HIV/AIDs, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights in President Donald Trump’s second State of the Union Address. Also today, public health experts have attributed to the opioid epidemic the recent alarming rise in the rate of hepatitis C virus infection. medical advice prompts unneeded emergency visits by patients with atrial fibrillation, and legal marijuana may complicate substance use disorder treatment in adolescents.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

HIV/AIDs, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights in President Donald Trump’s second State of the Union Address. Also today, public health experts have attributed to the opioid epidemic the recent alarming rise in the rate of hepatitis C virus infection. medical advice prompts unneeded emergency visits by patients with atrial fibrillation, and legal marijuana may complicate substance use disorder treatment in adolescents.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

HIV/AIDs, pediatric cancer research, abortion, prescription drug prices, and preexisting conditions were among the health care highlights in President Donald Trump’s second State of the Union Address. Also today, public health experts have attributed to the opioid epidemic the recent alarming rise in the rate of hepatitis C virus infection. medical advice prompts unneeded emergency visits by patients with atrial fibrillation, and legal marijuana may complicate substance use disorder treatment in adolescents.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify

The opioid emergency claims > 130 lives every day, says Health Resources and Services Administration (HRSA) Administrator George Sigounas, MS, PhD. By strengthening the health workforce, HRSA hopes to ensure that there are enough clinicians to cope with the growing epidemic.

That is why, in December 2018, HRSA launched a program that Sigounas says is “critical to HHS’ response to the opioid crisis.” The new National Health Service Corps (NHSC) Substance Use Disorder (SUD) Workforce Loan Repayment Program (LRP) will provide eligible health care clinicians with student loan repayment assistance in exchange for service in underserved communities.

A clinician may be awarded up to $75,000 for 3 years of full-time service at an NHSC-approved SUD site and $37,500 for part-time. Eligible providers use evidence-based treatment models to treat SUDs and must be trained and licensed to provide SUD treatment at NHSC-approved facilities. Qualification criteria are available at https://nhsc.hrsa.gov/loan-repayment/nhsc-sud-workforce-loan-repayment-program.html.

Clinicians also can apply to the NHSC Loan Repayment Program for primary care, dental, and behavioral health professionals. If accepted, they may receive up to $50,000 for 2 years of full-time service, $25,000 for part-time.

Military reservists also are eligible to participate in either the NHSC LRP or the NHSC Students to Service Loan Repayment Program. (Military training or service will not satisfy the NHSC service commitment.) More information is available at https://nhsc.hrsa.gov/loan-repayment/military-reservists.html.

Clinicians can only apply for 1 program. Sigounas says, “I am grateful to the clinicians who will apply and are looking to make a positive impact on patients, caregivers, and hard-hit communities throughout the country.”

The opioid emergency claims > 130 lives every day, says Health Resources and Services Administration (HRSA) Administrator George Sigounas, MS, PhD. By strengthening the health workforce, HRSA hopes to ensure that there are enough clinicians to cope with the growing epidemic.

That is why, in December 2018, HRSA launched a program that Sigounas says is “critical to HHS’ response to the opioid crisis.” The new National Health Service Corps (NHSC) Substance Use Disorder (SUD) Workforce Loan Repayment Program (LRP) will provide eligible health care clinicians with student loan repayment assistance in exchange for service in underserved communities.

A clinician may be awarded up to $75,000 for 3 years of full-time service at an NHSC-approved SUD site and $37,500 for part-time. Eligible providers use evidence-based treatment models to treat SUDs and must be trained and licensed to provide SUD treatment at NHSC-approved facilities. Qualification criteria are available at https://nhsc.hrsa.gov/loan-repayment/nhsc-sud-workforce-loan-repayment-program.html.

Clinicians also can apply to the NHSC Loan Repayment Program for primary care, dental, and behavioral health professionals. If accepted, they may receive up to $50,000 for 2 years of full-time service, $25,000 for part-time.

Military reservists also are eligible to participate in either the NHSC LRP or the NHSC Students to Service Loan Repayment Program. (Military training or service will not satisfy the NHSC service commitment.) More information is available at https://nhsc.hrsa.gov/loan-repayment/military-reservists.html.

Clinicians can only apply for 1 program. Sigounas says, “I am grateful to the clinicians who will apply and are looking to make a positive impact on patients, caregivers, and hard-hit communities throughout the country.”

The opioid emergency claims > 130 lives every day, says Health Resources and Services Administration (HRSA) Administrator George Sigounas, MS, PhD. By strengthening the health workforce, HRSA hopes to ensure that there are enough clinicians to cope with the growing epidemic.

That is why, in December 2018, HRSA launched a program that Sigounas says is “critical to HHS’ response to the opioid crisis.” The new National Health Service Corps (NHSC) Substance Use Disorder (SUD) Workforce Loan Repayment Program (LRP) will provide eligible health care clinicians with student loan repayment assistance in exchange for service in underserved communities.

A clinician may be awarded up to $75,000 for 3 years of full-time service at an NHSC-approved SUD site and $37,500 for part-time. Eligible providers use evidence-based treatment models to treat SUDs and must be trained and licensed to provide SUD treatment at NHSC-approved facilities. Qualification criteria are available at https://nhsc.hrsa.gov/loan-repayment/nhsc-sud-workforce-loan-repayment-program.html.

Clinicians also can apply to the NHSC Loan Repayment Program for primary care, dental, and behavioral health professionals. If accepted, they may receive up to $50,000 for 2 years of full-time service, $25,000 for part-time.

Military reservists also are eligible to participate in either the NHSC LRP or the NHSC Students to Service Loan Repayment Program. (Military training or service will not satisfy the NHSC service commitment.) More information is available at https://nhsc.hrsa.gov/loan-repayment/military-reservists.html.

Clinicians can only apply for 1 program. Sigounas says, “I am grateful to the clinicians who will apply and are looking to make a positive impact on patients, caregivers, and hard-hit communities throughout the country.”

Due to the dark and rapidly growing nodule, the FP immediately worried about melanoma.

He thought that he should biopsy the entire lesion with an elliptical excision, so he scheduled the patient for a biopsy during some protected surgical time later that week. The patient did not show up for this appointment. Several calls were placed, and she returned for the biopsy the following week. The FP performed a narrow margin (2 mm) elliptical excision oriented to match the lymphatic drainage of the arm. He closed the excision with a 2-layer closure. (See the Watch & Learn video on elliptical excision.) The pathology report confirmed that it was a nodular melanoma that was 8 mm in depth. This was clearly an aggressive tumor, so the patient was referred to Surgical Oncology for sentinel lymph node biopsy. One node was positive for metastasis.

After a wide excision with 2 cm margins by Surgical Oncology, the patient underwent a course of chemotherapy and remained disease free 2 years later. She was carefully monitored for metastasis and new primary lesions by a multidisciplinary team that included family medicine, dermatology, and oncology.

While this FP handled the case in an excellent matter, he was fortunate to have the skills and time to be able to perform a full elliptical excision. It’s important to note that a 6 mm punch biopsy or a deep shave biopsy (saucerization) at the base of the thickest portion of this tumor would almost certainly have provided the same diagnosis of melanoma and at least showed that the tumor was thicker than 4 mm (an important cut-off for management). This could have been done on the day of original presentation and might have avoided the problem of the patient not showing up for the next appointment or a long delay to see a dermatologist.

FPs should be empowered to perform biopsies on the most worrisome of lesions as these biopsies can save lives. While incomplete sampling can result in false negative results and misdiagnosis, the protection against this is to not accept a benign pathology report in what appears to be an obvious malignancy. If this occurs, the next step is always complete excision. Having options and understanding potential sampling errors can help FPs diagnose patients more rapidly. This is essential when cancers are rapidly growing and delays of months for surgical appointments or referrals to specialists can worsen a prognosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Melanoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1112-1123.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Due to the dark and rapidly growing nodule, the FP immediately worried about melanoma.

He thought that he should biopsy the entire lesion with an elliptical excision, so he scheduled the patient for a biopsy during some protected surgical time later that week. The patient did not show up for this appointment. Several calls were placed, and she returned for the biopsy the following week. The FP performed a narrow margin (2 mm) elliptical excision oriented to match the lymphatic drainage of the arm. He closed the excision with a 2-layer closure. (See the Watch & Learn video on elliptical excision.) The pathology report confirmed that it was a nodular melanoma that was 8 mm in depth. This was clearly an aggressive tumor, so the patient was referred to Surgical Oncology for sentinel lymph node biopsy. One node was positive for metastasis.

After a wide excision with 2 cm margins by Surgical Oncology, the patient underwent a course of chemotherapy and remained disease free 2 years later. She was carefully monitored for metastasis and new primary lesions by a multidisciplinary team that included family medicine, dermatology, and oncology.

While this FP handled the case in an excellent matter, he was fortunate to have the skills and time to be able to perform a full elliptical excision. It’s important to note that a 6 mm punch biopsy or a deep shave biopsy (saucerization) at the base of the thickest portion of this tumor would almost certainly have provided the same diagnosis of melanoma and at least showed that the tumor was thicker than 4 mm (an important cut-off for management). This could have been done on the day of original presentation and might have avoided the problem of the patient not showing up for the next appointment or a long delay to see a dermatologist.

FPs should be empowered to perform biopsies on the most worrisome of lesions as these biopsies can save lives. While incomplete sampling can result in false negative results and misdiagnosis, the protection against this is to not accept a benign pathology report in what appears to be an obvious malignancy. If this occurs, the next step is always complete excision. Having options and understanding potential sampling errors can help FPs diagnose patients more rapidly. This is essential when cancers are rapidly growing and delays of months for surgical appointments or referrals to specialists can worsen a prognosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Melanoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1112-1123.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Due to the dark and rapidly growing nodule, the FP immediately worried about melanoma.

