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Surgery residents cite time challenges to robotics training
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Although a majority of surgical residents plan to incorporate robotics in practice, 80% cited time commitment as a barrier to completing a nonmandatory robotics curriculum, according to a survey published online in the American Journal of Surgery.
Most surgery residents agree that robotics training is important, but most academic institutions have not yet established a mandatory training program, wrote Vernissia Tam, MD, of the University of Pittsburgh and her colleagues (Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051).
To determine resident attitudes about robotics and the impact of a robotics curriculum, the researchers surveyed 48 general surgery residents in 2014-2015 and 49 residents in 2016-2017 at a single academic center. Overall, 98% and 96% of the two groups, respectively, reported high interest improving robotic skills, and more than two-thirds reported plans to use robotics in their practices.
The introduction of a voluntary, structured robotics program yielded significant improvements in the percentage of residents using both a robotic backpack simulator (from 18% to 39%) and an inanimate box trainer (increased from 20% to 41%).
However, of 60 unique residents between the two survey time points, only 24 began the robotics curriculum (40%) and only 11 (18%) completed it. In a follow-up survey of residents who had not yet completed the robotics training, 80% said that “time away from clinical responsibilities and/or research was the most commonly cited barrier to curriculum completion,” Dr. Tam and her associates noted.
The study was limited in part by the use of data from a single center over a short period of time, but “we believe these results provide a broad needs assessment for a structured robotics program and identify barriers to implementing a novel curriculum,” the researchers wrote. Many health professionals argue that a competence-based program, rather than time-based, would be more effective and accessible to students, so “development of an inanimate deliberate practice system with weekly opportunities is a viable avenue to increase technical skills and learn surgical procedures,” they said.
The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
SOURCE: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
FROM THE AMERICAN JOURNAL OF SURGERY
Key clinical point: .
Major finding: 80% of surgical residents said that the length of time needed to complete a robotics curriculum was a barrier to doing so.
Data source: Survey of 97 general surgery residents conducted in 2014-2015 and 2016-2017.
Disclosures: The researchers had no financial conflicts to disclose. The study was supported in part by an Intuitive Surgical Education Grant.
Source: Tam V et al. Am J Surg. 2017. doi: 10.1016/j.amjsurg.2017.08.051.
Optimal Duration of Antiplatelet Therapy Following Acute Coronary Syndrome
ADA guidelines embrace heart health
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity. 
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and comorbid atherosclerotic cardiovascular disease (ASCVD).
Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metformin. But in its new position statement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD (Diabetes Care 2018;41(Suppl. 1):S86-S104. doi: 10.2337/dc18-S009).
The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A1c goals, said Rita R. Kalyani, MD, who led the ADA’s 12-member writing committee. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.
“A1c remains the main target of sequencing antihyperglycemic therapies, if it’s not reached after 3 months,” said Dr. Kalyani of Johns Hopkins University, Baltimore. “But, it could also be that the provider, after consulting with the patient, feels it’s appropriate to add one of these agents solely for cardioprotective benefit in patients with ASCVD.”
The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied,” said Dr. Kalyani.
The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This makes it especially clinically useful, Paul S. Jellinger, MD, said in an interview. A member of the writing committee of the American Association of Clinical Endocrinologists’ diabetes management guidelines, Dr. Jellinger feels ADA’s previous versions have not been as targeted as this new one and, he hopes, its subsequent iterations.
“This is a nice enhancement of previously published guidelines for diabetes therapy,” said Dr. Jellinger, professor of clinical medicine at the University of Miami. “For the first time, ADA is providing some guidance in terms of which agents to use. It’s definitely more prescriptive than it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidance about which agent to pick. The guidance for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”
While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify a preference for a specific drug class after metformin therapy in patients without ASCVD. Instead, it provides a detailed table listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents ( SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones, sulfonylureas, and insulins). The table notes the drugs’ general efficacy in diabetes, and their impact on hypoglycemia, weight gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.
Another helpful feature is a cost comparison of antidiabetic agents, Dr. Kalyani noted. “Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”
The pricing information is a very important addition to this guideline, and one that clinicians will appreciate, said Richard Hellman, MD, clinical professor of medicine at the University of Missouri–Kansas City.
“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than they can deal with. They present tables which compare the costs of the current blood glucose lowering agents used in the U.S., and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable,” said Dr. Hellman, a past president of AACE. “They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.
