Blood sample collection

Photo by Juan D. Alfonso

Analysis of circulating tumor cells (CTCs) can provide at least as much genetic information about multiple myeloma (MM) as a bone marrow (BM) biopsy, according to a new study.

Researchers found evidence to suggest that analyzing CTCs isolated from the peripheral blood of MM patients could help physicians monitor disease progression over time, track the emergence of drug resistance, and tailor therapies to individual patients.

Jens Lohr, MD, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and colleagues conducted this research and detailed their findings in Science Translational Medicine.

The researchers said they devised a method that was “highly sensitive” in detecting and sequencing single CTCs, even from patients with low tumor burden.

Specifically, the team found they could isolate CTCs from, and detect mutations in, blood samples from an MM patient who had achieved a very good partial response to treatment and a patient with monoclonal gammopathy of undetermined significance.

Overall, the researchers found that CTCs could be used to identify mutations relevant for prognosis, and some of these mutations were more abundant in CTCs than in BM samples.

For example, the team detected somatic mutations in the KRAS, BRAF, IRF4, and TP53 genes in single CTCs from 3 MM patients. And the same mutations were present in single BM-derived MM cells.

In another 3 patients, the proportion of CTCs harboring TP53 R273C, BRAF G469A, and NRAS G13D mutations was higher than that observed in BM-derived cells. In 2 of the patients, the mutations weren’t detectable in BM cells because of insufficient sample material.

The researchers also found that CTCs could reveal patients with an overabundance of molecules expressed by MM cells—such as CD38 and SLAMF7—that can be targeted by therapies currently approved to treat MM—such as daratumumab and elotuzumab.

The team therefore believes that, with further development, CTC analysis could be a valuable tool for advancing precision medicine in MM.

Blood sample collection

Photo by Juan D. Alfonso

Analysis of circulating tumor cells (CTCs) can provide at least as much genetic information about multiple myeloma (MM) as a bone marrow (BM) biopsy, according to a new study.

Researchers found evidence to suggest that analyzing CTCs isolated from the peripheral blood of MM patients could help physicians monitor disease progression over time, track the emergence of drug resistance, and tailor therapies to individual patients.

Jens Lohr, MD, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and colleagues conducted this research and detailed their findings in Science Translational Medicine.

The researchers said they devised a method that was “highly sensitive” in detecting and sequencing single CTCs, even from patients with low tumor burden.

Specifically, the team found they could isolate CTCs from, and detect mutations in, blood samples from an MM patient who had achieved a very good partial response to treatment and a patient with monoclonal gammopathy of undetermined significance.

Overall, the researchers found that CTCs could be used to identify mutations relevant for prognosis, and some of these mutations were more abundant in CTCs than in BM samples.

For example, the team detected somatic mutations in the KRAS, BRAF, IRF4, and TP53 genes in single CTCs from 3 MM patients. And the same mutations were present in single BM-derived MM cells.

In another 3 patients, the proportion of CTCs harboring TP53 R273C, BRAF G469A, and NRAS G13D mutations was higher than that observed in BM-derived cells. In 2 of the patients, the mutations weren’t detectable in BM cells because of insufficient sample material.

The researchers also found that CTCs could reveal patients with an overabundance of molecules expressed by MM cells—such as CD38 and SLAMF7—that can be targeted by therapies currently approved to treat MM—such as daratumumab and elotuzumab.

The team therefore believes that, with further development, CTC analysis could be a valuable tool for advancing precision medicine in MM.

Blood sample collection

Photo by Juan D. Alfonso

Analysis of circulating tumor cells (CTCs) can provide at least as much genetic information about multiple myeloma (MM) as a bone marrow (BM) biopsy, according to a new study.

Researchers found evidence to suggest that analyzing CTCs isolated from the peripheral blood of MM patients could help physicians monitor disease progression over time, track the emergence of drug resistance, and tailor therapies to individual patients.

Jens Lohr, MD, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and colleagues conducted this research and detailed their findings in Science Translational Medicine.

The researchers said they devised a method that was “highly sensitive” in detecting and sequencing single CTCs, even from patients with low tumor burden.

Specifically, the team found they could isolate CTCs from, and detect mutations in, blood samples from an MM patient who had achieved a very good partial response to treatment and a patient with monoclonal gammopathy of undetermined significance.

Overall, the researchers found that CTCs could be used to identify mutations relevant for prognosis, and some of these mutations were more abundant in CTCs than in BM samples.

For example, the team detected somatic mutations in the KRAS, BRAF, IRF4, and TP53 genes in single CTCs from 3 MM patients. And the same mutations were present in single BM-derived MM cells.

In another 3 patients, the proportion of CTCs harboring TP53 R273C, BRAF G469A, and NRAS G13D mutations was higher than that observed in BM-derived cells. In 2 of the patients, the mutations weren’t detectable in BM cells because of insufficient sample material.

The researchers also found that CTCs could reveal patients with an overabundance of molecules expressed by MM cells—such as CD38 and SLAMF7—that can be targeted by therapies currently approved to treat MM—such as daratumumab and elotuzumab.

The team therefore believes that, with further development, CTC analysis could be a valuable tool for advancing precision medicine in MM.

Every second of every day in the U.S. an older adult falls, according to CDC data. Falls are the number one cause of injuries and deaths from injury among older Americans. The report cites 29 million falls in 2014 alone.

“Older adult falls are increasing and, sadly, often herald the end of independence,” said CDC Director Tom Frieden, MD, MPH. But he adds: “Health care providers can make fall prevention a routine part of care in their practice, and older adults can take steps to protect themselves.”

Related: Preventing Falls and Saving Costs

The CDC created Stopping Elderly Accidents, Deaths, and Injuries (STEADI), an initiative to make fall prevention routine in health care. The program provides information on how to screen for falls, online training for providers, videos on conducting functional assessments, and brochures for health care providers (HCPs), patients, and caregivers.

Among the suggestions for HCPs:

• Ask patients whether they have fallen in the past year, feel unsteady, or worry about falling
• Review medications and stop, switch, or reduce medicines that could increase the risk of falls
• Recommend vitamin D supplements

For older adults, the CDC recommends:

• Talk to a HCP about falls and fall prevention
• Tell a HCP if you have fallen—fewer than half of Americans who fall tell their doctor
• Have your eyes checked, and update eye prescriptions
• Participate in evidence-based programs like tai chi to improve balance and strengthen legs
• Get rid of fall hazards in your home

Every second of every day in the U.S. an older adult falls, according to CDC data. Falls are the number one cause of injuries and deaths from injury among older Americans. The report cites 29 million falls in 2014 alone.

“Older adult falls are increasing and, sadly, often herald the end of independence,” said CDC Director Tom Frieden, MD, MPH. But he adds: “Health care providers can make fall prevention a routine part of care in their practice, and older adults can take steps to protect themselves.”

Related: Preventing Falls and Saving Costs

The CDC created Stopping Elderly Accidents, Deaths, and Injuries (STEADI), an initiative to make fall prevention routine in health care. The program provides information on how to screen for falls, online training for providers, videos on conducting functional assessments, and brochures for health care providers (HCPs), patients, and caregivers.