He thought that he should biopsy the entire lesion with an elliptical excision, so he scheduled the patient for a biopsy during some protected surgical time later that week. The patient did not show up for this appointment. Several calls were placed, and she returned for the biopsy the following week. The FP performed a narrow margin (2 mm) elliptical excision oriented to match the lymphatic drainage of the arm. He closed the excision with a 2-layer closure. (See the Watch & Learn video on elliptical excision.) The pathology report confirmed that it was a nodular melanoma that was 8 mm in depth. This was clearly an aggressive tumor, so the patient was referred to Surgical Oncology for sentinel lymph node biopsy. One node was positive for metastasis.

After a wide excision with 2 cm margins by Surgical Oncology, the patient underwent a course of chemotherapy and remained disease free 2 years later. She was carefully monitored for metastasis and new primary lesions by a multidisciplinary team that included family medicine, dermatology, and oncology.

While this FP handled the case in an excellent matter, he was fortunate to have the skills and time to be able to perform a full elliptical excision. It’s important to note that a 6 mm punch biopsy or a deep shave biopsy (saucerization) at the base of the thickest portion of this tumor would almost certainly have provided the same diagnosis of melanoma and at least showed that the tumor was thicker than 4 mm (an important cut-off for management). This could have been done on the day of original presentation and might have avoided the problem of the patient not showing up for the next appointment or a long delay to see a dermatologist.

FPs should be empowered to perform biopsies on the most worrisome of lesions as these biopsies can save lives. While incomplete sampling can result in false negative results and misdiagnosis, the protection against this is to not accept a benign pathology report in what appears to be an obvious malignancy. If this occurs, the next step is always complete excision. Having options and understanding potential sampling errors can help FPs diagnose patients more rapidly. This is essential when cancers are rapidly growing and delays of months for surgical appointments or referrals to specialists can worsen a prognosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Melanoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1112-1123.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

Around three-quarters of people with type 2 diabetes mellitus (T2DM) who undergo Roux-en-Y gastric bypass experience remission of their disease within a year of the surgery, according to published findings from a population-based observational study. However, one in four of those people will have relapsed by 5 years, the authors noted.

Researchers looked at the effect of Roux-en-Y gastric bypass (RYGB) in 1,111 individuals with T2DM, compared with 1,074 controls who also had T2DM but did not undergo gastric bypass.

By 6 months after surgery, 65% of those who had undergone RYGB met the criteria for remission – defined as no use of glucose-lowering drugs and an HbA_1c below 48 mmol/mol (less than 6.5%) or metformin monotherapy with HbA_1c below 42 mmol/mol (less than 6.0%).

By 1 year, 74% of those who had surgery had achieved remission, and 73% of those remained in remission 5 years after surgery. However, at 2 years, 6% of those who had achieved remission in the first year had already relapsed; by 3 years, 12% had relapsed; and by 4 years, 18% had relapsed. By 5 years after surgery, a total of 27% of those who originally achieved remission in the first year had relapsed.

The overall prevalence of remission remained at 70% for every 6-month period during the duration of the study, which suggests that, although some achieved remission early and then relapsed, others achieved remission later.

Individuals who were aged 50-60 years were 12% less likely to achieve remission, compared with those who were younger than 40 years, whereas those aged 60 years or more were 17% less likely to achieve remission.

A longer duration of diabetes was also associated with a lower likelihood of achieving remission after RYGB; individuals who had had diabetes for 8 years or more had a 27% lower likelihood of remission, compared with those who had had the disease for less than 2 years.

A higher HbA_1c (greater than 53 mmol/mol) was associated with a 19% lower likelihood of remission, and individuals using insulin had a 43% lower likelihood of remission.

“Overall, our findings add evidence to the importance of regular check-ups following RYGB, despite initial diabetes remission, and also suggest that timing of RYGB is important (i.e., consider RYGB while there are still functional pancreatic beta cells),” wrote Lene R. Madsen, MD, from the department of endocrinology and internal medicine at Aarhus (Denmark) University Hospital and her colleagues.

The study also examined the effect of RYGB on microvascular and macrovascular diabetes complications. This revealed that the incidence of diabetic retinopathy was nearly halved among individuals who had undergone gastric bypass, the incidence of hospital-coded diabetic kidney disease was 46% lower, and the incidence of diabetic neuropathy was 16% lower.

In particular, individuals who achieved remission in the first year after surgery had a 57% lower incidence of microvascular events, compared with those who did not have surgery.

The authors noted that individuals who did not reach the threshold for diabetes remission after surgery still showed signs of better glycemic control, compared with individuals who had not undergone surgery.

“This aligns with the theory of ‘metabolic memory’ introduced by Coleman et al. [Diabetes Care. 2016;39(8):1400-07], suggesting that time spent in diabetes remission after RYGB is not spent in vain when it comes to reducing the risk of subsequent microvascular complications,” they wrote.

The surgery was also associated with a 46% reduction in the incidence of ischemic heart disease. In the first 30 days after surgery, 7.5% of patients were readmitted to hospital for any surgical complication, but the 90-day mortality rate after surgery was less than 0.5%.

The study was supported by the Health Research Fund of Central Denmark, the Novo Nordisk Foundation, and the A.P. Møller Foundation. The authors reported no conflicts of interest.

SOURCE: Madsen LR et al. Diabetologia. 2019, Feb 6. doi: 10.1007/s00125-019-4816-2.

Around three-quarters of people with type 2 diabetes mellitus (T2DM) who undergo Roux-en-Y gastric bypass experience remission of their disease within a year of the surgery, according to published findings from a population-based observational study. However, one in four of those people will have relapsed by 5 years, the authors noted.

Researchers looked at the effect of Roux-en-Y gastric bypass (RYGB) in 1,111 individuals with T2DM, compared with 1,074 controls who also had T2DM but did not undergo gastric bypass.

By 6 months after surgery, 65% of those who had undergone RYGB met the criteria for remission – defined as no use of glucose-lowering drugs and an HbA_1c below 48 mmol/mol (less than 6.5%) or metformin monotherapy with HbA_1c below 42 mmol/mol (less than 6.0%).

By 1 year, 74% of those who had surgery had achieved remission, and 73% of those remained in remission 5 years after surgery. However, at 2 years, 6% of those who had achieved remission in the first year had already relapsed; by 3 years, 12% had relapsed; and by 4 years, 18% had relapsed. By 5 years after surgery, a total of 27% of those who originally achieved remission in the first year had relapsed.

The overall prevalence of remission remained at 70% for every 6-month period during the duration of the study, which suggests that, although some achieved remission early and then relapsed, others achieved remission later.

Individuals who were aged 50-60 years were 12% less likely to achieve remission, compared with those who were younger than 40 years, whereas those aged 60 years or more were 17% less likely to achieve remission.

A longer duration of diabetes was also associated with a lower likelihood of achieving remission after RYGB; individuals who had had diabetes for 8 years or more had a 27% lower likelihood of remission, compared with those who had had the disease for less than 2 years.

A higher HbA_1c (greater than 53 mmol/mol) was associated with a 19% lower likelihood of remission, and individuals using insulin had a 43% lower likelihood of remission.

“Overall, our findings add evidence to the importance of regular check-ups following RYGB, despite initial diabetes remission, and also suggest that timing of RYGB is important (i.e., consider RYGB while there are still functional pancreatic beta cells),” wrote Lene R. Madsen, MD, from the department of endocrinology and internal medicine at Aarhus (Denmark) University Hospital and her colleagues.

The study also examined the effect of RYGB on microvascular and macrovascular diabetes complications. This revealed that the incidence of diabetic retinopathy was nearly halved among individuals who had undergone gastric bypass, the incidence of hospital-coded diabetic kidney disease was 46% lower, and the incidence of diabetic neuropathy was 16% lower.

In particular, individuals who achieved remission in the first year after surgery had a 57% lower incidence of microvascular events, compared with those who did not have surgery.

The authors noted that individuals who did not reach the threshold for diabetes remission after surgery still showed signs of better glycemic control, compared with individuals who had not undergone surgery.

“This aligns with the theory of ‘metabolic memory’ introduced by Coleman et al. [Diabetes Care. 2016;39(8):1400-07], suggesting that time spent in diabetes remission after RYGB is not spent in vain when it comes to reducing the risk of subsequent microvascular complications,” they wrote.

The surgery was also associated with a 46% reduction in the incidence of ischemic heart disease. In the first 30 days after surgery, 7.5% of patients were readmitted to hospital for any surgical complication, but the 90-day mortality rate after surgery was less than 0.5%.

The study was supported by the Health Research Fund of Central Denmark, the Novo Nordisk Foundation, and the A.P. Møller Foundation. The authors reported no conflicts of interest.

SOURCE: Madsen LR et al. Diabetologia. 2019, Feb 6. doi: 10.1007/s00125-019-4816-2.

Around three-quarters of people with type 2 diabetes mellitus (T2DM) who undergo Roux-en-Y gastric bypass experience remission of their disease within a year of the surgery, according to published findings from a population-based observational study. However, one in four of those people will have relapsed by 5 years, the authors noted.

Researchers looked at the effect of Roux-en-Y gastric bypass (RYGB) in 1,111 individuals with T2DM, compared with 1,074 controls who also had T2DM but did not undergo gastric bypass.

By 6 months after surgery, 65% of those who had undergone RYGB met the criteria for remission – defined as no use of glucose-lowering drugs and an HbA_1c below 48 mmol/mol (less than 6.5%) or metformin monotherapy with HbA_1c below 42 mmol/mol (less than 6.0%).

