Kari Oakes

Officials at the Centers for Disease Control and Prevention have issued an expanded travel alert for regions where travelers may be at risk of contracting Zika virus.

The mosquito-borne flavivirus may be associated with an increased risk of microcephaly and other intracranial and neurologic abnormalities in infants whose mothers were infected with Zika virus during pregnancy. Women who are pregnant or considering becoming pregnant should consider avoiding travel to countries included in the Zika virus alert.

The CDC’s expanded warning includes Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa. This is in addition to the previous travel alert for Puerto Rico (a U.S. territory), Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Suriname, and Venezuela.

In the United States, about a dozen cases of Zika virus have been reported, according to the CDC. States thus far where individuals have tested positive for the virus are Texas, Florida, Illinois, New Jersey, and Hawaii. These dozen cases include two pregnant women who tested positive for the Zika virus in Illinois this week. In Hawaii, a woman who had lived in Brazil while pregnant has given birth to a baby with microcephaly and congenital Zika virus infection. To date, all confirmed cases of Zika virus in the U.S. have been in individuals who traveled to areas with Zika virus transmission.

Zika virus, a member of the family of viruses that includes dengue fever, is spread by mosquitoes of the Aedes species, according to Dr. Amesh Adalja.

Dr. Adalja, a member of the public health committee of the Infectious Disease Society of America and an instructor in the department of infectious diseases at the University of Pittsburgh Medical Center, noted that though the virus has been known since the 1940s, “it was not considered a major public health threat” because of the generally mild course of the disease.

Infection is asymptomatic in 80% of individuals, he said. Symptoms of Zika virus infection, if they appear, include initial fever, a maculopapular rash, arthralgia, and sometimes conjunctivitis. There is no treatment for the disease and care is supportive.

A recent explosion of Zika virus cases in Brazil, however, has been associated with a large increase in cases of microcephaly in newborns. Though the association has not been confirmed, Zika virus has been found in infants born with microcephaly and in the placentas of mothers of babies with microcephaly.

The CDC has issued interim guidance for diagnosis, treatment, and management of suspected Zika virus in pregnant women. All pregnant women should be asked about travel to countries with known Zika virus exposure, with surveillance by fetal ultrasound and, in some cases, testing for Zika virus guided by symptoms and likelihood of exposure.

The CDC recommends vigilance against mosquito bites for pregnant women who do travel to areas with Zika virus activity, including the use of effective insect repellent, protective clothing, and remaining in and sleeping in air-conditioned rooms when possible.

In the United States, there is reason to be concerned about Zika virus, since “the scale of travel is very, very high” to the Central and South American and Caribbean countries where Zika virus transmission is active, Dr. Adalja said. However, since the same vector also transmits dengue fever and the Chikungunya virus – currently the focus of increasing concern in the U.S. – aggressive vector control measures are already underway in parts of the country where Aedes species mosquitoes are resident.

Though the consequences of the apparent association between maternal Zika virus infection and infant microcephaly are devastating, said Dr. Adalja, “it’s important that people put this in the proper public health perspective. Dengue fever kills thousands of people each year.”*

Dr. Adalja said that he expects commercially available testing for Zika virus to be developed; currently, testing is currently only available from the CDC and from some states’ departments of public health.

Additional resources for physicians

American College of Obstetricians and Gynecologists: www.acog.org/About-ACOG/News-Room/Practice-Advisories

CDC: www.cdc.gov/zika/

*Correction, 1/25/2016: An earlier version of this story misstated the number of deaths from dengue fever.

[email protected]

On Twitter @karioakes

Officials at the Centers for Disease Control and Prevention have issued an expanded travel alert for regions where travelers may be at risk of contracting Zika virus.

The mosquito-borne flavivirus may be associated with an increased risk of microcephaly and other intracranial and neurologic abnormalities in infants whose mothers were infected with Zika virus during pregnancy. Women who are pregnant or considering becoming pregnant should consider avoiding travel to countries included in the Zika virus alert.

The CDC’s expanded warning includes Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa. This is in addition to the previous travel alert for Puerto Rico (a U.S. territory), Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Suriname, and Venezuela.

In the United States, about a dozen cases of Zika virus have been reported, according to the CDC. States thus far where individuals have tested positive for the virus are Texas, Florida, Illinois, New Jersey, and Hawaii. These dozen cases include two pregnant women who tested positive for the Zika virus in Illinois this week. In Hawaii, a woman who had lived in Brazil while pregnant has given birth to a baby with microcephaly and congenital Zika virus infection. To date, all confirmed cases of Zika virus in the U.S. have been in individuals who traveled to areas with Zika virus transmission.

Zika virus, a member of the family of viruses that includes dengue fever, is spread by mosquitoes of the Aedes species, according to Dr. Amesh Adalja.

Dr. Adalja, a member of the public health committee of the Infectious Disease Society of America and an instructor in the department of infectious diseases at the University of Pittsburgh Medical Center, noted that though the virus has been known since the 1940s, “it was not considered a major public health threat” because of the generally mild course of the disease.

Infection is asymptomatic in 80% of individuals, he said. Symptoms of Zika virus infection, if they appear, include initial fever, a maculopapular rash, arthralgia, and sometimes conjunctivitis. There is no treatment for the disease and care is supportive.

A recent explosion of Zika virus cases in Brazil, however, has been associated with a large increase in cases of microcephaly in newborns. Though the association has not been confirmed, Zika virus has been found in infants born with microcephaly and in the placentas of mothers of babies with microcephaly.

The CDC has issued interim guidance for diagnosis, treatment, and management of suspected Zika virus in pregnant women. All pregnant women should be asked about travel to countries with known Zika virus exposure, with surveillance by fetal ultrasound and, in some cases, testing for Zika virus guided by symptoms and likelihood of exposure.

The CDC recommends vigilance against mosquito bites for pregnant women who do travel to areas with Zika virus activity, including the use of effective insect repellent, protective clothing, and remaining in and sleeping in air-conditioned rooms when possible.

In the United States, there is reason to be concerned about Zika virus, since “the scale of travel is very, very high” to the Central and South American and Caribbean countries where Zika virus transmission is active, Dr. Adalja said. However, since the same vector also transmits dengue fever and the Chikungunya virus – currently the focus of increasing concern in the U.S. – aggressive vector control measures are already underway in parts of the country where Aedes species mosquitoes are resident.

Though the consequences of the apparent association between maternal Zika virus infection and infant microcephaly are devastating, said Dr. Adalja, “it’s important that people put this in the proper public health perspective. Dengue fever kills thousands of people each year.”*

Dr. Adalja said that he expects commercially available testing for Zika virus to be developed; currently, testing is currently only available from the CDC and from some states’ departments of public health.

Additional resources for physicians

American College of Obstetricians and Gynecologists: www.acog.org/About-ACOG/News-Room/Practice-Advisories

CDC: www.cdc.gov/zika/

*Correction, 1/25/2016: An earlier version of this story misstated the number of deaths from dengue fever.

[email protected]

On Twitter @karioakes

Officials at the Centers for Disease Control and Prevention have issued an expanded travel alert for regions where travelers may be at risk of contracting Zika virus.

The mosquito-borne flavivirus may be associated with an increased risk of microcephaly and other intracranial and neurologic abnormalities in infants whose mothers were infected with Zika virus during pregnancy. Women who are pregnant or considering becoming pregnant should consider avoiding travel to countries included in the Zika virus alert.

The CDC’s expanded warning includes Barbados, Bolivia, Ecuador, Guadeloupe, Saint Martin, Guyana, Cape Verde, and Samoa. This is in addition to the previous travel alert for Puerto Rico (a U.S. territory), Brazil, Colombia, El Salvador, French Guiana, Guatemala, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Suriname, and Venezuela.

In the United States, about a dozen cases of Zika virus have been reported, according to the CDC. States thus far where individuals have tested positive for the virus are Texas, Florida, Illinois, New Jersey, and Hawaii. These dozen cases include two pregnant women who tested positive for the Zika virus in Illinois this week. In Hawaii, a woman who had lived in Brazil while pregnant has given birth to a baby with microcephaly and congenital Zika virus infection. To date, all confirmed cases of Zika virus in the U.S. have been in individuals who traveled to areas with Zika virus transmission.

Zika virus, a member of the family of viruses that includes dengue fever, is spread by mosquitoes of the Aedes species, according to Dr. Amesh Adalja.

Dr. Adalja, a member of the public health committee of the Infectious Disease Society of America and an instructor in the department of infectious diseases at the University of Pittsburgh Medical Center, noted that though the virus has been known since the 1940s, “it was not considered a major public health threat” because of the generally mild course of the disease.

Infection is asymptomatic in 80% of individuals, he said. Symptoms of Zika virus infection, if they appear, include initial fever, a maculopapular rash, arthralgia, and sometimes conjunctivitis. There is no treatment for the disease and care is supportive.

A recent explosion of Zika virus cases in Brazil, however, has been associated with a large increase in cases of microcephaly in newborns. Though the association has not been confirmed, Zika virus has been found in infants born with microcephaly and in the placentas of mothers of babies with microcephaly.

The CDC has issued interim guidance for diagnosis, treatment, and management of suspected Zika virus in pregnant women. All pregnant women should be asked about travel to countries with known Zika virus exposure, with surveillance by fetal ultrasound and, in some cases, testing for Zika virus guided by symptoms and likelihood of exposure.

The CDC recommends vigilance against mosquito bites for pregnant women who do travel to areas with Zika virus activity, including the use of effective insect repellent, protective clothing, and remaining in and sleeping in air-conditioned rooms when possible.

In the United States, there is reason to be concerned about Zika virus, since “the scale of travel is very, very high” to the Central and South American and Caribbean countries where Zika virus transmission is active, Dr. Adalja said. However, since the same vector also transmits dengue fever and the Chikungunya virus – currently the focus of increasing concern in the U.S. – aggressive vector control measures are already underway in parts of the country where Aedes species mosquitoes are resident.

Though the consequences of the apparent association between maternal Zika virus infection and infant microcephaly are devastating, said Dr. Adalja, “it’s important that people put this in the proper public health perspective. Dengue fever kills thousands of people each year.”*

Dr. Adalja said that he expects commercially available testing for Zika virus to be developed; currently, testing is currently only available from the CDC and from some states’ departments of public health.

Additional resources for physicians

American College of Obstetricians and Gynecologists: www.acog.org/About-ACOG/News-Room/Practice-Advisories

CDC: www.cdc.gov/zika/

*Correction, 1/25/2016: An earlier version of this story misstated the number of deaths from dengue fever.

[email protected]

On Twitter @karioakes

HOLLYWOOD, FL. – Tattoos are common, but so are regrets. As tattoos become acceptable for the American mainstream, physicians are seeing more people who, for personal or professional reasons, wish to have a tattoo removed. And those who perform removal procedures benefit from having tools in their toolkit to eradicate an unwanted tattoo with minimal lasting skin damage.

Even with laser therapy – a common and effective tattoo removal technique – blue and green pigments can be especially difficult to eradicate.

©justtscott/Thinkstock

At the annual meeting of the American Academy of Cosmetic Surgery, Dr. Robert H. Burke, director of the Michigan Center for Cosmetic Surgery, Ann Arbor, shared results from a pilot study of removal of blue-green pigments with a unique oval-shaped beam from a ruby laser.

Lasers, which preferentially heat chromophores, work well for tattoo removal since a selected wavelength is preferentially absorbed by a particular chromophore, targeting tattooed tissue and sparing non-inked tissue.

Older laser technologies created a Gaussian distribution of intensity with decreasing energy distribution toward the perimeter of the laser field. Newer lasers can create a sharper focal beam, creating beams of different sizes and shapes with uniform intensity.

In the pilot study, four men and four women who had persistent blue-green tattoo colors, received treatment with a 694 nm uniform-intensity ruby laser with an oval beam configuration. The patients, whose mean age was about 31 years, had tattoos with an age range of four to 30 years. The mean age of tattoos was 11.4 years. Most patients had had prior tattoo removal sessions; one of the women had undergone 14 sessions.

Dr. Burke treated these patients two to four times with the oval beam 694 nm ruby laser; fluence ranged from 2-5 J/cm², with a spot size of 4-6 mm and a cycle of 2Hz.

The average tattoo pigment color clearance achieved with the oval beam 694 nm ruby laser was 60%, with a range from 40% to 90%. The study participants experienced no adverse events, Dr. Burke said.

The oval beam shape, he noted, deserves further investigation, because it should theoretically create less overlap and permit denser treatment – and may also allow the operator to follow a linear tattoo pattern more closely. This particular treatment regimen was also quicker, using 2 Hz rather than the more common 1 Hz, he pointed out.

Dr. Burke reported being on the physician advisory board for Suneva Medical.

[email protected]

On Twitter @karioakes

HOLLYWOOD, FL. – Tattoos are common, but so are regrets. As tattoos become acceptable for the American mainstream, physicians are seeing more people who, for personal or professional reasons, wish to have a tattoo removed. And those who perform removal procedures benefit from having tools in their toolkit to eradicate an unwanted tattoo with minimal lasting skin damage.

Even with laser therapy – a common and effective tattoo removal technique – blue and green pigments can be especially difficult to eradicate.

©justtscott/Thinkstock

At the annual meeting of the American Academy of Cosmetic Surgery, Dr. Robert H. Burke, director of the Michigan Center for Cosmetic Surgery, Ann Arbor, shared results from a pilot study of removal of blue-green pigments with a unique oval-shaped beam from a ruby laser.

Lasers, which preferentially heat chromophores, work well for tattoo removal since a selected wavelength is preferentially absorbed by a particular chromophore, targeting tattooed tissue and sparing non-inked tissue.

Older laser technologies created a Gaussian distribution of intensity with decreasing energy distribution toward the perimeter of the laser field. Newer lasers can create a sharper focal beam, creating beams of different sizes and shapes with uniform intensity.

In the pilot study, four men and four women who had persistent blue-green tattoo colors, received treatment with a 694 nm uniform-intensity ruby laser with an oval beam configuration. The patients, whose mean age was about 31 years, had tattoos with an age range of four to 30 years. The mean age of tattoos was 11.4 years. Most patients had had prior tattoo removal sessions; one of the women had undergone 14 sessions.

Dr. Burke treated these patients two to four times with the oval beam 694 nm ruby laser; fluence ranged from 2-5 J/cm², with a spot size of 4-6 mm and a cycle of 2Hz.

The average tattoo pigment color clearance achieved with the oval beam 694 nm ruby laser was 60%, with a range from 40% to 90%. The study participants experienced no adverse events, Dr. Burke said.

The oval beam shape, he noted, deserves further investigation, because it should theoretically create less overlap and permit denser treatment – and may also allow the operator to follow a linear tattoo pattern more closely. This particular treatment regimen was also quicker, using 2 Hz rather than the more common 1 Hz, he pointed out.

Dr. Burke reported being on the physician advisory board for Suneva Medical.

[email protected]

On Twitter @karioakes

HOLLYWOOD, FL. – Tattoos are common, but so are regrets. As tattoos become acceptable for the American mainstream, physicians are seeing more people who, for personal or professional reasons, wish to have a tattoo removed. And those who perform removal procedures benefit from having tools in their toolkit to eradicate an unwanted tattoo with minimal lasting skin damage.

Even with laser therapy – a common and effective tattoo removal technique – blue and green pigments can be especially difficult to eradicate.

