sanofi, and he is a consultant and/or speaker for Amarin, BI-Lilly, and Sanofi.

Dr. Eckel has received consultant/advisory board fees from Kowa, Novo Nordisk, and Provention Bio.

A new algorithm on lipid management and prevention of cardiovascular disease from the American Association of Clinical Endocrinologists* (AACE) and the American College of Endocrinology (ACE) is “a nice cookbook” that many clinicians, especially those who are not lipid experts, will find useful, according to writing committee chair Yehuda Handelsman, MD.

The algorithm, published Oct. 10 in Endocrine Practice as 10 slides, or as part of a more detailed consensus statement, is a companion to the 2017 AACE/ACE guidelines for lipid management and includes more recent information about new therapies.

“What we’re trying to do here is to say, ‘focus on LDL-C, triglycerides, high-risk patients, and lifestyle. Understand all the medications available to you to reduce LDL-C and reduce triglycerides,’ ” Dr. Handelsman, of the Metabolic Institute of America, Tarzana, Calif., explained in an interview.

“We touch on lipoprotein(a), which we still don’t have medication for, but it identifies people at high risk, and we need that.”

Clinicians also need to know “that we’ve got some newer drugs in the market that can manage people who have statin intolerance,” Dr. Handelsman added.

“We introduced new therapies like icosapent ethyl” (Vascepa, Amarin) for hypertriglyceridemia, “when to use it, and how to use it. Even though it was not part of the 2017 guideline, we gave recommendations based on current data in the algorithm.”

Although there is no good evidence that lowering triglycerides reduces heart disease, he continued, many experts believe that the target triglyceride level should be less than 150 mg/dL, and the algorithm explains how to treat to this goal.

“Last, and most importantly, I cannot fail to underscore the fact that lifestyle is very important,” he emphasized.

Robert H. Eckel, MD, of the University of Colorado at Denver, Aurora, and president of medicine and science at the American Diabetes Association, who was not involved with this algorithm, said in an interview that the algorithm is important since it offers “the clinician or health care practitioner an approach, a kind of a cookbook or application of the guidelines, for how to manage lipid disorders in patients at risk ... It’s geared for the nonexperts too,” he said.

Dyslipidemia treatment summarized in 10 slides

The AACE/ACE algorithm comprises 10 slides, one each for dyslipidemic states, secondary causes of lipid disorders, screening for and assessing lipid disorders and atherosclerotic CVD (ASCVD) risk, ASCVD risk categories and treatment goals, lifestyle recommendations, treating LDL-C to goal, managing statin intolerance and safety, management of hypertriglyceridemia and the role of icosapent ethyl, assessment and management of elevated lipoprotein(a), and profiles of medications for dyslipidemia.

The algorithm defines five ASCVD risk categories and recommends increasingly lower LDL-C, non–HDL-C, and apo B target levels with increasing risk, but the same triglyceride target for all.

First, “treatment of lipid disorders begins with lifestyle therapy to improve nutrition, physical activity, weight, and other factors that affect lipids,” the consensus statement authors stress.

Next, “LDL-C has been, and remains, the main focus of efforts to improve lipid profiles in individuals at risk for ASCVD” (see table).

Statement aligns with major guidelines

In general, the 2017 AACE/ACE guidelines and algorithm are “pretty similar” to other guidelines such as the 2018 ACC/American Heart Association (AHA) guidelines for cholesterol management, the 2019 ACC/AHA guidelines for primary prevention of CVD, and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidemia, according to Dr. Eckel.

They have “all have now taken into consideration the evidence behind PCSK9 inhibitors,” he noted. “That’s important because those drugs have proven to be effective.”

Two differences, he pointed out, are that the 2019 ESC/EAS guidelines suggest that lipoprotein(a) measurement be considered at least once in every adult’s lifetime, and they recommend apo B analysis in people with high triglycerides but normal LDL (or no higher than 100 mg/dL), to identify additional risk.
 

*AACE changes its name, broadens focus

Shortly after its algorithm was published, AACE announced that it has a new organization name and brand, the American Association of Clinical Endocrinology, which “more clearly defines AACE as a community of individuals who work together to elevate the practice of clinical endocrinology,” according to an Oct. 20 statement.

The change is meant to acknowledge AACE’s “more modern, inclusive approach to endocrinology that supports multidisciplinary care teams – with endocrinologists leading the way.”

Along with the name change is a new global website. The statement notes that “health care professionals and community members can access all of the valuable clinical content such as guidelines, disease state networks and important education by visiting the pro portal in the top right corner of the site, or by going directly to pro.aace.com.”

Dr. Handelsman discloses that he receives research grant support from Amgen, Applied Therapeutics, AstraZeneca, BMS, Gan & Lee, Novo Nordisk, and Sanofi, and he is a consultant and/or speaker for Amarin, BI-Lilly, and Sanofi.

Dr. Eckel has received consultant/advisory board fees from Kowa, Novo Nordisk, and Provention Bio.

Hackers have accessed patient records at Finland’s largest private psychotherapy system, emailing some patients to pay up or face having their private medical records released online.

Vastaamo treats about 40,000 patients and runs 25 centers across the country. Hackers emailed some of the centers’ patients asking for a blackmail payment of 200 euro in bitcoin, The Guardian reports.

Agencies such as the country’s National Bureau of Investigation are urging victims not to comply with the blackmailers’ demand and instead requesting that patients report these incidents to authorities and turn over incriminating emails. However, some data from patient records have already been released online.

“We deeply regret what happened and on behalf of our [patients] who have been compromised, we apologize for the shortcoming in data security, the consequences and human cost of which have been extremely heavy,” the center said in a statement. They added that the investigation into the situation is ongoing.
 

‘Sobering reminder’

In a comment, John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, Massachusetts, said this is “a sobering reminder that any digital data is subject to hacking.”

Torous is also chair of the American Psychiatric Association’s Health and Technology Committee.

“This is not the first time psychotherapy notes have been targeted and it actually happened, on a smaller scale, in the US in 2017,” he said.

In April of that year, confidential patient record information from a mental health center in Maine, including evaluations, session notes, and names of sex-abuse victims, was listed on the dark web.

Also in April, computer hackers released the WannaCry virus into the operating system of the United Kingdom’s National Health Service, which subsequently locked clinicians out of patient records and other digital tools for 3 days.

In addition, in 2016 hackers took Hollywood Presbyterian Medical Center in Los Angeles offline for more than a week after demanding a ransom of $3.6 million.
 

Criminal investigation

For Vastaamo, three of its employees were approached by the blackmailer via email at the end of September, the company reports. These incidents were immediately disclosed and the Central Criminal Police launched a criminal investigation.

In addition, several agencies were contacted, including the Finnish Cyber Security Center, the Data Protection Commission, and a cyber security company.

Investigators believe the breach, which led to the customer database theft, occurred back in November 2018. In addition, security “deficiencies” remained until March 2019.

“We do not know that the database was stolen after November 2018, but it is possible that individual data [have been] viewed or copied,” Vastaamo said in a press release. No additional “vulnerabilities were identified after March 2019.”

The center’s CEO, Ville Tapio, who did not disclose any of these incidents to the parent company and its board of directors, was subsequently fired.

Once the police investigation began, Vastaamo said it was not granted permission by the authorities to communicate the occurrence to its patients. However, after the blackmailer released some patient information online early on Oct. 21, permission to inform patients was granted.

The company noted that the blackmailer has started emailing victims, informing of the data breach, and demanding ransom. So far, the emails have not contained harmful digital content or “malware,” but authorities warn that any attachments should not be opened. The police have requested that such emails be kept so they can be used as evidence.

In a Q&A section on its website, Vastaamo noted that videos are never recorded during its centers’ telehealth sessions and patients should not be concerned about the possibility of leaked videos.

In addition, the cybercrime has not interrupted Vastaamo’s operations.

“The authorities and the response office will do their utmost to find out what happened, to prevent the dissemination of information, and to bring the perpetrators to justice,” the center said.

“The most important task ... is to support customers in the midst of an exceptionally serious and difficult situation,” it added.
 

“Worst-case scenario”

In a comment, Ipsit Vahia, MD, medical director at the Institute for Technology and Psychiatry at McLean Hospital, Belmont, Mass., said Vastaamo’s data breach “represents the worst-case scenario for digital health.”

He added that more information is needed about the specifics of the case, including exactly what happened, how the system was hacked, and what information was compromised.