Among the suggestions for HCPs:

• Ask patients whether they have fallen in the past year, feel unsteady, or worry about falling
• Review medications and stop, switch, or reduce medicines that could increase the risk of falls
• Recommend vitamin D supplements

For older adults, the CDC recommends:

• Talk to a HCP about falls and fall prevention
• Tell a HCP if you have fallen—fewer than half of Americans who fall tell their doctor
• Have your eyes checked, and update eye prescriptions
• Participate in evidence-based programs like tai chi to improve balance and strengthen legs
• Get rid of fall hazards in your home

Every second of every day in the U.S. an older adult falls, according to CDC data. Falls are the number one cause of injuries and deaths from injury among older Americans. The report cites 29 million falls in 2014 alone.

“Older adult falls are increasing and, sadly, often herald the end of independence,” said CDC Director Tom Frieden, MD, MPH. But he adds: “Health care providers can make fall prevention a routine part of care in their practice, and older adults can take steps to protect themselves.”

Related: Preventing Falls and Saving Costs

The CDC created Stopping Elderly Accidents, Deaths, and Injuries (STEADI), an initiative to make fall prevention routine in health care. The program provides information on how to screen for falls, online training for providers, videos on conducting functional assessments, and brochures for health care providers (HCPs), patients, and caregivers.

Among the suggestions for HCPs:

• Ask patients whether they have fallen in the past year, feel unsteady, or worry about falling
• Review medications and stop, switch, or reduce medicines that could increase the risk of falls
• Recommend vitamin D supplements

For older adults, the CDC recommends:

• Talk to a HCP about falls and fall prevention
• Tell a HCP if you have fallen—fewer than half of Americans who fall tell their doctor
• Have your eyes checked, and update eye prescriptions
• Participate in evidence-based programs like tai chi to improve balance and strengthen legs
• Get rid of fall hazards in your home

This 49-year-old man was first diagnosed with Darier disease at age 8. It has been contained, for the most part, by topical medications and acitretin. But the itching on his legs is especially severe, making it difficult for him to leave them alone.

EXAMINATION
Both legs have heavy scaling and lichenification from the lateral aspects of the knees down to the ankles. There is modest erythema but no suppurative signs. Other areas of scaling are seen on his chest and back, but these are less coarse and rough than the leg rash.

What is the diagnosis?

DISCUSSION
Lichen simplex chronicus (LSC) is the term given to this phenomenon. LSC is always secondary to a primary trigger, which can be dry skin, eczema, psoriasis, or even a bug bite. Excessive scratching induces more itching, and before the patient realizes it, he has jumped aboard the itch-scratch-itch train—a vicious cycle that can be hard to break.

The skin reacts to all this attention by thickening and becoming rough; on a microscopic level, the nerves become more sensitive. The urge to scratch becomes so irresistible that some patients fantasize about giving in.

The first goal of treating LSC is to stop the itching by helping the patient avoid contact with the site. High-potency topical steroids can be effective for this, especially if used under occlusion, which not only potentiates the steroid but also provides a barrier to protect the area from the patient’s fingernails (or hairbrush). Once the condition improves, steroids can be slowly withdrawn.

A biopsy, if it had been necessary, would have shown hypertrophic epidermis and acanthotic changes.

TAKE-HOME LEARNING POINTS
• Lichen simplex chronicus (LSC) is secondary to an inciting condition such as eczema, xerosis, psoriasis, or Darier disease.
• The manifestation of the itch-scratch-itch cycle leads to thickening and lichenification of the skin. The itch of LSC is so compelling that scratching is hard to resist.
• Despite treatment and patient education, recurrences are quite common.

This 49-year-old man was first diagnosed with Darier disease at age 8. It has been contained, for the most part, by topical medications and acitretin. But the itching on his legs is especially severe, making it difficult for him to leave them alone.

EXAMINATION
Both legs have heavy scaling and lichenification from the lateral aspects of the knees down to the ankles. There is modest erythema but no suppurative signs. Other areas of scaling are seen on his chest and back, but these are less coarse and rough than the leg rash.

What is the diagnosis?

DISCUSSION
Lichen simplex chronicus (LSC) is the term given to this phenomenon. LSC is always secondary to a primary trigger, which can be dry skin, eczema, psoriasis, or even a bug bite. Excessive scratching induces more itching, and before the patient realizes it, he has jumped aboard the itch-scratch-itch train—a vicious cycle that can be hard to break.

The skin reacts to all this attention by thickening and becoming rough; on a microscopic level, the nerves become more sensitive. The urge to scratch becomes so irresistible that some patients fantasize about giving in.

The first goal of treating LSC is to stop the itching by helping the patient avoid contact with the site. High-potency topical steroids can be effective for this, especially if used under occlusion, which not only potentiates the steroid but also provides a barrier to protect the area from the patient’s fingernails (or hairbrush). Once the condition improves, steroids can be slowly withdrawn.

A biopsy, if it had been necessary, would have shown hypertrophic epidermis and acanthotic changes.

TAKE-HOME LEARNING POINTS
• Lichen simplex chronicus (LSC) is secondary to an inciting condition such as eczema, xerosis, psoriasis, or Darier disease.
• The manifestation of the itch-scratch-itch cycle leads to thickening and lichenification of the skin. The itch of LSC is so compelling that scratching is hard to resist.
• Despite treatment and patient education, recurrences are quite common.

This 49-year-old man was first diagnosed with Darier disease at age 8. It has been contained, for the most part, by topical medications and acitretin. But the itching on his legs is especially severe, making it difficult for him to leave them alone.

EXAMINATION
Both legs have heavy scaling and lichenification from the lateral aspects of the knees down to the ankles. There is modest erythema but no suppurative signs. Other areas of scaling are seen on his chest and back, but these are less coarse and rough than the leg rash.

What is the diagnosis?

DISCUSSION
Lichen simplex chronicus (LSC) is the term given to this phenomenon. LSC is always secondary to a primary trigger, which can be dry skin, eczema, psoriasis, or even a bug bite. Excessive scratching induces more itching, and before the patient realizes it, he has jumped aboard the itch-scratch-itch train—a vicious cycle that can be hard to break.

The skin reacts to all this attention by thickening and becoming rough; on a microscopic level, the nerves become more sensitive. The urge to scratch becomes so irresistible that some patients fantasize about giving in.

The first goal of treating LSC is to stop the itching by helping the patient avoid contact with the site. High-potency topical steroids can be effective for this, especially if used under occlusion, which not only potentiates the steroid but also provides a barrier to protect the area from the patient’s fingernails (or hairbrush). Once the condition improves, steroids can be slowly withdrawn.

A biopsy, if it had been necessary, would have shown hypertrophic epidermis and acanthotic changes.