By 1 year, 74% of those who had surgery had achieved remission, and 73% of those remained in remission 5 years after surgery. However, at 2 years, 6% of those who had achieved remission in the first year had already relapsed; by 3 years, 12% had relapsed; and by 4 years, 18% had relapsed. By 5 years after surgery, a total of 27% of those who originally achieved remission in the first year had relapsed.

The overall prevalence of remission remained at 70% for every 6-month period during the duration of the study, which suggests that, although some achieved remission early and then relapsed, others achieved remission later.

Individuals who were aged 50-60 years were 12% less likely to achieve remission, compared with those who were younger than 40 years, whereas those aged 60 years or more were 17% less likely to achieve remission.

A longer duration of diabetes was also associated with a lower likelihood of achieving remission after RYGB; individuals who had had diabetes for 8 years or more had a 27% lower likelihood of remission, compared with those who had had the disease for less than 2 years.

A higher HbA_1c (greater than 53 mmol/mol) was associated with a 19% lower likelihood of remission, and individuals using insulin had a 43% lower likelihood of remission.

“Overall, our findings add evidence to the importance of regular check-ups following RYGB, despite initial diabetes remission, and also suggest that timing of RYGB is important (i.e., consider RYGB while there are still functional pancreatic beta cells),” wrote Lene R. Madsen, MD, from the department of endocrinology and internal medicine at Aarhus (Denmark) University Hospital and her colleagues.

The study also examined the effect of RYGB on microvascular and macrovascular diabetes complications. This revealed that the incidence of diabetic retinopathy was nearly halved among individuals who had undergone gastric bypass, the incidence of hospital-coded diabetic kidney disease was 46% lower, and the incidence of diabetic neuropathy was 16% lower.

In particular, individuals who achieved remission in the first year after surgery had a 57% lower incidence of microvascular events, compared with those who did not have surgery.

The authors noted that individuals who did not reach the threshold for diabetes remission after surgery still showed signs of better glycemic control, compared with individuals who had not undergone surgery.

“This aligns with the theory of ‘metabolic memory’ introduced by Coleman et al. [Diabetes Care. 2016;39(8):1400-07], suggesting that time spent in diabetes remission after RYGB is not spent in vain when it comes to reducing the risk of subsequent microvascular complications,” they wrote.

The surgery was also associated with a 46% reduction in the incidence of ischemic heart disease. In the first 30 days after surgery, 7.5% of patients were readmitted to hospital for any surgical complication, but the 90-day mortality rate after surgery was less than 0.5%.

The study was supported by the Health Research Fund of Central Denmark, the Novo Nordisk Foundation, and the A.P. Møller Foundation. The authors reported no conflicts of interest.

SOURCE: Madsen LR et al. Diabetologia. 2019, Feb 6. doi: 10.1007/s00125-019-4816-2.

Quit clowning around

Would you like a balloon giraffe, elephant, or hypodermic needle? A recently published study examined how the use of “medical clowns” eased the anxiety and pain of children during botulinum toxin injections. These injections are used to treat spasticity in children, and researchers hypothesized that a clown might be an effective distraction.

AlexRaths/Gettyimages

As anyone who has been to a circus can surmise, the clowns did not perform better than the control distractions.

Researchers concluded that the clowns were appreciated by the parents but not particularly effective on the children. Maybe that’s because the parents weren’t the ones being stuck with needles while some crazy person in clown makeup attempted to distract them. Or maybe they were all just big fans of Stephen King’s “It.”
 

Inked immunity

Starting to feel a bit under the weather? Head to the local tattoo artist for the cure! Research from the University of Alabama at Birmingham found evidence that the immune systems of heavily tattooed people are stronger than those without, proving once and for all that tats = toughness. Hell's Angels were on to something all along.

Venerala/gettyimages

While your immune system can actually grow temporarily weaker after one tattoo, multiple tattoos create a stronger immunological response. Researchers tested the immunoglobulin A levels in those getting a first tattoo and those with many tattoos. They found that the latter group had higher IgA levels.

Maybe that’s why Adam Levine showed off his ink at the Super Bowl halftime show – he was just signaling his strong immune system to the rest of us.

Brain surgery is a laughing matter

This certainly came as a surprise to us, but as it turns out, undergoing brain surgery while conscious and awake can be extremely stressful and panic inducing to the patient. We’re sure most people (including us) would prefer to be asleep for their surgery, but sometimes when dealing with the brain, the surgeon needs to be able to talk to the patient to accurately assess their faculties in case they damage something important.

akesak/thinkstock /thinkstock

So the question is: How do you keep brain surgery patients from panicking? Why, with the power of laughter, of course! Specifically, a group at Emory University, Atlanta, published a case study in the Journal of Clinical Investigation about their treatment of a patient with moderate anxiety. When the patient woke up from initial anesthesia, she began to panic. However, after electrical stimulation of the cingulum bundle, the patient immediately turned her frown upside down and began laughing and joking with the surgeons.

Sadly, while the team did not report on the quality of the jokes being told, we can only assume the phrase “this isn’t brain surgery” was thrown around multiple times.

A male brain is a terrible thing to waste

In the future, comedy may mean pressing a button to stimulate your cingulum bundle, but for now we still have jokes. One old joke goes like this: Some aliens land on earth and want to learn about humans, so they go into a store to buy some brains. “Why does the male brain cost twice as much as the female brain?” one asks the store owner, who replies, “It’s hardly been used.”

sturti/gettyimages

There may be another explanation: Womens’ brains appear to age more slowly than mens’, investigators at Washington University, St. Louis, said in the Proceedings of the National Academy of Sciences.

They performed PET scans on 121 women and 84 men aged 20-82 years to determine the fraction of sugar committed to aerobic glycolysis in various regions of the brain, and then a machine-learning algorithm used those data to calculate metabolic ages.

The womens’ brains were younger than the mens’ brains, with various calculations producing average differences of 2.7-5.3 years, they reported.

The male brain, it seems, is used for something, and after one LOTME staffer spent 5 minutes explaining total quarterback rating (QBR) to his wife, we think we’ve figured out what it is: sports trivia.

Quit clowning around

Would you like a balloon giraffe, elephant, or hypodermic needle? A recently published study examined how the use of “medical clowns” eased the anxiety and pain of children during botulinum toxin injections. These injections are used to treat spasticity in children, and researchers hypothesized that a clown might be an effective distraction.

AlexRaths/Gettyimages

As anyone who has been to a circus can surmise, the clowns did not perform better than the control distractions.

Researchers concluded that the clowns were appreciated by the parents but not particularly effective on the children. Maybe that’s because the parents weren’t the ones being stuck with needles while some crazy person in clown makeup attempted to distract them. Or maybe they were all just big fans of Stephen King’s “It.”
 

Inked immunity

Starting to feel a bit under the weather? Head to the local tattoo artist for the cure! Research from the University of Alabama at Birmingham found evidence that the immune systems of heavily tattooed people are stronger than those without, proving once and for all that tats = toughness. Hell's Angels were on to something all along.

Venerala/gettyimages

While your immune system can actually grow temporarily weaker after one tattoo, multiple tattoos create a stronger immunological response. Researchers tested the immunoglobulin A levels in those getting a first tattoo and those with many tattoos. They found that the latter group had higher IgA levels.

Maybe that’s why Adam Levine showed off his ink at the Super Bowl halftime show – he was just signaling his strong immune system to the rest of us.

Brain surgery is a laughing matter

This certainly came as a surprise to us, but as it turns out, undergoing brain surgery while conscious and awake can be extremely stressful and panic inducing to the patient. We’re sure most people (including us) would prefer to be asleep for their surgery, but sometimes when dealing with the brain, the surgeon needs to be able to talk to the patient to accurately assess their faculties in case they damage something important.

akesak/thinkstock /thinkstock

So the question is: How do you keep brain surgery patients from panicking? Why, with the power of laughter, of course! Specifically, a group at Emory University, Atlanta, published a case study in the Journal of Clinical Investigation about their treatment of a patient with moderate anxiety. When the patient woke up from initial anesthesia, she began to panic. However, after electrical stimulation of the cingulum bundle, the patient immediately turned her frown upside down and began laughing and joking with the surgeons.

Sadly, while the team did not report on the quality of the jokes being told, we can only assume the phrase “this isn’t brain surgery” was thrown around multiple times.

A male brain is a terrible thing to waste

In the future, comedy may mean pressing a button to stimulate your cingulum bundle, but for now we still have jokes. One old joke goes like this: Some aliens land on earth and want to learn about humans, so they go into a store to buy some brains. “Why does the male brain cost twice as much as the female brain?” one asks the store owner, who replies, “It’s hardly been used.”

sturti/gettyimages

There may be another explanation: Womens’ brains appear to age more slowly than mens’, investigators at Washington University, St. Louis, said in the Proceedings of the National Academy of Sciences.

They performed PET scans on 121 women and 84 men aged 20-82 years to determine the fraction of sugar committed to aerobic glycolysis in various regions of the brain, and then a machine-learning algorithm used those data to calculate metabolic ages.

The womens’ brains were younger than the mens’ brains, with various calculations producing average differences of 2.7-5.3 years, they reported.

The male brain, it seems, is used for something, and after one LOTME staffer spent 5 minutes explaining total quarterback rating (QBR) to his wife, we think we’ve figured out what it is: sports trivia.

Quit clowning around

Would you like a balloon giraffe, elephant, or hypodermic needle? A recently published study examined how the use of “medical clowns” eased the anxiety and pain of children during botulinum toxin injections. These injections are used to treat spasticity in children, and researchers hypothesized that a clown might be an effective distraction.