Still, “it raises fundamental questions that healthcare systems, clinicians, and patients everywhere should be asking about what measures are in place to protect electronic medical records and other personal digital information,” said Dr. Vahia.

“This incident also serves as another reminder that the issue of data security and privacy is foundational to digital mental health. Ultimately, without a commitment from all stakeholders to maintaining the strictest levels of security, as well as transparency around how data are handled there will be little to no trust from clinicians or patients,” he said. All of that could prevent digital healthcare from achieving its full potential, he added.

In addition, Dr. Vahia noted that the rapid uptick of telemedicine because of the pandemic has accelerated the use of other forms of digital information in mental healthcare.

“This unfortunate incident should serve as a wake-up call and bring the issue of data protection back firmly into the spotlight,” said Dr. Vahia.

Now that telehealth has become a larger part of clinical practice, said Torous, it’s important for clinicians to be vigilant regarding security procedures.

“Telehealth and digital data are here to stay, and with them new benefits as well as risks. We can continue to work to minimize the risks and protect privacy while ensuring the benefits to patients expand,” he added.

This article first appeared on Medscape.com.

Hackers have accessed patient records at Finland’s largest private psychotherapy system, emailing some patients to pay up or face having their private medical records released online.

Vastaamo treats about 40,000 patients and runs 25 centers across the country. Hackers emailed some of the centers’ patients asking for a blackmail payment of 200 euro in bitcoin, The Guardian reports.

Agencies such as the country’s National Bureau of Investigation are urging victims not to comply with the blackmailers’ demand and instead requesting that patients report these incidents to authorities and turn over incriminating emails. However, some data from patient records have already been released online.

“We deeply regret what happened and on behalf of our [patients] who have been compromised, we apologize for the shortcoming in data security, the consequences and human cost of which have been extremely heavy,” the center said in a statement. They added that the investigation into the situation is ongoing.
 

‘Sobering reminder’

In a comment, John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, Massachusetts, said this is “a sobering reminder that any digital data is subject to hacking.”

Torous is also chair of the American Psychiatric Association’s Health and Technology Committee.

“This is not the first time psychotherapy notes have been targeted and it actually happened, on a smaller scale, in the US in 2017,” he said.

In April of that year, confidential patient record information from a mental health center in Maine, including evaluations, session notes, and names of sex-abuse victims, was listed on the dark web.

Also in April, computer hackers released the WannaCry virus into the operating system of the United Kingdom’s National Health Service, which subsequently locked clinicians out of patient records and other digital tools for 3 days.

In addition, in 2016 hackers took Hollywood Presbyterian Medical Center in Los Angeles offline for more than a week after demanding a ransom of $3.6 million.
 

Criminal investigation

For Vastaamo, three of its employees were approached by the blackmailer via email at the end of September, the company reports. These incidents were immediately disclosed and the Central Criminal Police launched a criminal investigation.

In addition, several agencies were contacted, including the Finnish Cyber Security Center, the Data Protection Commission, and a cyber security company.

Investigators believe the breach, which led to the customer database theft, occurred back in November 2018. In addition, security “deficiencies” remained until March 2019.

“We do not know that the database was stolen after November 2018, but it is possible that individual data [have been] viewed or copied,” Vastaamo said in a press release. No additional “vulnerabilities were identified after March 2019.”

The center’s CEO, Ville Tapio, who did not disclose any of these incidents to the parent company and its board of directors, was subsequently fired.

Once the police investigation began, Vastaamo said it was not granted permission by the authorities to communicate the occurrence to its patients. However, after the blackmailer released some patient information online early on Oct. 21, permission to inform patients was granted.

The company noted that the blackmailer has started emailing victims, informing of the data breach, and demanding ransom. So far, the emails have not contained harmful digital content or “malware,” but authorities warn that any attachments should not be opened. The police have requested that such emails be kept so they can be used as evidence.

In a Q&A section on its website, Vastaamo noted that videos are never recorded during its centers’ telehealth sessions and patients should not be concerned about the possibility of leaked videos.

In addition, the cybercrime has not interrupted Vastaamo’s operations.

“The authorities and the response office will do their utmost to find out what happened, to prevent the dissemination of information, and to bring the perpetrators to justice,” the center said.

“The most important task ... is to support customers in the midst of an exceptionally serious and difficult situation,” it added.
 

“Worst-case scenario”

In a comment, Ipsit Vahia, MD, medical director at the Institute for Technology and Psychiatry at McLean Hospital, Belmont, Mass., said Vastaamo’s data breach “represents the worst-case scenario for digital health.”

He added that more information is needed about the specifics of the case, including exactly what happened, how the system was hacked, and what information was compromised.

Still, “it raises fundamental questions that healthcare systems, clinicians, and patients everywhere should be asking about what measures are in place to protect electronic medical records and other personal digital information,” said Dr. Vahia.

“This incident also serves as another reminder that the issue of data security and privacy is foundational to digital mental health. Ultimately, without a commitment from all stakeholders to maintaining the strictest levels of security, as well as transparency around how data are handled there will be little to no trust from clinicians or patients,” he said. All of that could prevent digital healthcare from achieving its full potential, he added.

In addition, Dr. Vahia noted that the rapid uptick of telemedicine because of the pandemic has accelerated the use of other forms of digital information in mental healthcare.

“This unfortunate incident should serve as a wake-up call and bring the issue of data protection back firmly into the spotlight,” said Dr. Vahia.

Now that telehealth has become a larger part of clinical practice, said Torous, it’s important for clinicians to be vigilant regarding security procedures.

“Telehealth and digital data are here to stay, and with them new benefits as well as risks. We can continue to work to minimize the risks and protect privacy while ensuring the benefits to patients expand,” he added.

This article first appeared on Medscape.com.

Hackers have accessed patient records at Finland’s largest private psychotherapy system, emailing some patients to pay up or face having their private medical records released online.

Vastaamo treats about 40,000 patients and runs 25 centers across the country. Hackers emailed some of the centers’ patients asking for a blackmail payment of 200 euro in bitcoin, The Guardian reports.

Agencies such as the country’s National Bureau of Investigation are urging victims not to comply with the blackmailers’ demand and instead requesting that patients report these incidents to authorities and turn over incriminating emails. However, some data from patient records have already been released online.

“We deeply regret what happened and on behalf of our [patients] who have been compromised, we apologize for the shortcoming in data security, the consequences and human cost of which have been extremely heavy,” the center said in a statement. They added that the investigation into the situation is ongoing.
 

‘Sobering reminder’

In a comment, John Torous, MD, director of digital psychiatry at Beth Israel Deaconess Medical Center, Boston, Massachusetts, said this is “a sobering reminder that any digital data is subject to hacking.”

Torous is also chair of the American Psychiatric Association’s Health and Technology Committee.

“This is not the first time psychotherapy notes have been targeted and it actually happened, on a smaller scale, in the US in 2017,” he said.

In April of that year, confidential patient record information from a mental health center in Maine, including evaluations, session notes, and names of sex-abuse victims, was listed on the dark web.

Also in April, computer hackers released the WannaCry virus into the operating system of the United Kingdom’s National Health Service, which subsequently locked clinicians out of patient records and other digital tools for 3 days.

In addition, in 2016 hackers took Hollywood Presbyterian Medical Center in Los Angeles offline for more than a week after demanding a ransom of $3.6 million.
 

Criminal investigation

For Vastaamo, three of its employees were approached by the blackmailer via email at the end of September, the company reports. These incidents were immediately disclosed and the Central Criminal Police launched a criminal investigation.

In addition, several agencies were contacted, including the Finnish Cyber Security Center, the Data Protection Commission, and a cyber security company.

Investigators believe the breach, which led to the customer database theft, occurred back in November 2018. In addition, security “deficiencies” remained until March 2019.

“We do not know that the database was stolen after November 2018, but it is possible that individual data [have been] viewed or copied,” Vastaamo said in a press release. No additional “vulnerabilities were identified after March 2019.”

The center’s CEO, Ville Tapio, who did not disclose any of these incidents to the parent company and its board of directors, was subsequently fired.

Once the police investigation began, Vastaamo said it was not granted permission by the authorities to communicate the occurrence to its patients. However, after the blackmailer released some patient information online early on Oct. 21, permission to inform patients was granted.

The company noted that the blackmailer has started emailing victims, informing of the data breach, and demanding ransom. So far, the emails have not contained harmful digital content or “malware,” but authorities warn that any attachments should not be opened. The police have requested that such emails be kept so they can be used as evidence.