The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found that 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity (Diabetes Educ. 2017;43:260-71. doi: 10.1177/0145721717699890).
“Another thing the document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor,” Dr. Hellman said. “The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. We have so many better tools to manage this disease, but so many of these tools are unaffordable.”
While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendation may stir the pot a bit, Dr. Hellman noted. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American Heart Association and the American College of Cardiology.
“This difference in recommendations is very important and will be controversial,” Dr. Hellman said, adding that he agrees with this clinical point.
Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from the SPRINT trial, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group,” Dr. Hellman said.
But large well-designed randomized controlled trials of intensive blood pressure lowering in people with diabetes, such as ACCORD-BP, did not demonstrate that intensive blood-pressure lowering targeting a systolic less than120 mm Hg had a significant benefit on the composite primary cardiovascular endpoint. And while the ADVANCE BP trial found that the composite endpoint was improved with intensive blood pressure lowering, the blood pressure level achieved in the intervention group was 136/73 mm Hg.
“This recommendation is based on current evidence for people with diabetes,” Dr. Kalyani said. “We maintain our definition of hypertension as 140/90 mm Hg or higher based on the results of large clinical trials specifically in people with diabetes but emphasize that intensification of antihypertensive therapy to target lower blood pressures (less than 130/80 mm Hg) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of new studies for potential incorporation into recommendations in the future.”
Dr. Kalyani and Dr. Hellman had no financial disclosures. Dr. Jellinger has been a speaker for several pharmaceutical companies.
SOURCE: Kalyani R et al. Diabetes Care 2018;41(Suppl. 1):S86-S104 doi: 10.2337/dc18-S009
This article was updated 12/21/17.
EXPERT ANALYSIS FROM DIABETES CARE
Applications due Feb. 1 for VAM Scholarships, Research Fellowship
SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarship to attend the 2018 Vascular Annual Meeting.
VAM will be held June 20 to 23, 2018, in Boston. (Plenaries are June 21-23 and exhibits are open June 21-22.) The Society for Vascular Surgery offers travel awards, including complimentary VAM registration, to be used toward the cost of travel, housing and meals.
Two awards are available, the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.
The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada.
Urge students you know with an interest in research to apply today.
SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarship to attend the 2018 Vascular Annual Meeting.
VAM will be held June 20 to 23, 2018, in Boston. (Plenaries are June 21-23 and exhibits are open June 21-22.) The Society for Vascular Surgery offers travel awards, including complimentary VAM registration, to be used toward the cost of travel, housing and meals.
Two awards are available, the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.
The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada.
Urge students you know with an interest in research to apply today.
SVS members, please encourage medical or pre-med students interested in vascular surgery to apply for scholarship to attend the 2018 Vascular Annual Meeting.
VAM will be held June 20 to 23, 2018, in Boston. (Plenaries are June 21-23 and exhibits are open June 21-22.) The Society for Vascular Surgery offers travel awards, including complimentary VAM registration, to be used toward the cost of travel, housing and meals.
Two awards are available, the General Surgery Resident/Medical Student Travel Scholarship and the Diversity Medical Student Travel Scholarship. Recipients become part of the hugely popular scholarship program, designed to let residents and students explore their interest in vascular surgery.
The SVS Foundation seeks applicants for its Student Research Fellowship awards, designed to stimulate laboratory and clinical vascular research by undergraduate college students and medical students attending universities in the United States and Canada.
Urge students you know with an interest in research to apply today.
DDSEP® 8 Quick Quiz - January 2018 Question 2
Q2. CORRECT ANSWER: C
RATIONALE
In a population study of U.S. veterans infected with hepatitis C (n = 110,484), a cox proportional hazards model was used to determine risk of developing cirrhosis and hepatocellular carcinoma for genotypes 1-4, after adjusting for age, period of service, race, sex, human immunodeficiency virus (HIV) infection, alcohol use, diabetes, body mass index, and antiviral treatment. Despite genotype 3 patients being younger, their risk of developing cirrhosis was highest with hazard ratio = 1.30 (1.22, 1.39), compared to genotype 1 (reference, HR 1.0), genotype 2 with HR = 0.68 (0.64, 0.73), and genotype 4 with HR = 0.94 (0.78, 1.14). Likewise, the risk of development of HCC was highest for genotype 3 HCV with HR = 1.80 (1.60, 2.03), compared to a genotype 2 (HR = 0.55; 0.47, 0.63), and genotype 4 (0.99; 0.68, 1.45).