AlexRaths/Gettyimages

As anyone who has been to a circus can surmise, the clowns did not perform better than the control distractions.

Researchers concluded that the clowns were appreciated by the parents but not particularly effective on the children. Maybe that’s because the parents weren’t the ones being stuck with needles while some crazy person in clown makeup attempted to distract them. Or maybe they were all just big fans of Stephen King’s “It.”
 

Inked immunity

Starting to feel a bit under the weather? Head to the local tattoo artist for the cure! Research from the University of Alabama at Birmingham found evidence that the immune systems of heavily tattooed people are stronger than those without, proving once and for all that tats = toughness. Hell's Angels were on to something all along.

Venerala/gettyimages

While your immune system can actually grow temporarily weaker after one tattoo, multiple tattoos create a stronger immunological response. Researchers tested the immunoglobulin A levels in those getting a first tattoo and those with many tattoos. They found that the latter group had higher IgA levels.

Maybe that’s why Adam Levine showed off his ink at the Super Bowl halftime show – he was just signaling his strong immune system to the rest of us.

Brain surgery is a laughing matter

This certainly came as a surprise to us, but as it turns out, undergoing brain surgery while conscious and awake can be extremely stressful and panic inducing to the patient. We’re sure most people (including us) would prefer to be asleep for their surgery, but sometimes when dealing with the brain, the surgeon needs to be able to talk to the patient to accurately assess their faculties in case they damage something important.

akesak/thinkstock /thinkstock

So the question is: How do you keep brain surgery patients from panicking? Why, with the power of laughter, of course! Specifically, a group at Emory University, Atlanta, published a case study in the Journal of Clinical Investigation about their treatment of a patient with moderate anxiety. When the patient woke up from initial anesthesia, she began to panic. However, after electrical stimulation of the cingulum bundle, the patient immediately turned her frown upside down and began laughing and joking with the surgeons.

Sadly, while the team did not report on the quality of the jokes being told, we can only assume the phrase “this isn’t brain surgery” was thrown around multiple times.

A male brain is a terrible thing to waste

In the future, comedy may mean pressing a button to stimulate your cingulum bundle, but for now we still have jokes. One old joke goes like this: Some aliens land on earth and want to learn about humans, so they go into a store to buy some brains. “Why does the male brain cost twice as much as the female brain?” one asks the store owner, who replies, “It’s hardly been used.”

sturti/gettyimages

There may be another explanation: Womens’ brains appear to age more slowly than mens’, investigators at Washington University, St. Louis, said in the Proceedings of the National Academy of Sciences.

They performed PET scans on 121 women and 84 men aged 20-82 years to determine the fraction of sugar committed to aerobic glycolysis in various regions of the brain, and then a machine-learning algorithm used those data to calculate metabolic ages.

The womens’ brains were younger than the mens’ brains, with various calculations producing average differences of 2.7-5.3 years, they reported.

The male brain, it seems, is used for something, and after one LOTME staffer spent 5 minutes explaining total quarterback rating (QBR) to his wife, we think we’ve figured out what it is: sports trivia.

More people are using medical cannabis as it becomes legal in more states, but the lack of standardization in states’ data collection hindered investigators’ efforts to track that use.

Legalized medical cannabis is now available in 33 states and the District of Columbia, and the number of users has risen from just over 72,000 in 2009 to almost 814,000 in 2017. That 814,000, however, covers only 16 states and D.C., since 1 state (Connecticut) does not publish reports on medical cannabis use, 12 did not have statistics available, 2 (New York and Vermont) didn’t report data for 2017, and 2 (California and Maine) have voluntary registries that are unlikely to be accurate, according to Kevin F. Boehnke, PhD, of the University of Michigan, Ann Arbor, and his associates.

Michigan had the largest reported number of patients enrolled in its medical cannabis program in 2017, almost 270,000. California – the state with the oldest medical cannabis legislation (passed in 1996) and the largest overall population but a voluntary cannabis registry – reported its highest number of enrollees, 12,659, in 2009-2010, the investigators said. Colorado had more than 116,000 patients in its medical cannabis program in 2010 (Health Aff. 2019;38[2]:295-302).

The “many inconsistencies in data quality across states [suggest] the need for further standardization of data collection. Such standardization would add transparency to understanding how medical cannabis programs are used, which would help guide both research and policy needs,” Dr. Boehnke and his associates wrote.

More consistency was seen in the reasons for using medical cannabis. Chronic pain made up 62.2% of all qualifying conditions reported by patients during 1999-2016, with the annual average varying between 33.3% and 73%. Multiple sclerosis spasticity symptoms had the second-highest number of reports over the study period, followed by chemotherapy-induced nausea and vomiting, posttraumatic stress disorder, and cancer, they reported.

The investigators also looked at the appropriateness of cannabis and determined that its use in 85.5% of patient-reported conditions was “supported by conclusive or substantial evidence of therapeutic effectiveness, according to the 2017 National Academies report” on the health effects of cannabis.

“We believe not only that it is inappropriate for cannabis to remain a Schedule I substance, but also that state and federal policy makers should begin evaluating evidence-based ways for safely integrating cannabis research and products into the health care system,” they concluded.

rfranki@mdedge.com

SOURCE: Boehnke KF et al. Health Aff. 2019;38(2):295-302.
 

More people are using medical cannabis as it becomes legal in more states, but the lack of standardization in states’ data collection hindered investigators’ efforts to track that use.

Legalized medical cannabis is now available in 33 states and the District of Columbia, and the number of users has risen from just over 72,000 in 2009 to almost 814,000 in 2017. That 814,000, however, covers only 16 states and D.C., since 1 state (Connecticut) does not publish reports on medical cannabis use, 12 did not have statistics available, 2 (New York and Vermont) didn’t report data for 2017, and 2 (California and Maine) have voluntary registries that are unlikely to be accurate, according to Kevin F. Boehnke, PhD, of the University of Michigan, Ann Arbor, and his associates.

Michigan had the largest reported number of patients enrolled in its medical cannabis program in 2017, almost 270,000. California – the state with the oldest medical cannabis legislation (passed in 1996) and the largest overall population but a voluntary cannabis registry – reported its highest number of enrollees, 12,659, in 2009-2010, the investigators said. Colorado had more than 116,000 patients in its medical cannabis program in 2010 (Health Aff. 2019;38[2]:295-302).

The “many inconsistencies in data quality across states [suggest] the need for further standardization of data collection. Such standardization would add transparency to understanding how medical cannabis programs are used, which would help guide both research and policy needs,” Dr. Boehnke and his associates wrote.

More consistency was seen in the reasons for using medical cannabis. Chronic pain made up 62.2% of all qualifying conditions reported by patients during 1999-2016, with the annual average varying between 33.3% and 73%. Multiple sclerosis spasticity symptoms had the second-highest number of reports over the study period, followed by chemotherapy-induced nausea and vomiting, posttraumatic stress disorder, and cancer, they reported.

The investigators also looked at the appropriateness of cannabis and determined that its use in 85.5% of patient-reported conditions was “supported by conclusive or substantial evidence of therapeutic effectiveness, according to the 2017 National Academies report” on the health effects of cannabis.

“We believe not only that it is inappropriate for cannabis to remain a Schedule I substance, but also that state and federal policy makers should begin evaluating evidence-based ways for safely integrating cannabis research and products into the health care system,” they concluded.

rfranki@mdedge.com

SOURCE: Boehnke KF et al. Health Aff. 2019;38(2):295-302.
 

More people are using medical cannabis as it becomes legal in more states, but the lack of standardization in states’ data collection hindered investigators’ efforts to track that use.

Legalized medical cannabis is now available in 33 states and the District of Columbia, and the number of users has risen from just over 72,000 in 2009 to almost 814,000 in 2017. That 814,000, however, covers only 16 states and D.C., since 1 state (Connecticut) does not publish reports on medical cannabis use, 12 did not have statistics available, 2 (New York and Vermont) didn’t report data for 2017, and 2 (California and Maine) have voluntary registries that are unlikely to be accurate, according to Kevin F. Boehnke, PhD, of the University of Michigan, Ann Arbor, and his associates.

Michigan had the largest reported number of patients enrolled in its medical cannabis program in 2017, almost 270,000. California – the state with the oldest medical cannabis legislation (passed in 1996) and the largest overall population but a voluntary cannabis registry – reported its highest number of enrollees, 12,659, in 2009-2010, the investigators said. Colorado had more than 116,000 patients in its medical cannabis program in 2010 (Health Aff. 2019;38[2]:295-302).

The “many inconsistencies in data quality across states [suggest] the need for further standardization of data collection. Such standardization would add transparency to understanding how medical cannabis programs are used, which would help guide both research and policy needs,” Dr. Boehnke and his associates wrote.

More consistency was seen in the reasons for using medical cannabis. Chronic pain made up 62.2% of all qualifying conditions reported by patients during 1999-2016, with the annual average varying between 33.3% and 73%. Multiple sclerosis spasticity symptoms had the second-highest number of reports over the study period, followed by chemotherapy-induced nausea and vomiting, posttraumatic stress disorder, and cancer, they reported.

The investigators also looked at the appropriateness of cannabis and determined that its use in 85.5% of patient-reported conditions was “supported by conclusive or substantial evidence of therapeutic effectiveness, according to the 2017 National Academies report” on the health effects of cannabis.

“We believe not only that it is inappropriate for cannabis to remain a Schedule I substance, but also that state and federal policy makers should begin evaluating evidence-based ways for safely integrating cannabis research and products into the health care system,” they concluded.

rfranki@mdedge.com

SOURCE: Boehnke KF et al. Health Aff. 2019;38(2):295-302.
 