In a Q&A section on its website, Vastaamo noted that videos are never recorded during its centers’ telehealth sessions and patients should not be concerned about the possibility of leaked videos.

In addition, the cybercrime has not interrupted Vastaamo’s operations.

“The authorities and the response office will do their utmost to find out what happened, to prevent the dissemination of information, and to bring the perpetrators to justice,” the center said.

“The most important task ... is to support customers in the midst of an exceptionally serious and difficult situation,” it added.
 

“Worst-case scenario”

In a comment, Ipsit Vahia, MD, medical director at the Institute for Technology and Psychiatry at McLean Hospital, Belmont, Mass., said Vastaamo’s data breach “represents the worst-case scenario for digital health.”

He added that more information is needed about the specifics of the case, including exactly what happened, how the system was hacked, and what information was compromised.

Still, “it raises fundamental questions that healthcare systems, clinicians, and patients everywhere should be asking about what measures are in place to protect electronic medical records and other personal digital information,” said Dr. Vahia.

“This incident also serves as another reminder that the issue of data security and privacy is foundational to digital mental health. Ultimately, without a commitment from all stakeholders to maintaining the strictest levels of security, as well as transparency around how data are handled there will be little to no trust from clinicians or patients,” he said. All of that could prevent digital healthcare from achieving its full potential, he added.

In addition, Dr. Vahia noted that the rapid uptick of telemedicine because of the pandemic has accelerated the use of other forms of digital information in mental healthcare.

“This unfortunate incident should serve as a wake-up call and bring the issue of data protection back firmly into the spotlight,” said Dr. Vahia.

Now that telehealth has become a larger part of clinical practice, said Torous, it’s important for clinicians to be vigilant regarding security procedures.

“Telehealth and digital data are here to stay, and with them new benefits as well as risks. We can continue to work to minimize the risks and protect privacy while ensuring the benefits to patients expand,” he added.

This article first appeared on Medscape.com.

A mutation of the ODC1 gene, which plays a key role in polyamine metabolism, has been implicated in a syndromic neurodevelopmental disorder first described in 2018 and linked to a number of dysmorphic features and brain abnormalities, but it may be treated with diet modifications and available therapies, according to the researcher whose group first identified the disorder.

Lance Rodan, MD, of Boston Children’s Hospital and Harvard Medical School, reported on research into ODC1 gain-of-function disorder –named for ornithine decarboxylase 1, the rate-limiting enzyme involved in polyamine synthesis – in the Linda De Meirleir Neurometabolic award lecture at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Dr. Rodan and colleagues first described ODC1 disorder in a multicenter case series.

Dr. Rodan noted that dysregulated polyamine levels are associated with cancer, and that ODC1 is expressed “ubiquitously” throughout the body.
 

Pathophysiology and phenotypes

In an interview, he described the metabolic process more fully. “GI flora can produce putrescine, which is the polyamine that accumulates in excess in the ODC1 gain-of-function disorder. It is yet to be elucidated if decreasing putrescine production by GI flora and/or reducing dietary sources of putrescine may play a role in the management of this disorder.” 

In the De Meirleir lecture, Dr. Rodan described four patients from his group’s published case series, all found to have heterozygous de novo variants in the ODC1 gene, along with a fifth patient reported by Caleb Bupp, MD, and colleagues at Michigan State University, East Lansing.

“There’s a recognizable phenotype to this disorder,” Dr. Rodan said. “These individuals have neurodevelopment abnormalities. They may have behavioral concerns. They have low-tone central hypertonia and macrocephaly.”

One of the most distinctive characteristics of ODC1 disorder is alopecia, he said, “which in almost everybody with this condition involves the eyebrows and eyelashes and in some individuals also involves the scalp hair.”

These patients also have what Dr. Rodan called “a common yet subtle facial gestalt.” That can include hypertelorism, spareness of the eyebrows and eyelashes, and a tubular- shaped nose with a short columella and a short philtrum.

They may also have abnormalities of the nails and cryptorchidism, and typically a prenatal history of polyhydramnios, he said.

MRI findings include prominent perivascular spaces, periventricular cysts, abnormal white matter and corpus callosum abnormalities, he said, adding that the fetal case MRI demonstrated subepidermal cysts, white matter cysts in the temporal pole, deficiency of the falx cerebri and abnormal white-matter signals.

Biochemical features of ODC1 disorder include increased N-acetylputrescine levels with normal spermine and spermidine levels, Dr. Rodan said. He also noted that Dr. Bupp’s group reported increased putrescine in fibroblasts and increased ODC1 protein levels in red blood cells.

Dr. Rodan also described possible molecular mechanisms in ODC1 disorder. One was the location of the ODC1 variants: all were reported closely located to truncating variants in the final exon of the ODC1 gene. This allows truncating proteins to survive, adding to the degradation that results in a net gain-of-function of ODC1 enzyme activity.

With regard to pathophysiology of ODC1 disorder, Dr. Rodan noted that research has implicated chronically elevated putrescine levels in the alopecia, a finding animal models support. “Since putrescine is a precursor for gamma-aminobutyric acid, it’s possible perturbed GABA levels may also be involved,” he said. Abnormal modulation N-methyl-D-aspirate receptors may also be involved, he said.

Another hypothesis purports that potential of elevated levels of toxic aldehydes/H₂O₂ similar to Snyder-Robinson syndrome, the better known polyamine-related neurometabolic disorder. “Along those lines, maybe there’s also a secondary mitochondrial or lysosomal dysfunction, but this is something that’s still being actively studied,” Dr. Rodan said.
 

Treatment

Because ODC1 disorder was only first described 2 years ago, research into treatment is nascent. “In terms of management, I think one of the more fundamental questions is whether this is more of a static developmental disorder or whether this actually represents a progressive degenerative disorder,” Dr. Rodan said.

One potential treatment that has been explored, he said, is difluoromethylornithine, a synthetic ODC1 inhibitor already Food and Drug Administration approved for African sleeping sickness and as a topical treatment for hirsutism. It is also the subject of ongoing clinical trials in colon cancer and neuroblastoma. Potential side effects include myelosuppression, seizures and hearing loss.

Dr. Rodan noted that a single-center study reported that difluoromethylornithine in a 3-year-old patient with ODC1 disorder reduced ODC protein activity and putrescine to control levels.

Other potential treatments include the natural ODC1 inhibitors agmatine and turmeric/curcumin, flagyl/rifaximin to decrease putrescine production in the gut, a low-dairy diet to lower putrescine levels, and antioxidants. “There could be a role for antioxidant stress similar to what is seen in Snyder-Robinson syndrome,” Dr. Rodan said.

Based on mouse studies, patients with ODC1 may be at risk of skin cancer, so regular skin checks along with sun protection should be part of management, he said. “This also raises the question of whether there should be surveillance for other types of cancer given the role of polyamine in various types of tumors.”

Dr. Rodan has no relevant financial relationships to disclose.

A mutation of the ODC1 gene, which plays a key role in polyamine metabolism, has been implicated in a syndromic neurodevelopmental disorder first described in 2018 and linked to a number of dysmorphic features and brain abnormalities, but it may be treated with diet modifications and available therapies, according to the researcher whose group first identified the disorder.

Lance Rodan, MD, of Boston Children’s Hospital and Harvard Medical School, reported on research into ODC1 gain-of-function disorder –named for ornithine decarboxylase 1, the rate-limiting enzyme involved in polyamine synthesis – in the Linda De Meirleir Neurometabolic award lecture at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Dr. Rodan and colleagues first described ODC1 disorder in a multicenter case series.

Dr. Rodan noted that dysregulated polyamine levels are associated with cancer, and that ODC1 is expressed “ubiquitously” throughout the body.
 

Pathophysiology and phenotypes

In an interview, he described the metabolic process more fully. “GI flora can produce putrescine, which is the polyamine that accumulates in excess in the ODC1 gain-of-function disorder. It is yet to be elucidated if decreasing putrescine production by GI flora and/or reducing dietary sources of putrescine may play a role in the management of this disorder.” 

In the De Meirleir lecture, Dr. Rodan described four patients from his group’s published case series, all found to have heterozygous de novo variants in the ODC1 gene, along with a fifth patient reported by Caleb Bupp, MD, and colleagues at Michigan State University, East Lansing.

“There’s a recognizable phenotype to this disorder,” Dr. Rodan said. “These individuals have neurodevelopment abnormalities. They may have behavioral concerns. They have low-tone central hypertonia and macrocephaly.”