TAKE-HOME LEARNING POINTS
• Lichen simplex chronicus (LSC) is secondary to an inciting condition such as eczema, xerosis, psoriasis, or Darier disease.
• The manifestation of the itch-scratch-itch cycle leads to thickening and lichenification of the skin. The itch of LSC is so compelling that scratching is hard to resist.
• Despite treatment and patient education, recurrences are quite common.

Pain was introduced as the “fifth vital sign” in the 1990s, ranking it as important a measure as blood pressure, heart and respiratory rate, and temperature.¹ The American Pain Society promoted this notion to increase awareness of pain treatment among health care professionals. Emphasizing its importance, the Veterans Health Administration in 1999 launched the “Pain as the 5th Vital Sign” initiative, which mandated a pain intensity rating at all clinical encounters.²

Interestingly, the Joint Commission standards never stated that pain needed to be treated as a vital sign. But many organizations started to require documentation of routine pain screening for all patients. Health care providers were instructed to inquire about pain and to treat it as an essential element of health history.

These changes were quite controversial. The additional measure, while important, competed with other priority screening needs, including diabetes, cancer, and hypertension. There was—and continues to be—quite the debate on whether pain actually can be measured and what impact that information has on the quality of care.

I do not intend to enter that debate here. Instead, I want to discuss what continues to be a conundrum for me: the paradox of pain management.

For many patients, especially those in acute or emergency care settings, the presenting complaint is pain. I would submit that for many the expectation is for pain to be immediately and permanently relieved. But is this a realistic goal?

I recall a lecture on pain management I attended years ago; at that time, the approach involved early identification and prompt, aggressive treatment. When asked “How much medication and for how long?” the lecturer used diabetes as a treatment model, stating, “You would increase insulin until the blood glucose was controlled—don’t be afraid to increase pain medication until the pain is controlled.” In the early days of pain management, that was the accepted norm. The possibility that a “zero” on the pain scale was unattainable for some patients was not considered.

Yet seemingly overnight, once pain was decreed a vital sign, health care providers were mandated to measure it and faced with the responsibility to treat it. This resulted in a vague 0-10 pain scale and providers who were inadequately educated on how to begin pain management. Unlike with diabetes or hypertension, there was no protocol, algorithm, or standard upon which to base a plan of care. Moreover, there was a lack of differentiation between pain that was a short-lived nuisance and pain that interfered with quality of life.

Faced with growing concern for undertreated pain in the US, however, many of us strove to achieve a balance of sufficient yet appropriate treatment. We struggled to determine how to relieve the pain our patients experienced without creating other problems, such as undesirable side effects, misuse, or addiction. That ­predicament, paired with the ever-increasing direct-to-consumer advertisements about pain relief and the insistence by (some, not all) patients that nonnarcotic pain medication is ineffective, bred the crisis of opioid overuse and addiction we now face.

But just as I chose not to debate the impact of pain measurement on quality of care, I also choose not to debate the existence of the opioid crisis. What I want to emphasize is that all policy changes have consequences. I reach out to you, my colleagues, for innovative ideas to strike the delicate balance of appropriate use of narcotics. How do we address the needs of patients whose pain is more than just an inconvenience and for whom daily use of a narcotic allows them to function—while also avoiding the pitfalls that we are now regularly warned about?

I have no doubt that each of us knows at least one person—a patient, a family member, a neighbor—for whom pain is a daily occurrence. But we must put that in perspective; not all pain is a barrier to physical and emotional functioning. Data suggest that a “33% to 50% decrease in pain intensity is meaningful from a patient’s perspective and represents a reasonable standard of intervention efficacy.”³ For those who deal with chronic pain, even a slight improvement is progress.

So, while the American Medical Association and the American Pain Society bicker about whether pain is the “fifth vital sign,” we must find a better means to resolve the discord in our society.⁴ Banning all opioid use is not the answer, but neither is considering narcotics the default treatment for pain.

We must remind our patients, our policymakers, and ourselves that identifying and assessing pain is not equated with writing an opioid or narcotic prescription. Nor will removing those medications from our formulary mitigate the crisis. We need to communicate a clear, consistent message that pain is real, that some pain is a fact of life, and that we will help our patients.

However, it is incumbent upon us to adopt a systematic yet personalized plan of care that is effective, cost conscious, culturally and developmentally appropriate, and safe—and that plan may or may not include prescribing narcotics. We have much work ahead of us in order to minimize the potential for misuse of these medications without impeding patients’ access to necessary health care.

Please share your thoughts on this conundrum by writing to NPEditor@frontlinemedcom.com.

Pain was introduced as the “fifth vital sign” in the 1990s, ranking it as important a measure as blood pressure, heart and respiratory rate, and temperature.¹ The American Pain Society promoted this notion to increase awareness of pain treatment among health care professionals. Emphasizing its importance, the Veterans Health Administration in 1999 launched the “Pain as the 5th Vital Sign” initiative, which mandated a pain intensity rating at all clinical encounters.²

Interestingly, the Joint Commission standards never stated that pain needed to be treated as a vital sign. But many organizations started to require documentation of routine pain screening for all patients. Health care providers were instructed to inquire about pain and to treat it as an essential element of health history.

These changes were quite controversial. The additional measure, while important, competed with other priority screening needs, including diabetes, cancer, and hypertension. There was—and continues to be—quite the debate on whether pain actually can be measured and what impact that information has on the quality of care.

I do not intend to enter that debate here. Instead, I want to discuss what continues to be a conundrum for me: the paradox of pain management.

For many patients, especially those in acute or emergency care settings, the presenting complaint is pain. I would submit that for many the expectation is for pain to be immediately and permanently relieved. But is this a realistic goal?

I recall a lecture on pain management I attended years ago; at that time, the approach involved early identification and prompt, aggressive treatment. When asked “How much medication and for how long?” the lecturer used diabetes as a treatment model, stating, “You would increase insulin until the blood glucose was controlled—don’t be afraid to increase pain medication until the pain is controlled.” In the early days of pain management, that was the accepted norm. The possibility that a “zero” on the pain scale was unattainable for some patients was not considered.

Yet seemingly overnight, once pain was decreed a vital sign, health care providers were mandated to measure it and faced with the responsibility to treat it. This resulted in a vague 0-10 pain scale and providers who were inadequately educated on how to begin pain management. Unlike with diabetes or hypertension, there was no protocol, algorithm, or standard upon which to base a plan of care. Moreover, there was a lack of differentiation between pain that was a short-lived nuisance and pain that interfered with quality of life.

Faced with growing concern for undertreated pain in the US, however, many of us strove to achieve a balance of sufficient yet appropriate treatment. We struggled to determine how to relieve the pain our patients experienced without creating other problems, such as undesirable side effects, misuse, or addiction. That ­predicament, paired with the ever-increasing direct-to-consumer advertisements about pain relief and the insistence by (some, not all) patients that nonnarcotic pain medication is ineffective, bred the crisis of opioid overuse and addiction we now face.