The etiology of psoriasis is multifactorial, and it is attributed to both genetic and environmental components.¹ One of the lesser-studied aspects of psoriasis pathogenesis is the involvement of the nervous system. It is thought that the pathogenesis involves inflammation of the cutaneous nerves,² and cutaneous denervation has been shown to improve acanthosis and IL-23 expression in mice with psoriasiform skin.³ There also have been reports of psoriasis remission following peripheral and central nervous system injury from surgical nerve resection⁴ as well as cerebrovascular accident.⁵ We present a case of total psoriasis clearance following ischemic stroke.

Case Report

A 52-year-old man with psoriasis presented to the dermatology clinic for follow-up. The patient had been using topical clobetasol and apremilast with limited success but had not previously tried biologics. On physical examination he was noted to have erythematous, scaly, indurated papules and plaques on the chest, abdomen, back, arms, and legs, consistent with psoriasis. Affected body surface area was approximately 10%. Ustekinumab was prescribed, but the patient did not pick it up from the pharmacy.

Approximately 1 month later, the patient presented to the emergency department with left-sided weakness and numbness. He was hospitalized for treatment of stroke. During hospitalization, the patient was started on lisinopril, aspirin, and atorvastatin. He also was given subcutaneous enoxaparin with plans to initiate warfarin as an outpatient. His psoriasis was not treated with topical or systemic medications during the course of his admission. He was discharged to a skilled nursing facility after 3 days.

Three months following discharge, the patient returned to the dermatology clinic for follow-up. After his stroke, he reported that his psoriasis had cleared and had not returned. On physical examination his skin was clear of psoriatic lesions.

Comment

The nervous system is thought to play an important role in the pathophysiology of psoriasis. Evidence for this involvement includes the exacerbation of psoriasis with stress and the often symmetric distribution of psoriatic lesions.⁶

Moreover, numerous neuropeptides have been identified in the pathophysiology of psoriasis. Farber et al⁷ first proposed that release of substance P (SP) from cutaneous sensory nerve fibers causes a local neurogenic response that triggers psoriasis in predisposed individuals. The role of SP in psoriasis is unclear, as there have been reports of both higher⁸ and lower⁹ levels in involved and noninvolved skin of psoriatic patients compared to skin in healthy individuals. It has been suggested that numerous other neuropeptides, including nerve growth factor (NGF), calcitonin gene-related peptide, and vasoactive intestinal peptide, play a part in psoriasis.^2,10 Specifically, NGF prevents apoptosis of keratinocytes¹¹ and is found in higher levels in psoriatic skin compared to controls.¹² Calcitonin gene-related peptide has been shown to stimulate keratinocyte proliferation¹³ and has been found at increased levels in psoriatic skin.¹⁴ Vasoactive intestinal peptide-positive nerve fibers in the epidermis and dermis are found in higher quantities in psoriatic plaques compared to nonlesional and normal skin.⁸

Neuropeptides also might play a role in the itching and Köbner phenomenon that accompany psoriasis. Increased levels of NGF in nonlesional skin of patients with psoriasis is thought to contribute to the development of psoriatic plaques following trauma by inducing an inflammatory response that upregulates other neuropeptides, such as SP and calcitonin gene-related peptide. These neuropeptides induce keratinocyte proliferation, which further increases NGF expression, thus creating a cycle of inflammation and formation of psoriatic lesions.⁶ Moreover, there is a notable correlation between pruritus severity and density of NGF-immunoreactive keratinocytes, high-affinity NGF receptors, protein gene product 9.5–immunoreactive intraepidermal fibers, and immunoreactive vessels for E-selectin.¹⁵

Spontaneous remission of psoriasis after cerebrovascular accident was first reported in 1998.⁵ Moreover, there have been cases of protective effects from psoriasis and psoriatic arthritis in limbs affected by poliomyelitis.^16,17 In cases in which patients regained neurologic function, Zhu et al¹⁰ found that recurrence of skin lesions in areas corresponding to nervous system injury also occurred. However, in cases of permanent nerve damage, psoriasis did not return,¹⁰ confirming the role of peripheral nerves in the pathogenesis of psoriasis. It is thought that peripheral nerve damage results in decreased secretion of neuropeptides³ and that central nervous system injury also can cause similar downstream effects.¹⁰

Other reasons for the patient’s remission also were considered. Although it is possible that the sudden change in the patient’s usual environment could have induced remission of psoriasis, it seems more likely that the stress of the situation would have worsened his symptoms. Medications used during the patient’s hospitalization also were considered as reasons for symptom improvement. One study using a case-control and case-crossover design found psoriasis to be associated with nonsteroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors (odds ratio, 4.0 and 2.1, respectively).¹⁸ Atorvastatin has been investigated as a potential treatment of psoriasis, though no therapeutic benefit has been proven.^19,20 Heparin has been shown in case reports to improve psoriasis symptoms but was used in addition to standard psoriasis therapies and not as monotherapy.²¹

A more thorough understanding of which neuropeptides are directly implicated in the neurologic-mediated clearance of psoriasis might contribute to better targeted therapies. For example, infusion of peptide T, a vasoactive intestinal peptide analogue, was shown to have some effect in clearing the skin in 14 psoriasis patients.²² Although this finding has not been replicated, it demonstrates the potential utility of therapies targeted toward the neurologic aspects of psoriasis. More research is needed to evaluate the potential of targeting other neuropeptides for treatment of psoriatic plaques.

The etiology of psoriasis is multifactorial, and it is attributed to both genetic and environmental components.¹ One of the lesser-studied aspects of psoriasis pathogenesis is the involvement of the nervous system. It is thought that the pathogenesis involves inflammation of the cutaneous nerves,² and cutaneous denervation has been shown to improve acanthosis and IL-23 expression in mice with psoriasiform skin.³ There also have been reports of psoriasis remission following peripheral and central nervous system injury from surgical nerve resection⁴ as well as cerebrovascular accident.⁵ We present a case of total psoriasis clearance following ischemic stroke.

Case Report

A 52-year-old man with psoriasis presented to the dermatology clinic for follow-up. The patient had been using topical clobetasol and apremilast with limited success but had not previously tried biologics. On physical examination he was noted to have erythematous, scaly, indurated papules and plaques on the chest, abdomen, back, arms, and legs, consistent with psoriasis. Affected body surface area was approximately 10%. Ustekinumab was prescribed, but the patient did not pick it up from the pharmacy.

Approximately 1 month later, the patient presented to the emergency department with left-sided weakness and numbness. He was hospitalized for treatment of stroke. During hospitalization, the patient was started on lisinopril, aspirin, and atorvastatin. He also was given subcutaneous enoxaparin with plans to initiate warfarin as an outpatient. His psoriasis was not treated with topical or systemic medications during the course of his admission. He was discharged to a skilled nursing facility after 3 days.

Three months following discharge, the patient returned to the dermatology clinic for follow-up. After his stroke, he reported that his psoriasis had cleared and had not returned. On physical examination his skin was clear of psoriatic lesions.

Comment

The nervous system is thought to play an important role in the pathophysiology of psoriasis. Evidence for this involvement includes the exacerbation of psoriasis with stress and the often symmetric distribution of psoriatic lesions.⁶

Moreover, numerous neuropeptides have been identified in the pathophysiology of psoriasis. Farber et al⁷ first proposed that release of substance P (SP) from cutaneous sensory nerve fibers causes a local neurogenic response that triggers psoriasis in predisposed individuals. The role of SP in psoriasis is unclear, as there have been reports of both higher⁸ and lower⁹ levels in involved and noninvolved skin of psoriatic patients compared to skin in healthy individuals. It has been suggested that numerous other neuropeptides, including nerve growth factor (NGF), calcitonin gene-related peptide, and vasoactive intestinal peptide, play a part in psoriasis.^2,10 Specifically, NGF prevents apoptosis of keratinocytes¹¹ and is found in higher levels in psoriatic skin compared to controls.¹² Calcitonin gene-related peptide has been shown to stimulate keratinocyte proliferation¹³ and has been found at increased levels in psoriatic skin.¹⁴ Vasoactive intestinal peptide-positive nerve fibers in the epidermis and dermis are found in higher quantities in psoriatic plaques compared to nonlesional and normal skin.⁸

Neuropeptides also might play a role in the itching and Köbner phenomenon that accompany psoriasis. Increased levels of NGF in nonlesional skin of patients with psoriasis is thought to contribute to the development of psoriatic plaques following trauma by inducing an inflammatory response that upregulates other neuropeptides, such as SP and calcitonin gene-related peptide. These neuropeptides induce keratinocyte proliferation, which further increases NGF expression, thus creating a cycle of inflammation and formation of psoriatic lesions.⁶ Moreover, there is a notable correlation between pruritus severity and density of NGF-immunoreactive keratinocytes, high-affinity NGF receptors, protein gene product 9.5–immunoreactive intraepidermal fibers, and immunoreactive vessels for E-selectin.¹⁵

Spontaneous remission of psoriasis after cerebrovascular accident was first reported in 1998.⁵ Moreover, there have been cases of protective effects from psoriasis and psoriatic arthritis in limbs affected by poliomyelitis.^16,17 In cases in which patients regained neurologic function, Zhu et al¹⁰ found that recurrence of skin lesions in areas corresponding to nervous system injury also occurred. However, in cases of permanent nerve damage, psoriasis did not return,¹⁰ confirming the role of peripheral nerves in the pathogenesis of psoriasis. It is thought that peripheral nerve damage results in decreased secretion of neuropeptides³ and that central nervous system injury also can cause similar downstream effects.¹⁰

Other reasons for the patient’s remission also were considered. Although it is possible that the sudden change in the patient’s usual environment could have induced remission of psoriasis, it seems more likely that the stress of the situation would have worsened his symptoms. Medications used during the patient’s hospitalization also were considered as reasons for symptom improvement. One study using a case-control and case-crossover design found psoriasis to be associated with nonsteroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors (odds ratio, 4.0 and 2.1, respectively).¹⁸ Atorvastatin has been investigated as a potential treatment of psoriasis, though no therapeutic benefit has been proven.^19,20 Heparin has been shown in case reports to improve psoriasis symptoms but was used in addition to standard psoriasis therapies and not as monotherapy.²¹

A more thorough understanding of which neuropeptides are directly implicated in the neurologic-mediated clearance of psoriasis might contribute to better targeted therapies. For example, infusion of peptide T, a vasoactive intestinal peptide analogue, was shown to have some effect in clearing the skin in 14 psoriasis patients.²² Although this finding has not been replicated, it demonstrates the potential utility of therapies targeted toward the neurologic aspects of psoriasis. More research is needed to evaluate the potential of targeting other neuropeptides for treatment of psoriatic plaques.