One of the most distinctive characteristics of ODC1 disorder is alopecia, he said, “which in almost everybody with this condition involves the eyebrows and eyelashes and in some individuals also involves the scalp hair.”

These patients also have what Dr. Rodan called “a common yet subtle facial gestalt.” That can include hypertelorism, spareness of the eyebrows and eyelashes, and a tubular- shaped nose with a short columella and a short philtrum.

They may also have abnormalities of the nails and cryptorchidism, and typically a prenatal history of polyhydramnios, he said.

MRI findings include prominent perivascular spaces, periventricular cysts, abnormal white matter and corpus callosum abnormalities, he said, adding that the fetal case MRI demonstrated subepidermal cysts, white matter cysts in the temporal pole, deficiency of the falx cerebri and abnormal white-matter signals.

Biochemical features of ODC1 disorder include increased N-acetylputrescine levels with normal spermine and spermidine levels, Dr. Rodan said. He also noted that Dr. Bupp’s group reported increased putrescine in fibroblasts and increased ODC1 protein levels in red blood cells.

Dr. Rodan also described possible molecular mechanisms in ODC1 disorder. One was the location of the ODC1 variants: all were reported closely located to truncating variants in the final exon of the ODC1 gene. This allows truncating proteins to survive, adding to the degradation that results in a net gain-of-function of ODC1 enzyme activity.

With regard to pathophysiology of ODC1 disorder, Dr. Rodan noted that research has implicated chronically elevated putrescine levels in the alopecia, a finding animal models support. “Since putrescine is a precursor for gamma-aminobutyric acid, it’s possible perturbed GABA levels may also be involved,” he said. Abnormal modulation N-methyl-D-aspirate receptors may also be involved, he said.

Another hypothesis purports that potential of elevated levels of toxic aldehydes/H₂O₂ similar to Snyder-Robinson syndrome, the better known polyamine-related neurometabolic disorder. “Along those lines, maybe there’s also a secondary mitochondrial or lysosomal dysfunction, but this is something that’s still being actively studied,” Dr. Rodan said.
 

Treatment

Because ODC1 disorder was only first described 2 years ago, research into treatment is nascent. “In terms of management, I think one of the more fundamental questions is whether this is more of a static developmental disorder or whether this actually represents a progressive degenerative disorder,” Dr. Rodan said.

One potential treatment that has been explored, he said, is difluoromethylornithine, a synthetic ODC1 inhibitor already Food and Drug Administration approved for African sleeping sickness and as a topical treatment for hirsutism. It is also the subject of ongoing clinical trials in colon cancer and neuroblastoma. Potential side effects include myelosuppression, seizures and hearing loss.

Dr. Rodan noted that a single-center study reported that difluoromethylornithine in a 3-year-old patient with ODC1 disorder reduced ODC protein activity and putrescine to control levels.

Other potential treatments include the natural ODC1 inhibitors agmatine and turmeric/curcumin, flagyl/rifaximin to decrease putrescine production in the gut, a low-dairy diet to lower putrescine levels, and antioxidants. “There could be a role for antioxidant stress similar to what is seen in Snyder-Robinson syndrome,” Dr. Rodan said.

Based on mouse studies, patients with ODC1 may be at risk of skin cancer, so regular skin checks along with sun protection should be part of management, he said. “This also raises the question of whether there should be surveillance for other types of cancer given the role of polyamine in various types of tumors.”

Dr. Rodan has no relevant financial relationships to disclose.

A mutation of the ODC1 gene, which plays a key role in polyamine metabolism, has been implicated in a syndromic neurodevelopmental disorder first described in 2018 and linked to a number of dysmorphic features and brain abnormalities, but it may be treated with diet modifications and available therapies, according to the researcher whose group first identified the disorder.

Lance Rodan, MD, of Boston Children’s Hospital and Harvard Medical School, reported on research into ODC1 gain-of-function disorder –named for ornithine decarboxylase 1, the rate-limiting enzyme involved in polyamine synthesis – in the Linda De Meirleir Neurometabolic award lecture at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year. Dr. Rodan and colleagues first described ODC1 disorder in a multicenter case series.

Dr. Rodan noted that dysregulated polyamine levels are associated with cancer, and that ODC1 is expressed “ubiquitously” throughout the body.
 

Pathophysiology and phenotypes

In an interview, he described the metabolic process more fully. “GI flora can produce putrescine, which is the polyamine that accumulates in excess in the ODC1 gain-of-function disorder. It is yet to be elucidated if decreasing putrescine production by GI flora and/or reducing dietary sources of putrescine may play a role in the management of this disorder.” 

In the De Meirleir lecture, Dr. Rodan described four patients from his group’s published case series, all found to have heterozygous de novo variants in the ODC1 gene, along with a fifth patient reported by Caleb Bupp, MD, and colleagues at Michigan State University, East Lansing.

“There’s a recognizable phenotype to this disorder,” Dr. Rodan said. “These individuals have neurodevelopment abnormalities. They may have behavioral concerns. They have low-tone central hypertonia and macrocephaly.”

One of the most distinctive characteristics of ODC1 disorder is alopecia, he said, “which in almost everybody with this condition involves the eyebrows and eyelashes and in some individuals also involves the scalp hair.”

These patients also have what Dr. Rodan called “a common yet subtle facial gestalt.” That can include hypertelorism, spareness of the eyebrows and eyelashes, and a tubular- shaped nose with a short columella and a short philtrum.

They may also have abnormalities of the nails and cryptorchidism, and typically a prenatal history of polyhydramnios, he said.

MRI findings include prominent perivascular spaces, periventricular cysts, abnormal white matter and corpus callosum abnormalities, he said, adding that the fetal case MRI demonstrated subepidermal cysts, white matter cysts in the temporal pole, deficiency of the falx cerebri and abnormal white-matter signals.

Biochemical features of ODC1 disorder include increased N-acetylputrescine levels with normal spermine and spermidine levels, Dr. Rodan said. He also noted that Dr. Bupp’s group reported increased putrescine in fibroblasts and increased ODC1 protein levels in red blood cells.

Dr. Rodan also described possible molecular mechanisms in ODC1 disorder. One was the location of the ODC1 variants: all were reported closely located to truncating variants in the final exon of the ODC1 gene. This allows truncating proteins to survive, adding to the degradation that results in a net gain-of-function of ODC1 enzyme activity.

With regard to pathophysiology of ODC1 disorder, Dr. Rodan noted that research has implicated chronically elevated putrescine levels in the alopecia, a finding animal models support. “Since putrescine is a precursor for gamma-aminobutyric acid, it’s possible perturbed GABA levels may also be involved,” he said. Abnormal modulation N-methyl-D-aspirate receptors may also be involved, he said.

Another hypothesis purports that potential of elevated levels of toxic aldehydes/H₂O₂ similar to Snyder-Robinson syndrome, the better known polyamine-related neurometabolic disorder. “Along those lines, maybe there’s also a secondary mitochondrial or lysosomal dysfunction, but this is something that’s still being actively studied,” Dr. Rodan said.
 

Treatment

Because ODC1 disorder was only first described 2 years ago, research into treatment is nascent. “In terms of management, I think one of the more fundamental questions is whether this is more of a static developmental disorder or whether this actually represents a progressive degenerative disorder,” Dr. Rodan said.

One potential treatment that has been explored, he said, is difluoromethylornithine, a synthetic ODC1 inhibitor already Food and Drug Administration approved for African sleeping sickness and as a topical treatment for hirsutism. It is also the subject of ongoing clinical trials in colon cancer and neuroblastoma. Potential side effects include myelosuppression, seizures and hearing loss.

Dr. Rodan noted that a single-center study reported that difluoromethylornithine in a 3-year-old patient with ODC1 disorder reduced ODC protein activity and putrescine to control levels.

Other potential treatments include the natural ODC1 inhibitors agmatine and turmeric/curcumin, flagyl/rifaximin to decrease putrescine production in the gut, a low-dairy diet to lower putrescine levels, and antioxidants. “There could be a role for antioxidant stress similar to what is seen in Snyder-Robinson syndrome,” Dr. Rodan said.

Based on mouse studies, patients with ODC1 may be at risk of skin cancer, so regular skin checks along with sun protection should be part of management, he said. “This also raises the question of whether there should be surveillance for other types of cancer given the role of polyamine in various types of tumors.”

Dr. Rodan has no relevant financial relationships to disclose.