©justtscott/Thinkstock

At the annual meeting of the American Academy of Cosmetic Surgery, Dr. Robert H. Burke, director of the Michigan Center for Cosmetic Surgery, Ann Arbor, shared results from a pilot study of removal of blue-green pigments with a unique oval-shaped beam from a ruby laser.

Lasers, which preferentially heat chromophores, work well for tattoo removal since a selected wavelength is preferentially absorbed by a particular chromophore, targeting tattooed tissue and sparing non-inked tissue.

Older laser technologies created a Gaussian distribution of intensity with decreasing energy distribution toward the perimeter of the laser field. Newer lasers can create a sharper focal beam, creating beams of different sizes and shapes with uniform intensity.

In the pilot study, four men and four women who had persistent blue-green tattoo colors, received treatment with a 694 nm uniform-intensity ruby laser with an oval beam configuration. The patients, whose mean age was about 31 years, had tattoos with an age range of four to 30 years. The mean age of tattoos was 11.4 years. Most patients had had prior tattoo removal sessions; one of the women had undergone 14 sessions.

Dr. Burke treated these patients two to four times with the oval beam 694 nm ruby laser; fluence ranged from 2-5 J/cm², with a spot size of 4-6 mm and a cycle of 2Hz.

The average tattoo pigment color clearance achieved with the oval beam 694 nm ruby laser was 60%, with a range from 40% to 90%. The study participants experienced no adverse events, Dr. Burke said.

The oval beam shape, he noted, deserves further investigation, because it should theoretically create less overlap and permit denser treatment – and may also allow the operator to follow a linear tattoo pattern more closely. This particular treatment regimen was also quicker, using 2 Hz rather than the more common 1 Hz, he pointed out.

Dr. Burke reported being on the physician advisory board for Suneva Medical.

[email protected]

On Twitter @karioakes

Eastern Kentucky is drowning in pills.

The Bluegrass State, especially its eastern half, has been hit hard by the national opioid abuse epidemic. In 2011, more than 15% of all 18- to 25-year-olds in the state were illegally using opioids, and hospital admissions and deaths from drug overdoses were spiking, with drug overdose death rates rivaling those for car crashes.

©thegoodphoto/Thinkstock.com

In 2012, attempting to address the crisis that was killing young and old alike and fracturing families, the Kentucky lawmakers passed legislation targeting opioid abuse. Among other measures, that year’s House Bill 1 took aim at "pill mills" by preventing nonphysicians from owning pain management clinics, and also significantly expanded the state's prescription drug monitoring program (PDMP), known as KASPER.

Because the regulations were written from a law enforcement – rather than a medical – perspective, the new law contained measures that proved difficult for prescribers to understand, let alone comply with. That meant a bad situation looked to be getting worse for doctors in Kentucky who wanted to make things better but weren’t always sure where to start.

So, Dr. Greg Hood, an internist in Lexington, Ky., decided to do something about it.

Already interested in health policy issues and active in his state’s chapter of the American College of Physicians, Dr. Hood worked with ACP leaders to formulate an education and implementation plan to help primary care practices shift toward rational opioid prescribing.

As an internist, he understood the realities of day-to-day medical practice in this hard-hit region, and he knew that effective change would need a multipronged approach.

Dr. Hood and his collaborators in the Kentucky ACP chapter, the national ACP, and the Johns Hopkins Bloomberg School of Public Health, Baltimore, put together a proposal, “Enhancing Effective, Safe Chronic Pain Management in PCMH-Recognized and ACO-Participating Primary Care Practices: A Kentucky ACP Chapter Quality Network Initiative.”

With partial funding from Pfizer and support from the ACP, the quality improvement (QI) project focused on achievable, practice-friendly steps.

The initiative involved eight primary care practices from two accountable care organizations (ACOs), a total of 41 providers participated, and each practice named a physician and a nonphysician “QI champion” to lead education and change efforts.

The whole health care team, from schedulers and medical assistants to nursing staff and prescribers, was involved, so all staff members would know why they were being asked to make changes.

The program had four primary objectives: to engage primary care teams, implement a QI program to enhance chronic pain management, evaluate the program’s impact, and, finally, further disseminate the program.

Before any practice improvement began, an ACP Quality Connect practice assessment tool gathered information about the state of chronic pain care in practices. At the outset, though about 60% of practices were screening for depression, nearly three-quarters of practices were not assessing and managing chronic pain effectively, and almost half were not consistently using opioid agreement forms and incorporating urine drug testing into practice.

Performance measures in the QI program included documented screening for clinical depression, documented pain assessments, and increased use of opioid agreements and urine drug testing – all evidence-based measures to ensure more appropriate opioid prescribing and reduce the risk of abuse or diversion.

Various practice improvement strategies were brought to the study sites and led by the QI champions. These included educational webinars about pain and mental health assessments, as well as opioid contracts and risk assessment. Nationally known QI experts participated in coaching calls with team members as implementation got underway. A patient brochure about opioids and controlled substance agreements was developed and brought into use.

After the holistic set of interventions was fully implemented, practices were again surveyed about how they were caring for their chronic pain patients.

What happened? As Dr. Hood suspected, things changed.

“Physicians and practices are capable of change if you design a project that gives offices what they need,” he said.

The average improvement from baseline for depression screening, for example, was 24%. Strikingly, one practice that never screened for depression before the QI initiative achieved a 92% screening rate post intervention. Urine drug testing and controlled substance agreement use jumped by 23%, with one practice going from 0% before intervention to 100% at follow-up.

Practices showed even more improvement – an average of 48% – in administering pain assessments, because six of the eight practices never administered pain assessments before the intervention. Improvements in this group ranged from 60% to 100%.

Lessons learned from the QI initiative, said Dr. Hood, included the importance of multilevel, ongoing engagement with all team members. Some financial support to help offset the time commitment came from Pfizer.

A good solution also has to work within the framework of the social and emotional context surrounding chronic pain. One important thing to confront, said Dr. Hood, was the “unspoken assumption that you need a controlled substance” for certain types of pain.

Although it’s not supported by the medical literature, there’s “still this tug from the patient that you’re holding something back from me” if a complaint of pain, especially chronic pain, doesn’t get an opioid prescription. The continued widespread use of an unproven treatment in chronic pain care stands out from other areas of medical care, where evidence-backed treatment is increasingly the norm, Dr. Hood noted.

Part of changing the conversation within a practice, and then expanding the dialogue to include the patient, is to reframe the discussion.

“It’s not more care or less care, but different care,” said Dr. Hood. He spoke of a patient who had been on very high opioid doses – equivalent to 200 mg morphine daily – for neuropathic pain. Within the framework of the physician-patient relationship and with a lot of talking, Dr. Hood was able to transition the patient to a regimen appropriate for his pain. Within 6 weeks, the patient’s opioid dose was equivalent to less than 80 mg morphine daily, his pain was better managed, and his quality of life was greatly improved.

The significant side-effect burden of opioids often includes a degree of constipation, which many patients won’t talk about, but which is a very real and daily struggle for those who are on high doses. This was the case for Dr. Hood’s patient with neuropathic pain, and the improvement in that symptom alone helped the patient’s willingness to stick with the transition away from an opioid-based regimen.

Keeping the patient at the center of chronic pain care, while still using available tools and knowledge to provide high-quality rational care, is an achievable goal, he said.

“We’ve proved we can make the change, and we’ve proved we can achieve adherence to the regulations,” he said. “Now, how do we further improve the care of the patient? The job’s not done.”

In development are adaptive tablet-based surveys that tailor themselves to patient responses, yielding more accurate information about patient characteristics and substance use profiles in a more user-friendly format.

Dr. Hood and his project collaborators hope to seek grant funding to disseminate the project beyond the borders of the state of Kentucky. The scalability of the QI process is a strength, he said.

In the process of developing the QI program, Dr. Hood and his collaborators met with key thought leaders in the pharmaceutical industry to build support for educational initiatives such as the ACP Quality Connect program.

As for the sometimes tainted history of the use of opioids for chronic nonmalignant pain? “That’s the past,” Dr. Hood declared. “We now have an opportunity to turn to the future. ... This needs to happen to alleviate the suffering of these patients.”

[email protected]

On Twitter @karioakes

Eastern Kentucky is drowning in pills.

The Bluegrass State, especially its eastern half, has been hit hard by the national opioid abuse epidemic. In 2011, more than 15% of all 18- to 25-year-olds in the state were illegally using opioids, and hospital admissions and deaths from drug overdoses were spiking, with drug overdose death rates rivaling those for car crashes.

©thegoodphoto/Thinkstock.com

In 2012, attempting to address the crisis that was killing young and old alike and fracturing families, the Kentucky lawmakers passed legislation targeting opioid abuse. Among other measures, that year’s House Bill 1 took aim at "pill mills" by preventing nonphysicians from owning pain management clinics, and also significantly expanded the state's prescription drug monitoring program (PDMP), known as KASPER.

Because the regulations were written from a law enforcement – rather than a medical – perspective, the new law contained measures that proved difficult for prescribers to understand, let alone comply with. That meant a bad situation looked to be getting worse for doctors in Kentucky who wanted to make things better but weren’t always sure where to start.

So, Dr. Greg Hood, an internist in Lexington, Ky., decided to do something about it.

Already interested in health policy issues and active in his state’s chapter of the American College of Physicians, Dr. Hood worked with ACP leaders to formulate an education and implementation plan to help primary care practices shift toward rational opioid prescribing.

As an internist, he understood the realities of day-to-day medical practice in this hard-hit region, and he knew that effective change would need a multipronged approach.

Dr. Hood and his collaborators in the Kentucky ACP chapter, the national ACP, and the Johns Hopkins Bloomberg School of Public Health, Baltimore, put together a proposal, “Enhancing Effective, Safe Chronic Pain Management in PCMH-Recognized and ACO-Participating Primary Care Practices: A Kentucky ACP Chapter Quality Network Initiative.”

With partial funding from Pfizer and support from the ACP, the quality improvement (QI) project focused on achievable, practice-friendly steps.

The initiative involved eight primary care practices from two accountable care organizations (ACOs), a total of 41 providers participated, and each practice named a physician and a nonphysician “QI champion” to lead education and change efforts.

The whole health care team, from schedulers and medical assistants to nursing staff and prescribers, was involved, so all staff members would know why they were being asked to make changes.

The program had four primary objectives: to engage primary care teams, implement a QI program to enhance chronic pain management, evaluate the program’s impact, and, finally, further disseminate the program.

Before any practice improvement began, an ACP Quality Connect practice assessment tool gathered information about the state of chronic pain care in practices. At the outset, though about 60% of practices were screening for depression, nearly three-quarters of practices were not assessing and managing chronic pain effectively, and almost half were not consistently using opioid agreement forms and incorporating urine drug testing into practice.

Performance measures in the QI program included documented screening for clinical depression, documented pain assessments, and increased use of opioid agreements and urine drug testing – all evidence-based measures to ensure more appropriate opioid prescribing and reduce the risk of abuse or diversion.

Various practice improvement strategies were brought to the study sites and led by the QI champions. These included educational webinars about pain and mental health assessments, as well as opioid contracts and risk assessment. Nationally known QI experts participated in coaching calls with team members as implementation got underway. A patient brochure about opioids and controlled substance agreements was developed and brought into use.

After the holistic set of interventions was fully implemented, practices were again surveyed about how they were caring for their chronic pain patients.

What happened? As Dr. Hood suspected, things changed.

“Physicians and practices are capable of change if you design a project that gives offices what they need,” he said.

The average improvement from baseline for depression screening, for example, was 24%. Strikingly, one practice that never screened for depression before the QI initiative achieved a 92% screening rate post intervention. Urine drug testing and controlled substance agreement use jumped by 23%, with one practice going from 0% before intervention to 100% at follow-up.

Practices showed even more improvement – an average of 48% – in administering pain assessments, because six of the eight practices never administered pain assessments before the intervention. Improvements in this group ranged from 60% to 100%.

Lessons learned from the QI initiative, said Dr. Hood, included the importance of multilevel, ongoing engagement with all team members. Some financial support to help offset the time commitment came from Pfizer.

A good solution also has to work within the framework of the social and emotional context surrounding chronic pain. One important thing to confront, said Dr. Hood, was the “unspoken assumption that you need a controlled substance” for certain types of pain.

Although it’s not supported by the medical literature, there’s “still this tug from the patient that you’re holding something back from me” if a complaint of pain, especially chronic pain, doesn’t get an opioid prescription. The continued widespread use of an unproven treatment in chronic pain care stands out from other areas of medical care, where evidence-backed treatment is increasingly the norm, Dr. Hood noted.

Part of changing the conversation within a practice, and then expanding the dialogue to include the patient, is to reframe the discussion.

“It’s not more care or less care, but different care,” said Dr. Hood. He spoke of a patient who had been on very high opioid doses – equivalent to 200 mg morphine daily – for neuropathic pain. Within the framework of the physician-patient relationship and with a lot of talking, Dr. Hood was able to transition the patient to a regimen appropriate for his pain. Within 6 weeks, the patient’s opioid dose was equivalent to less than 80 mg morphine daily, his pain was better managed, and his quality of life was greatly improved.

The significant side-effect burden of opioids often includes a degree of constipation, which many patients won’t talk about, but which is a very real and daily struggle for those who are on high doses. This was the case for Dr. Hood’s patient with neuropathic pain, and the improvement in that symptom alone helped the patient’s willingness to stick with the transition away from an opioid-based regimen.

Keeping the patient at the center of chronic pain care, while still using available tools and knowledge to provide high-quality rational care, is an achievable goal, he said.

“We’ve proved we can make the change, and we’ve proved we can achieve adherence to the regulations,” he said. “Now, how do we further improve the care of the patient? The job’s not done.”

In development are adaptive tablet-based surveys that tailor themselves to patient responses, yielding more accurate information about patient characteristics and substance use profiles in a more user-friendly format.

Dr. Hood and his project collaborators hope to seek grant funding to disseminate the project beyond the borders of the state of Kentucky. The scalability of the QI process is a strength, he said.

In the process of developing the QI program, Dr. Hood and his collaborators met with key thought leaders in the pharmaceutical industry to build support for educational initiatives such as the ACP Quality Connect program.

As for the sometimes tainted history of the use of opioids for chronic nonmalignant pain? “That’s the past,” Dr. Hood declared. “We now have an opportunity to turn to the future. ... This needs to happen to alleviate the suffering of these patients.”

[email protected]

On Twitter @karioakes

Eastern Kentucky is drowning in pills.

The Bluegrass State, especially its eastern half, has been hit hard by the national opioid abuse epidemic. In 2011, more than 15% of all 18- to 25-year-olds in the state were illegally using opioids, and hospital admissions and deaths from drug overdoses were spiking, with drug overdose death rates rivaling those for car crashes.

©thegoodphoto/Thinkstock.com

In 2012, attempting to address the crisis that was killing young and old alike and fracturing families, the Kentucky lawmakers passed legislation targeting opioid abuse. Among other measures, that year’s House Bill 1 took aim at "pill mills" by preventing nonphysicians from owning pain management clinics, and also significantly expanded the state's prescription drug monitoring program (PDMP), known as KASPER.