The etiology of psoriasis is multifactorial, and it is attributed to both genetic and environmental components.¹ One of the lesser-studied aspects of psoriasis pathogenesis is the involvement of the nervous system. It is thought that the pathogenesis involves inflammation of the cutaneous nerves,² and cutaneous denervation has been shown to improve acanthosis and IL-23 expression in mice with psoriasiform skin.³ There also have been reports of psoriasis remission following peripheral and central nervous system injury from surgical nerve resection⁴ as well as cerebrovascular accident.⁵ We present a case of total psoriasis clearance following ischemic stroke.

Case Report

A 52-year-old man with psoriasis presented to the dermatology clinic for follow-up. The patient had been using topical clobetasol and apremilast with limited success but had not previously tried biologics. On physical examination he was noted to have erythematous, scaly, indurated papules and plaques on the chest, abdomen, back, arms, and legs, consistent with psoriasis. Affected body surface area was approximately 10%. Ustekinumab was prescribed, but the patient did not pick it up from the pharmacy.

Approximately 1 month later, the patient presented to the emergency department with left-sided weakness and numbness. He was hospitalized for treatment of stroke. During hospitalization, the patient was started on lisinopril, aspirin, and atorvastatin. He also was given subcutaneous enoxaparin with plans to initiate warfarin as an outpatient. His psoriasis was not treated with topical or systemic medications during the course of his admission. He was discharged to a skilled nursing facility after 3 days.

Three months following discharge, the patient returned to the dermatology clinic for follow-up. After his stroke, he reported that his psoriasis had cleared and had not returned. On physical examination his skin was clear of psoriatic lesions.

Comment

The nervous system is thought to play an important role in the pathophysiology of psoriasis. Evidence for this involvement includes the exacerbation of psoriasis with stress and the often symmetric distribution of psoriatic lesions.⁶

Moreover, numerous neuropeptides have been identified in the pathophysiology of psoriasis. Farber et al⁷ first proposed that release of substance P (SP) from cutaneous sensory nerve fibers causes a local neurogenic response that triggers psoriasis in predisposed individuals. The role of SP in psoriasis is unclear, as there have been reports of both higher⁸ and lower⁹ levels in involved and noninvolved skin of psoriatic patients compared to skin in healthy individuals. It has been suggested that numerous other neuropeptides, including nerve growth factor (NGF), calcitonin gene-related peptide, and vasoactive intestinal peptide, play a part in psoriasis.^2,10 Specifically, NGF prevents apoptosis of keratinocytes¹¹ and is found in higher levels in psoriatic skin compared to controls.¹² Calcitonin gene-related peptide has been shown to stimulate keratinocyte proliferation¹³ and has been found at increased levels in psoriatic skin.¹⁴ Vasoactive intestinal peptide-positive nerve fibers in the epidermis and dermis are found in higher quantities in psoriatic plaques compared to nonlesional and normal skin.⁸

Neuropeptides also might play a role in the itching and Köbner phenomenon that accompany psoriasis. Increased levels of NGF in nonlesional skin of patients with psoriasis is thought to contribute to the development of psoriatic plaques following trauma by inducing an inflammatory response that upregulates other neuropeptides, such as SP and calcitonin gene-related peptide. These neuropeptides induce keratinocyte proliferation, which further increases NGF expression, thus creating a cycle of inflammation and formation of psoriatic lesions.⁶ Moreover, there is a notable correlation between pruritus severity and density of NGF-immunoreactive keratinocytes, high-affinity NGF receptors, protein gene product 9.5–immunoreactive intraepidermal fibers, and immunoreactive vessels for E-selectin.¹⁵

Spontaneous remission of psoriasis after cerebrovascular accident was first reported in 1998.⁵ Moreover, there have been cases of protective effects from psoriasis and psoriatic arthritis in limbs affected by poliomyelitis.^16,17 In cases in which patients regained neurologic function, Zhu et al¹⁰ found that recurrence of skin lesions in areas corresponding to nervous system injury also occurred. However, in cases of permanent nerve damage, psoriasis did not return,¹⁰ confirming the role of peripheral nerves in the pathogenesis of psoriasis. It is thought that peripheral nerve damage results in decreased secretion of neuropeptides³ and that central nervous system injury also can cause similar downstream effects.¹⁰

Other reasons for the patient’s remission also were considered. Although it is possible that the sudden change in the patient’s usual environment could have induced remission of psoriasis, it seems more likely that the stress of the situation would have worsened his symptoms. Medications used during the patient’s hospitalization also were considered as reasons for symptom improvement. One study using a case-control and case-crossover design found psoriasis to be associated with nonsteroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors (odds ratio, 4.0 and 2.1, respectively).¹⁸ Atorvastatin has been investigated as a potential treatment of psoriasis, though no therapeutic benefit has been proven.^19,20 Heparin has been shown in case reports to improve psoriasis symptoms but was used in addition to standard psoriasis therapies and not as monotherapy.²¹

A more thorough understanding of which neuropeptides are directly implicated in the neurologic-mediated clearance of psoriasis might contribute to better targeted therapies. For example, infusion of peptide T, a vasoactive intestinal peptide analogue, was shown to have some effect in clearing the skin in 14 psoriasis patients.²² Although this finding has not been replicated, it demonstrates the potential utility of therapies targeted toward the neurologic aspects of psoriasis. More research is needed to evaluate the potential of targeting other neuropeptides for treatment of psoriatic plaques.

The Food and Drug Administration has approved caplacizumab (Cablivi) in combination with plasma exchange and immunosuppressive therapy for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP).

Caplacizumab is an anti–von Willebrand factor nanobody designed to inhibit the interaction between von Willebrand factor and platelets. The injection previously received orphan drug designation from the FDA and was approved under priority review.

The FDA’s approval of caplacizumab was based on results from the phase 3 HERCULES trial (N Engl J Med 2019 Jan 24;380:335-46).

The trial (NCT02553317) included 145 adults with aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73), in addition to plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization), which was defined as a platelet count of at least 150 x 10⁹/L with subsequent stop of daily plasma exchange within 5 days.

There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm – 2.69 days and 2.88 days, respectively. The platelet normalization rate ratio was 1.55 (P less than .01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12% in the caplacizumab arm and 49% in the placebo arm (P less than .001).

The most common treatment-emergent adverse events (occurring in at least 15% of patients in the caplacizumab and placebo arms, respectively) were epistaxis (32% and 3%), headache (23% and 8%), urticaria (17% and 7%), and hypokalemia (9% and 19%).

During the treatment period, there were no deaths in the caplacizumab arm and three deaths in the placebo arm. There was one death (from cerebral ischemia) in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.

For more details on caplacizumab, see the full prescribing information.

jensmith@mdedge.com

The Food and Drug Administration has approved caplacizumab (Cablivi) in combination with plasma exchange and immunosuppressive therapy for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP).

Caplacizumab is an anti–von Willebrand factor nanobody designed to inhibit the interaction between von Willebrand factor and platelets. The injection previously received orphan drug designation from the FDA and was approved under priority review.

The FDA’s approval of caplacizumab was based on results from the phase 3 HERCULES trial (N Engl J Med 2019 Jan 24;380:335-46).

The trial (NCT02553317) included 145 adults with aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73), in addition to plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization), which was defined as a platelet count of at least 150 x 10⁹/L with subsequent stop of daily plasma exchange within 5 days.

There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm – 2.69 days and 2.88 days, respectively. The platelet normalization rate ratio was 1.55 (P less than .01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12% in the caplacizumab arm and 49% in the placebo arm (P less than .001).

The most common treatment-emergent adverse events (occurring in at least 15% of patients in the caplacizumab and placebo arms, respectively) were epistaxis (32% and 3%), headache (23% and 8%), urticaria (17% and 7%), and hypokalemia (9% and 19%).

During the treatment period, there were no deaths in the caplacizumab arm and three deaths in the placebo arm. There was one death (from cerebral ischemia) in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.

For more details on caplacizumab, see the full prescribing information.

jensmith@mdedge.com

The Food and Drug Administration has approved caplacizumab (Cablivi) in combination with plasma exchange and immunosuppressive therapy for the treatment of adults with acquired thrombotic thrombocytopenic purpura (aTTP).

Caplacizumab is an anti–von Willebrand factor nanobody designed to inhibit the interaction between von Willebrand factor and platelets. The injection previously received orphan drug designation from the FDA and was approved under priority review.