But just as I chose not to debate the impact of pain measurement on quality of care, I also choose not to debate the existence of the opioid crisis. What I want to emphasize is that all policy changes have consequences. I reach out to you, my colleagues, for innovative ideas to strike the delicate balance of appropriate use of narcotics. How do we address the needs of patients whose pain is more than just an inconvenience and for whom daily use of a narcotic allows them to function—while also avoiding the pitfalls that we are now regularly warned about?

I have no doubt that each of us knows at least one person—a patient, a family member, a neighbor—for whom pain is a daily occurrence. But we must put that in perspective; not all pain is a barrier to physical and emotional functioning. Data suggest that a “33% to 50% decrease in pain intensity is meaningful from a patient’s perspective and represents a reasonable standard of intervention efficacy.”³ For those who deal with chronic pain, even a slight improvement is progress.

So, while the American Medical Association and the American Pain Society bicker about whether pain is the “fifth vital sign,” we must find a better means to resolve the discord in our society.⁴ Banning all opioid use is not the answer, but neither is considering narcotics the default treatment for pain.

We must remind our patients, our policymakers, and ourselves that identifying and assessing pain is not equated with writing an opioid or narcotic prescription. Nor will removing those medications from our formulary mitigate the crisis. We need to communicate a clear, consistent message that pain is real, that some pain is a fact of life, and that we will help our patients.

However, it is incumbent upon us to adopt a systematic yet personalized plan of care that is effective, cost conscious, culturally and developmentally appropriate, and safe—and that plan may or may not include prescribing narcotics. We have much work ahead of us in order to minimize the potential for misuse of these medications without impeding patients’ access to necessary health care.

Please share your thoughts on this conundrum by writing to NPEditor@frontlinemedcom.com.

Pain was introduced as the “fifth vital sign” in the 1990s, ranking it as important a measure as blood pressure, heart and respiratory rate, and temperature.¹ The American Pain Society promoted this notion to increase awareness of pain treatment among health care professionals. Emphasizing its importance, the Veterans Health Administration in 1999 launched the “Pain as the 5th Vital Sign” initiative, which mandated a pain intensity rating at all clinical encounters.²

Interestingly, the Joint Commission standards never stated that pain needed to be treated as a vital sign. But many organizations started to require documentation of routine pain screening for all patients. Health care providers were instructed to inquire about pain and to treat it as an essential element of health history.

These changes were quite controversial. The additional measure, while important, competed with other priority screening needs, including diabetes, cancer, and hypertension. There was—and continues to be—quite the debate on whether pain actually can be measured and what impact that information has on the quality of care.

I do not intend to enter that debate here. Instead, I want to discuss what continues to be a conundrum for me: the paradox of pain management.

For many patients, especially those in acute or emergency care settings, the presenting complaint is pain. I would submit that for many the expectation is for pain to be immediately and permanently relieved. But is this a realistic goal?

I recall a lecture on pain management I attended years ago; at that time, the approach involved early identification and prompt, aggressive treatment. When asked “How much medication and for how long?” the lecturer used diabetes as a treatment model, stating, “You would increase insulin until the blood glucose was controlled—don’t be afraid to increase pain medication until the pain is controlled.” In the early days of pain management, that was the accepted norm. The possibility that a “zero” on the pain scale was unattainable for some patients was not considered.

Yet seemingly overnight, once pain was decreed a vital sign, health care providers were mandated to measure it and faced with the responsibility to treat it. This resulted in a vague 0-10 pain scale and providers who were inadequately educated on how to begin pain management. Unlike with diabetes or hypertension, there was no protocol, algorithm, or standard upon which to base a plan of care. Moreover, there was a lack of differentiation between pain that was a short-lived nuisance and pain that interfered with quality of life.

Faced with growing concern for undertreated pain in the US, however, many of us strove to achieve a balance of sufficient yet appropriate treatment. We struggled to determine how to relieve the pain our patients experienced without creating other problems, such as undesirable side effects, misuse, or addiction. That ­predicament, paired with the ever-increasing direct-to-consumer advertisements about pain relief and the insistence by (some, not all) patients that nonnarcotic pain medication is ineffective, bred the crisis of opioid overuse and addiction we now face.

But just as I chose not to debate the impact of pain measurement on quality of care, I also choose not to debate the existence of the opioid crisis. What I want to emphasize is that all policy changes have consequences. I reach out to you, my colleagues, for innovative ideas to strike the delicate balance of appropriate use of narcotics. How do we address the needs of patients whose pain is more than just an inconvenience and for whom daily use of a narcotic allows them to function—while also avoiding the pitfalls that we are now regularly warned about?

I have no doubt that each of us knows at least one person—a patient, a family member, a neighbor—for whom pain is a daily occurrence. But we must put that in perspective; not all pain is a barrier to physical and emotional functioning. Data suggest that a “33% to 50% decrease in pain intensity is meaningful from a patient’s perspective and represents a reasonable standard of intervention efficacy.”³ For those who deal with chronic pain, even a slight improvement is progress.

So, while the American Medical Association and the American Pain Society bicker about whether pain is the “fifth vital sign,” we must find a better means to resolve the discord in our society.⁴ Banning all opioid use is not the answer, but neither is considering narcotics the default treatment for pain.

We must remind our patients, our policymakers, and ourselves that identifying and assessing pain is not equated with writing an opioid or narcotic prescription. Nor will removing those medications from our formulary mitigate the crisis. We need to communicate a clear, consistent message that pain is real, that some pain is a fact of life, and that we will help our patients.

However, it is incumbent upon us to adopt a systematic yet personalized plan of care that is effective, cost conscious, culturally and developmentally appropriate, and safe—and that plan may or may not include prescribing narcotics. We have much work ahead of us in order to minimize the potential for misuse of these medications without impeding patients’ access to necessary health care.

Please share your thoughts on this conundrum by writing to NPEditor@frontlinemedcom.com.

Clear contracts with payers are critical as physicians enter into value-based care arrangements. During a recent webinar presented by the American Bar Association, legal experts provided guidance on how doctors can successfully draft pay-for-performance contracts and prevent disputes with payers.

1. Clearly define terms

Contract terms and definitions should be clearly outlined and understood by both parties before value-based agreements are signed, said Melissa J. Hulke, a director in the Berkeley Research Group, LLC health analytics practice.

2. Review payment calculations

Ensure that payment formulas are examined and agreed upon.

3. Monitor results

Actively monitor projected-to-actual financial performance under the contract. If performance is not being monitored and results are not being tested, it’s impossible to tell whether the contract is succeeding or failing, Ms. Hulke said.

It’s a good idea to monitor projected-to-actual financial performance monthly or at least quarterly, she advised.

“Tracking budget to actual performance and investigating successes and failures are important if the contracts are material to the provider’s business,” Ms. Hulke said.
 

4. Institute time frames for government methodologies

Be specific about when contracts are linked to Medicare reimbursement methodologies.

If commercial payers are tying payment rates to government programs, which often occurs, contracts should include whether the reimbursement is based on Medicare rates and methodologies as of a particular date and time, according to Ms. Hulke. For instance, the contract could specify that rates are tied to Medicare methodologies at the time the contract was executed. Alternatively, contracts could allow the physician payment rate to fluctuate depending on changes the government makes to Medicare rates and methodologies during the span of the contract.