Because the regulations were written from a law enforcement – rather than a medical – perspective, the new law contained measures that proved difficult for prescribers to understand, let alone comply with. That meant a bad situation looked to be getting worse for doctors in Kentucky who wanted to make things better but weren’t always sure where to start.

So, Dr. Greg Hood, an internist in Lexington, Ky., decided to do something about it.

Already interested in health policy issues and active in his state’s chapter of the American College of Physicians, Dr. Hood worked with ACP leaders to formulate an education and implementation plan to help primary care practices shift toward rational opioid prescribing.

As an internist, he understood the realities of day-to-day medical practice in this hard-hit region, and he knew that effective change would need a multipronged approach.

Dr. Hood and his collaborators in the Kentucky ACP chapter, the national ACP, and the Johns Hopkins Bloomberg School of Public Health, Baltimore, put together a proposal, “Enhancing Effective, Safe Chronic Pain Management in PCMH-Recognized and ACO-Participating Primary Care Practices: A Kentucky ACP Chapter Quality Network Initiative.”

With partial funding from Pfizer and support from the ACP, the quality improvement (QI) project focused on achievable, practice-friendly steps.

The initiative involved eight primary care practices from two accountable care organizations (ACOs), a total of 41 providers participated, and each practice named a physician and a nonphysician “QI champion” to lead education and change efforts.

The whole health care team, from schedulers and medical assistants to nursing staff and prescribers, was involved, so all staff members would know why they were being asked to make changes.

The program had four primary objectives: to engage primary care teams, implement a QI program to enhance chronic pain management, evaluate the program’s impact, and, finally, further disseminate the program.

Before any practice improvement began, an ACP Quality Connect practice assessment tool gathered information about the state of chronic pain care in practices. At the outset, though about 60% of practices were screening for depression, nearly three-quarters of practices were not assessing and managing chronic pain effectively, and almost half were not consistently using opioid agreement forms and incorporating urine drug testing into practice.

Performance measures in the QI program included documented screening for clinical depression, documented pain assessments, and increased use of opioid agreements and urine drug testing – all evidence-based measures to ensure more appropriate opioid prescribing and reduce the risk of abuse or diversion.

Various practice improvement strategies were brought to the study sites and led by the QI champions. These included educational webinars about pain and mental health assessments, as well as opioid contracts and risk assessment. Nationally known QI experts participated in coaching calls with team members as implementation got underway. A patient brochure about opioids and controlled substance agreements was developed and brought into use.

After the holistic set of interventions was fully implemented, practices were again surveyed about how they were caring for their chronic pain patients.

What happened? As Dr. Hood suspected, things changed.

“Physicians and practices are capable of change if you design a project that gives offices what they need,” he said.

The average improvement from baseline for depression screening, for example, was 24%. Strikingly, one practice that never screened for depression before the QI initiative achieved a 92% screening rate post intervention. Urine drug testing and controlled substance agreement use jumped by 23%, with one practice going from 0% before intervention to 100% at follow-up.

Practices showed even more improvement – an average of 48% – in administering pain assessments, because six of the eight practices never administered pain assessments before the intervention. Improvements in this group ranged from 60% to 100%.

Lessons learned from the QI initiative, said Dr. Hood, included the importance of multilevel, ongoing engagement with all team members. Some financial support to help offset the time commitment came from Pfizer.

A good solution also has to work within the framework of the social and emotional context surrounding chronic pain. One important thing to confront, said Dr. Hood, was the “unspoken assumption that you need a controlled substance” for certain types of pain.

Although it’s not supported by the medical literature, there’s “still this tug from the patient that you’re holding something back from me” if a complaint of pain, especially chronic pain, doesn’t get an opioid prescription. The continued widespread use of an unproven treatment in chronic pain care stands out from other areas of medical care, where evidence-backed treatment is increasingly the norm, Dr. Hood noted.

Part of changing the conversation within a practice, and then expanding the dialogue to include the patient, is to reframe the discussion.

“It’s not more care or less care, but different care,” said Dr. Hood. He spoke of a patient who had been on very high opioid doses – equivalent to 200 mg morphine daily – for neuropathic pain. Within the framework of the physician-patient relationship and with a lot of talking, Dr. Hood was able to transition the patient to a regimen appropriate for his pain. Within 6 weeks, the patient’s opioid dose was equivalent to less than 80 mg morphine daily, his pain was better managed, and his quality of life was greatly improved.

The significant side-effect burden of opioids often includes a degree of constipation, which many patients won’t talk about, but which is a very real and daily struggle for those who are on high doses. This was the case for Dr. Hood’s patient with neuropathic pain, and the improvement in that symptom alone helped the patient’s willingness to stick with the transition away from an opioid-based regimen.

Keeping the patient at the center of chronic pain care, while still using available tools and knowledge to provide high-quality rational care, is an achievable goal, he said.

“We’ve proved we can make the change, and we’ve proved we can achieve adherence to the regulations,” he said. “Now, how do we further improve the care of the patient? The job’s not done.”

In development are adaptive tablet-based surveys that tailor themselves to patient responses, yielding more accurate information about patient characteristics and substance use profiles in a more user-friendly format.

Dr. Hood and his project collaborators hope to seek grant funding to disseminate the project beyond the borders of the state of Kentucky. The scalability of the QI process is a strength, he said.

In the process of developing the QI program, Dr. Hood and his collaborators met with key thought leaders in the pharmaceutical industry to build support for educational initiatives such as the ACP Quality Connect program.

As for the sometimes tainted history of the use of opioids for chronic nonmalignant pain? “That’s the past,” Dr. Hood declared. “We now have an opportunity to turn to the future. ... This needs to happen to alleviate the suffering of these patients.”

[email protected]

On Twitter @karioakes

HOLLYWOOD, FLA. – As more patients seek facial rejuvenation, they find themselves concerned with the mismatch between their refreshed facial appearance and the weathered, aged appearance of their hands. As more resurfacing treatments and fillers are being used beyond the face, options for hand rejuvenation expand.

Dr. Rania Agha, a dermatologist in private practice in Oakbrook Terrace, Ill., discussed a comprehensive approach to hand rejuvenation that addresses photoaging, vein prominence, and atrophy.

©Courtesy Wikimedia Commons/Marina Guimaraes/Creative Commons SA-2.0

Sun exposure is the largest extrinsic factor that affects the appearance of hands. Resultant changes can include actinic keratosis, seborrheic keratosis, dermatoheliosis, and solar lentigines.

Intrinsic factors that contribute to hand aging include loss of collagen and fatty tissue, resulting in epidermal and dermal atrophy and loss of elasticity. Reduced hydration follows as well. Though hyaluronic acid is less than 1% of dermal dry weight, the loss of glycosaminoglycan-proteoglycan complexes means dermal tissue is much less effective at binding and retaining water, said Dr. Agha.

The consequences are wrinkles and prominence of bones and tendons, large intermetacarpal space, and prominent reticular veins. For many of her patients, “there will be a discordance of the face and the hands,” Dr. Agha nnoted.

Grading scales are available to evaluate hand aging, better to compare apparent hand age before and after treatment. The Merz Hand Grading Scale is used commonly and ranges from 0-4, with increasing scores for more wrinkles, bone and tendon prominence, and photodamage.

Where protuberant veins are a concern, sclerotherapy of the veins on the dorsum of the hand will reduce their prominence. Sclerotherapy options for the hand, where typical vessel size ranges from 1mm to 6 mm, are 0.5% sodium tetradecyl sulfate or polidocanol 1.5% or 3%. Post-sclerotherapy compression is recommended. An option of foam sclerotherapy, mixing the sclerosing agent with carbon dioxide or room air, can have greater efficacy because it prolongs contact between the sclerosant and the vein wall, but it theoretically carries some of the systemic risks associated with air emboli.

Adverse events from sclerotherapy can include telangiectatic matting, or microscopic revascularization; Dr. Agha said the reported incidence neared 15% in one study. Some pain, edema, and ecchymosis may occur; rare radial nerve neuropraxia has been reported. Other rare complications can include ulceration and hyperpigmentation.

Many energy-based, mechanical, and chemical rejuvenation techniques that are used on the face can also be used on the hands, though intensity or duration of treatment has to be modulated in some cases.

Superficial chemical peels only penetrate the epidermis; examples include 70% glycolic acid, salicylic acid, 50% resorcinol, Jessner’s solution, and trichloroacetic acid 10%-20%. Trichloroacetic acid at 30% or greater is an example of a medium-depth peel that extends to the papillary dermis. Deep peels that extend to the midreticular dermis, such as phenol, are not for use on the hands.

Even with light to medium peels, though, caution should be used. Reported complications can include maceration, desquamation, and delayed healing; also, practitioners should take care not to create a line of demarcation between the hand and forearm. “Be conservative and perform these gradually and serially over several weeks,” said Dr. Agha.

A wide range of laser and light therapies can be useful. Q-switched lasers are useful for solar lentigines and other photodamage; intense pulsed light, photodynamic therapy, Nd:YAG lasers, fractionated lasers, and the 2940 erbium:YAG laser are all options, depending on patient preference and what options are available.

“With light therapy, start at lower fluences,” said Dr. Agha. “Limit the number of passes, and the density, if you’re using a fractionated laser.” Complications can include erythema, hypo- or hyper-pigmentation, scarring, textural changes, crusting, and prolonged bleeding. Prompt local wound care can help mitigate long-term effects if any complications are seen post-treatment.

“Strict sun protection, whether with physical block or sunscreen, is a must after hand resurfacing,” whether the procedures are chemical or energy-based, said Dr. Agha.

Another option for hand rejuvenation is to use dermal fillers to plump the dorsum of the hand and obscure some of the exposed hand anatomy. Autologous fat can be used, but more demand is being seen for calcium hydroxylapatite microsphere (Radiesse) fillers, said Dr. Agha. “It is highly biocompatible; therefore, allergic reactions are extremely rare,” she said.

Calcium hydroxylapatite was approved by the Food and Drug Administration for hand rejuvenation in 2015. The particle size of 25-50 micrometers stimulates collagen formation and fibrosis when injected, and the product’s effects can last up to 18 months. In clinical trials, the product produced significant improvement in hand appearance without serious side effects in followup through 1 year.

Dr. Agha reviewed recommended administration of calcium hydroxylapatite, which is meant to be injected in bolus fashion midway between the dorsal crease of the wrist and the metacarpophalangeal joints, in a zone between the second and the fifth metacarpal bones. Dr. Agha says that in her practice, she has the patient make a tight fist, and then she performs vigorous massage of the hand immediately to distribute the product.

This is followed by application of a soapy cleanser, icing, and hand elevation for the first 24 hours post-injection. It’s important that patients be advised to expect moderate edema for up to 10 days, and that they avoid vigorous manual activities in the first week, said Dr. Agha.

Results from clinical trials indicate that between 70% and 80% of patients can expect an improvement of at least one point on a clinician-rated hand appearance scale, while over 98% of patients consider their hands subjectively improved at 1 month after treatment, and 86% of patients still feeling their hands are improved at 1 year post-treatment with calcium hydroxylapatite.

Dr. Agha reported being on the advisory boards of Taro Pharmaceutical Industries and Aqua Pharmaceutical.

[email protected]

On Twitter @karioakes

HOLLYWOOD, FLA. – As more patients seek facial rejuvenation, they find themselves concerned with the mismatch between their refreshed facial appearance and the weathered, aged appearance of their hands. As more resurfacing treatments and fillers are being used beyond the face, options for hand rejuvenation expand.

Dr. Rania Agha, a dermatologist in private practice in Oakbrook Terrace, Ill., discussed a comprehensive approach to hand rejuvenation that addresses photoaging, vein prominence, and atrophy.

©Courtesy Wikimedia Commons/Marina Guimaraes/Creative Commons SA-2.0

Sun exposure is the largest extrinsic factor that affects the appearance of hands. Resultant changes can include actinic keratosis, seborrheic keratosis, dermatoheliosis, and solar lentigines.

Intrinsic factors that contribute to hand aging include loss of collagen and fatty tissue, resulting in epidermal and dermal atrophy and loss of elasticity. Reduced hydration follows as well. Though hyaluronic acid is less than 1% of dermal dry weight, the loss of glycosaminoglycan-proteoglycan complexes means dermal tissue is much less effective at binding and retaining water, said Dr. Agha.

The consequences are wrinkles and prominence of bones and tendons, large intermetacarpal space, and prominent reticular veins. For many of her patients, “there will be a discordance of the face and the hands,” Dr. Agha nnoted.

Grading scales are available to evaluate hand aging, better to compare apparent hand age before and after treatment. The Merz Hand Grading Scale is used commonly and ranges from 0-4, with increasing scores for more wrinkles, bone and tendon prominence, and photodamage.

Where protuberant veins are a concern, sclerotherapy of the veins on the dorsum of the hand will reduce their prominence. Sclerotherapy options for the hand, where typical vessel size ranges from 1mm to 6 mm, are 0.5% sodium tetradecyl sulfate or polidocanol 1.5% or 3%. Post-sclerotherapy compression is recommended. An option of foam sclerotherapy, mixing the sclerosing agent with carbon dioxide or room air, can have greater efficacy because it prolongs contact between the sclerosant and the vein wall, but it theoretically carries some of the systemic risks associated with air emboli.

Adverse events from sclerotherapy can include telangiectatic matting, or microscopic revascularization; Dr. Agha said the reported incidence neared 15% in one study. Some pain, edema, and ecchymosis may occur; rare radial nerve neuropraxia has been reported. Other rare complications can include ulceration and hyperpigmentation.

Many energy-based, mechanical, and chemical rejuvenation techniques that are used on the face can also be used on the hands, though intensity or duration of treatment has to be modulated in some cases.

Superficial chemical peels only penetrate the epidermis; examples include 70% glycolic acid, salicylic acid, 50% resorcinol, Jessner’s solution, and trichloroacetic acid 10%-20%. Trichloroacetic acid at 30% or greater is an example of a medium-depth peel that extends to the papillary dermis. Deep peels that extend to the midreticular dermis, such as phenol, are not for use on the hands.

Even with light to medium peels, though, caution should be used. Reported complications can include maceration, desquamation, and delayed healing; also, practitioners should take care not to create a line of demarcation between the hand and forearm. “Be conservative and perform these gradually and serially over several weeks,” said Dr. Agha.

A wide range of laser and light therapies can be useful. Q-switched lasers are useful for solar lentigines and other photodamage; intense pulsed light, photodynamic therapy, Nd:YAG lasers, fractionated lasers, and the 2940 erbium:YAG laser are all options, depending on patient preference and what options are available.

“With light therapy, start at lower fluences,” said Dr. Agha. “Limit the number of passes, and the density, if you’re using a fractionated laser.” Complications can include erythema, hypo- or hyper-pigmentation, scarring, textural changes, crusting, and prolonged bleeding. Prompt local wound care can help mitigate long-term effects if any complications are seen post-treatment.

“Strict sun protection, whether with physical block or sunscreen, is a must after hand resurfacing,” whether the procedures are chemical or energy-based, said Dr. Agha.

Another option for hand rejuvenation is to use dermal fillers to plump the dorsum of the hand and obscure some of the exposed hand anatomy. Autologous fat can be used, but more demand is being seen for calcium hydroxylapatite microsphere (Radiesse) fillers, said Dr. Agha. “It is highly biocompatible; therefore, allergic reactions are extremely rare,” she said.