The FDA’s approval of caplacizumab was based on results from the phase 3 HERCULES trial (N Engl J Med 2019 Jan 24;380:335-46).

The trial (NCT02553317) included 145 adults with aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73), in addition to plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization), which was defined as a platelet count of at least 150 x 10⁹/L with subsequent stop of daily plasma exchange within 5 days.

There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm – 2.69 days and 2.88 days, respectively. The platelet normalization rate ratio was 1.55 (P less than .01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12% in the caplacizumab arm and 49% in the placebo arm (P less than .001).

The most common treatment-emergent adverse events (occurring in at least 15% of patients in the caplacizumab and placebo arms, respectively) were epistaxis (32% and 3%), headache (23% and 8%), urticaria (17% and 7%), and hypokalemia (9% and 19%).

During the treatment period, there were no deaths in the caplacizumab arm and three deaths in the placebo arm. There was one death (from cerebral ischemia) in the caplacizumab arm during the follow-up period, but it was considered unrelated to caplacizumab.

For more details on caplacizumab, see the full prescribing information.

jensmith@mdedge.com

Robotic resection of colorectal liver metastases provides surgical and oncologic outcomes comparable with what has been previously reported for laparoscopy or open surgery, according to researchers who conducted a recent multi-institutional analysis.

The proportion of margin-negative resections was 92% in a series of 59 patients who underwent resection at one of three tertiary hospitals, the study authors reported.

The 3-year disease-free survival and overall survival rates were 41.9% and 66%, respectively, in the 44 patients for whom longer-term follow-up was available, according to the investigators, led by Francesco Guerra, MD, of Ospedali Riuniti Marche Nord Hospital in Pesaro, Italy.

“These findings are consistent with those of patients resected via conventional laparoscopy or open surgery in contemporary series,” Dr. Guerra and his coauthors wrote in a report published in Surgical Oncology.

It’s still a matter of debate, however, whether robotic surgery has clear advantages over conventional laparoscopy for liver surgery, according to the investigators. Direct comparisons of robotic versus conventional laparoscopic liver resection are scarce, with most available data stemming from often heterogeneous case-control series with no long-term oncologic outcome data.

“Most centers have consolidated experience either in laparoscopic or in robotic liver resection,” the authors wrote. “Hence, reliable comparative analyses are likely difficult to carry out.”

Because of the scarcity of results, Dr. Guerra and his colleagues sought to investigate short- and long-term outcomes for a consecutive series of 59 patients who underwent minimally invasive, ultrasound-guided robotic surgery between 2008 and 2018 at one of three tertiary facilities. Each procedure had been performed by surgeons experienced in both liver surgery and robotics. The median age of patients undergoing the procedure was 64 years, 63% were male, and the median body mass index was 26 kg/m².

Almost half the patients (46%) had multiple lesions removed, while about one-quarter had concomitant procedures, mainly cholecystectomy, according to the report.

Robotic surgeries were converted to open procedures in seven patients, or about 12%, a statistic comparable with other reports of laparoscopic or robotic surgery, the investigators noted.

Postoperative complications were seen in 16 patients, or 27%. That included 13 patients with class I-II complications and 3 patients with class III-IV complications, including 2 cases of heart failure and 1 case of postoperative bile leak requiring radiologic and endoscopic therapy.

The reported 3-year disease-free and overall survival of 41.9% and 66.1% was based on a mean follow-up of 19.5 months in 44 patients for whom longer-term data were available. There were 16 cases of recurrent disease, including 10 patients with evidence of liver recurrence.

“Taken together, our data show that robotics is an effective option to resect colorectal liver metastases, providing an oncological outcome similar to that of laparoscopy and open surgery,” the investigators wrote.

Dr. Guerra and colleagues reported no disclosures related to their research.

SOURCE: Guerra F et al. Surg Oncol. 2018 Nov 1. doi: 10.1016/j.suronc.2018.10.011.

Robotic resection of colorectal liver metastases provides surgical and oncologic outcomes comparable with what has been previously reported for laparoscopy or open surgery, according to researchers who conducted a recent multi-institutional analysis.

The proportion of margin-negative resections was 92% in a series of 59 patients who underwent resection at one of three tertiary hospitals, the study authors reported.

The 3-year disease-free survival and overall survival rates were 41.9% and 66%, respectively, in the 44 patients for whom longer-term follow-up was available, according to the investigators, led by Francesco Guerra, MD, of Ospedali Riuniti Marche Nord Hospital in Pesaro, Italy.

“These findings are consistent with those of patients resected via conventional laparoscopy or open surgery in contemporary series,” Dr. Guerra and his coauthors wrote in a report published in Surgical Oncology.

It’s still a matter of debate, however, whether robotic surgery has clear advantages over conventional laparoscopy for liver surgery, according to the investigators. Direct comparisons of robotic versus conventional laparoscopic liver resection are scarce, with most available data stemming from often heterogeneous case-control series with no long-term oncologic outcome data.

“Most centers have consolidated experience either in laparoscopic or in robotic liver resection,” the authors wrote. “Hence, reliable comparative analyses are likely difficult to carry out.”

Because of the scarcity of results, Dr. Guerra and his colleagues sought to investigate short- and long-term outcomes for a consecutive series of 59 patients who underwent minimally invasive, ultrasound-guided robotic surgery between 2008 and 2018 at one of three tertiary facilities. Each procedure had been performed by surgeons experienced in both liver surgery and robotics. The median age of patients undergoing the procedure was 64 years, 63% were male, and the median body mass index was 26 kg/m².

Almost half the patients (46%) had multiple lesions removed, while about one-quarter had concomitant procedures, mainly cholecystectomy, according to the report.

Robotic surgeries were converted to open procedures in seven patients, or about 12%, a statistic comparable with other reports of laparoscopic or robotic surgery, the investigators noted.

Postoperative complications were seen in 16 patients, or 27%. That included 13 patients with class I-II complications and 3 patients with class III-IV complications, including 2 cases of heart failure and 1 case of postoperative bile leak requiring radiologic and endoscopic therapy.

The reported 3-year disease-free and overall survival of 41.9% and 66.1% was based on a mean follow-up of 19.5 months in 44 patients for whom longer-term data were available. There were 16 cases of recurrent disease, including 10 patients with evidence of liver recurrence.

“Taken together, our data show that robotics is an effective option to resect colorectal liver metastases, providing an oncological outcome similar to that of laparoscopy and open surgery,” the investigators wrote.

Dr. Guerra and colleagues reported no disclosures related to their research.

SOURCE: Guerra F et al. Surg Oncol. 2018 Nov 1. doi: 10.1016/j.suronc.2018.10.011.

Robotic resection of colorectal liver metastases provides surgical and oncologic outcomes comparable with what has been previously reported for laparoscopy or open surgery, according to researchers who conducted a recent multi-institutional analysis.

The proportion of margin-negative resections was 92% in a series of 59 patients who underwent resection at one of three tertiary hospitals, the study authors reported.

The 3-year disease-free survival and overall survival rates were 41.9% and 66%, respectively, in the 44 patients for whom longer-term follow-up was available, according to the investigators, led by Francesco Guerra, MD, of Ospedali Riuniti Marche Nord Hospital in Pesaro, Italy.

“These findings are consistent with those of patients resected via conventional laparoscopy or open surgery in contemporary series,” Dr. Guerra and his coauthors wrote in a report published in Surgical Oncology.

It’s still a matter of debate, however, whether robotic surgery has clear advantages over conventional laparoscopy for liver surgery, according to the investigators. Direct comparisons of robotic versus conventional laparoscopic liver resection are scarce, with most available data stemming from often heterogeneous case-control series with no long-term oncologic outcome data.

“Most centers have consolidated experience either in laparoscopic or in robotic liver resection,” the authors wrote. “Hence, reliable comparative analyses are likely difficult to carry out.”

Because of the scarcity of results, Dr. Guerra and his colleagues sought to investigate short- and long-term outcomes for a consecutive series of 59 patients who underwent minimally invasive, ultrasound-guided robotic surgery between 2008 and 2018 at one of three tertiary facilities. Each procedure had been performed by surgeons experienced in both liver surgery and robotics. The median age of patients undergoing the procedure was 64 years, 63% were male, and the median body mass index was 26 kg/m².

Almost half the patients (46%) had multiple lesions removed, while about one-quarter had concomitant procedures, mainly cholecystectomy, according to the report.

Robotic surgeries were converted to open procedures in seven patients, or about 12%, a statistic comparable with other reports of laparoscopic or robotic surgery, the investigators noted.

Postoperative complications were seen in 16 patients, or 27%. That included 13 patients with class I-II complications and 3 patients with class III-IV complications, including 2 cases of heart failure and 1 case of postoperative bile leak requiring radiologic and endoscopic therapy.

The reported 3-year disease-free and overall survival of 41.9% and 66.1% was based on a mean follow-up of 19.5 months in 44 patients for whom longer-term data were available. There were 16 cases of recurrent disease, including 10 patients with evidence of liver recurrence.

“Taken together, our data show that robotics is an effective option to resect colorectal liver metastases, providing an oncological outcome similar to that of laparoscopy and open surgery,” the investigators wrote.

Dr. Guerra and colleagues reported no disclosures related to their research.

SOURCE: Guerra F et al. Surg Oncol. 2018 Nov 1. doi: 10.1016/j.suronc.2018.10.011.

BROOKLYN, N.Y. – As a target of therapy in children with a psychiatric disorder, irritability expressed as grumpy mood or anger should be uncoupled from irritability expressed as threatening behavior, according to an exploration of this common clinical issue at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

Ted Bosworth/MDedge News

“Irritability is like fever,” reported Gabrielle A. Carlson, MD, professor of psychiatry and pediatrics, State University of New York at Stony Brook. “It is a nonspecific symptom that only tells you that something is wrong.”