It is speculated that the hepatic steatosis that is a direct result of genotype 3 HCV may contribute to the accelerated progression to cirrhosis and HCC, but this has not been proven and was not evaluated in this Veteran Affairs study.
REFERENCE
1. Kanwal F., Kramer J.R., Ilyas J., et al. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014;60(1):98-105.
Q2. CORRECT ANSWER: C
RATIONALE
In a population study of U.S. veterans infected with hepatitis C (n = 110,484), a cox proportional hazards model was used to determine risk of developing cirrhosis and hepatocellular carcinoma for genotypes 1-4, after adjusting for age, period of service, race, sex, human immunodeficiency virus (HIV) infection, alcohol use, diabetes, body mass index, and antiviral treatment. Despite genotype 3 patients being younger, their risk of developing cirrhosis was highest with hazard ratio = 1.30 (1.22, 1.39), compared to genotype 1 (reference, HR 1.0), genotype 2 with HR = 0.68 (0.64, 0.73), and genotype 4 with HR = 0.94 (0.78, 1.14). Likewise, the risk of development of HCC was highest for genotype 3 HCV with HR = 1.80 (1.60, 2.03), compared to a genotype 2 (HR = 0.55; 0.47, 0.63), and genotype 4 (0.99; 0.68, 1.45).
It is speculated that the hepatic steatosis that is a direct result of genotype 3 HCV may contribute to the accelerated progression to cirrhosis and HCC, but this has not been proven and was not evaluated in this Veteran Affairs study.
REFERENCE
1. Kanwal F., Kramer J.R., Ilyas J., et al. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014;60(1):98-105.
Q2. CORRECT ANSWER: C
RATIONALE
In a population study of U.S. veterans infected with hepatitis C (n = 110,484), a cox proportional hazards model was used to determine risk of developing cirrhosis and hepatocellular carcinoma for genotypes 1-4, after adjusting for age, period of service, race, sex, human immunodeficiency virus (HIV) infection, alcohol use, diabetes, body mass index, and antiviral treatment. Despite genotype 3 patients being younger, their risk of developing cirrhosis was highest with hazard ratio = 1.30 (1.22, 1.39), compared to genotype 1 (reference, HR 1.0), genotype 2 with HR = 0.68 (0.64, 0.73), and genotype 4 with HR = 0.94 (0.78, 1.14). Likewise, the risk of development of HCC was highest for genotype 3 HCV with HR = 1.80 (1.60, 2.03), compared to a genotype 2 (HR = 0.55; 0.47, 0.63), and genotype 4 (0.99; 0.68, 1.45).
It is speculated that the hepatic steatosis that is a direct result of genotype 3 HCV may contribute to the accelerated progression to cirrhosis and HCC, but this has not been proven and was not evaluated in this Veteran Affairs study.
REFERENCE
1. Kanwal F., Kramer J.R., Ilyas J., et al. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology. 2014;60(1):98-105.
Which HCV genotype is associated with the highest risk of cirrhosis and hepatocellular carcinoma?
MACRA Monday: Depression screening
If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.
Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.
Consider this measure:
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Measure #134: Preventive Care and Screening: Screening for Depression and Follow-Up Plan
This measure aims to capture the percentage of patients aged 12 years and older who have been screened for depression and have a documented follow-up plan of care, if appropriate.
What you need to do: Use an age-appropriate, standardized tool to screen patients for depression during the visit. If they screen positive, develop a follow-up plan during the visit and document it.
Eligible cases include patients who were aged 12 years or older on the date of the encounter and have a patient encounter during the performance period. Applicable codes include (CPT or HCPCS): 90791, 90792, 90832, 90834, 90837, 92625, 96116, 96118, 96150, 96151, 97165, 97166, 97167, 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215, G0101, G0402, G0438, G0439, G0444.
To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, G8431 indicates that depression screening was positive and a follow-up plan was documented, while G8510 indicates that the depression screening was negative and a follow-up plan is not required. Use exclusion code G9717 if the patient has an active diagnosis of depression for bipolar disorder.
CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.
Certain clinicians are exempt from reporting and do not face a penalty under MIPS:
- Those who enrolled in Medicare for the first time during a performance period.