Calcium hydroxylapatite was approved by the Food and Drug Administration for hand rejuvenation in 2015. The particle size of 25-50 micrometers stimulates collagen formation and fibrosis when injected, and the product’s effects can last up to 18 months. In clinical trials, the product produced significant improvement in hand appearance without serious side effects in followup through 1 year.

Dr. Agha reviewed recommended administration of calcium hydroxylapatite, which is meant to be injected in bolus fashion midway between the dorsal crease of the wrist and the metacarpophalangeal joints, in a zone between the second and the fifth metacarpal bones. Dr. Agha says that in her practice, she has the patient make a tight fist, and then she performs vigorous massage of the hand immediately to distribute the product.

This is followed by application of a soapy cleanser, icing, and hand elevation for the first 24 hours post-injection. It’s important that patients be advised to expect moderate edema for up to 10 days, and that they avoid vigorous manual activities in the first week, said Dr. Agha.

Results from clinical trials indicate that between 70% and 80% of patients can expect an improvement of at least one point on a clinician-rated hand appearance scale, while over 98% of patients consider their hands subjectively improved at 1 month after treatment, and 86% of patients still feeling their hands are improved at 1 year post-treatment with calcium hydroxylapatite.

Dr. Agha reported being on the advisory boards of Taro Pharmaceutical Industries and Aqua Pharmaceutical.

[email protected]

On Twitter @karioakes

HOLLYWOOD, FLA. – As more patients seek facial rejuvenation, they find themselves concerned with the mismatch between their refreshed facial appearance and the weathered, aged appearance of their hands. As more resurfacing treatments and fillers are being used beyond the face, options for hand rejuvenation expand.

Dr. Rania Agha, a dermatologist in private practice in Oakbrook Terrace, Ill., discussed a comprehensive approach to hand rejuvenation that addresses photoaging, vein prominence, and atrophy.

©Courtesy Wikimedia Commons/Marina Guimaraes/Creative Commons SA-2.0

Sun exposure is the largest extrinsic factor that affects the appearance of hands. Resultant changes can include actinic keratosis, seborrheic keratosis, dermatoheliosis, and solar lentigines.

Intrinsic factors that contribute to hand aging include loss of collagen and fatty tissue, resulting in epidermal and dermal atrophy and loss of elasticity. Reduced hydration follows as well. Though hyaluronic acid is less than 1% of dermal dry weight, the loss of glycosaminoglycan-proteoglycan complexes means dermal tissue is much less effective at binding and retaining water, said Dr. Agha.

The consequences are wrinkles and prominence of bones and tendons, large intermetacarpal space, and prominent reticular veins. For many of her patients, “there will be a discordance of the face and the hands,” Dr. Agha nnoted.

Grading scales are available to evaluate hand aging, better to compare apparent hand age before and after treatment. The Merz Hand Grading Scale is used commonly and ranges from 0-4, with increasing scores for more wrinkles, bone and tendon prominence, and photodamage.

Where protuberant veins are a concern, sclerotherapy of the veins on the dorsum of the hand will reduce their prominence. Sclerotherapy options for the hand, where typical vessel size ranges from 1mm to 6 mm, are 0.5% sodium tetradecyl sulfate or polidocanol 1.5% or 3%. Post-sclerotherapy compression is recommended. An option of foam sclerotherapy, mixing the sclerosing agent with carbon dioxide or room air, can have greater efficacy because it prolongs contact between the sclerosant and the vein wall, but it theoretically carries some of the systemic risks associated with air emboli.

Adverse events from sclerotherapy can include telangiectatic matting, or microscopic revascularization; Dr. Agha said the reported incidence neared 15% in one study. Some pain, edema, and ecchymosis may occur; rare radial nerve neuropraxia has been reported. Other rare complications can include ulceration and hyperpigmentation.

Many energy-based, mechanical, and chemical rejuvenation techniques that are used on the face can also be used on the hands, though intensity or duration of treatment has to be modulated in some cases.

Superficial chemical peels only penetrate the epidermis; examples include 70% glycolic acid, salicylic acid, 50% resorcinol, Jessner’s solution, and trichloroacetic acid 10%-20%. Trichloroacetic acid at 30% or greater is an example of a medium-depth peel that extends to the papillary dermis. Deep peels that extend to the midreticular dermis, such as phenol, are not for use on the hands.

Even with light to medium peels, though, caution should be used. Reported complications can include maceration, desquamation, and delayed healing; also, practitioners should take care not to create a line of demarcation between the hand and forearm. “Be conservative and perform these gradually and serially over several weeks,” said Dr. Agha.

A wide range of laser and light therapies can be useful. Q-switched lasers are useful for solar lentigines and other photodamage; intense pulsed light, photodynamic therapy, Nd:YAG lasers, fractionated lasers, and the 2940 erbium:YAG laser are all options, depending on patient preference and what options are available.

“With light therapy, start at lower fluences,” said Dr. Agha. “Limit the number of passes, and the density, if you’re using a fractionated laser.” Complications can include erythema, hypo- or hyper-pigmentation, scarring, textural changes, crusting, and prolonged bleeding. Prompt local wound care can help mitigate long-term effects if any complications are seen post-treatment.

“Strict sun protection, whether with physical block or sunscreen, is a must after hand resurfacing,” whether the procedures are chemical or energy-based, said Dr. Agha.

Another option for hand rejuvenation is to use dermal fillers to plump the dorsum of the hand and obscure some of the exposed hand anatomy. Autologous fat can be used, but more demand is being seen for calcium hydroxylapatite microsphere (Radiesse) fillers, said Dr. Agha. “It is highly biocompatible; therefore, allergic reactions are extremely rare,” she said.

Calcium hydroxylapatite was approved by the Food and Drug Administration for hand rejuvenation in 2015. The particle size of 25-50 micrometers stimulates collagen formation and fibrosis when injected, and the product’s effects can last up to 18 months. In clinical trials, the product produced significant improvement in hand appearance without serious side effects in followup through 1 year.

Dr. Agha reviewed recommended administration of calcium hydroxylapatite, which is meant to be injected in bolus fashion midway between the dorsal crease of the wrist and the metacarpophalangeal joints, in a zone between the second and the fifth metacarpal bones. Dr. Agha says that in her practice, she has the patient make a tight fist, and then she performs vigorous massage of the hand immediately to distribute the product.

This is followed by application of a soapy cleanser, icing, and hand elevation for the first 24 hours post-injection. It’s important that patients be advised to expect moderate edema for up to 10 days, and that they avoid vigorous manual activities in the first week, said Dr. Agha.

Results from clinical trials indicate that between 70% and 80% of patients can expect an improvement of at least one point on a clinician-rated hand appearance scale, while over 98% of patients consider their hands subjectively improved at 1 month after treatment, and 86% of patients still feeling their hands are improved at 1 year post-treatment with calcium hydroxylapatite.

Dr. Agha reported being on the advisory boards of Taro Pharmaceutical Industries and Aqua Pharmaceutical.

[email protected]

On Twitter @karioakes

A dual point-of-care test for syphilis and HIV performed well in a field trial, giving real-world data about a rapid and effective testing mechanism for two serious sexually transmitted infections (STIs).

A recent study detailing field testing results showed that the dual test was 100% specific for both syphilis and HIV, with sensitivity of 93.8% for the HIV antibody component and 81% for the Treponema pallidum antibody component.

©jarun011/Thinkstock

Syphilis and HIV infections present a particular threat to certain high-risk groups, including sex workers, migrants, men who have sex with men, and pregnant women. “Coinfection is common, and syphilis may increase the risk of HIV acquisition and transmission,” wrote Claire Bristow, Ph.D., and her coauthors (Sex Trans Dis. 2015 Jan 16;43[1]:57-60. doi:10.1097/OLQ.0000000000000387). “Implementing an accurate, simple, and affordable dual screening strategy for HIV and syphilis could improve case finding and reduce time to treatment.”

Dr. Bristow, a postdoctoral fellow at the University of California, San Diego, and her colleagues shared findings from a study conducted in a Peruvian port town near Lima, targeting populations at high risk for HIV and syphilis. Outreach sites included transgender sex worker housing and a beauty salon. The participants, all adults, included sex workers, men who have sex with men, and transgender women.

The study compared the results from dual qualitative rapid immunoassays for serum antibodies to T. pallidum and HIV 1/2 (manufactured by Medmira Inc., Halifax, N.S., and dubbed the “Multiplo Rapid TP/HIV Antibody Test”) to reference serum laboratory testing of the same venipuncture sample. For T. pallidum, a particle agglutination test and rapid plasma reagin tests were performed. The HIV reference test was a fourth-generation enzyme immunoassay; all positive specimens also underwent a confirmatory Western blot test for HIV.

Of the 205 tests conducted, 174 were judged to be valid, meaning that the reagent control line for each test component was visible and complete. One further Multiplo test had an indeterminate (and therefore invalid) result for only the syphilis component of the test. Altogether, the Multiplo test yielded 15 positive results for HIV and 17 positive results for syphilis.

Concordance between the experimental Multiplo test and the reference HIV test was 0.97 calculated using Cohen kappa coefficient; one negative Multiplo result was positive using the reference test. The less sensitive Multiplo syphilis test achieved concordance of 0.88 with the reference test, with four samples found negative for syphilis with Multiplo testing returning a positive result on the reference assay.

Two trained staff members independently interpreted all test results, with 100% concordance. Dr. Bristow and her colleagues noted that though testing conditions were realistic overall, test results were interpreted by highly trained, highly motivated study investigators. Under investigation are optical readers that could give more reliable and easily interpreted results for the dual test, to help eliminate the possibility of haphazard interpretation.

In discussion, Dr. Bristow and her collaborators also noted the relatively high proportion of Multiplo tests that had invalid control lines, recommending improvement in control testing.

Citing the need for an easily-administered and easily-interpreted test for multiple STIs, Dr. Bristow and her colleagues urged more study and fine-tuning of this promising test. “Further research is warranted to determine how a dual test would perform and can be integrated into the flow of a busy sexual health clinic.”

The authors reported no conflicts of interest. The National Institute of Allergy and Infectious Diseases, National Institutes of Health, funded the study. All test materials were donated by Medmira Inc.

[email protected]

On Twitter @karioakes

A dual point-of-care test for syphilis and HIV performed well in a field trial, giving real-world data about a rapid and effective testing mechanism for two serious sexually transmitted infections (STIs).

A recent study detailing field testing results showed that the dual test was 100% specific for both syphilis and HIV, with sensitivity of 93.8% for the HIV antibody component and 81% for the Treponema pallidum antibody component.

©jarun011/Thinkstock

Syphilis and HIV infections present a particular threat to certain high-risk groups, including sex workers, migrants, men who have sex with men, and pregnant women. “Coinfection is common, and syphilis may increase the risk of HIV acquisition and transmission,” wrote Claire Bristow, Ph.D., and her coauthors (Sex Trans Dis. 2015 Jan 16;43[1]:57-60. doi:10.1097/OLQ.0000000000000387). “Implementing an accurate, simple, and affordable dual screening strategy for HIV and syphilis could improve case finding and reduce time to treatment.”

Dr. Bristow, a postdoctoral fellow at the University of California, San Diego, and her colleagues shared findings from a study conducted in a Peruvian port town near Lima, targeting populations at high risk for HIV and syphilis. Outreach sites included transgender sex worker housing and a beauty salon. The participants, all adults, included sex workers, men who have sex with men, and transgender women.

The study compared the results from dual qualitative rapid immunoassays for serum antibodies to T. pallidum and HIV 1/2 (manufactured by Medmira Inc., Halifax, N.S., and dubbed the “Multiplo Rapid TP/HIV Antibody Test”) to reference serum laboratory testing of the same venipuncture sample. For T. pallidum, a particle agglutination test and rapid plasma reagin tests were performed. The HIV reference test was a fourth-generation enzyme immunoassay; all positive specimens also underwent a confirmatory Western blot test for HIV.

Of the 205 tests conducted, 174 were judged to be valid, meaning that the reagent control line for each test component was visible and complete. One further Multiplo test had an indeterminate (and therefore invalid) result for only the syphilis component of the test. Altogether, the Multiplo test yielded 15 positive results for HIV and 17 positive results for syphilis.

Concordance between the experimental Multiplo test and the reference HIV test was 0.97 calculated using Cohen kappa coefficient; one negative Multiplo result was positive using the reference test. The less sensitive Multiplo syphilis test achieved concordance of 0.88 with the reference test, with four samples found negative for syphilis with Multiplo testing returning a positive result on the reference assay.

Two trained staff members independently interpreted all test results, with 100% concordance. Dr. Bristow and her colleagues noted that though testing conditions were realistic overall, test results were interpreted by highly trained, highly motivated study investigators. Under investigation are optical readers that could give more reliable and easily interpreted results for the dual test, to help eliminate the possibility of haphazard interpretation.

In discussion, Dr. Bristow and her collaborators also noted the relatively high proportion of Multiplo tests that had invalid control lines, recommending improvement in control testing.

Citing the need for an easily-administered and easily-interpreted test for multiple STIs, Dr. Bristow and her colleagues urged more study and fine-tuning of this promising test. “Further research is warranted to determine how a dual test would perform and can be integrated into the flow of a busy sexual health clinic.”

The authors reported no conflicts of interest. The National Institute of Allergy and Infectious Diseases, National Institutes of Health, funded the study. All test materials were donated by Medmira Inc.

[email protected]

On Twitter @karioakes

A dual point-of-care test for syphilis and HIV performed well in a field trial, giving real-world data about a rapid and effective testing mechanism for two serious sexually transmitted infections (STIs).

A recent study detailing field testing results showed that the dual test was 100% specific for both syphilis and HIV, with sensitivity of 93.8% for the HIV antibody component and 81% for the Treponema pallidum antibody component.

©jarun011/Thinkstock

Syphilis and HIV infections present a particular threat to certain high-risk groups, including sex workers, migrants, men who have sex with men, and pregnant women. “Coinfection is common, and syphilis may increase the risk of HIV acquisition and transmission,” wrote Claire Bristow, Ph.D., and her coauthors (Sex Trans Dis. 2015 Jan 16;43[1]:57-60. doi:10.1097/OLQ.0000000000000387). “Implementing an accurate, simple, and affordable dual screening strategy for HIV and syphilis could improve case finding and reduce time to treatment.”

Dr. Bristow, a postdoctoral fellow at the University of California, San Diego, and her colleagues shared findings from a study conducted in a Peruvian port town near Lima, targeting populations at high risk for HIV and syphilis. Outreach sites included transgender sex worker housing and a beauty salon. The participants, all adults, included sex workers, men who have sex with men, and transgender women.

The study compared the results from dual qualitative rapid immunoassays for serum antibodies to T. pallidum and HIV 1/2 (manufactured by Medmira Inc., Halifax, N.S., and dubbed the “Multiplo Rapid TP/HIV Antibody Test”) to reference serum laboratory testing of the same venipuncture sample. For T. pallidum, a particle agglutination test and rapid plasma reagin tests were performed. The HIV reference test was a fourth-generation enzyme immunoassay; all positive specimens also underwent a confirmatory Western blot test for HIV.

Of the 205 tests conducted, 174 were judged to be valid, meaning that the reagent control line for each test component was visible and complete. One further Multiplo test had an indeterminate (and therefore invalid) result for only the syphilis component of the test. Altogether, the Multiplo test yielded 15 positive results for HIV and 17 positive results for syphilis.