Irritability might be nothing more than a negative mood, but it also can be the source of explosive aggression, leading to tantrums and destructive behaviors, according to Dr. Carlson. She placed them into two different categories when considering treatment. Irritability leading to annoyance, grumpiness, withdrawal, or persistent anger is characterized as the “internalizing” or “tonic” form of the symptom. As opposed to the aggressive subtype, the tonic form is more closely associated with depression or anxiety. Irritability leading to extreme verbal outbursts or physical violence is characterized as the “externalizing” or “phasic” form, Dr. Carlson said. This type of irritability, defined by behavior more than mood, might signal disruptive mood dysregulation disorder (DMDD). But it is important to recognize that DMDD can overlap with other conditions, such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, oppositional defiant disorder (ODD), and autism spectrum disorders.

In defining the impact of treatments on tonic versus phasic symptoms of irritability within the context of the underlying diagnoses, studies have not done a good job in separating relative effects on the two key forms of irritability, Dr. Carlson said.

“Irritability needs to be measured not only by how one feels but what one does,” said Dr. Carlson, explaining that the impact of therapy has not always been adequately described in therapy studies.

For the tonic form, irritability is likely to improve or resolve with control of the underlying psychiatric condition. Although this might also be true of the phasic form, this type of irritability often accompanies conditions that are less readily controlled even through the threat of self-harm, harm to others, or other destructive behaviors invites intervention specifically targeted at this symptom.

Unfortunately, the best approach to irritability is unclear for many underling pathologies.

“Clinicians should recognize that empirical evidence is still lacking as to aggression-targeted treatments with favorable benefit-risk profiles for children and adolescents with ADHD and severe aggression,” said Dr. Carlson, providing ADHD as one of several examples.

Psychological interventions, such as dialectical behavior therapy in children (DBT-C), have been associated with control of both tonic and phasic forms of irritability, but Dr. Carlson cautioned that few studies have adequately differentiated improvement in irritability as measured by behavior relative to mood. In addition, the baseline severity and the degree to which improvement meant adequate control have been unclear.

“Many psychological treatments are school based or group delivered, making it likely that patients are less impaired than explosive kids in psychiatry clinics and hospitals,” Dr. Carlson said.

Providing some practical tips for addressing the phasic form of irritability, Dr. Carlson suggested keeping careful records of the frequency, intensity, number, and duration of disruptive outbursts. She advised clinicians to “maximize the treatment of the base condition” but to add pharmacologic therapies to psychological interventions if symptoms persist.

“Our pendulum has swung from dishing out atypicals to eschewing them completely,” Dr. Carlson noted. Although she agreed these are no longer appropriate as first-line therapies, she suggested they might be employed judiciously if weight gain is monitored carefully.

“If they don’t work, stop them. If they do work, try to limit the duration of use,” Dr. Carlson said.

She reported having no relevant financial relationships to disclose.

BROOKLYN, N.Y. – As a target of therapy in children with a psychiatric disorder, irritability expressed as grumpy mood or anger should be uncoupled from irritability expressed as threatening behavior, according to an exploration of this common clinical issue at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

Ted Bosworth/MDedge News

“Irritability is like fever,” reported Gabrielle A. Carlson, MD, professor of psychiatry and pediatrics, State University of New York at Stony Brook. “It is a nonspecific symptom that only tells you that something is wrong.”

Irritability might be nothing more than a negative mood, but it also can be the source of explosive aggression, leading to tantrums and destructive behaviors, according to Dr. Carlson. She placed them into two different categories when considering treatment. Irritability leading to annoyance, grumpiness, withdrawal, or persistent anger is characterized as the “internalizing” or “tonic” form of the symptom. As opposed to the aggressive subtype, the tonic form is more closely associated with depression or anxiety. Irritability leading to extreme verbal outbursts or physical violence is characterized as the “externalizing” or “phasic” form, Dr. Carlson said. This type of irritability, defined by behavior more than mood, might signal disruptive mood dysregulation disorder (DMDD). But it is important to recognize that DMDD can overlap with other conditions, such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, oppositional defiant disorder (ODD), and autism spectrum disorders.

In defining the impact of treatments on tonic versus phasic symptoms of irritability within the context of the underlying diagnoses, studies have not done a good job in separating relative effects on the two key forms of irritability, Dr. Carlson said.

“Irritability needs to be measured not only by how one feels but what one does,” said Dr. Carlson, explaining that the impact of therapy has not always been adequately described in therapy studies.

For the tonic form, irritability is likely to improve or resolve with control of the underlying psychiatric condition. Although this might also be true of the phasic form, this type of irritability often accompanies conditions that are less readily controlled even through the threat of self-harm, harm to others, or other destructive behaviors invites intervention specifically targeted at this symptom.

Unfortunately, the best approach to irritability is unclear for many underling pathologies.

“Clinicians should recognize that empirical evidence is still lacking as to aggression-targeted treatments with favorable benefit-risk profiles for children and adolescents with ADHD and severe aggression,” said Dr. Carlson, providing ADHD as one of several examples.

Psychological interventions, such as dialectical behavior therapy in children (DBT-C), have been associated with control of both tonic and phasic forms of irritability, but Dr. Carlson cautioned that few studies have adequately differentiated improvement in irritability as measured by behavior relative to mood. In addition, the baseline severity and the degree to which improvement meant adequate control have been unclear.

“Many psychological treatments are school based or group delivered, making it likely that patients are less impaired than explosive kids in psychiatry clinics and hospitals,” Dr. Carlson said.

Providing some practical tips for addressing the phasic form of irritability, Dr. Carlson suggested keeping careful records of the frequency, intensity, number, and duration of disruptive outbursts. She advised clinicians to “maximize the treatment of the base condition” but to add pharmacologic therapies to psychological interventions if symptoms persist.

“Our pendulum has swung from dishing out atypicals to eschewing them completely,” Dr. Carlson noted. Although she agreed these are no longer appropriate as first-line therapies, she suggested they might be employed judiciously if weight gain is monitored carefully.

“If they don’t work, stop them. If they do work, try to limit the duration of use,” Dr. Carlson said.

She reported having no relevant financial relationships to disclose.

BROOKLYN, N.Y. – As a target of therapy in children with a psychiatric disorder, irritability expressed as grumpy mood or anger should be uncoupled from irritability expressed as threatening behavior, according to an exploration of this common clinical issue at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

Ted Bosworth/MDedge News

“Irritability is like fever,” reported Gabrielle A. Carlson, MD, professor of psychiatry and pediatrics, State University of New York at Stony Brook. “It is a nonspecific symptom that only tells you that something is wrong.”

Irritability might be nothing more than a negative mood, but it also can be the source of explosive aggression, leading to tantrums and destructive behaviors, according to Dr. Carlson. She placed them into two different categories when considering treatment. Irritability leading to annoyance, grumpiness, withdrawal, or persistent anger is characterized as the “internalizing” or “tonic” form of the symptom. As opposed to the aggressive subtype, the tonic form is more closely associated with depression or anxiety. Irritability leading to extreme verbal outbursts or physical violence is characterized as the “externalizing” or “phasic” form, Dr. Carlson said. This type of irritability, defined by behavior more than mood, might signal disruptive mood dysregulation disorder (DMDD). But it is important to recognize that DMDD can overlap with other conditions, such as attention-deficit/hyperactivity disorder (ADHD), bipolar disorder, oppositional defiant disorder (ODD), and autism spectrum disorders.

In defining the impact of treatments on tonic versus phasic symptoms of irritability within the context of the underlying diagnoses, studies have not done a good job in separating relative effects on the two key forms of irritability, Dr. Carlson said.

“Irritability needs to be measured not only by how one feels but what one does,” said Dr. Carlson, explaining that the impact of therapy has not always been adequately described in therapy studies.

For the tonic form, irritability is likely to improve or resolve with control of the underlying psychiatric condition. Although this might also be true of the phasic form, this type of irritability often accompanies conditions that are less readily controlled even through the threat of self-harm, harm to others, or other destructive behaviors invites intervention specifically targeted at this symptom.

Unfortunately, the best approach to irritability is unclear for many underling pathologies.

“Clinicians should recognize that empirical evidence is still lacking as to aggression-targeted treatments with favorable benefit-risk profiles for children and adolescents with ADHD and severe aggression,” said Dr. Carlson, providing ADHD as one of several examples.

Psychological interventions, such as dialectical behavior therapy in children (DBT-C), have been associated with control of both tonic and phasic forms of irritability, but Dr. Carlson cautioned that few studies have adequately differentiated improvement in irritability as measured by behavior relative to mood. In addition, the baseline severity and the degree to which improvement meant adequate control have been unclear.

“Many psychological treatments are school based or group delivered, making it likely that patients are less impaired than explosive kids in psychiatry clinics and hospitals,” Dr. Carlson said.

Providing some practical tips for addressing the phasic form of irritability, Dr. Carlson suggested keeping careful records of the frequency, intensity, number, and duration of disruptive outbursts. She advised clinicians to “maximize the treatment of the base condition” but to add pharmacologic therapies to psychological interventions if symptoms persist.

“Our pendulum has swung from dishing out atypicals to eschewing them completely,” Dr. Carlson noted. Although she agreed these are no longer appropriate as first-line therapies, she suggested they might be employed judiciously if weight gain is monitored carefully.

“If they don’t work, stop them. If they do work, try to limit the duration of use,” Dr. Carlson said.

She reported having no relevant financial relationships to disclose.