References

1. National Institute of Health. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. www.covid19treatmentguidelines.nih.gov/. Updated October 22, 2020. Accessed October 28, 2020.

References

1. National Institute of Health. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. www.covid19treatmentguidelines.nih.gov/. Updated October 22, 2020. Accessed October 28, 2020.

References

1. National Institute of Health. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. www.covid19treatmentguidelines.nih.gov/. Updated October 22, 2020. Accessed October 28, 2020.

Regular consumption of foods rich in omega-3 fatty acids was associated with improved prognosis after ST-segment myocardial infarction (STEMI) in a new observational study.

Dmitriy Danilchenko/Shutterstock

The prospective study, which involved 944 patients with STEMI who underwent primary percutaneous coronary intervention (PCI), showed that plasma levels of fatty acids at the time of the STEMI were inversely associated with both incident major adverse cardiovascular events (MACE) and cardiovascular readmissions (adjusted hazard ratio, 0.76 and 0.74 for 1-SD increase; for both, P < .05).

No association was seen for the endpoint of all-cause mortality.

“What we showed is that your consumption of fish and other sources of omega-3 fatty acids before the heart attack impacts your prognosis after the heart attack. It’s a novel approach because it’s not primary prevention or secondary prevention,” said Aleix Sala-Vila, PharmD, PhD, from the Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) in Barcelona, Spain.

Sala-Vila, co–senior author Antoni Bayés-Genís, MD, PhD, Heart Universitari Germans Trias I Pujol, Barcelona, and first author Iolanda Lázaro, PhD, also from IMIM, reported their findings online Oct. 26 in the Journal of the American College of Cardiology.

It has been established that dietary omega-3 eicosapentaenoic acid (EPA) has cardioprotective properties, but observational studies and randomized trials of EPA intake have yielded disparate findings.

This study avoided the usual traps of nutritional epidemiology research – self-reported food diaries and intake questionnaires. For this study, the researchers measured tissue levels of EPA and alpha-linolenic acid (ALA) by measuring serum phosphatidylcholine (PC) levels, which reflect dietary intake during the previous 3 or 4 weeks.

This technique, said Sala-Vila, not only provides a more reliable measure of fatty acid intake over time but also avoids measurement errors related to fatty acid content variation.

For example, “The EPA content of a piece of fish eaten in January could be very different from one eaten in June,” explained Sala-Vila.

That said, he acknowledged that this technique, which uses gas chromatography, does not at present have a clear clinical application. “It’s quite difficult just to convert levels of serum-PC EPA into consumption of fatty fish. We feel that the best advice at this point is that given by the American Heart Association to eat two servings of fatty fish a week.”
 

EPA and ALA: Partners in prevention?

In addition to the findings regarding EPA, the researchers also found that serum-PC ALA was inversely related to all-cause mortality after STEMI (HR, 0.65 for 1-SD increase; P < .05).

A trend was seen for an association between ALA and lower risk for incident MACE (P = .093).

ALA is readily available from inexpensive plant sources (eg, chia seeds, flax seeds, walnuts, soy beans) and has been associated with lower all-cause mortality in high-risk individuals.

This omega-3 fatty acid is often given short shrift in the fatty acid world because of the seven-step enzymatic process needed to convert it into more beneficial forms.

“We know that the conversion of ALA to EPA or DHA [docohexaenoic acid] is marginal, but we decided to include it in the study because we feel that this fatty acid is becoming more important because there are some issues with fish consumption – people are concerned about pollutants and sustainability, and some just don’t like it,” explained Sala-Vila.

“We were shocked to see that the marine-derived and vegetable-derived fatty acids don’t appear to compete, but rather they act synergistically,” said Sala-Villa. The researchers suggested that marine and vegetable omega-3 fatty acids may act as “partners in prevention.”

“We are not metabolically adapted to converting ALA to EPA, but despite this, there is a large body of evidence showing that one way to increase the status of EPA and DHA in our membranes is by eating these sources of fatty acids,” said Sala-Vila.

For almost 20 years, Sala-Vila has been studying how the consumption of foods rich in omega-3 affects disease. Two of his current projects involve studying levels of ALA in red blood cell membranes as a risk factor for ischemic stroke and omega-3 status in individuals with cognitive impairment who are at high risk for Alzheimer’s disease.
 

Applicable to all patients with atherosclerosis

In comments to theheart.org | Medscape Cardiology, Deepak Bhatt, MD, called the study “terrific,” adding that the effort is “as good as it gets” for observational nutrition research.

“I think one has to view these findings in the larger universe of what is really a revolution in omega-3 fatty acid research,” said Bhatt.

This universe, he said, includes a wealth of observational research showing the benefits of omega-3s, two outcome trials – JELIS and REDUCE-IT – that showed the benefits of EPA supplementation, and two imaging studies – EVAPORATE and CHERRY – that showed favorable effects of EPA on the vasculature.

REDUCE-IT, for which Bhatt served as principal investigator, showed that treatment with icosapent ethyl (Vascepa), a high-dose purified form of EPA, led to a 25% relative risk reduction in MACE in an at-risk Western population.

The results, said Bhatt, who co-wrote an editorial that accompanies the current Sala-Vila article, “likely apply to all patients with atherosclerosis or who are at high risk for it” and supports the practice of counseling patients to increase their intake of food rich in omega-3 fatty acids.

The field may be due for a shake-up, he noted. At next month’s American Heart Association meeting, the results of another trial of another prescription-grade EPA/DHA supplement will be presented, and they are expected to be negative.

AstraZeneca announced in January 2020 the early closure of the STRENGTH trial of Epanova after an interim analysis showed a low likelihood of their product demonstrating benefit in the enrolled population.

Epanova is a fish-oil derived mixture of free fatty acids, primarily EPA and DHA. It is approved in the United States and is indicated as an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. This indication is not affected by the data from the STRENGTH trial, according to a company press release.

Sala-Vila has received grants and support from the California Walnut Commission, including a grant to support part of this study. Bayés-Genís and Bhatt have relationships with a number of companies.
 

This article first appeared on Medscape.com.

Regular consumption of foods rich in omega-3 fatty acids was associated with improved prognosis after ST-segment myocardial infarction (STEMI) in a new observational study.

Dmitriy Danilchenko/Shutterstock

The prospective study, which involved 944 patients with STEMI who underwent primary percutaneous coronary intervention (PCI), showed that plasma levels of fatty acids at the time of the STEMI were inversely associated with both incident major adverse cardiovascular events (MACE) and cardiovascular readmissions (adjusted hazard ratio, 0.76 and 0.74 for 1-SD increase; for both, P < .05).

No association was seen for the endpoint of all-cause mortality.

“What we showed is that your consumption of fish and other sources of omega-3 fatty acids before the heart attack impacts your prognosis after the heart attack. It’s a novel approach because it’s not primary prevention or secondary prevention,” said Aleix Sala-Vila, PharmD, PhD, from the Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) in Barcelona, Spain.

Sala-Vila, co–senior author Antoni Bayés-Genís, MD, PhD, Heart Universitari Germans Trias I Pujol, Barcelona, and first author Iolanda Lázaro, PhD, also from IMIM, reported their findings online Oct. 26 in the Journal of the American College of Cardiology.

It has been established that dietary omega-3 eicosapentaenoic acid (EPA) has cardioprotective properties, but observational studies and randomized trials of EPA intake have yielded disparate findings.

This study avoided the usual traps of nutritional epidemiology research – self-reported food diaries and intake questionnaires. For this study, the researchers measured tissue levels of EPA and alpha-linolenic acid (ALA) by measuring serum phosphatidylcholine (PC) levels, which reflect dietary intake during the previous 3 or 4 weeks.

This technique, said Sala-Vila, not only provides a more reliable measure of fatty acid intake over time but also avoids measurement errors related to fatty acid content variation.

For example, “The EPA content of a piece of fish eaten in January could be very different from one eaten in June,” explained Sala-Vila.

That said, he acknowledged that this technique, which uses gas chromatography, does not at present have a clear clinical application. “It’s quite difficult just to convert levels of serum-PC EPA into consumption of fatty fish. We feel that the best advice at this point is that given by the American Heart Association to eat two servings of fatty fish a week.”
 

EPA and ALA: Partners in prevention?

In addition to the findings regarding EPA, the researchers also found that serum-PC ALA was inversely related to all-cause mortality after STEMI (HR, 0.65 for 1-SD increase; P < .05).