- Those who have Medicare Part B allowed charges of $30,000 or less.
- Those who have 100 or fewer Medicare Part B patients.
- Those who are significantly participating in an Advanced Alternative Payment Model (APM).
If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.
Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.
Consider this measure:
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Measure #134: Preventive Care and Screening: Screening for Depression and Follow-Up Plan
This measure aims to capture the percentage of patients aged 12 years and older who have been screened for depression and have a documented follow-up plan of care, if appropriate.
What you need to do: Use an age-appropriate, standardized tool to screen patients for depression during the visit. If they screen positive, develop a follow-up plan during the visit and document it.
Eligible cases include patients who were aged 12 years or older on the date of the encounter and have a patient encounter during the performance period. Applicable codes include (CPT or HCPCS): 90791, 90792, 90832, 90834, 90837, 92625, 96116, 96118, 96150, 96151, 97165, 97166, 97167, 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215, G0101, G0402, G0438, G0439, G0444.
To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, G8431 indicates that depression screening was positive and a follow-up plan was documented, while G8510 indicates that the depression screening was negative and a follow-up plan is not required. Use exclusion code G9717 if the patient has an active diagnosis of depression for bipolar disorder.
CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.
Certain clinicians are exempt from reporting and do not face a penalty under MIPS:
- Those who enrolled in Medicare for the first time during a performance period.
- Those who have Medicare Part B allowed charges of $30,000 or less.
- Those who have 100 or fewer Medicare Part B patients.
- Those who are significantly participating in an Advanced Alternative Payment Model (APM).
If you haven’t started reporting quality data for the Merit-Based Incentive Payment System (MIPS), there’s still time to avoid a 4% cut to your Medicare payments.
Under the Pick Your Pace approach being offered this year, the Centers for Medicare & Medicaid Services allows clinicians to test the system by reporting on one quality measure for one patient through paper-based claims. Be sure to append a Quality Data Code (QDC) to the claim form for care provided up to Dec. 31, 2017, in order to avoid a penalty in payment year 2019.
Consider this measure:
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Measure #134: Preventive Care and Screening: Screening for Depression and Follow-Up Plan
This measure aims to capture the percentage of patients aged 12 years and older who have been screened for depression and have a documented follow-up plan of care, if appropriate.
What you need to do: Use an age-appropriate, standardized tool to screen patients for depression during the visit. If they screen positive, develop a follow-up plan during the visit and document it.
Eligible cases include patients who were aged 12 years or older on the date of the encounter and have a patient encounter during the performance period. Applicable codes include (CPT or HCPCS): 90791, 90792, 90832, 90834, 90837, 92625, 96116, 96118, 96150, 96151, 97165, 97166, 97167, 99201, 99202, 99203, 99204, 99205, 99212, 99213, 99214, 99215, G0101, G0402, G0438, G0439, G0444.
To get credit under MIPS, be sure to include a QDC that shows that you successfully performed the measure or had a good reason for not doing so. For instance, G8431 indicates that depression screening was positive and a follow-up plan was documented, while G8510 indicates that the depression screening was negative and a follow-up plan is not required. Use exclusion code G9717 if the patient has an active diagnosis of depression for bipolar disorder.
CMS has a full list measures available for claims-based reporting at qpp.cms.gov. The American Medical Association has also created a step-by-step guide for reporting on one quality measure.
Certain clinicians are exempt from reporting and do not face a penalty under MIPS:
- Those who enrolled in Medicare for the first time during a performance period.
- Those who have Medicare Part B allowed charges of $30,000 or less.
- Those who have 100 or fewer Medicare Part B patients.
- Those who are significantly participating in an Advanced Alternative Payment Model (APM).