Concordance between the experimental Multiplo test and the reference HIV test was 0.97 calculated using Cohen kappa coefficient; one negative Multiplo result was positive using the reference test. The less sensitive Multiplo syphilis test achieved concordance of 0.88 with the reference test, with four samples found negative for syphilis with Multiplo testing returning a positive result on the reference assay.

Two trained staff members independently interpreted all test results, with 100% concordance. Dr. Bristow and her colleagues noted that though testing conditions were realistic overall, test results were interpreted by highly trained, highly motivated study investigators. Under investigation are optical readers that could give more reliable and easily interpreted results for the dual test, to help eliminate the possibility of haphazard interpretation.

In discussion, Dr. Bristow and her collaborators also noted the relatively high proportion of Multiplo tests that had invalid control lines, recommending improvement in control testing.

Citing the need for an easily-administered and easily-interpreted test for multiple STIs, Dr. Bristow and her colleagues urged more study and fine-tuning of this promising test. “Further research is warranted to determine how a dual test would perform and can be integrated into the flow of a busy sexual health clinic.”

The authors reported no conflicts of interest. The National Institute of Allergy and Infectious Diseases, National Institutes of Health, funded the study. All test materials were donated by Medmira Inc.

[email protected]

On Twitter @karioakes

The Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee voted 12-7 on Jan. 12 to approve a subdermal depot formulation of buprenorphine, despite some reservations about who should be using – and implanting – the drug. To be marketed as Probuphine by Braeburn Pharmaceuticals, the long-lasting version of the partial mu opioid receptor agonist is meant for people with opioid addiction who have been stable on 8 mg/day or fewer of transmucosal buprenorphine therapy.

The pivotal phase III clinical study upon which the submission was based, PRO-814, enrolled subjects stable on 8 mg or less of transmucosal buprenorphine for at least 90 days. The double-blind, double-dummy trial randomized 87 patients to receive Probuphine and placebo transmucosal buprenorphine, and 90 patients to receive sham implants and active transmucosal buprenorphine. Participants received scheduled and random urine drug testing, and the study kept track of requirements for additional transmucosal buprenorphine.

Participants could have 2 months during the study period with a positive urine drug screen and/or self-reported illicit opioid use within the study period and still be considered responders; though data were tracked, there was no cap on additional buprenorphine requirements. Braeburn’s analysis of a modified intention-to-treat population showed that the Probuphine group met the primary endpoint of 20% noninferiority over the standard of care arm by a statistically significant margin (proportion difference, 0.088; 95% confidence interval, 0.009-0.167; P = .034).

The approval vote came after a long day of discussion that circled around three main areas of concern for the committee’s panelists. First, committee members struggled with the study’s definition of the eligible population, which consisted of people who had been on buprenorphine for at least 24 lifetime-weeks, with 3 months of negative urine drug testing before enrollment. Panelists expressed concern that a patient who was not fully stabilized on buprenorphine might be at grave risk of relapse during the week or so after implantation, when the drug is reaching steady-state.

The identification of eligible subjects informed another aspect of the study, the allowance of additional “rescue” transmucosal buprenorphine in both study arms. One public health aim of developing depot formulations of substances with abuse and diversion potential is to avoid having pills in the home, since these can be ingested by young children or be diverted. If people on Probuphine might need occasional rescue medication, this public health aim might be largely unmet. Committee members generally felt that some rescue medication soon after implantation would be acceptable but would consider people with ongoing rescue needs nonresponders to Probuphine.

Another set of concerns had to do with data analysis. Three subjects were very quickly lost to follow-up, and those patients were not included in the study sponsor’s analysis of their data. This methodology was roundly criticized by the study panel. However, when the FDA’s sensitivity analyses included these three missing patients as treatment failures, the study still met its predetermined 20% noninferiority endpoint.

Another point of contention within the data analysis was the sponsor’s imputation of a mix of positive and negative results to missing or incomplete urine toxicology screenings. Several clinicians in the room noted that they always assume a missing test is a positive test when working in addiction medicine. However, when the FDA imputed positive results to all the missing or urine toxicology data, Probuphine again met its primary noninferiority endpoint.

Some presenters felt that the sponsor’s inclusion of individuals with up to two positive urine drug tests during the 6-month study period was too lenient. Dr. Rachel Skeete, the FDA’s clinical reviewer, said, “We think that the analysis in which any positive months represent a treatment failure comes closer.”

However, Dr. Dawn F. Ionescu of the Depression Clinical and Research Program, Massachusetts General Hospital, Boston, argued against an expectation of perfection in this difficult population, pointing out that “If you think about other chronic conditions, our patients don’t come in with perfect blood pressure or perfect glucose.”

Finally, there were concerns about the implantation and removal of the subdermal implants. Many buprenorphine prescribers are not experienced proceduralists, several panelists noted. The recommended removal procedure requires suturing, a skill not kept current by all prescribers. Only four sites, two on each arm, are currently identified by the study sponsor. Though Braeburn plans to do pharmacokinetic studies to assess whether implantation sites can be reused, that’s not currently known. For some panelists, this was a big deal. Dr. Margaret Kotz, professor of psychiatry and anesthesiology at Case Western Reserve University, Cleveland, explaining her “no” vote, said, “What do you do after 2 years? That still is a huge question for me.”

This was Probuphine’s second bid for approval; the first, brought forward in March 2013 by Titan Pharmaceuticals, was for approval for individuals who had been taking up to 16 mg of buprenorphine daily. However, pharmacokinetic data indicated that the four 26mm subdermally implanted rods, each containing 80 mg of buprenorphine in a depot formulation, would yield a steady-state plasma concentration equivalent to a 12 mg/day transmucosal dose, over a 6-month period.

A risk evaluation and mitigation strategy (REMS) for both prescribers and those inserting and removing Probuphine will be required.

The agency usually follows the recommendations of its advisory panels, but the recommendations are not binding.

[email protected]

On Twitter @karioakes

The Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee voted 12-7 on Jan. 12 to approve a subdermal depot formulation of buprenorphine, despite some reservations about who should be using – and implanting – the drug. To be marketed as Probuphine by Braeburn Pharmaceuticals, the long-lasting version of the partial mu opioid receptor agonist is meant for people with opioid addiction who have been stable on 8 mg/day or fewer of transmucosal buprenorphine therapy.

The pivotal phase III clinical study upon which the submission was based, PRO-814, enrolled subjects stable on 8 mg or less of transmucosal buprenorphine for at least 90 days. The double-blind, double-dummy trial randomized 87 patients to receive Probuphine and placebo transmucosal buprenorphine, and 90 patients to receive sham implants and active transmucosal buprenorphine. Participants received scheduled and random urine drug testing, and the study kept track of requirements for additional transmucosal buprenorphine.

Participants could have 2 months during the study period with a positive urine drug screen and/or self-reported illicit opioid use within the study period and still be considered responders; though data were tracked, there was no cap on additional buprenorphine requirements. Braeburn’s analysis of a modified intention-to-treat population showed that the Probuphine group met the primary endpoint of 20% noninferiority over the standard of care arm by a statistically significant margin (proportion difference, 0.088; 95% confidence interval, 0.009-0.167; P = .034).

The approval vote came after a long day of discussion that circled around three main areas of concern for the committee’s panelists. First, committee members struggled with the study’s definition of the eligible population, which consisted of people who had been on buprenorphine for at least 24 lifetime-weeks, with 3 months of negative urine drug testing before enrollment. Panelists expressed concern that a patient who was not fully stabilized on buprenorphine might be at grave risk of relapse during the week or so after implantation, when the drug is reaching steady-state.

The identification of eligible subjects informed another aspect of the study, the allowance of additional “rescue” transmucosal buprenorphine in both study arms. One public health aim of developing depot formulations of substances with abuse and diversion potential is to avoid having pills in the home, since these can be ingested by young children or be diverted. If people on Probuphine might need occasional rescue medication, this public health aim might be largely unmet. Committee members generally felt that some rescue medication soon after implantation would be acceptable but would consider people with ongoing rescue needs nonresponders to Probuphine.

Another set of concerns had to do with data analysis. Three subjects were very quickly lost to follow-up, and those patients were not included in the study sponsor’s analysis of their data. This methodology was roundly criticized by the study panel. However, when the FDA’s sensitivity analyses included these three missing patients as treatment failures, the study still met its predetermined 20% noninferiority endpoint.

Another point of contention within the data analysis was the sponsor’s imputation of a mix of positive and negative results to missing or incomplete urine toxicology screenings. Several clinicians in the room noted that they always assume a missing test is a positive test when working in addiction medicine. However, when the FDA imputed positive results to all the missing or urine toxicology data, Probuphine again met its primary noninferiority endpoint.

Some presenters felt that the sponsor’s inclusion of individuals with up to two positive urine drug tests during the 6-month study period was too lenient. Dr. Rachel Skeete, the FDA’s clinical reviewer, said, “We think that the analysis in which any positive months represent a treatment failure comes closer.”

However, Dr. Dawn F. Ionescu of the Depression Clinical and Research Program, Massachusetts General Hospital, Boston, argued against an expectation of perfection in this difficult population, pointing out that “If you think about other chronic conditions, our patients don’t come in with perfect blood pressure or perfect glucose.”

Finally, there were concerns about the implantation and removal of the subdermal implants. Many buprenorphine prescribers are not experienced proceduralists, several panelists noted. The recommended removal procedure requires suturing, a skill not kept current by all prescribers. Only four sites, two on each arm, are currently identified by the study sponsor. Though Braeburn plans to do pharmacokinetic studies to assess whether implantation sites can be reused, that’s not currently known. For some panelists, this was a big deal. Dr. Margaret Kotz, professor of psychiatry and anesthesiology at Case Western Reserve University, Cleveland, explaining her “no” vote, said, “What do you do after 2 years? That still is a huge question for me.”

This was Probuphine’s second bid for approval; the first, brought forward in March 2013 by Titan Pharmaceuticals, was for approval for individuals who had been taking up to 16 mg of buprenorphine daily. However, pharmacokinetic data indicated that the four 26mm subdermally implanted rods, each containing 80 mg of buprenorphine in a depot formulation, would yield a steady-state plasma concentration equivalent to a 12 mg/day transmucosal dose, over a 6-month period.

A risk evaluation and mitigation strategy (REMS) for both prescribers and those inserting and removing Probuphine will be required.

The agency usually follows the recommendations of its advisory panels, but the recommendations are not binding.

[email protected]

On Twitter @karioakes

The Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee voted 12-7 on Jan. 12 to approve a subdermal depot formulation of buprenorphine, despite some reservations about who should be using – and implanting – the drug. To be marketed as Probuphine by Braeburn Pharmaceuticals, the long-lasting version of the partial mu opioid receptor agonist is meant for people with opioid addiction who have been stable on 8 mg/day or fewer of transmucosal buprenorphine therapy.

The pivotal phase III clinical study upon which the submission was based, PRO-814, enrolled subjects stable on 8 mg or less of transmucosal buprenorphine for at least 90 days. The double-blind, double-dummy trial randomized 87 patients to receive Probuphine and placebo transmucosal buprenorphine, and 90 patients to receive sham implants and active transmucosal buprenorphine. Participants received scheduled and random urine drug testing, and the study kept track of requirements for additional transmucosal buprenorphine.

Participants could have 2 months during the study period with a positive urine drug screen and/or self-reported illicit opioid use within the study period and still be considered responders; though data were tracked, there was no cap on additional buprenorphine requirements. Braeburn’s analysis of a modified intention-to-treat population showed that the Probuphine group met the primary endpoint of 20% noninferiority over the standard of care arm by a statistically significant margin (proportion difference, 0.088; 95% confidence interval, 0.009-0.167; P = .034).

The approval vote came after a long day of discussion that circled around three main areas of concern for the committee’s panelists. First, committee members struggled with the study’s definition of the eligible population, which consisted of people who had been on buprenorphine for at least 24 lifetime-weeks, with 3 months of negative urine drug testing before enrollment. Panelists expressed concern that a patient who was not fully stabilized on buprenorphine might be at grave risk of relapse during the week or so after implantation, when the drug is reaching steady-state.

The identification of eligible subjects informed another aspect of the study, the allowance of additional “rescue” transmucosal buprenorphine in both study arms. One public health aim of developing depot formulations of substances with abuse and diversion potential is to avoid having pills in the home, since these can be ingested by young children or be diverted. If people on Probuphine might need occasional rescue medication, this public health aim might be largely unmet. Committee members generally felt that some rescue medication soon after implantation would be acceptable but would consider people with ongoing rescue needs nonresponders to Probuphine.

Another set of concerns had to do with data analysis. Three subjects were very quickly lost to follow-up, and those patients were not included in the study sponsor’s analysis of their data. This methodology was roundly criticized by the study panel. However, when the FDA’s sensitivity analyses included these three missing patients as treatment failures, the study still met its predetermined 20% noninferiority endpoint.

Another point of contention within the data analysis was the sponsor’s imputation of a mix of positive and negative results to missing or incomplete urine toxicology screenings. Several clinicians in the room noted that they always assume a missing test is a positive test when working in addiction medicine. However, when the FDA imputed positive results to all the missing or urine toxicology data, Probuphine again met its primary noninferiority endpoint.

Some presenters felt that the sponsor’s inclusion of individuals with up to two positive urine drug tests during the 6-month study period was too lenient. Dr. Rachel Skeete, the FDA’s clinical reviewer, said, “We think that the analysis in which any positive months represent a treatment failure comes closer.”

However, Dr. Dawn F. Ionescu of the Depression Clinical and Research Program, Massachusetts General Hospital, Boston, argued against an expectation of perfection in this difficult population, pointing out that “If you think about other chronic conditions, our patients don’t come in with perfect blood pressure or perfect glucose.”

Finally, there were concerns about the implantation and removal of the subdermal implants. Many buprenorphine prescribers are not experienced proceduralists, several panelists noted. The recommended removal procedure requires suturing, a skill not kept current by all prescribers. Only four sites, two on each arm, are currently identified by the study sponsor. Though Braeburn plans to do pharmacokinetic studies to assess whether implantation sites can be reused, that’s not currently known. For some panelists, this was a big deal. Dr. Margaret Kotz, professor of psychiatry and anesthesiology at Case Western Reserve University, Cleveland, explaining her “no” vote, said, “What do you do after 2 years? That still is a huge question for me.”

This was Probuphine’s second bid for approval; the first, brought forward in March 2013 by Titan Pharmaceuticals, was for approval for individuals who had been taking up to 16 mg of buprenorphine daily. However, pharmacokinetic data indicated that the four 26mm subdermally implanted rods, each containing 80 mg of buprenorphine in a depot formulation, would yield a steady-state plasma concentration equivalent to a 12 mg/day transmucosal dose, over a 6-month period.

A risk evaluation and mitigation strategy (REMS) for both prescribers and those inserting and removing Probuphine will be required.

The agency usually follows the recommendations of its advisory panels, but the recommendations are not binding.

[email protected]

On Twitter @karioakes

Hepatitis C could be reduced by 90% or more in the United States by the year 2040 with the use of direct-acting antivirals, near-universal screening, and enhanced treatment capacity, according to a study in Clinical Infectious Diseases.