A trend was seen for an association between ALA and lower risk for incident MACE (P = .093).

ALA is readily available from inexpensive plant sources (eg, chia seeds, flax seeds, walnuts, soy beans) and has been associated with lower all-cause mortality in high-risk individuals.

This omega-3 fatty acid is often given short shrift in the fatty acid world because of the seven-step enzymatic process needed to convert it into more beneficial forms.

“We know that the conversion of ALA to EPA or DHA [docohexaenoic acid] is marginal, but we decided to include it in the study because we feel that this fatty acid is becoming more important because there are some issues with fish consumption – people are concerned about pollutants and sustainability, and some just don’t like it,” explained Sala-Vila.

“We were shocked to see that the marine-derived and vegetable-derived fatty acids don’t appear to compete, but rather they act synergistically,” said Sala-Villa. The researchers suggested that marine and vegetable omega-3 fatty acids may act as “partners in prevention.”

“We are not metabolically adapted to converting ALA to EPA, but despite this, there is a large body of evidence showing that one way to increase the status of EPA and DHA in our membranes is by eating these sources of fatty acids,” said Sala-Vila.

For almost 20 years, Sala-Vila has been studying how the consumption of foods rich in omega-3 affects disease. Two of his current projects involve studying levels of ALA in red blood cell membranes as a risk factor for ischemic stroke and omega-3 status in individuals with cognitive impairment who are at high risk for Alzheimer’s disease.
 

Applicable to all patients with atherosclerosis

In comments to theheart.org | Medscape Cardiology, Deepak Bhatt, MD, called the study “terrific,” adding that the effort is “as good as it gets” for observational nutrition research.

“I think one has to view these findings in the larger universe of what is really a revolution in omega-3 fatty acid research,” said Bhatt.

This universe, he said, includes a wealth of observational research showing the benefits of omega-3s, two outcome trials – JELIS and REDUCE-IT – that showed the benefits of EPA supplementation, and two imaging studies – EVAPORATE and CHERRY – that showed favorable effects of EPA on the vasculature.

REDUCE-IT, for which Bhatt served as principal investigator, showed that treatment with icosapent ethyl (Vascepa), a high-dose purified form of EPA, led to a 25% relative risk reduction in MACE in an at-risk Western population.

The results, said Bhatt, who co-wrote an editorial that accompanies the current Sala-Vila article, “likely apply to all patients with atherosclerosis or who are at high risk for it” and supports the practice of counseling patients to increase their intake of food rich in omega-3 fatty acids.

The field may be due for a shake-up, he noted. At next month’s American Heart Association meeting, the results of another trial of another prescription-grade EPA/DHA supplement will be presented, and they are expected to be negative.

AstraZeneca announced in January 2020 the early closure of the STRENGTH trial of Epanova after an interim analysis showed a low likelihood of their product demonstrating benefit in the enrolled population.

Epanova is a fish-oil derived mixture of free fatty acids, primarily EPA and DHA. It is approved in the United States and is indicated as an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. This indication is not affected by the data from the STRENGTH trial, according to a company press release.

Sala-Vila has received grants and support from the California Walnut Commission, including a grant to support part of this study. Bayés-Genís and Bhatt have relationships with a number of companies.
 

This article first appeared on Medscape.com.

Regular consumption of foods rich in omega-3 fatty acids was associated with improved prognosis after ST-segment myocardial infarction (STEMI) in a new observational study.

Dmitriy Danilchenko/Shutterstock

The prospective study, which involved 944 patients with STEMI who underwent primary percutaneous coronary intervention (PCI), showed that plasma levels of fatty acids at the time of the STEMI were inversely associated with both incident major adverse cardiovascular events (MACE) and cardiovascular readmissions (adjusted hazard ratio, 0.76 and 0.74 for 1-SD increase; for both, P < .05).

No association was seen for the endpoint of all-cause mortality.

“What we showed is that your consumption of fish and other sources of omega-3 fatty acids before the heart attack impacts your prognosis after the heart attack. It’s a novel approach because it’s not primary prevention or secondary prevention,” said Aleix Sala-Vila, PharmD, PhD, from the Institut Hospital del Mar d’Investigacions Mèdiques (IMIM) in Barcelona, Spain.

Sala-Vila, co–senior author Antoni Bayés-Genís, MD, PhD, Heart Universitari Germans Trias I Pujol, Barcelona, and first author Iolanda Lázaro, PhD, also from IMIM, reported their findings online Oct. 26 in the Journal of the American College of Cardiology.

It has been established that dietary omega-3 eicosapentaenoic acid (EPA) has cardioprotective properties, but observational studies and randomized trials of EPA intake have yielded disparate findings.

This study avoided the usual traps of nutritional epidemiology research – self-reported food diaries and intake questionnaires. For this study, the researchers measured tissue levels of EPA and alpha-linolenic acid (ALA) by measuring serum phosphatidylcholine (PC) levels, which reflect dietary intake during the previous 3 or 4 weeks.

This technique, said Sala-Vila, not only provides a more reliable measure of fatty acid intake over time but also avoids measurement errors related to fatty acid content variation.

For example, “The EPA content of a piece of fish eaten in January could be very different from one eaten in June,” explained Sala-Vila.

That said, he acknowledged that this technique, which uses gas chromatography, does not at present have a clear clinical application. “It’s quite difficult just to convert levels of serum-PC EPA into consumption of fatty fish. We feel that the best advice at this point is that given by the American Heart Association to eat two servings of fatty fish a week.”
 

EPA and ALA: Partners in prevention?

In addition to the findings regarding EPA, the researchers also found that serum-PC ALA was inversely related to all-cause mortality after STEMI (HR, 0.65 for 1-SD increase; P < .05).

A trend was seen for an association between ALA and lower risk for incident MACE (P = .093).

ALA is readily available from inexpensive plant sources (eg, chia seeds, flax seeds, walnuts, soy beans) and has been associated with lower all-cause mortality in high-risk individuals.

This omega-3 fatty acid is often given short shrift in the fatty acid world because of the seven-step enzymatic process needed to convert it into more beneficial forms.

“We know that the conversion of ALA to EPA or DHA [docohexaenoic acid] is marginal, but we decided to include it in the study because we feel that this fatty acid is becoming more important because there are some issues with fish consumption – people are concerned about pollutants and sustainability, and some just don’t like it,” explained Sala-Vila.

“We were shocked to see that the marine-derived and vegetable-derived fatty acids don’t appear to compete, but rather they act synergistically,” said Sala-Villa. The researchers suggested that marine and vegetable omega-3 fatty acids may act as “partners in prevention.”

“We are not metabolically adapted to converting ALA to EPA, but despite this, there is a large body of evidence showing that one way to increase the status of EPA and DHA in our membranes is by eating these sources of fatty acids,” said Sala-Vila.

For almost 20 years, Sala-Vila has been studying how the consumption of foods rich in omega-3 affects disease. Two of his current projects involve studying levels of ALA in red blood cell membranes as a risk factor for ischemic stroke and omega-3 status in individuals with cognitive impairment who are at high risk for Alzheimer’s disease.
 

Applicable to all patients with atherosclerosis

In comments to theheart.org | Medscape Cardiology, Deepak Bhatt, MD, called the study “terrific,” adding that the effort is “as good as it gets” for observational nutrition research.

“I think one has to view these findings in the larger universe of what is really a revolution in omega-3 fatty acid research,” said Bhatt.

This universe, he said, includes a wealth of observational research showing the benefits of omega-3s, two outcome trials – JELIS and REDUCE-IT – that showed the benefits of EPA supplementation, and two imaging studies – EVAPORATE and CHERRY – that showed favorable effects of EPA on the vasculature.

REDUCE-IT, for which Bhatt served as principal investigator, showed that treatment with icosapent ethyl (Vascepa), a high-dose purified form of EPA, led to a 25% relative risk reduction in MACE in an at-risk Western population.

The results, said Bhatt, who co-wrote an editorial that accompanies the current Sala-Vila article, “likely apply to all patients with atherosclerosis or who are at high risk for it” and supports the practice of counseling patients to increase their intake of food rich in omega-3 fatty acids.

The field may be due for a shake-up, he noted. At next month’s American Heart Association meeting, the results of another trial of another prescription-grade EPA/DHA supplement will be presented, and they are expected to be negative.

AstraZeneca announced in January 2020 the early closure of the STRENGTH trial of Epanova after an interim analysis showed a low likelihood of their product demonstrating benefit in the enrolled population.