“If this is not defined, when Medicare makes a change, the parties may have differing opinions on the appropriate rate of reimbursement that’s being paid,” she said.
 

5. Structure around state and federal laws

Conduct a regulatory analysis before inking any value based payment arrangement/transaction, and structure and document around potential legal constraints, Ms. Hanna said.

Know the laws in your state, she advised. Some states have requirements for provider incentive programs, while others may have rules for provider organizations or intermediaries that assume certain financial risk. When working with federal health care payers, review the Stark Law and Anti-Kickback regulations and ensure that if triggered by the arrangement, the venture falls within an exception of the statutes. Other legal considerations when drafting contracts include:

• HIPAA and state privacy laws.

• Antitrust laws.

• Telemedicine and telehealth laws.

• Medicare Advantage benefit guidelines for programs designed for specific Medicare Advantage populations.

• Scope of practice laws applicable to mid-level medical providers.

6. Design a dispute-resolution strategy

Include a thorough dispute-resolution strategy within the contract. The strategies help facilitate an orderly process for resolving disputes cost effectively, Ms. Hanna said. She suggested that policies start with an informal dispute-resolution process that sends unresolved matters to senior executives at each organization.

“This allows business leaders – and not the lawyers – to find a business solution to a thorny and potentially costly problem before each party gets entrenched in its own position and own sense of having been wronged,” she said in an interview. “The business solution may or may not rely on contract language but may be tailored to keep the relationship moving forward. However, if the informal process proves unsuccessful, then the process gets punted to the legal system – whether in a court proceeding or arbitration.”
 

7. Have an exit strategy

Include an exit strategy that ensures an end to the arrangement goes as smoothly and fairly as possible. The strategy will depend on the nature and structure of the payer-provider alignment and the value-based payment arrangement, Ms. Hanna said in an interview.

For example, in a true, corporate joint venture, the exit strategy may include buyout rights of the newly formed entity. In this case, it’s important to consider and negotiate the price of the buyout and what circumstances that will trigger the buyout. Termination rights should also be included in an exit strategy, Ms. Hanna said. One option is to allow termination “without case,” by either party.

“Clients often do not like this approach because the intention of the parties going in is to build a strong, long-term relationship where provider and payer benefit,” she said. “A ‘without cause’ termination rights gives the parties a safety valve if circumstances change or the relationship is just not successful.”

An alternative is to allow the relationship time to mature and grow before either party can exercise a without cause termination. A related approach is to develop triggering events that would give one or both parties the right to terminate the agreement, without the other party “having committed a bad act,” Ms. Hanna said in the interview.

“For instance, if the relationship does not meet certain financial or other benchmarks within an agreed-upon time frame, this may be a sufficient reason to terminate the relationship, abandon, or renegotiate the value-based purchasing payment formula or, perhaps, end an exclusive or other preferential relationship,” she said.
 

agallegos@frontlinemedcom.com

On Twitter @legal_med

Clear contracts with payers are critical as physicians enter into value-based care arrangements. During a recent webinar presented by the American Bar Association, legal experts provided guidance on how doctors can successfully draft pay-for-performance contracts and prevent disputes with payers.

1. Clearly define terms

Contract terms and definitions should be clearly outlined and understood by both parties before value-based agreements are signed, said Melissa J. Hulke, a director in the Berkeley Research Group, LLC health analytics practice.

2. Review payment calculations

Ensure that payment formulas are examined and agreed upon.

3. Monitor results

Actively monitor projected-to-actual financial performance under the contract. If performance is not being monitored and results are not being tested, it’s impossible to tell whether the contract is succeeding or failing, Ms. Hulke said.

It’s a good idea to monitor projected-to-actual financial performance monthly or at least quarterly, she advised.

“Tracking budget to actual performance and investigating successes and failures are important if the contracts are material to the provider’s business,” Ms. Hulke said.
 

4. Institute time frames for government methodologies

Be specific about when contracts are linked to Medicare reimbursement methodologies.

If commercial payers are tying payment rates to government programs, which often occurs, contracts should include whether the reimbursement is based on Medicare rates and methodologies as of a particular date and time, according to Ms. Hulke. For instance, the contract could specify that rates are tied to Medicare methodologies at the time the contract was executed. Alternatively, contracts could allow the physician payment rate to fluctuate depending on changes the government makes to Medicare rates and methodologies during the span of the contract.

“If this is not defined, when Medicare makes a change, the parties may have differing opinions on the appropriate rate of reimbursement that’s being paid,” she said.
 

5. Structure around state and federal laws

Conduct a regulatory analysis before inking any value based payment arrangement/transaction, and structure and document around potential legal constraints, Ms. Hanna said.

Know the laws in your state, she advised. Some states have requirements for provider incentive programs, while others may have rules for provider organizations or intermediaries that assume certain financial risk. When working with federal health care payers, review the Stark Law and Anti-Kickback regulations and ensure that if triggered by the arrangement, the venture falls within an exception of the statutes. Other legal considerations when drafting contracts include:

• HIPAA and state privacy laws.

• Antitrust laws.

• Telemedicine and telehealth laws.

• Medicare Advantage benefit guidelines for programs designed for specific Medicare Advantage populations.

• Scope of practice laws applicable to mid-level medical providers.

6. Design a dispute-resolution strategy

Include a thorough dispute-resolution strategy within the contract. The strategies help facilitate an orderly process for resolving disputes cost effectively, Ms. Hanna said. She suggested that policies start with an informal dispute-resolution process that sends unresolved matters to senior executives at each organization.

“This allows business leaders – and not the lawyers – to find a business solution to a thorny and potentially costly problem before each party gets entrenched in its own position and own sense of having been wronged,” she said in an interview. “The business solution may or may not rely on contract language but may be tailored to keep the relationship moving forward. However, if the informal process proves unsuccessful, then the process gets punted to the legal system – whether in a court proceeding or arbitration.”
 

7. Have an exit strategy

Include an exit strategy that ensures an end to the arrangement goes as smoothly and fairly as possible. The strategy will depend on the nature and structure of the payer-provider alignment and the value-based payment arrangement, Ms. Hanna said in an interview.

For example, in a true, corporate joint venture, the exit strategy may include buyout rights of the newly formed entity. In this case, it’s important to consider and negotiate the price of the buyout and what circumstances that will trigger the buyout. Termination rights should also be included in an exit strategy, Ms. Hanna said. One option is to allow termination “without case,” by either party.

“Clients often do not like this approach because the intention of the parties going in is to build a strong, long-term relationship where provider and payer benefit,” she said. “A ‘without cause’ termination rights gives the parties a safety valve if circumstances change or the relationship is just not successful.”

An alternative is to allow the relationship time to mature and grow before either party can exercise a without cause termination. A related approach is to develop triggering events that would give one or both parties the right to terminate the agreement, without the other party “having committed a bad act,” Ms. Hanna said in the interview.