A research team led by Jeffrey Townsend, Ph.D., of Yale School of Public Health, New Haven, Conn., said that new direct-acting antivirals (DAAs) alone could reduce the prevalence of hepatitis C virus (HCV) by 80% by the year 2040. When near-universal screening and enhanced treatment capacity are added to the equation, HCV could be eliminated in the United States, though cost and reimbursement issues may impede implementation.

©Martynasfoto/thinkstockphotos.com

“The key finding is that a fourfold increase to the number of patients treated each year could virtually eliminate HCV from the noninjecting population within a decade,” said Dr. Townsend, senior author of the study, in a statement accompanying the study [Clin Infect Dis. 2015. doi: 10.1093/cid/civ894].

First author David Durham, Ph.D., also of the Yale School of Public Health, and his collaborators analyzed currently available data and constructed a sophisticated model to generate projections of how future DAA treatment will change HCV prevalence. Dr. Durham and his colleagues also built models to account for varying levels of screening in the general population and for people who inject drugs (PWIDs).

More than 5 million people with chronic hepatitis C infection are thought to live in the United States, and just about 100,000 of those currently receive treatment each year. The treatment burden and relatively low cure rate of interferon-based therapies have historically been significant impediments for many patients. New DAAs promise a sustained virologic response (SVR) in up to 95% of patients with a well-tolerated, once-daily, one-pill several-week regimen.

Without enhanced screening or treatment rates, the model predicted an 80% decline in U.S. HCV prevalence by the year 2040. The 80% benchmark would be reached by the year 2025 if the annual treatment rate increased to 400,000, with 256,315 fewer HCV-related deaths through 2040. Just doubling the treatment rate to 200,000 patients per year would result in an 80% decrease in HCV prevalence by 2031, with 143,055 fewer deaths by 2040.

However, “more than half of those with chronic HCV are unaware of their status, including up to two-thirds of people who inject drugs,” wrote Dr. Durham and his coauthors. Therefore, enhanced HCV screening, especially among PWIDs, could provide a significant further reduction in morbidity and mortality from HCV.

Targeted screening of PWIDs to achieve a 20% screening rate (compared with the current 4.1%), combined with a treatment rate of at least 30%, would yield a 90% reduction of prevalence in HCV by 2040. Universal screening, combined with a treatment rate of at least 20%, would achieve a 90% reduction in the incidence of new infections by 2040, according to the model.

The drop in prevalence in the models took into account not only an increased SVR rate, but also the reduced transmission rate when more persons with HCV achieve an SVR. This dynamic transmission analysis “captures the impact of treatment on both chronic disease and transmission dynamics, distinguishes screening and treatment as separate but related public health objectives, and accounts for underreporting … of national HCV prevalence,” according to Dr. Durham and his coauthors.

Morbidity and mortality were accounted for by projecting the number of HCV patients in each treatment and screening condition who would spontaneously clear disease, become chronically infected, develop increasing levels of liver disease and cirrhosis, require transplant, become reinfected, or die.

As always, real world considerations temper what’s achievable. For DAAs, a chief factor is the cost of the regimens, which currently hovers around $90,000. “The improvement of health outcomes expected from greater acceptance might be tempered by the high costs of treatment and by limited insurance coverage and willingness to treat PWIDs,” Dr. Durham and his coauthors wrote.

Study limitations included some “simplifying assumptions” in the modeling, which did not account for the varying incidence of fibrosis and transmissibility among different HCV genotypes. Still, wrote Dr. Durham and his collaborators, “our analysis provides a forecast for the potential impact of DAAs in reducing HCV-associated liver disease, demonstrating that achievable expansion of HCV treatment at current screening rates can substantially reduce morbidity and mortality.”

The study was funded by the Notsew Orm Sands Foundation and Merck. Dr. Durham, Dr. Galvani, and Dr. Townsend have consulted for and received research funding from Sanofi Pasteur and Merck. Dr. Elbasha is employed by Merck and holds stock and stock options in the company. The other authors reported no conflicts of interest.

AGA Resource

Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

[email protected]

On Twitter @karioakes

Hepatitis C could be reduced by 90% or more in the United States by the year 2040 with the use of direct-acting antivirals, near-universal screening, and enhanced treatment capacity, according to a study in Clinical Infectious Diseases.

A research team led by Jeffrey Townsend, Ph.D., of Yale School of Public Health, New Haven, Conn., said that new direct-acting antivirals (DAAs) alone could reduce the prevalence of hepatitis C virus (HCV) by 80% by the year 2040. When near-universal screening and enhanced treatment capacity are added to the equation, HCV could be eliminated in the United States, though cost and reimbursement issues may impede implementation.

©Martynasfoto/thinkstockphotos.com

“The key finding is that a fourfold increase to the number of patients treated each year could virtually eliminate HCV from the noninjecting population within a decade,” said Dr. Townsend, senior author of the study, in a statement accompanying the study [Clin Infect Dis. 2015. doi: 10.1093/cid/civ894].

First author David Durham, Ph.D., also of the Yale School of Public Health, and his collaborators analyzed currently available data and constructed a sophisticated model to generate projections of how future DAA treatment will change HCV prevalence. Dr. Durham and his colleagues also built models to account for varying levels of screening in the general population and for people who inject drugs (PWIDs).

More than 5 million people with chronic hepatitis C infection are thought to live in the United States, and just about 100,000 of those currently receive treatment each year. The treatment burden and relatively low cure rate of interferon-based therapies have historically been significant impediments for many patients. New DAAs promise a sustained virologic response (SVR) in up to 95% of patients with a well-tolerated, once-daily, one-pill several-week regimen.

Without enhanced screening or treatment rates, the model predicted an 80% decline in U.S. HCV prevalence by the year 2040. The 80% benchmark would be reached by the year 2025 if the annual treatment rate increased to 400,000, with 256,315 fewer HCV-related deaths through 2040. Just doubling the treatment rate to 200,000 patients per year would result in an 80% decrease in HCV prevalence by 2031, with 143,055 fewer deaths by 2040.

However, “more than half of those with chronic HCV are unaware of their status, including up to two-thirds of people who inject drugs,” wrote Dr. Durham and his coauthors. Therefore, enhanced HCV screening, especially among PWIDs, could provide a significant further reduction in morbidity and mortality from HCV.

Targeted screening of PWIDs to achieve a 20% screening rate (compared with the current 4.1%), combined with a treatment rate of at least 30%, would yield a 90% reduction of prevalence in HCV by 2040. Universal screening, combined with a treatment rate of at least 20%, would achieve a 90% reduction in the incidence of new infections by 2040, according to the model.

The drop in prevalence in the models took into account not only an increased SVR rate, but also the reduced transmission rate when more persons with HCV achieve an SVR. This dynamic transmission analysis “captures the impact of treatment on both chronic disease and transmission dynamics, distinguishes screening and treatment as separate but related public health objectives, and accounts for underreporting … of national HCV prevalence,” according to Dr. Durham and his coauthors.

Morbidity and mortality were accounted for by projecting the number of HCV patients in each treatment and screening condition who would spontaneously clear disease, become chronically infected, develop increasing levels of liver disease and cirrhosis, require transplant, become reinfected, or die.

As always, real world considerations temper what’s achievable. For DAAs, a chief factor is the cost of the regimens, which currently hovers around $90,000. “The improvement of health outcomes expected from greater acceptance might be tempered by the high costs of treatment and by limited insurance coverage and willingness to treat PWIDs,” Dr. Durham and his coauthors wrote.

Study limitations included some “simplifying assumptions” in the modeling, which did not account for the varying incidence of fibrosis and transmissibility among different HCV genotypes. Still, wrote Dr. Durham and his collaborators, “our analysis provides a forecast for the potential impact of DAAs in reducing HCV-associated liver disease, demonstrating that achievable expansion of HCV treatment at current screening rates can substantially reduce morbidity and mortality.”

The study was funded by the Notsew Orm Sands Foundation and Merck. Dr. Durham, Dr. Galvani, and Dr. Townsend have consulted for and received research funding from Sanofi Pasteur and Merck. Dr. Elbasha is employed by Merck and holds stock and stock options in the company. The other authors reported no conflicts of interest.

AGA Resource

Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

[email protected]

On Twitter @karioakes

Hepatitis C could be reduced by 90% or more in the United States by the year 2040 with the use of direct-acting antivirals, near-universal screening, and enhanced treatment capacity, according to a study in Clinical Infectious Diseases.

A research team led by Jeffrey Townsend, Ph.D., of Yale School of Public Health, New Haven, Conn., said that new direct-acting antivirals (DAAs) alone could reduce the prevalence of hepatitis C virus (HCV) by 80% by the year 2040. When near-universal screening and enhanced treatment capacity are added to the equation, HCV could be eliminated in the United States, though cost and reimbursement issues may impede implementation.

©Martynasfoto/thinkstockphotos.com

“The key finding is that a fourfold increase to the number of patients treated each year could virtually eliminate HCV from the noninjecting population within a decade,” said Dr. Townsend, senior author of the study, in a statement accompanying the study [Clin Infect Dis. 2015. doi: 10.1093/cid/civ894].

First author David Durham, Ph.D., also of the Yale School of Public Health, and his collaborators analyzed currently available data and constructed a sophisticated model to generate projections of how future DAA treatment will change HCV prevalence. Dr. Durham and his colleagues also built models to account for varying levels of screening in the general population and for people who inject drugs (PWIDs).

More than 5 million people with chronic hepatitis C infection are thought to live in the United States, and just about 100,000 of those currently receive treatment each year. The treatment burden and relatively low cure rate of interferon-based therapies have historically been significant impediments for many patients. New DAAs promise a sustained virologic response (SVR) in up to 95% of patients with a well-tolerated, once-daily, one-pill several-week regimen.

Without enhanced screening or treatment rates, the model predicted an 80% decline in U.S. HCV prevalence by the year 2040. The 80% benchmark would be reached by the year 2025 if the annual treatment rate increased to 400,000, with 256,315 fewer HCV-related deaths through 2040. Just doubling the treatment rate to 200,000 patients per year would result in an 80% decrease in HCV prevalence by 2031, with 143,055 fewer deaths by 2040.

However, “more than half of those with chronic HCV are unaware of their status, including up to two-thirds of people who inject drugs,” wrote Dr. Durham and his coauthors. Therefore, enhanced HCV screening, especially among PWIDs, could provide a significant further reduction in morbidity and mortality from HCV.

Targeted screening of PWIDs to achieve a 20% screening rate (compared with the current 4.1%), combined with a treatment rate of at least 30%, would yield a 90% reduction of prevalence in HCV by 2040. Universal screening, combined with a treatment rate of at least 20%, would achieve a 90% reduction in the incidence of new infections by 2040, according to the model.

The drop in prevalence in the models took into account not only an increased SVR rate, but also the reduced transmission rate when more persons with HCV achieve an SVR. This dynamic transmission analysis “captures the impact of treatment on both chronic disease and transmission dynamics, distinguishes screening and treatment as separate but related public health objectives, and accounts for underreporting … of national HCV prevalence,” according to Dr. Durham and his coauthors.

Morbidity and mortality were accounted for by projecting the number of HCV patients in each treatment and screening condition who would spontaneously clear disease, become chronically infected, develop increasing levels of liver disease and cirrhosis, require transplant, become reinfected, or die.

As always, real world considerations temper what’s achievable. For DAAs, a chief factor is the cost of the regimens, which currently hovers around $90,000. “The improvement of health outcomes expected from greater acceptance might be tempered by the high costs of treatment and by limited insurance coverage and willingness to treat PWIDs,” Dr. Durham and his coauthors wrote.

Study limitations included some “simplifying assumptions” in the modeling, which did not account for the varying incidence of fibrosis and transmissibility among different HCV genotypes. Still, wrote Dr. Durham and his collaborators, “our analysis provides a forecast for the potential impact of DAAs in reducing HCV-associated liver disease, demonstrating that achievable expansion of HCV treatment at current screening rates can substantially reduce morbidity and mortality.”

The study was funded by the Notsew Orm Sands Foundation and Merck. Dr. Durham, Dr. Galvani, and Dr. Townsend have consulted for and received research funding from Sanofi Pasteur and Merck. Dr. Elbasha is employed by Merck and holds stock and stock options in the company. The other authors reported no conflicts of interest.

AGA Resource

Through the AGA Roadmap to the Future of Practice, AGA offers a Hepatitis C Clinical Service line to support high-quality patient care, which is available at http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c.

[email protected]

On Twitter @karioakes

For children of a parent with a severe mental illness, taking a stimulant for attention-deficit/hyperactivity disorder might be associated with an increased risk of psychotic symptoms, such as delusions and hallucinations.

In a study of 141 children whose parents had bipolar disorder, major depressive disorder, or schizophrenia, 62.5% of the children and young adults who had taken stimulants experienced psychotic symptoms, compared with 27.4% of those who had never taken stimulants (Pediatrics. 2016;137[1]:e20152486).

©mik38/thinkstockphotos.com

Lynn E. MacKenzie and her coauthors used a comprehensive testing battery to uncover the association in a cohort of children and young adults enrolled in a study of developmental psychopathology in sons and daughters of parents with severe mental illness. The study built on previous work showing a genetic overlap for adults between stimulant-induced psychosis and risk for schizophrenia, and on other work indicating that for those at familial risk, stimulants can cause schizophrenia. “To our knowledge, psychotic adverse effects of stimulant medication have not been studied in youth at familial risk for mental illness,” wrote Ms. MacKenzie, a PhD candidate in clinical psychology at Dalhousie University, Halifax, N.S., and her coauthors.

The children and young adults in the study group were aged 6-21 (mean, 11.8 years). A total of 24 participants (17%) in the study group had taken stimulants, and 33 (23.4%) had a confirmed diagnosis of attention-deficit/hyperactivity disorder (ADHD). This group did not fully overlap with the group taking stimulants, since 17 of 33 participants with ADHD received stimulants while the remaining 16 did not. Overall, 15 of the 24 participants (62.5%) who had taken stimulants experienced psychotic and related symptoms, compared with 32 of 117 participants (27.4%) who had never taken stimulants.

All of the participants who experienced psychotic symptoms had parents with major depressive disorder or bipolar disorder. Hallucinations were the most frequent psychotic symptoms that children experienced while taking stimulants; methylphenidate was the most common stimulant taken.

The association between stimulant administration and psychotic symptoms persisted even after Ms. MacKenzie and her coauthors adjusted for potential confounding variables, with an odds ratio (OR) of 4.41 (95% confidence interval [CI], 1.8-10.69; P = .001) for psychotic symptoms in those taking stimulants. The study found temporal association between psychotic symptoms and stimulant administration, and also found that hallucinations ceased when children were off stimulants. Those findings provided further support for a causal relationship, the researchers noted.

Though the numbers in the study were small, “the association between current use of stimulant medication and current psychotic symptoms was strong and significant (OR, 7.25; 95% CI: 1.76-29.92; P = .006),” wrote Ms. MacKenzie and her coauthors.

“Our experience suggests that stimulants are a double-edged sword – we see a lot of benefits, but we have also found that the psychotic side effects may be much more common than previously thought – at least in kids who have mental illness in the family,” senior author Dr. Rudolf Uher said in an interview. Doctors “should know about history of depression or other mental illness in the family and should ask the children if they have had unusual experiences when taking stimulants. Children usually do not tell adults unless they ask them,” said Dr. Uher, associate professor of psychiatry and Canada Research Chair in early intervention at Dalhousie University.