Medication-Induced Pruritus From Direct Oral Anticoagulants
Pruritus is a subjective report of itching, which can be caused by dermatologic or systemic conditions. Pruritus accounts for about 5% of all skin adverse drug reactions (ADRs) after administration.1 Mechanisms by which medication-induced pruritus occurs are still unknown and have been understudied. Treatment modalities also have been understudied; however, the understood method for treatment is cessation of the causative agent.2
Anticoagulants commonly are used in several conditions, including prevention of ischemic cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) as well as for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE).3 Traditionally, warfarin was the gold standard anticoagulant. With the relatively recent approval of several direct oral anticoagulants (DOACs), such as rivaroxaban, apixaban, and dabigatran, the landscape of anticoagulation is changing. One benefit of using DOACs as opposed to warfarin is that they often require less frequent laboratory monitoring. However, rare ADRs not detected during clinical trials have appeared following drug approval.4
In a VA anticoagulation clinic that managed more than 60 patients taking DOACs, the authors identified 2 cases of pruritus, possibly associated with DOAC agents. These 2 cases point to a higher incidence rate than the rate reported in the rivaroxaban package insert (2%).5 Of note, pruritus is not mentioned in the apixaban package insert.6
Patient 1 Case Presentation
Patient 1 was a 69-year-old male with AF who was switched to rivaroxaban after 5 years of warfarin therapy. Past medical history included iron deficiency anemia, hypertension, type 2 diabetes mellitus, systolic heart failure, hyperlipidemia, hepatic steatosis, benign prostatic hyperplasia, and gastroesophageal reflux disease. The patient reported “itching all over” soon after initiation of rivaroxaban and that the itching was intolerable and always began 90 to 120 minutes after each dose of rivaroxaban with no associated rash.
After about 6 months of treatment with rivaroxaban, the patient was switched to apixaban; however, the pruritus persisted even after the switch. The onset of itching had similar timing with regard to the apixaban doses. When apixaban was initiated, the patient also was started on amiodarone and tamsulosin. A full pharmacotherapy review of the patient’s medication list for the incidence of pruritus was conducted. Regarding amiodarone and tamsulosin, incidence of pruritus was < 1%.7,8 Neither agent had yet been started during the rivaroxaban therapy; therefore, it was unlikely that either of these 2 medications were the causative agent of the pruritic ADR.
In response to the itching, the patient was given diphenhydramine 25 mg twice daily, taken with each dose of apixaban. Shortly thereafter, the patient reported that diphenhydramine lessened the severity of the pruritus. He was switched to loratadine 10 mg twice daily with each dose of apixaban, to avoid drowsiness as well as the increased anticholinergic ADRs of first-generation antihistamines. The patient reported that the itching was tolerable.
Patient 2 Case Presentation
Patient 2 was a 63-year-old male with AF and hypertension who was initially started on rivaroxaban and reported pruritus after about 1 month. Despite the uncomfortable itch, the patient elected to continue therapy and began diphenhydramine 25 mg daily with each dose of rivaroxaban. Diphenhydramine seemed to improve the pruritus but did not completely alleviate it. While on rivaroxaban, the patient experienced an acute drop in hemoglobin; however, no source of bleeding was found. Although the pruritus was largely resolved, he was switched to apixaban due to its favorable bleeding profile.9 The patient continued to have pruritus on apixaban; however, he reported that pruritus was less severe than it had been while taking rivaroxaban. The patient restarted on diphenhydramine twice daily with each dose of apixaban and reported cessation of pruritus.
Discussion
After observing both cases in relation to the timing between the administration of a DOAC and onset of pruritus, it seemed likely that the causative agent could be the DOAC. A Naranjo Nomogram was used to determine the likeliness of each drug to be the causative agent of the ADR.10 This nomogram is scaled from a low score of -4 to a high score of 13. Patients 1 and 2 had a score of 4, which is reflective of a possible ADR (score 1-4). Using the nomogram as well as the subjective information provided by the patients, it is reasonable to conclude that the pruritus was possibly associated with the use of the DOACs. Nonadherence to anticoagulants may lead to potentially fatal adverse outcomes, such as stroke. Medication-associated pruritus could lead to medication nonadherence if left unaddressed. It is notable that prescribing an antihistamine that is taken at the time of the anticoagulant dose allowed these patients with possible DOAC-associated pruritus to continue therapy with the selected anticoagulant. Further research on this topic is needed.
1. Reich A, Ständer S, Szepietowski C. Drug-induced pruritus: a review. Acta Derm Venereol. 2009;89(3):236-244.
2. Ebata T. Drug-induced itch management. Curr Probl Dermatol. 2016;50:155-163.
3. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-232.
4. U.S. Department of Health and Human Services, U.S. Food & Drug Administration. FDA Adverse Events Reporting System (FAERS) public dashboard. Apixaban. https://fis.fda.gov/sense/app/777e9f4d-0cf8-448e-8068-f564c31baa25/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis. Updated August 31, 2017. Accessed November 8, 2017.
5. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2011.
6. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; New York, NY: Pfizer Inc; 2016.
7. Pacerone [package insert]. Minneapolis, MN: Upsher-Smith Laboratories Inc; 2008. Minneapolis, MN.
8. Flomax [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2016.
9. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patient with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
10. Michel DJ, Knodel LC. Comparison of three algorithms used to evaluate adverse drug reactions. Am J Hosp Pharm. 1986;43(7):1709-1714.
Pruritus is a subjective report of itching, which can be caused by dermatologic or systemic conditions. Pruritus accounts for about 5% of all skin adverse drug reactions (ADRs) after administration.1 Mechanisms by which medication-induced pruritus occurs are still unknown and have been understudied. Treatment modalities also have been understudied; however, the understood method for treatment is cessation of the causative agent.2
Anticoagulants commonly are used in several conditions, including prevention of ischemic cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) as well as for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE).3 Traditionally, warfarin was the gold standard anticoagulant. With the relatively recent approval of several direct oral anticoagulants (DOACs), such as rivaroxaban, apixaban, and dabigatran, the landscape of anticoagulation is changing. One benefit of using DOACs as opposed to warfarin is that they often require less frequent laboratory monitoring. However, rare ADRs not detected during clinical trials have appeared following drug approval.4
In a VA anticoagulation clinic that managed more than 60 patients taking DOACs, the authors identified 2 cases of pruritus, possibly associated with DOAC agents. These 2 cases point to a higher incidence rate than the rate reported in the rivaroxaban package insert (2%).5 Of note, pruritus is not mentioned in the apixaban package insert.6
Patient 1 Case Presentation
Patient 1 was a 69-year-old male with AF who was switched to rivaroxaban after 5 years of warfarin therapy. Past medical history included iron deficiency anemia, hypertension, type 2 diabetes mellitus, systolic heart failure, hyperlipidemia, hepatic steatosis, benign prostatic hyperplasia, and gastroesophageal reflux disease. The patient reported “itching all over” soon after initiation of rivaroxaban and that the itching was intolerable and always began 90 to 120 minutes after each dose of rivaroxaban with no associated rash.
After about 6 months of treatment with rivaroxaban, the patient was switched to apixaban; however, the pruritus persisted even after the switch. The onset of itching had similar timing with regard to the apixaban doses. When apixaban was initiated, the patient also was started on amiodarone and tamsulosin. A full pharmacotherapy review of the patient’s medication list for the incidence of pruritus was conducted. Regarding amiodarone and tamsulosin, incidence of pruritus was < 1%.7,8 Neither agent had yet been started during the rivaroxaban therapy; therefore, it was unlikely that either of these 2 medications were the causative agent of the pruritic ADR.
In response to the itching, the patient was given diphenhydramine 25 mg twice daily, taken with each dose of apixaban. Shortly thereafter, the patient reported that diphenhydramine lessened the severity of the pruritus. He was switched to loratadine 10 mg twice daily with each dose of apixaban, to avoid drowsiness as well as the increased anticholinergic ADRs of first-generation antihistamines. The patient reported that the itching was tolerable.
Patient 2 Case Presentation
Patient 2 was a 63-year-old male with AF and hypertension who was initially started on rivaroxaban and reported pruritus after about 1 month. Despite the uncomfortable itch, the patient elected to continue therapy and began diphenhydramine 25 mg daily with each dose of rivaroxaban. Diphenhydramine seemed to improve the pruritus but did not completely alleviate it. While on rivaroxaban, the patient experienced an acute drop in hemoglobin; however, no source of bleeding was found. Although the pruritus was largely resolved, he was switched to apixaban due to its favorable bleeding profile.9 The patient continued to have pruritus on apixaban; however, he reported that pruritus was less severe than it had been while taking rivaroxaban. The patient restarted on diphenhydramine twice daily with each dose of apixaban and reported cessation of pruritus.