“For instance, if the relationship does not meet certain financial or other benchmarks within an agreed-upon time frame, this may be a sufficient reason to terminate the relationship, abandon, or renegotiate the value-based purchasing payment formula or, perhaps, end an exclusive or other preferential relationship,” she said.
 

agallegos@frontlinemedcom.com

On Twitter @legal_med

Clear contracts with payers are critical as physicians enter into value-based care arrangements. During a recent webinar presented by the American Bar Association, legal experts provided guidance on how doctors can successfully draft pay-for-performance contracts and prevent disputes with payers.

1. Clearly define terms

Contract terms and definitions should be clearly outlined and understood by both parties before value-based agreements are signed, said Melissa J. Hulke, a director in the Berkeley Research Group, LLC health analytics practice.

2. Review payment calculations

Ensure that payment formulas are examined and agreed upon.

3. Monitor results

Actively monitor projected-to-actual financial performance under the contract. If performance is not being monitored and results are not being tested, it’s impossible to tell whether the contract is succeeding or failing, Ms. Hulke said.

It’s a good idea to monitor projected-to-actual financial performance monthly or at least quarterly, she advised.

“Tracking budget to actual performance and investigating successes and failures are important if the contracts are material to the provider’s business,” Ms. Hulke said.
 

4. Institute time frames for government methodologies

Be specific about when contracts are linked to Medicare reimbursement methodologies.

If commercial payers are tying payment rates to government programs, which often occurs, contracts should include whether the reimbursement is based on Medicare rates and methodologies as of a particular date and time, according to Ms. Hulke. For instance, the contract could specify that rates are tied to Medicare methodologies at the time the contract was executed. Alternatively, contracts could allow the physician payment rate to fluctuate depending on changes the government makes to Medicare rates and methodologies during the span of the contract.

“If this is not defined, when Medicare makes a change, the parties may have differing opinions on the appropriate rate of reimbursement that’s being paid,” she said.
 

5. Structure around state and federal laws

Conduct a regulatory analysis before inking any value based payment arrangement/transaction, and structure and document around potential legal constraints, Ms. Hanna said.

Know the laws in your state, she advised. Some states have requirements for provider incentive programs, while others may have rules for provider organizations or intermediaries that assume certain financial risk. When working with federal health care payers, review the Stark Law and Anti-Kickback regulations and ensure that if triggered by the arrangement, the venture falls within an exception of the statutes. Other legal considerations when drafting contracts include:

• HIPAA and state privacy laws.

• Antitrust laws.

• Telemedicine and telehealth laws.

• Medicare Advantage benefit guidelines for programs designed for specific Medicare Advantage populations.

• Scope of practice laws applicable to mid-level medical providers.

6. Design a dispute-resolution strategy

Include a thorough dispute-resolution strategy within the contract. The strategies help facilitate an orderly process for resolving disputes cost effectively, Ms. Hanna said. She suggested that policies start with an informal dispute-resolution process that sends unresolved matters to senior executives at each organization.

“This allows business leaders – and not the lawyers – to find a business solution to a thorny and potentially costly problem before each party gets entrenched in its own position and own sense of having been wronged,” she said in an interview. “The business solution may or may not rely on contract language but may be tailored to keep the relationship moving forward. However, if the informal process proves unsuccessful, then the process gets punted to the legal system – whether in a court proceeding or arbitration.”
 

7. Have an exit strategy

Include an exit strategy that ensures an end to the arrangement goes as smoothly and fairly as possible. The strategy will depend on the nature and structure of the payer-provider alignment and the value-based payment arrangement, Ms. Hanna said in an interview.

For example, in a true, corporate joint venture, the exit strategy may include buyout rights of the newly formed entity. In this case, it’s important to consider and negotiate the price of the buyout and what circumstances that will trigger the buyout. Termination rights should also be included in an exit strategy, Ms. Hanna said. One option is to allow termination “without case,” by either party.

“Clients often do not like this approach because the intention of the parties going in is to build a strong, long-term relationship where provider and payer benefit,” she said. “A ‘without cause’ termination rights gives the parties a safety valve if circumstances change or the relationship is just not successful.”

An alternative is to allow the relationship time to mature and grow before either party can exercise a without cause termination. A related approach is to develop triggering events that would give one or both parties the right to terminate the agreement, without the other party “having committed a bad act,” Ms. Hanna said in the interview.

“For instance, if the relationship does not meet certain financial or other benchmarks within an agreed-upon time frame, this may be a sufficient reason to terminate the relationship, abandon, or renegotiate the value-based purchasing payment formula or, perhaps, end an exclusive or other preferential relationship,” she said.
 

agallegos@frontlinemedcom.com

On Twitter @legal_med

After 3 years of work, Anne Hanson and I are delighted that our book, “Committed: The Battle over Involuntary Psychiatric Care” was officially released Nov. 1! Our publisher, Johns Hopkins University Press, asked me to write a post for its blog to start the launch and with permission, Clinical Psychiatry News has let me begin the story of our research here as well.

So how did I find myself sitting in courtrooms and riding alongside a police officer? Let me tell you a little about the process of writing this book, because it was a quite the adventure for me. The title implies that this is another book by psychiatrists for psychiatrists, but for me, the days I spent working on this manuscript were days off from psychiatry. Those mornings I woke up a psychiatrist and felt like I walked into a phone booth (maybe it was just my shower) and emerged as a journalist.

After 3 years of work, Anne Hanson and I are delighted that our book, “Committed: The Battle over Involuntary Psychiatric Care” was officially released Nov. 1! Our publisher, Johns Hopkins University Press, asked me to write a post for its blog to start the launch and with permission, Clinical Psychiatry News has let me begin the story of our research here as well.

So how did I find myself sitting in courtrooms and riding alongside a police officer? Let me tell you a little about the process of writing this book, because it was a quite the adventure for me. The title implies that this is another book by psychiatrists for psychiatrists, but for me, the days I spent working on this manuscript were days off from psychiatry. Those mornings I woke up a psychiatrist and felt like I walked into a phone booth (maybe it was just my shower) and emerged as a journalist.

After 3 years of work, Anne Hanson and I are delighted that our book, “Committed: The Battle over Involuntary Psychiatric Care” was officially released Nov. 1! Our publisher, Johns Hopkins University Press, asked me to write a post for its blog to start the launch and with permission, Clinical Psychiatry News has let me begin the story of our research here as well.

So how did I find myself sitting in courtrooms and riding alongside a police officer? Let me tell you a little about the process of writing this book, because it was a quite the adventure for me. The title implies that this is another book by psychiatrists for psychiatrists, but for me, the days I spent working on this manuscript were days off from psychiatry. Those mornings I woke up a psychiatrist and felt like I walked into a phone booth (maybe it was just my shower) and emerged as a journalist.

LOS ANGELES – Female sex and the absence of wheezing were the only factors significantly associated with vocal cord dysfunction in patients with high pretest probability of disease, a retrospective analysis showed.