The researchers actively sought out the experience of hallucinations or delusions in the study cohort, using several instruments and verifying findings with blinded consensus from child psychiatrists. How can the results of this study inform real-world decisions? For clinicians, Ms. MacKenzie said in an interview, it’s important to ask the right questions of patients and families when stimulants are prescribed. “Stimulant medications can be very beneficial for children, including children with family history of mental illness,” she said. “Our findings indicate that prescribing physicians should inquire about psychotic symptoms in children and adolescents taking stimulant medication.”

Because the prompt for a child to be assessed and treated for ADHD frequently comes from a child’s teachers, Dr. Uher said he thinks it is important for teachers and schools to understand that “prescription of stimulant medication is a complex decision, and that they do not [pressure] parents into having their children treated. Stimulants are effective medications for ADHD, but they may not be suitable for every child with attention problems,” he said.

“We do not want the message to be for or against stimulants,” Dr. Uher added. “It is important that doctors, families, and teachers know and understand the pros and cons, and make the best decisions for a particular child.”

The authors reported no conflicts of interest. The Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Canada Research Chairs Program, and the Department of Psychiatry of Dalhousie University funded the study.

[email protected]

On Twitter @karioakes

For children of a parent with a severe mental illness, taking a stimulant for attention-deficit/hyperactivity disorder might be associated with an increased risk of psychotic symptoms, such as delusions and hallucinations.

In a study of 141 children whose parents had bipolar disorder, major depressive disorder, or schizophrenia, 62.5% of the children and young adults who had taken stimulants experienced psychotic symptoms, compared with 27.4% of those who had never taken stimulants (Pediatrics. 2016;137[1]:e20152486).

©mik38/thinkstockphotos.com

Lynn E. MacKenzie and her coauthors used a comprehensive testing battery to uncover the association in a cohort of children and young adults enrolled in a study of developmental psychopathology in sons and daughters of parents with severe mental illness. The study built on previous work showing a genetic overlap for adults between stimulant-induced psychosis and risk for schizophrenia, and on other work indicating that for those at familial risk, stimulants can cause schizophrenia. “To our knowledge, psychotic adverse effects of stimulant medication have not been studied in youth at familial risk for mental illness,” wrote Ms. MacKenzie, a PhD candidate in clinical psychology at Dalhousie University, Halifax, N.S., and her coauthors.

The children and young adults in the study group were aged 6-21 (mean, 11.8 years). A total of 24 participants (17%) in the study group had taken stimulants, and 33 (23.4%) had a confirmed diagnosis of attention-deficit/hyperactivity disorder (ADHD). This group did not fully overlap with the group taking stimulants, since 17 of 33 participants with ADHD received stimulants while the remaining 16 did not. Overall, 15 of the 24 participants (62.5%) who had taken stimulants experienced psychotic and related symptoms, compared with 32 of 117 participants (27.4%) who had never taken stimulants.

All of the participants who experienced psychotic symptoms had parents with major depressive disorder or bipolar disorder. Hallucinations were the most frequent psychotic symptoms that children experienced while taking stimulants; methylphenidate was the most common stimulant taken.

The association between stimulant administration and psychotic symptoms persisted even after Ms. MacKenzie and her coauthors adjusted for potential confounding variables, with an odds ratio (OR) of 4.41 (95% confidence interval [CI], 1.8-10.69; P = .001) for psychotic symptoms in those taking stimulants. The study found temporal association between psychotic symptoms and stimulant administration, and also found that hallucinations ceased when children were off stimulants. Those findings provided further support for a causal relationship, the researchers noted.

Though the numbers in the study were small, “the association between current use of stimulant medication and current psychotic symptoms was strong and significant (OR, 7.25; 95% CI: 1.76-29.92; P = .006),” wrote Ms. MacKenzie and her coauthors.

“Our experience suggests that stimulants are a double-edged sword – we see a lot of benefits, but we have also found that the psychotic side effects may be much more common than previously thought – at least in kids who have mental illness in the family,” senior author Dr. Rudolf Uher said in an interview. Doctors “should know about history of depression or other mental illness in the family and should ask the children if they have had unusual experiences when taking stimulants. Children usually do not tell adults unless they ask them,” said Dr. Uher, associate professor of psychiatry and Canada Research Chair in early intervention at Dalhousie University.

The researchers actively sought out the experience of hallucinations or delusions in the study cohort, using several instruments and verifying findings with blinded consensus from child psychiatrists. How can the results of this study inform real-world decisions? For clinicians, Ms. MacKenzie said in an interview, it’s important to ask the right questions of patients and families when stimulants are prescribed. “Stimulant medications can be very beneficial for children, including children with family history of mental illness,” she said. “Our findings indicate that prescribing physicians should inquire about psychotic symptoms in children and adolescents taking stimulant medication.”

Because the prompt for a child to be assessed and treated for ADHD frequently comes from a child’s teachers, Dr. Uher said he thinks it is important for teachers and schools to understand that “prescription of stimulant medication is a complex decision, and that they do not [pressure] parents into having their children treated. Stimulants are effective medications for ADHD, but they may not be suitable for every child with attention problems,” he said.

“We do not want the message to be for or against stimulants,” Dr. Uher added. “It is important that doctors, families, and teachers know and understand the pros and cons, and make the best decisions for a particular child.”

The authors reported no conflicts of interest. The Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Canada Research Chairs Program, and the Department of Psychiatry of Dalhousie University funded the study.

[email protected]

On Twitter @karioakes

For children of a parent with a severe mental illness, taking a stimulant for attention-deficit/hyperactivity disorder might be associated with an increased risk of psychotic symptoms, such as delusions and hallucinations.

In a study of 141 children whose parents had bipolar disorder, major depressive disorder, or schizophrenia, 62.5% of the children and young adults who had taken stimulants experienced psychotic symptoms, compared with 27.4% of those who had never taken stimulants (Pediatrics. 2016;137[1]:e20152486).

©mik38/thinkstockphotos.com

Lynn E. MacKenzie and her coauthors used a comprehensive testing battery to uncover the association in a cohort of children and young adults enrolled in a study of developmental psychopathology in sons and daughters of parents with severe mental illness. The study built on previous work showing a genetic overlap for adults between stimulant-induced psychosis and risk for schizophrenia, and on other work indicating that for those at familial risk, stimulants can cause schizophrenia. “To our knowledge, psychotic adverse effects of stimulant medication have not been studied in youth at familial risk for mental illness,” wrote Ms. MacKenzie, a PhD candidate in clinical psychology at Dalhousie University, Halifax, N.S., and her coauthors.

The children and young adults in the study group were aged 6-21 (mean, 11.8 years). A total of 24 participants (17%) in the study group had taken stimulants, and 33 (23.4%) had a confirmed diagnosis of attention-deficit/hyperactivity disorder (ADHD). This group did not fully overlap with the group taking stimulants, since 17 of 33 participants with ADHD received stimulants while the remaining 16 did not. Overall, 15 of the 24 participants (62.5%) who had taken stimulants experienced psychotic and related symptoms, compared with 32 of 117 participants (27.4%) who had never taken stimulants.

All of the participants who experienced psychotic symptoms had parents with major depressive disorder or bipolar disorder. Hallucinations were the most frequent psychotic symptoms that children experienced while taking stimulants; methylphenidate was the most common stimulant taken.

The association between stimulant administration and psychotic symptoms persisted even after Ms. MacKenzie and her coauthors adjusted for potential confounding variables, with an odds ratio (OR) of 4.41 (95% confidence interval [CI], 1.8-10.69; P = .001) for psychotic symptoms in those taking stimulants. The study found temporal association between psychotic symptoms and stimulant administration, and also found that hallucinations ceased when children were off stimulants. Those findings provided further support for a causal relationship, the researchers noted.

Though the numbers in the study were small, “the association between current use of stimulant medication and current psychotic symptoms was strong and significant (OR, 7.25; 95% CI: 1.76-29.92; P = .006),” wrote Ms. MacKenzie and her coauthors.

“Our experience suggests that stimulants are a double-edged sword – we see a lot of benefits, but we have also found that the psychotic side effects may be much more common than previously thought – at least in kids who have mental illness in the family,” senior author Dr. Rudolf Uher said in an interview. Doctors “should know about history of depression or other mental illness in the family and should ask the children if they have had unusual experiences when taking stimulants. Children usually do not tell adults unless they ask them,” said Dr. Uher, associate professor of psychiatry and Canada Research Chair in early intervention at Dalhousie University.

The researchers actively sought out the experience of hallucinations or delusions in the study cohort, using several instruments and verifying findings with blinded consensus from child psychiatrists. How can the results of this study inform real-world decisions? For clinicians, Ms. MacKenzie said in an interview, it’s important to ask the right questions of patients and families when stimulants are prescribed. “Stimulant medications can be very beneficial for children, including children with family history of mental illness,” she said. “Our findings indicate that prescribing physicians should inquire about psychotic symptoms in children and adolescents taking stimulant medication.”

Because the prompt for a child to be assessed and treated for ADHD frequently comes from a child’s teachers, Dr. Uher said he thinks it is important for teachers and schools to understand that “prescription of stimulant medication is a complex decision, and that they do not [pressure] parents into having their children treated. Stimulants are effective medications for ADHD, but they may not be suitable for every child with attention problems,” he said.

“We do not want the message to be for or against stimulants,” Dr. Uher added. “It is important that doctors, families, and teachers know and understand the pros and cons, and make the best decisions for a particular child.”

The authors reported no conflicts of interest. The Canadian Institutes of Health Research, the Nova Scotia Health Research Foundation, the Canada Research Chairs Program, and the Department of Psychiatry of Dalhousie University funded the study.

[email protected]

On Twitter @karioakes

For researchers, community engagement needs to start long before the recruitment begins. Authentic community-engaged research is hard and complicated – but worth it, according to Dr. Vanessa Northington Gamble, University Professor of Medical Humanities at George Washington University, Washington.

Speaking at a bioethics forum, “Research with Human Participants – the National Debates,” hosted by the University of Minnesota, Minneapolis, Dr. Gamble spoke of the classic town-gown dynamic she saw in her upbringing.

“I grew up in the shadow of an academic medical center” in West Philadelphia, said Dr. Gamble, a graduate of the University of Pennsylvania, Philadelphia. Her community, she said, didn’t have much to do with the institution that sat in its midst.

This dynamic, and the lack of engagement between the university of the day and its surrounding communities, typifies the barriers that community-engaged research seeks to overcome. Dr. Gamble spoke of community-engaged research as collaboration with groups of people affiliated by geography, proximity, special interest, or similar situations in ways that affect the well-being of these people. “We’re talking about working with and through communities, which is a very different paradigm,” she said during a live webcast of the forum Dec. 2.

The growth of community-engaged research has happened in part because of federal mandates and subsequent increased funding opportunities. However, community demands and institutional initiatives aimed at reducing inequality also have contributed to the increase in community-engaged research.

In 1997, at the meeting where he publicly apologized on behalf of the American people for the infamous Tuskegee syphilis study, President Bill Clinton directed Donna E. Shalala, then secretary of Health and Human Services and now president of the Clinton Foundation, to produce a report about how best to involve communities, and particularly those including minorities, in health care and in research. The report focused on enhancing community engagement and trust, and bringing community groups to the table from the beginning of the process, Dr. Gamble said.

Healthy People 2010 was a Clinton-era initiative that, in part, sought to eliminate racial and ethnic inequities in health care. The agenda was developed by a collaborative process, and “emphasized the role of community partnerships, particularly with nontraditional partners as effective tools for improving health in communities,” Dr. Gamble said.

In 2002, the Institute of Medicine issued a report, “Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care” that focused primarily on the African American population, and acknowledged the importance of a balanced and representative research population.

More progress was made, said Dr. Gamble, with the inception of the Patient-Centered Outcomes Research Institute (PCORI), which signaled a true commitment on the part of federal funders to transition from focusing solely on the individual to collaboration with communities.

The continuum of community engagement can range from simple outreach to true shared leadership. Dr. Gamble said she was struck by the differing levels of authenticity in engagement when she conducted site visits for a Robert Wood Johnson Foundation program some time ago. At some sites, she said, community members were brought to the table only when recruitment efforts began, and the collaboration seemed contrived for expediency.

By contrast, she recalled a conversation she had with a community leader who ran the site visit at another venue. Dr. Gamble pulled her aside and asked whether the community members were in fact leading these efforts, or whether this was just showboating. “It’s real, but it took time,” said the community leader. “It took time, and it took some people getting their feelings hurt.”

What she’s learned, Dr. Gamble said, is that doing community-engaged research “is very difficult. It’s very, very time consuming.”

True engagement begins early: “So it’s about being at the table at the beginning,” Dr. Gamble said. In 2013, the Presidential Commission for the Study of Bioethical Issues issued a report on community engagement, stressing that early engagement in the research process allows community members to articulate concerns and priorities that can shape the direction of the research.

Another factor, she said, is to define the stakeholders, and acknowledge the role a community can play in identifying unmet needs and pain points. This approach can allow the community to become teachers of the researchers, leading them to ask the questions that are really important to the community members.

“Let’s talk about trust, because it’s a critical component of community-engaged research,” Dr. Gamble said. Trust can be interpersonal, as between a physician and her patient, or social, as when an individual trusts an institution like a church or a college. These two types of trust are not mutually exclusive, Dr. Gamble said.

Dr. Gamble said researchers should acknowledge that African Americans, as well as members of other racial and ethnic minorities, are not necessarily inherently mistrustful. Most, she said, have the same degree of trust in medicine and in biomedical research as any reasonable person. At the same time, she said, community attitudes and history must be respected, and community engagement and consultation must be authentic and present from the inception of the research project.

It’s a fine line to walk between realism and cynicism when building an engagement strategy. “Recruitmentology,” she said, is the evolving discipline of learning – and then implementing – the best ways to be successful in recruiting the so-called hard-to-recruit populations. The term, coined by Steven Epstein, Ph.D., professor of sociology at Northwestern University, Evanston, Ill., reflects a sociologist’s perspective on the tensions inherent in the relationships between the individual, the community, the recruiter, and the research team. Wrote Dr. Epstein: “[P]ressures to enroll underrepresented groups have stimulated the development in the U.S. of an auxiliary science I term ‘recruitmentology’: an empirical body of studies scientifically evaluating the efficacy of various social, cultural, psychological, technological, and economic means of convincing people (especially members of ‘hard-to-recruit populations’) that they want to become, and remain, human subjects.”

Another thorny question is how to extend the protections of the individual that were codified in the Belmont principles to the community. “These things are needed today,” said Dr. Gamble, but researchers and communities are still struggling with implementation.

Many questions remain, she said: How can [institutional review boards] become more competent in this area, and what ethical codes should apply when community-researcher relationships are assessed? Are the Belmont principles adequate to address the new facets of research that are entailed in community-engaged research? “What measures are needed to increase IRB confidence in community-engaged research?”

On the academic side of the equation, should faculty members be penalized in tenure and promotion decisions if their publication schedule is slowed by the time it takes to build community engagement?