Epanova is a fish-oil derived mixture of free fatty acids, primarily EPA and DHA. It is approved in the United States and is indicated as an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. This indication is not affected by the data from the STRENGTH trial, according to a company press release.

Sala-Vila has received grants and support from the California Walnut Commission, including a grant to support part of this study. Bayés-Genís and Bhatt have relationships with a number of companies.
 

This article first appeared on Medscape.com.

Statin use may significantly lower the risk of colorectal cancer (CRC) in patients with or without inflammatory bowel disease (IBD), based on a meta-analysis and systematic review.

In more than 15,000 patients with IBD, statin use was associated with a 60% reduced risk of CRC, reported lead author Kevin N. Singh, MD, of NYU Langone Medical Center in New York, and colleagues.

“Statin use has been linked with a risk reduction for cancers including hepatocellular carcinoma, breast, gastric, pancreatic, and biliary tract cancers, but data supporting the use of statins for chemoprevention against CRC is conflicting,” Dr. Singh said during a virtual presentation at the annual meeting of the American College of Gastroenterology.

He noted a 2014 meta-analysis by Lytras and colleagues that reported a 9% CRC risk reduction in statin users who did not have IBD. In patients with IBD, data are scarce, according to Dr. Singh.

To further explore the relationship between statin use and CRC in patients without IBD, the investigators analyzed data from 52 studies, including 8 randomized clinical trials, 17 cohort studies, and 27 case-control studies. Of the 11,459,306 patients involved, approximately 2 million used statins and roughly 9 million did not.

To evaluate the same relationship in patients with IBD, the investigators conducted a separate meta-analysis involving 15,342 patients from 5 observational studies, 1 of which was an unpublished abstract. In the 4 published studies, 1,161 patients used statins while 12,145 did not.

In the non-IBD population, statin use was associated with a 20% reduced risk of CRC (pooled odds ratio, 0.80; 95% confidence interval, 0.73-0.88; P less than .001). In patients with IBD, statin use was associated with a 60% CRC risk reduction (pooled OR, 0.40; 95% CI, 0.19-0.86, P = .019).

Dr. Singh noted “significant heterogeneity” in both analyses (I2 greater than 75), most prominently in the IBD populations, which he ascribed to “differences in demographic features, ethnic groups, and risk factors for CRC.”

While publication bias was absent from the non-IBD analysis, it was detected in the IBD portion of the study. Dr. Singh said that selection bias may also have been present in the IBD analysis, due to exclusive use of observational studies.

“Prospective trials are needed to confirm the risk reduction of CRC in the IBD population, including whether the effects of statins differ between ulcerative colitis and Crohn’s disease patients,” Dr. Singh said.

Additional analyses are underway, he added, including one that will account for the potentially confounding effect of aspirin use.

According to David E. Kaplan, MD, of the University of Pennsylvania, Philadelphia, “The finding that statins are associated with reduced CRC in IBD provides additional support for the clinical importance of the antineoplastic effects of statins. This effect has been strongly observed in liver cancer, and is pending prospective validation.”

Dr. Kaplan also offered some mechanistic insight into why statins have an anticancer effect, pointing to “the centrality of cholesterol biosynthesis for development and/or progression of malignancy.”

The investigators and Dr. Kaplan reported no relevant conflicts of interest.

Statin use may significantly lower the risk of colorectal cancer (CRC) in patients with or without inflammatory bowel disease (IBD), based on a meta-analysis and systematic review.

In more than 15,000 patients with IBD, statin use was associated with a 60% reduced risk of CRC, reported lead author Kevin N. Singh, MD, of NYU Langone Medical Center in New York, and colleagues.

“Statin use has been linked with a risk reduction for cancers including hepatocellular carcinoma, breast, gastric, pancreatic, and biliary tract cancers, but data supporting the use of statins for chemoprevention against CRC is conflicting,” Dr. Singh said during a virtual presentation at the annual meeting of the American College of Gastroenterology.

He noted a 2014 meta-analysis by Lytras and colleagues that reported a 9% CRC risk reduction in statin users who did not have IBD. In patients with IBD, data are scarce, according to Dr. Singh.

To further explore the relationship between statin use and CRC in patients without IBD, the investigators analyzed data from 52 studies, including 8 randomized clinical trials, 17 cohort studies, and 27 case-control studies. Of the 11,459,306 patients involved, approximately 2 million used statins and roughly 9 million did not.

To evaluate the same relationship in patients with IBD, the investigators conducted a separate meta-analysis involving 15,342 patients from 5 observational studies, 1 of which was an unpublished abstract. In the 4 published studies, 1,161 patients used statins while 12,145 did not.

In the non-IBD population, statin use was associated with a 20% reduced risk of CRC (pooled odds ratio, 0.80; 95% confidence interval, 0.73-0.88; P less than .001). In patients with IBD, statin use was associated with a 60% CRC risk reduction (pooled OR, 0.40; 95% CI, 0.19-0.86, P = .019).

Dr. Singh noted “significant heterogeneity” in both analyses (I2 greater than 75), most prominently in the IBD populations, which he ascribed to “differences in demographic features, ethnic groups, and risk factors for CRC.”

While publication bias was absent from the non-IBD analysis, it was detected in the IBD portion of the study. Dr. Singh said that selection bias may also have been present in the IBD analysis, due to exclusive use of observational studies.

“Prospective trials are needed to confirm the risk reduction of CRC in the IBD population, including whether the effects of statins differ between ulcerative colitis and Crohn’s disease patients,” Dr. Singh said.

Additional analyses are underway, he added, including one that will account for the potentially confounding effect of aspirin use.

According to David E. Kaplan, MD, of the University of Pennsylvania, Philadelphia, “The finding that statins are associated with reduced CRC in IBD provides additional support for the clinical importance of the antineoplastic effects of statins. This effect has been strongly observed in liver cancer, and is pending prospective validation.”

Dr. Kaplan also offered some mechanistic insight into why statins have an anticancer effect, pointing to “the centrality of cholesterol biosynthesis for development and/or progression of malignancy.”

The investigators and Dr. Kaplan reported no relevant conflicts of interest.

Statin use may significantly lower the risk of colorectal cancer (CRC) in patients with or without inflammatory bowel disease (IBD), based on a meta-analysis and systematic review.

In more than 15,000 patients with IBD, statin use was associated with a 60% reduced risk of CRC, reported lead author Kevin N. Singh, MD, of NYU Langone Medical Center in New York, and colleagues.

“Statin use has been linked with a risk reduction for cancers including hepatocellular carcinoma, breast, gastric, pancreatic, and biliary tract cancers, but data supporting the use of statins for chemoprevention against CRC is conflicting,” Dr. Singh said during a virtual presentation at the annual meeting of the American College of Gastroenterology.

He noted a 2014 meta-analysis by Lytras and colleagues that reported a 9% CRC risk reduction in statin users who did not have IBD. In patients with IBD, data are scarce, according to Dr. Singh.

To further explore the relationship between statin use and CRC in patients without IBD, the investigators analyzed data from 52 studies, including 8 randomized clinical trials, 17 cohort studies, and 27 case-control studies. Of the 11,459,306 patients involved, approximately 2 million used statins and roughly 9 million did not.

To evaluate the same relationship in patients with IBD, the investigators conducted a separate meta-analysis involving 15,342 patients from 5 observational studies, 1 of which was an unpublished abstract. In the 4 published studies, 1,161 patients used statins while 12,145 did not.

In the non-IBD population, statin use was associated with a 20% reduced risk of CRC (pooled odds ratio, 0.80; 95% confidence interval, 0.73-0.88; P less than .001). In patients with IBD, statin use was associated with a 60% CRC risk reduction (pooled OR, 0.40; 95% CI, 0.19-0.86, P = .019).

Dr. Singh noted “significant heterogeneity” in both analyses (I2 greater than 75), most prominently in the IBD populations, which he ascribed to “differences in demographic features, ethnic groups, and risk factors for CRC.”

While publication bias was absent from the non-IBD analysis, it was detected in the IBD portion of the study. Dr. Singh said that selection bias may also have been present in the IBD analysis, due to exclusive use of observational studies.

“Prospective trials are needed to confirm the risk reduction of CRC in the IBD population, including whether the effects of statins differ between ulcerative colitis and Crohn’s disease patients,” Dr. Singh said.

Additional analyses are underway, he added, including one that will account for the potentially confounding effect of aspirin use.