The findings differ from those of the Pittsburgh Vocal Cord Index, which identified symptoms of throat tightness, dysphonia, absence of wheezing, and the presence of odors as key features predictive of vocal cord dysfunction (VCD). “This proves the point that VCD is an elusive diagnosis,” lead study author Phalgoon Shah, MD, said, in an interview, at the annual meeting of the American College of Chest Physicians.

Doug Brunk/Frontline Medical News

LOS ANGELES – Female sex and the absence of wheezing were the only factors significantly associated with vocal cord dysfunction in patients with high pretest probability of disease, a retrospective analysis showed.

The findings differ from those of the Pittsburgh Vocal Cord Index, which identified symptoms of throat tightness, dysphonia, absence of wheezing, and the presence of odors as key features predictive of vocal cord dysfunction (VCD). “This proves the point that VCD is an elusive diagnosis,” lead study author Phalgoon Shah, MD, said, in an interview, at the annual meeting of the American College of Chest Physicians.

Doug Brunk/Frontline Medical News

LOS ANGELES – Female sex and the absence of wheezing were the only factors significantly associated with vocal cord dysfunction in patients with high pretest probability of disease, a retrospective analysis showed.

The findings differ from those of the Pittsburgh Vocal Cord Index, which identified symptoms of throat tightness, dysphonia, absence of wheezing, and the presence of odors as key features predictive of vocal cord dysfunction (VCD). “This proves the point that VCD is an elusive diagnosis,” lead study author Phalgoon Shah, MD, said, in an interview, at the annual meeting of the American College of Chest Physicians.

Doug Brunk/Frontline Medical News

A triple-drug antiretroviral therapy given to HIV-infected pregnant women significantly reduced transmission of the disease to their newborns, but with greater risk of adverse outcomes for mothers and infants, a study showed.

The findings were based on data from three treatment regimens in approximately 3,500 women and infant sets. The three treatments were zidovudine plus intrapartum single-dose nevirapine with 6-14 days of tenofovir and emtricitabine post partum (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based antiretroviral therapy [ART]); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). All infants received nevirapine once daily, and infants of mothers coinfected with hepatitis B also received hepatitis B vaccination.

MattZ90/Thinkstock.com

A triple-drug antiretroviral therapy given to HIV-infected pregnant women significantly reduced transmission of the disease to their newborns, but with greater risk of adverse outcomes for mothers and infants, a study showed.

The findings were based on data from three treatment regimens in approximately 3,500 women and infant sets. The three treatments were zidovudine plus intrapartum single-dose nevirapine with 6-14 days of tenofovir and emtricitabine post partum (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based antiretroviral therapy [ART]); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). All infants received nevirapine once daily, and infants of mothers coinfected with hepatitis B also received hepatitis B vaccination.

MattZ90/Thinkstock.com

A triple-drug antiretroviral therapy given to HIV-infected pregnant women significantly reduced transmission of the disease to their newborns, but with greater risk of adverse outcomes for mothers and infants, a study showed.

The findings were based on data from three treatment regimens in approximately 3,500 women and infant sets. The three treatments were zidovudine plus intrapartum single-dose nevirapine with 6-14 days of tenofovir and emtricitabine post partum (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based antiretroviral therapy [ART]); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). All infants received nevirapine once daily, and infants of mothers coinfected with hepatitis B also received hepatitis B vaccination.

MattZ90/Thinkstock.com

Two patients taking the immune checkpoint inhibitors nivolumab and ipilimumab for metastatic melanoma developed fulminant, fatal myocarditis, investigators reported in the New England Journal of Medicine.

Even though this adverse effect is rare, “clinicians should be vigilant for immune-mediated myocarditis, particularly because of its early onset, nonspecific symptomatology, and fulminant progression,” said Douglas B. Johnson, MD, of Vanderbilt University Medical Center, Nashville, and his associates.

The first case involved a 65-year-old woman with no cardiac risk factors who was admitted to the hospital with chest pain, dyspnea, and fatigue 12 days after she received her first dose of the combination therapy. She was found to have myocarditis and myositis with rhabdomylysis. Despite treatment with high-dose glucocorticoids, she developed intraventricular conduction delay within 24 hours, followed by complete heart block. She died from multisystem organ failure and refractory ventricular tachycardia.

The second case involved a 63-year-old man with no cardiac risk factors who was admitted with fatigue and myalgias 15 days after he received his first dose of the combination therapy. He showed profound ST-segment depression, an intraventricular conduction delay, myocarditis, and myositis. He also was treated with high-dose glucocorticoids but developed complete heart block and died from cardiac arrest.

Both patients had “strikingly elevated troponin levels and refractory conduction-system abnormalities with preserved cardiac function,” the investigators noted. Postmortem assessments showed intense lymphocytic infiltrates only in striated cardiac and skeletal muscle and in metastases; adjacent smooth muscle and other tissues were unaffected. Pathology results “were reminiscent of those observed in patients with acute allograft rejection after cardiac transplantation,” Dr. Johnson and his associates said (N Engl J Med. 2016 Nov 3. doi: 10.1056/NEJMoa1609214).

To assess the frequency of myocarditis and myositis in patients receiving immune checkpoint inhibitors for many different cancers, the investigators searched Bristol-Myers Squibb safety databases. They found 18 drug-related cases of severe myocarditis among 20,594 patients, for a frequency of 0.09%. Patients who received combined nivolumab and ipilimumab had more frequent and more severe myocarditis than those who took either agent alone.

“There are no known data regarding what monitoring strategy may be of value; in our practice, we are performing baseline ECG and weekly testing of troponin levels during weeks 1-3 for patients receiving combination immunotherapy,” the researchers noted.

This work was supported by the Bready Family Foundation, the National Cancer Institute, Vanderbilt-Ingram Cancer Center Ambassadors, the Breast Cancer Specialized Program of Research Excellence, the National Comprehensive Cancer Network, the National Institutes of Health, the Howard Hughes Medical Institute, and Gilead Life Sciences. Dr. Johnson reported receiving personal fees from Genoptix and Bristol-Myers Squibb, and his associates reported ties to numerous industry sources.

Two patients taking the immune checkpoint inhibitors nivolumab and ipilimumab for metastatic melanoma developed fulminant, fatal myocarditis, investigators reported in the New England Journal of Medicine.

Even though this adverse effect is rare, “clinicians should be vigilant for immune-mediated myocarditis, particularly because of its early onset, nonspecific symptomatology, and fulminant progression,” said Douglas B. Johnson, MD, of Vanderbilt University Medical Center, Nashville, and his associates.

The first case involved a 65-year-old woman with no cardiac risk factors who was admitted to the hospital with chest pain, dyspnea, and fatigue 12 days after she received her first dose of the combination therapy. She was found to have myocarditis and myositis with rhabdomylysis. Despite treatment with high-dose glucocorticoids, she developed intraventricular conduction delay within 24 hours, followed by complete heart block. She died from multisystem organ failure and refractory ventricular tachycardia.