Dr. Gamble said that though the way forward is difficult, clinical researchers will find an honest journey worthwhile. Recently, she said, she’s been favoring the concept of cultural humility, rather than cultural competence. Cultural humility is a term drawn from work begun by Dr. Melanie Tervalon, a physician with a private consulting practice, and Dr. Jann Murray-Garcia, adjunct assistant professor at the Betty Irene Moore School of Nursing at the University of California, Davis.

Cultural competence, she said, can be used in the service of opportunistic research, as was arguably the case with the Tuskegee syphilis study, where African American recruiters sought out African American institutions and their leaders to recruit research subjects who were members of that community. In contrast, she said, cultural humility involves ”a lifelong commitment to self-evaluation and self-critique,” with a focus on developing mutually beneficial partnerships and a commitment to ongoing active engagement.

These days, there’s another elephant in the room, said Dr. Gamble, and it takes the form of the Black Lives Matter movement. The concerns raised by this movement’s spokespeople move the conversation beyond the walls of the laboratory and the exam room.

“Because if we are serious about eliminating racial and ethnic disparities ... we cannot just use the medical model,” Dr. Gamble said. Conversations she is having about the realities of stubborn health disparities are increasingly engaging the criminal justice system, and addressing income inequality and educational inequalities, she said.

It’s not really a matter of town vs. gown any more, according to Dr. Gamble. Benefits flow both ways, because once academic medicine taps the wisdom that’s available, the community becomes a source of strength, knowledge, and expertise.

Dr. Gamble had no disclosures to report.

[email protected]

On Twitter @karioakes

For researchers, community engagement needs to start long before the recruitment begins. Authentic community-engaged research is hard and complicated – but worth it, according to Dr. Vanessa Northington Gamble, University Professor of Medical Humanities at George Washington University, Washington.

Speaking at a bioethics forum, “Research with Human Participants – the National Debates,” hosted by the University of Minnesota, Minneapolis, Dr. Gamble spoke of the classic town-gown dynamic she saw in her upbringing.

“I grew up in the shadow of an academic medical center” in West Philadelphia, said Dr. Gamble, a graduate of the University of Pennsylvania, Philadelphia. Her community, she said, didn’t have much to do with the institution that sat in its midst.

This dynamic, and the lack of engagement between the university of the day and its surrounding communities, typifies the barriers that community-engaged research seeks to overcome. Dr. Gamble spoke of community-engaged research as collaboration with groups of people affiliated by geography, proximity, special interest, or similar situations in ways that affect the well-being of these people. “We’re talking about working with and through communities, which is a very different paradigm,” she said during a live webcast of the forum Dec. 2.

The growth of community-engaged research has happened in part because of federal mandates and subsequent increased funding opportunities. However, community demands and institutional initiatives aimed at reducing inequality also have contributed to the increase in community-engaged research.

In 1997, at the meeting where he publicly apologized on behalf of the American people for the infamous Tuskegee syphilis study, President Bill Clinton directed Donna E. Shalala, then secretary of Health and Human Services and now president of the Clinton Foundation, to produce a report about how best to involve communities, and particularly those including minorities, in health care and in research. The report focused on enhancing community engagement and trust, and bringing community groups to the table from the beginning of the process, Dr. Gamble said.

Healthy People 2010 was a Clinton-era initiative that, in part, sought to eliminate racial and ethnic inequities in health care. The agenda was developed by a collaborative process, and “emphasized the role of community partnerships, particularly with nontraditional partners as effective tools for improving health in communities,” Dr. Gamble said.

In 2002, the Institute of Medicine issued a report, “Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care” that focused primarily on the African American population, and acknowledged the importance of a balanced and representative research population.

More progress was made, said Dr. Gamble, with the inception of the Patient-Centered Outcomes Research Institute (PCORI), which signaled a true commitment on the part of federal funders to transition from focusing solely on the individual to collaboration with communities.

The continuum of community engagement can range from simple outreach to true shared leadership. Dr. Gamble said she was struck by the differing levels of authenticity in engagement when she conducted site visits for a Robert Wood Johnson Foundation program some time ago. At some sites, she said, community members were brought to the table only when recruitment efforts began, and the collaboration seemed contrived for expediency.

By contrast, she recalled a conversation she had with a community leader who ran the site visit at another venue. Dr. Gamble pulled her aside and asked whether the community members were in fact leading these efforts, or whether this was just showboating. “It’s real, but it took time,” said the community leader. “It took time, and it took some people getting their feelings hurt.”

What she’s learned, Dr. Gamble said, is that doing community-engaged research “is very difficult. It’s very, very time consuming.”

True engagement begins early: “So it’s about being at the table at the beginning,” Dr. Gamble said. In 2013, the Presidential Commission for the Study of Bioethical Issues issued a report on community engagement, stressing that early engagement in the research process allows community members to articulate concerns and priorities that can shape the direction of the research.

Another factor, she said, is to define the stakeholders, and acknowledge the role a community can play in identifying unmet needs and pain points. This approach can allow the community to become teachers of the researchers, leading them to ask the questions that are really important to the community members.

“Let’s talk about trust, because it’s a critical component of community-engaged research,” Dr. Gamble said. Trust can be interpersonal, as between a physician and her patient, or social, as when an individual trusts an institution like a church or a college. These two types of trust are not mutually exclusive, Dr. Gamble said.

Dr. Gamble said researchers should acknowledge that African Americans, as well as members of other racial and ethnic minorities, are not necessarily inherently mistrustful. Most, she said, have the same degree of trust in medicine and in biomedical research as any reasonable person. At the same time, she said, community attitudes and history must be respected, and community engagement and consultation must be authentic and present from the inception of the research project.

It’s a fine line to walk between realism and cynicism when building an engagement strategy. “Recruitmentology,” she said, is the evolving discipline of learning – and then implementing – the best ways to be successful in recruiting the so-called hard-to-recruit populations. The term, coined by Steven Epstein, Ph.D., professor of sociology at Northwestern University, Evanston, Ill., reflects a sociologist’s perspective on the tensions inherent in the relationships between the individual, the community, the recruiter, and the research team. Wrote Dr. Epstein: “[P]ressures to enroll underrepresented groups have stimulated the development in the U.S. of an auxiliary science I term ‘recruitmentology’: an empirical body of studies scientifically evaluating the efficacy of various social, cultural, psychological, technological, and economic means of convincing people (especially members of ‘hard-to-recruit populations’) that they want to become, and remain, human subjects.”

Another thorny question is how to extend the protections of the individual that were codified in the Belmont principles to the community. “These things are needed today,” said Dr. Gamble, but researchers and communities are still struggling with implementation.

Many questions remain, she said: How can [institutional review boards] become more competent in this area, and what ethical codes should apply when community-researcher relationships are assessed? Are the Belmont principles adequate to address the new facets of research that are entailed in community-engaged research? “What measures are needed to increase IRB confidence in community-engaged research?”

On the academic side of the equation, should faculty members be penalized in tenure and promotion decisions if their publication schedule is slowed by the time it takes to build community engagement?

Dr. Gamble said that though the way forward is difficult, clinical researchers will find an honest journey worthwhile. Recently, she said, she’s been favoring the concept of cultural humility, rather than cultural competence. Cultural humility is a term drawn from work begun by Dr. Melanie Tervalon, a physician with a private consulting practice, and Dr. Jann Murray-Garcia, adjunct assistant professor at the Betty Irene Moore School of Nursing at the University of California, Davis.

Cultural competence, she said, can be used in the service of opportunistic research, as was arguably the case with the Tuskegee syphilis study, where African American recruiters sought out African American institutions and their leaders to recruit research subjects who were members of that community. In contrast, she said, cultural humility involves ”a lifelong commitment to self-evaluation and self-critique,” with a focus on developing mutually beneficial partnerships and a commitment to ongoing active engagement.

These days, there’s another elephant in the room, said Dr. Gamble, and it takes the form of the Black Lives Matter movement. The concerns raised by this movement’s spokespeople move the conversation beyond the walls of the laboratory and the exam room.

“Because if we are serious about eliminating racial and ethnic disparities ... we cannot just use the medical model,” Dr. Gamble said. Conversations she is having about the realities of stubborn health disparities are increasingly engaging the criminal justice system, and addressing income inequality and educational inequalities, she said.

It’s not really a matter of town vs. gown any more, according to Dr. Gamble. Benefits flow both ways, because once academic medicine taps the wisdom that’s available, the community becomes a source of strength, knowledge, and expertise.

Dr. Gamble had no disclosures to report.

[email protected]

On Twitter @karioakes

For researchers, community engagement needs to start long before the recruitment begins. Authentic community-engaged research is hard and complicated – but worth it, according to Dr. Vanessa Northington Gamble, University Professor of Medical Humanities at George Washington University, Washington.

Speaking at a bioethics forum, “Research with Human Participants – the National Debates,” hosted by the University of Minnesota, Minneapolis, Dr. Gamble spoke of the classic town-gown dynamic she saw in her upbringing.

“I grew up in the shadow of an academic medical center” in West Philadelphia, said Dr. Gamble, a graduate of the University of Pennsylvania, Philadelphia. Her community, she said, didn’t have much to do with the institution that sat in its midst.

This dynamic, and the lack of engagement between the university of the day and its surrounding communities, typifies the barriers that community-engaged research seeks to overcome. Dr. Gamble spoke of community-engaged research as collaboration with groups of people affiliated by geography, proximity, special interest, or similar situations in ways that affect the well-being of these people. “We’re talking about working with and through communities, which is a very different paradigm,” she said during a live webcast of the forum Dec. 2.

The growth of community-engaged research has happened in part because of federal mandates and subsequent increased funding opportunities. However, community demands and institutional initiatives aimed at reducing inequality also have contributed to the increase in community-engaged research.

In 1997, at the meeting where he publicly apologized on behalf of the American people for the infamous Tuskegee syphilis study, President Bill Clinton directed Donna E. Shalala, then secretary of Health and Human Services and now president of the Clinton Foundation, to produce a report about how best to involve communities, and particularly those including minorities, in health care and in research. The report focused on enhancing community engagement and trust, and bringing community groups to the table from the beginning of the process, Dr. Gamble said.

Healthy People 2010 was a Clinton-era initiative that, in part, sought to eliminate racial and ethnic inequities in health care. The agenda was developed by a collaborative process, and “emphasized the role of community partnerships, particularly with nontraditional partners as effective tools for improving health in communities,” Dr. Gamble said.

In 2002, the Institute of Medicine issued a report, “Unequal Treatment: Confronting Racial and Ethnic Disparities in Health Care” that focused primarily on the African American population, and acknowledged the importance of a balanced and representative research population.

More progress was made, said Dr. Gamble, with the inception of the Patient-Centered Outcomes Research Institute (PCORI), which signaled a true commitment on the part of federal funders to transition from focusing solely on the individual to collaboration with communities.

The continuum of community engagement can range from simple outreach to true shared leadership. Dr. Gamble said she was struck by the differing levels of authenticity in engagement when she conducted site visits for a Robert Wood Johnson Foundation program some time ago. At some sites, she said, community members were brought to the table only when recruitment efforts began, and the collaboration seemed contrived for expediency.

By contrast, she recalled a conversation she had with a community leader who ran the site visit at another venue. Dr. Gamble pulled her aside and asked whether the community members were in fact leading these efforts, or whether this was just showboating. “It’s real, but it took time,” said the community leader. “It took time, and it took some people getting their feelings hurt.”

What she’s learned, Dr. Gamble said, is that doing community-engaged research “is very difficult. It’s very, very time consuming.”

True engagement begins early: “So it’s about being at the table at the beginning,” Dr. Gamble said. In 2013, the Presidential Commission for the Study of Bioethical Issues issued a report on community engagement, stressing that early engagement in the research process allows community members to articulate concerns and priorities that can shape the direction of the research.

Another factor, she said, is to define the stakeholders, and acknowledge the role a community can play in identifying unmet needs and pain points. This approach can allow the community to become teachers of the researchers, leading them to ask the questions that are really important to the community members.

“Let’s talk about trust, because it’s a critical component of community-engaged research,” Dr. Gamble said. Trust can be interpersonal, as between a physician and her patient, or social, as when an individual trusts an institution like a church or a college. These two types of trust are not mutually exclusive, Dr. Gamble said.

Dr. Gamble said researchers should acknowledge that African Americans, as well as members of other racial and ethnic minorities, are not necessarily inherently mistrustful. Most, she said, have the same degree of trust in medicine and in biomedical research as any reasonable person. At the same time, she said, community attitudes and history must be respected, and community engagement and consultation must be authentic and present from the inception of the research project.

It’s a fine line to walk between realism and cynicism when building an engagement strategy. “Recruitmentology,” she said, is the evolving discipline of learning – and then implementing – the best ways to be successful in recruiting the so-called hard-to-recruit populations. The term, coined by Steven Epstein, Ph.D., professor of sociology at Northwestern University, Evanston, Ill., reflects a sociologist’s perspective on the tensions inherent in the relationships between the individual, the community, the recruiter, and the research team. Wrote Dr. Epstein: “[P]ressures to enroll underrepresented groups have stimulated the development in the U.S. of an auxiliary science I term ‘recruitmentology’: an empirical body of studies scientifically evaluating the efficacy of various social, cultural, psychological, technological, and economic means of convincing people (especially members of ‘hard-to-recruit populations’) that they want to become, and remain, human subjects.”

Another thorny question is how to extend the protections of the individual that were codified in the Belmont principles to the community. “These things are needed today,” said Dr. Gamble, but researchers and communities are still struggling with implementation.

Many questions remain, she said: How can [institutional review boards] become more competent in this area, and what ethical codes should apply when community-researcher relationships are assessed? Are the Belmont principles adequate to address the new facets of research that are entailed in community-engaged research? “What measures are needed to increase IRB confidence in community-engaged research?”

On the academic side of the equation, should faculty members be penalized in tenure and promotion decisions if their publication schedule is slowed by the time it takes to build community engagement?

Dr. Gamble said that though the way forward is difficult, clinical researchers will find an honest journey worthwhile. Recently, she said, she’s been favoring the concept of cultural humility, rather than cultural competence. Cultural humility is a term drawn from work begun by Dr. Melanie Tervalon, a physician with a private consulting practice, and Dr. Jann Murray-Garcia, adjunct assistant professor at the Betty Irene Moore School of Nursing at the University of California, Davis.

Cultural competence, she said, can be used in the service of opportunistic research, as was arguably the case with the Tuskegee syphilis study, where African American recruiters sought out African American institutions and their leaders to recruit research subjects who were members of that community. In contrast, she said, cultural humility involves ”a lifelong commitment to self-evaluation and self-critique,” with a focus on developing mutually beneficial partnerships and a commitment to ongoing active engagement.

These days, there’s another elephant in the room, said Dr. Gamble, and it takes the form of the Black Lives Matter movement. The concerns raised by this movement’s spokespeople move the conversation beyond the walls of the laboratory and the exam room.

“Because if we are serious about eliminating racial and ethnic disparities ... we cannot just use the medical model,” Dr. Gamble said. Conversations she is having about the realities of stubborn health disparities are increasingly engaging the criminal justice system, and addressing income inequality and educational inequalities, she said.

It’s not really a matter of town vs. gown any more, according to Dr. Gamble. Benefits flow both ways, because once academic medicine taps the wisdom that’s available, the community becomes a source of strength, knowledge, and expertise.

Dr. Gamble had no disclosures to report.

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