Discussion
After observing both cases in relation to the timing between the administration of a DOAC and onset of pruritus, it seemed likely that the causative agent could be the DOAC. A Naranjo Nomogram was used to determine the likeliness of each drug to be the causative agent of the ADR.10 This nomogram is scaled from a low score of -4 to a high score of 13. Patients 1 and 2 had a score of 4, which is reflective of a possible ADR (score 1-4). Using the nomogram as well as the subjective information provided by the patients, it is reasonable to conclude that the pruritus was possibly associated with the use of the DOACs. Nonadherence to anticoagulants may lead to potentially fatal adverse outcomes, such as stroke. Medication-associated pruritus could lead to medication nonadherence if left unaddressed. It is notable that prescribing an antihistamine that is taken at the time of the anticoagulant dose allowed these patients with possible DOAC-associated pruritus to continue therapy with the selected anticoagulant. Further research on this topic is needed.
Pruritus is a subjective report of itching, which can be caused by dermatologic or systemic conditions. Pruritus accounts for about 5% of all skin adverse drug reactions (ADRs) after administration.1 Mechanisms by which medication-induced pruritus occurs are still unknown and have been understudied. Treatment modalities also have been understudied; however, the understood method for treatment is cessation of the causative agent.2
Anticoagulants commonly are used in several conditions, including prevention of ischemic cerebrovascular accident (CVA) in patients with atrial fibrillation (AF) as well as for the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE).3 Traditionally, warfarin was the gold standard anticoagulant. With the relatively recent approval of several direct oral anticoagulants (DOACs), such as rivaroxaban, apixaban, and dabigatran, the landscape of anticoagulation is changing. One benefit of using DOACs as opposed to warfarin is that they often require less frequent laboratory monitoring. However, rare ADRs not detected during clinical trials have appeared following drug approval.4
In a VA anticoagulation clinic that managed more than 60 patients taking DOACs, the authors identified 2 cases of pruritus, possibly associated with DOAC agents. These 2 cases point to a higher incidence rate than the rate reported in the rivaroxaban package insert (2%).5 Of note, pruritus is not mentioned in the apixaban package insert.6
Patient 1 Case Presentation
Patient 1 was a 69-year-old male with AF who was switched to rivaroxaban after 5 years of warfarin therapy. Past medical history included iron deficiency anemia, hypertension, type 2 diabetes mellitus, systolic heart failure, hyperlipidemia, hepatic steatosis, benign prostatic hyperplasia, and gastroesophageal reflux disease. The patient reported “itching all over” soon after initiation of rivaroxaban and that the itching was intolerable and always began 90 to 120 minutes after each dose of rivaroxaban with no associated rash.
After about 6 months of treatment with rivaroxaban, the patient was switched to apixaban; however, the pruritus persisted even after the switch. The onset of itching had similar timing with regard to the apixaban doses. When apixaban was initiated, the patient also was started on amiodarone and tamsulosin. A full pharmacotherapy review of the patient’s medication list for the incidence of pruritus was conducted. Regarding amiodarone and tamsulosin, incidence of pruritus was < 1%.7,8 Neither agent had yet been started during the rivaroxaban therapy; therefore, it was unlikely that either of these 2 medications were the causative agent of the pruritic ADR.
In response to the itching, the patient was given diphenhydramine 25 mg twice daily, taken with each dose of apixaban. Shortly thereafter, the patient reported that diphenhydramine lessened the severity of the pruritus. He was switched to loratadine 10 mg twice daily with each dose of apixaban, to avoid drowsiness as well as the increased anticholinergic ADRs of first-generation antihistamines. The patient reported that the itching was tolerable.
Patient 2 Case Presentation
Patient 2 was a 63-year-old male with AF and hypertension who was initially started on rivaroxaban and reported pruritus after about 1 month. Despite the uncomfortable itch, the patient elected to continue therapy and began diphenhydramine 25 mg daily with each dose of rivaroxaban. Diphenhydramine seemed to improve the pruritus but did not completely alleviate it. While on rivaroxaban, the patient experienced an acute drop in hemoglobin; however, no source of bleeding was found. Although the pruritus was largely resolved, he was switched to apixaban due to its favorable bleeding profile.9 The patient continued to have pruritus on apixaban; however, he reported that pruritus was less severe than it had been while taking rivaroxaban. The patient restarted on diphenhydramine twice daily with each dose of apixaban and reported cessation of pruritus.