The second case involved a 63-year-old man with no cardiac risk factors who was admitted with fatigue and myalgias 15 days after he received his first dose of the combination therapy. He showed profound ST-segment depression, an intraventricular conduction delay, myocarditis, and myositis. He also was treated with high-dose glucocorticoids but developed complete heart block and died from cardiac arrest.

Both patients had “strikingly elevated troponin levels and refractory conduction-system abnormalities with preserved cardiac function,” the investigators noted. Postmortem assessments showed intense lymphocytic infiltrates only in striated cardiac and skeletal muscle and in metastases; adjacent smooth muscle and other tissues were unaffected. Pathology results “were reminiscent of those observed in patients with acute allograft rejection after cardiac transplantation,” Dr. Johnson and his associates said (N Engl J Med. 2016 Nov 3. doi: 10.1056/NEJMoa1609214).

To assess the frequency of myocarditis and myositis in patients receiving immune checkpoint inhibitors for many different cancers, the investigators searched Bristol-Myers Squibb safety databases. They found 18 drug-related cases of severe myocarditis among 20,594 patients, for a frequency of 0.09%. Patients who received combined nivolumab and ipilimumab had more frequent and more severe myocarditis than those who took either agent alone.

“There are no known data regarding what monitoring strategy may be of value; in our practice, we are performing baseline ECG and weekly testing of troponin levels during weeks 1-3 for patients receiving combination immunotherapy,” the researchers noted.

This work was supported by the Bready Family Foundation, the National Cancer Institute, Vanderbilt-Ingram Cancer Center Ambassadors, the Breast Cancer Specialized Program of Research Excellence, the National Comprehensive Cancer Network, the National Institutes of Health, the Howard Hughes Medical Institute, and Gilead Life Sciences. Dr. Johnson reported receiving personal fees from Genoptix and Bristol-Myers Squibb, and his associates reported ties to numerous industry sources.

Two patients taking the immune checkpoint inhibitors nivolumab and ipilimumab for metastatic melanoma developed fulminant, fatal myocarditis, investigators reported in the New England Journal of Medicine.

Even though this adverse effect is rare, “clinicians should be vigilant for immune-mediated myocarditis, particularly because of its early onset, nonspecific symptomatology, and fulminant progression,” said Douglas B. Johnson, MD, of Vanderbilt University Medical Center, Nashville, and his associates.

The first case involved a 65-year-old woman with no cardiac risk factors who was admitted to the hospital with chest pain, dyspnea, and fatigue 12 days after she received her first dose of the combination therapy. She was found to have myocarditis and myositis with rhabdomylysis. Despite treatment with high-dose glucocorticoids, she developed intraventricular conduction delay within 24 hours, followed by complete heart block. She died from multisystem organ failure and refractory ventricular tachycardia.

The second case involved a 63-year-old man with no cardiac risk factors who was admitted with fatigue and myalgias 15 days after he received his first dose of the combination therapy. He showed profound ST-segment depression, an intraventricular conduction delay, myocarditis, and myositis. He also was treated with high-dose glucocorticoids but developed complete heart block and died from cardiac arrest.

Both patients had “strikingly elevated troponin levels and refractory conduction-system abnormalities with preserved cardiac function,” the investigators noted. Postmortem assessments showed intense lymphocytic infiltrates only in striated cardiac and skeletal muscle and in metastases; adjacent smooth muscle and other tissues were unaffected. Pathology results “were reminiscent of those observed in patients with acute allograft rejection after cardiac transplantation,” Dr. Johnson and his associates said (N Engl J Med. 2016 Nov 3. doi: 10.1056/NEJMoa1609214).

To assess the frequency of myocarditis and myositis in patients receiving immune checkpoint inhibitors for many different cancers, the investigators searched Bristol-Myers Squibb safety databases. They found 18 drug-related cases of severe myocarditis among 20,594 patients, for a frequency of 0.09%. Patients who received combined nivolumab and ipilimumab had more frequent and more severe myocarditis than those who took either agent alone.

“There are no known data regarding what monitoring strategy may be of value; in our practice, we are performing baseline ECG and weekly testing of troponin levels during weeks 1-3 for patients receiving combination immunotherapy,” the researchers noted.

This work was supported by the Bready Family Foundation, the National Cancer Institute, Vanderbilt-Ingram Cancer Center Ambassadors, the Breast Cancer Specialized Program of Research Excellence, the National Comprehensive Cancer Network, the National Institutes of Health, the Howard Hughes Medical Institute, and Gilead Life Sciences. Dr. Johnson reported receiving personal fees from Genoptix and Bristol-Myers Squibb, and his associates reported ties to numerous industry sources.

The American Academy of Pediatrics released a new set of recommendations for the appropriate amount of screen time for children and adolescents in October 2016.

Among other changes, the AAP now recommends no screen time (except for video chatting) for infants and children up to 18 months old. For 18- to 24-month-olds, the AAP discourages screen time, recommending that parents introduce only selected “high-quality” programming and cowatch with their children. Likewise, for children up to 5 years old, the AAP urges parents to limit all screen time to 1 hour/day, half of its previous recommendation, and again recommends that parents cowatch with their children and use only reliable providers of quality content, such as the Public Broadcasting Service (PBS). For older children, the AAP does not set specific time limits, but recommends that parents collaborate with the children on a media plan that limits screen time so that it does not interfere with other important activities, including homework, social time, exercise, and sleep.

BunnyHollywood/iStockphoto.com

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@frontlinemedcom.com.

The American Academy of Pediatrics released a new set of recommendations for the appropriate amount of screen time for children and adolescents in October 2016.

Among other changes, the AAP now recommends no screen time (except for video chatting) for infants and children up to 18 months old. For 18- to 24-month-olds, the AAP discourages screen time, recommending that parents introduce only selected “high-quality” programming and cowatch with their children. Likewise, for children up to 5 years old, the AAP urges parents to limit all screen time to 1 hour/day, half of its previous recommendation, and again recommends that parents cowatch with their children and use only reliable providers of quality content, such as the Public Broadcasting Service (PBS). For older children, the AAP does not set specific time limits, but recommends that parents collaborate with the children on a media plan that limits screen time so that it does not interfere with other important activities, including homework, social time, exercise, and sleep.

BunnyHollywood/iStockphoto.com

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@frontlinemedcom.com.

The American Academy of Pediatrics released a new set of recommendations for the appropriate amount of screen time for children and adolescents in October 2016.

Among other changes, the AAP now recommends no screen time (except for video chatting) for infants and children up to 18 months old. For 18- to 24-month-olds, the AAP discourages screen time, recommending that parents introduce only selected “high-quality” programming and cowatch with their children. Likewise, for children up to 5 years old, the AAP urges parents to limit all screen time to 1 hour/day, half of its previous recommendation, and again recommends that parents cowatch with their children and use only reliable providers of quality content, such as the Public Broadcasting Service (PBS). For older children, the AAP does not set specific time limits, but recommends that parents collaborate with the children on a media plan that limits screen time so that it does not interfere with other important activities, including homework, social time, exercise, and sleep.

BunnyHollywood/iStockphoto.com

Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@frontlinemedcom.com.