According to David E. Kaplan, MD, of the University of Pennsylvania, Philadelphia, “The finding that statins are associated with reduced CRC in IBD provides additional support for the clinical importance of the antineoplastic effects of statins. This effect has been strongly observed in liver cancer, and is pending prospective validation.”

Dr. Kaplan also offered some mechanistic insight into why statins have an anticancer effect, pointing to “the centrality of cholesterol biosynthesis for development and/or progression of malignancy.”

The investigators and Dr. Kaplan reported no relevant conflicts of interest.

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

Clinicians have numerous pharmacotherapy options available to treat ADHD in their toolbox. How do you know which formulation or combination of therapies is right for your patient with ADHD?

According to Jeffrey R. Strawn, MD, the answer depends on onset and duration of the medication and how that fits in to the patient’s current needs.

The most common treatment for ADHD, stimulants, are amphetamine-based and methylphenidate-based compounds known for improving core symptoms of inattention, impulsivity, and hyperactivity and are “probably associated with the most efficacy relative to the other interventions,” Dr. Strawn, associate professor of psychiatry, pediatrics, and clinical pharmacology at Cincinnati Children’s Hospital Medical Center, said at Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “But what I think is also really important for us to remember as clinicians is that they improve adherence, social interactions, [and] academic efficiency as well as accuracy.”

Other ADHD pharmacotherapy options include nonstimulant norepinephrine reuptake inhibitors (NRIs) like atomoxetine, and alpha-2 agonists like the extended-release forms of guanfacine and clonidine. All are Food and Drug Administration–approved for the treatment of ADHD, and the FDA has approved some combination alpha-2 agonists and stimulants treatments for ADHD as well.

When making decisions about formulations for ADHD pharmacotherapy, clinicians should think about whether the patient has issues swallowing tablets or capsules. Tablets, capsules, and chewable tablets may be appropriate for patients who can easily take these medications, while patients who have problems with swallowing pills may benefit from dissolvable tablets, solutions, and transdermal applications. Each of these options “have differences in terms of absorption, also differences in terms of intestinal transit time in younger children, as well as patients perhaps with irritable bowel, as well as other conditions that may affect absorption,” Dr. Strawn said. Different formulations have unique considerations: liquid formulations have the benefit of making precise adjustments, sublingual formulations may have quick absorption and onset, and oral dissolvable tablets can improve treatment adherence and reduce misuse of medication.

Formulations can be available as a delayed release, extended release, pulsatile release, targeted release, or a combination of immediate, delayed, and/or extended release. “Ultimately, what this gives rise to is differences in onset of action and duration, as well as differences in the elimination profile of the medication,” he said.

Transdermal formulations “avoid the first-pass metabolism, which may reduce side effects or increase efficacy,” but patients converting from an oral formulation may require reducing the dose. “It’s always important to remember, for example, with something like Daytrana, the transdermal methylphenidate formulation, if we’re converting a patient from an oral methylphenidate, we roughly need to use half the dose for the transdermal formulation,” Dr. Strawn explained. Transdermal formulations can carry benefits of steady plasma concentrations and longer duration of action but may cause skin irritation or accidentally be removed. “It’s really important they’re properly disposed of because oftentimes they do contain some active medication within the residual matrix.”
 

Methylphenidate, mixed amphetamine salt–based preparations

Modified-release formulations include matrix- or reservoir-based formulations and are most importantly differentiated from other formulations by their gastrointestinal (GI) transit time and the permeation through the GI membrane. When considering what formulation to choose, “it’s important to consider that, even with an ‘extended release formulation,’ all of these medications have some percentage that is immediately released, and that percentage varies considerably from formulation to formulation,” Dr. Strawn said.

He noted that brand names are sometimes used for formulations “because it’s often very difficult for us as clinicians and even for pharmacists to distinguish between these various formulations of the medication, which often have the same ‘extended’ or ‘delayed release’ modifying term within the name of the medication.”

Examples of medications that have greater immediate release include Metadate CD (30%), Aptensio XR (37%), long-acting methylphenidate (50%), dexmethylphenidate extended-release (50%), and Mixed Salts amphetamine extended release (50%). Formulations with a less immediate release include Quillivant solution or Quillichew chewable tablets (20%), Dyanaval XR solution (20%), OROS methylphenidate (22%), Daytrana that begins within 1 or 2 hours and lasts for 9 hours, or lisdexamfetamine that begins within 1 hour and lasts for 9 hours.

Depending on a patient’s needs, one particular formulation may work better than another. Dexmethylphenidate (Focalin XR) has a 50% immediate release and 50% extended release formulation, which “may be really important for a high school student who has first period precalculus followed by second period human geography,” Dr. Strawn said, while “a patient who may have first period study hall and second period art” may benefit from OROS methylphenidate.

Clinicians should also consider the effect of counterclockwise hysteresis when adding a short-acting stimulant later in the day. “There seems to be something really magic about having that ascending concentration time curve that, when we’re on the descending loop of that concentration time curve, we really seem to get a dramatic waning of the effect of the medication, even though technically the concentration is within the ‘therapeutic range,’ ” Dr. Strawn said. “With counterclockwise hysteresis, we see that the effect increases with time for a given concentration of the medication.”
 

Combining ADHD pharmacotherapies

For children and adolescents with ADHD, atomoxetine is a nonstimulant, FDA-approved treatment option. “It seems to be effective not just in terms of total ADHD symptoms, but also in terms of hyperactive and impulsive symptoms as well as the inattentive symptoms,” Dr. Strawn said.

Pharmacogenetics can be a guide for selecting an atomoxetine for a patient with ADHD, he noted. “What I think is most relevant here is the way in which pharmacogenetics can actually help guide our dosing, which then optimizes tolerability, potentially efficacy of atomoxetine,” he said. “Atomoxetine is pretty extensively metabolized by [CYP]2D6, and it’s one of about 300 medications that actually has specific labeling from the FDA on dosing based on genotype. It recommends a slower titration, as well as a lower target dose of atomoxetine in individuals who are P450 2D6 poor metabolizers relative to those patients who are ultra-rapid or normal metabolizers.”

Atomoxetine is most often combined with methylphenidate and has some evidence of benefit in children or adolescents who do not have an adequate response to stimulants alone. When combining stimulants with the alpha-2 agonists guanfacine or clonidine, “there are some improvements in terms of the combination treatment relative to the monotherapy,” Dr. Strawn said. He also emphasized that patients taking guanfacine immediate release tend to have better absorption and faster onset, compared with the extended release formulation. “This is something that potentially is very important when we think beyond steady state and we think about the practical use of this medication,” he said.
 

Baseline history is important

Overall, taking a baseline history of a patient with ADHD is “critically important” before starting them on stimulants, Dr. Strawn said. “Specifically, I would recommend documenting a negative history of syncope, family history of sudden cardiac death, as well as the lack of any known history of structural cardiac abnormalities,” he said. “Without a consultation with the cardiologist specifically around this question, I’m very, very, very hesitant – as in I don’t – use stimulants in patients who have histories of aortic stenosis, Wolff-Parkinson-White, as well as arrhythmogenic right ventricular dysplasia.”

Although patients with ADHD were typically followed with routine hemodynamic monitoring every 3 months prior to the COVID-19 pandemic, some clinicians see their patients with ADHD less frequently if they have been stabilized on a stimulant. “It is important to check not just with the patient, but also with parents and teachers as we’re adjusting medication dose and trying to optimize the treatment regimen, particularly in young children. In adults, it may also be very helpful to talk with spouses,” Dr. Strawn said.

Dr. Strawn also called attention to a recommendation to perform a routine electrocardiogram (EKG) in patients with ADHD who might receive stimulants. “At present, there is no recommendation to obtain a routine screening EKG in these patients, provided that we have an absence of those other red flags on the history,” he said. “Certainly, I would consider it in situations where I do have persistent tachycardia or hypertension, or there are other treatment-emergent symptoms, although really in many of these situations, I’m actually speaking on the phone with my pediatric or adult cardiology colleagues.”

Global Academy and this news organization are owned by the same parent company. Dr. Strawn reported receiving research support from Allergan, the FDA, the National Institutes of Health, Neuronetics, and Otsuka; serving as a consultant and receiving material support from Myriad; receiving royalties from Springer Publishing; and serving as a consultant for Intra-Cellular Therapies. In addition, he has been on the speaker’s bureau for the Neuroscience Education Institute and CMEology, and Medscape.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.