Discussion
After observing both cases in relation to the timing between the administration of a DOAC and onset of pruritus, it seemed likely that the causative agent could be the DOAC. A Naranjo Nomogram was used to determine the likeliness of each drug to be the causative agent of the ADR.10 This nomogram is scaled from a low score of -4 to a high score of 13. Patients 1 and 2 had a score of 4, which is reflective of a possible ADR (score 1-4). Using the nomogram as well as the subjective information provided by the patients, it is reasonable to conclude that the pruritus was possibly associated with the use of the DOACs. Nonadherence to anticoagulants may lead to potentially fatal adverse outcomes, such as stroke. Medication-associated pruritus could lead to medication nonadherence if left unaddressed. It is notable that prescribing an antihistamine that is taken at the time of the anticoagulant dose allowed these patients with possible DOAC-associated pruritus to continue therapy with the selected anticoagulant. Further research on this topic is needed.
1. Reich A, Ständer S, Szepietowski C. Drug-induced pruritus: a review. Acta Derm Venereol. 2009;89(3):236-244.
2. Ebata T. Drug-induced itch management. Curr Probl Dermatol. 2016;50:155-163.
3. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-232.
4. U.S. Department of Health and Human Services, U.S. Food & Drug Administration. FDA Adverse Events Reporting System (FAERS) public dashboard. Apixaban. https://fis.fda.gov/sense/app/777e9f4d-0cf8-448e-8068-f564c31baa25/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis. Updated August 31, 2017. Accessed November 8, 2017.
5. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2011.
6. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; New York, NY: Pfizer Inc; 2016.
7. Pacerone [package insert]. Minneapolis, MN: Upsher-Smith Laboratories Inc; 2008. Minneapolis, MN.
8. Flomax [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2016.
9. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patient with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
10. Michel DJ, Knodel LC. Comparison of three algorithms used to evaluate adverse drug reactions. Am J Hosp Pharm. 1986;43(7):1709-1714.
1. Reich A, Ständer S, Szepietowski C. Drug-induced pruritus: a review. Acta Derm Venereol. 2009;89(3):236-244.
2. Ebata T. Drug-induced itch management. Curr Probl Dermatol. 2016;50:155-163.
3. Burnett AE, Mahan CE, Vazquez SR, Oertel LB, Garcia DA, Ansell J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J Thromb Thrombolysis. 2016;41(1):206-232.
4. U.S. Department of Health and Human Services, U.S. Food & Drug Administration. FDA Adverse Events Reporting System (FAERS) public dashboard. Apixaban. https://fis.fda.gov/sense/app/777e9f4d-0cf8-448e-8068-f564c31baa25/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis. Updated August 31, 2017. Accessed November 8, 2017.
5. Xarelto [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2011.
6. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; New York, NY: Pfizer Inc; 2016.
7. Pacerone [package insert]. Minneapolis, MN: Upsher-Smith Laboratories Inc; 2008. Minneapolis, MN.
8. Flomax [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 2016.
9. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patient with atrial fibrillation. N Engl J Med. 2011;365(11):981-992.
10. Michel DJ, Knodel LC. Comparison of three algorithms used to evaluate adverse drug reactions. Am J Hosp Pharm. 1986;43(7):1709-1714.
Ruxolitinib improves survival for MF patients in CP-e
ATLANTA—A new study suggests the JAK2 inhibitor ruxolitinib has the potential to significantly improve survival in patients who have chronic phase (CP) myelofibrosis (MF), with or without elevated blasts.
In this retrospective study, researchers found evidence to suggest that MF patients in CP with elevated blasts (CP-e) should be considered a high-risk group.
However, ruxolitinib significantly improved overall survival (OS) in CP-e patients—who had 5% to 9% blasts in the bone marrow or peripheral blood—and in patients with CP and less than 5% blasts.
On the other hand, ruxolitinib had no impact on the rate of progression to acute myeloid leukemia (AML) in CP or CP-e patients.
Lucia Masarova, MD, of The University of Texas MD Anderson Cancer Center in Houston, presented these findings at the 2017 ASH Annual Meeting (abstract 201).
Clinical characteristics of MF CP-e patients are not well described, and the outcome of available therapy in this population is largely unknown. Therefore, Dr Masarova and her colleagues set out to evaluate the effects of ruxolitinib on CP-e patients.
The team conducted a retrospective chart review of 1199 MF patients, 832 with primary MF, 169 with post-essential thrombocythemia MF, and 198 with post-polycythemia vera MF. About two-thirds of the patients were newly diagnosed.
The majority of patients (85%, n=1020) were in CP with less than 5% blasts, 10% (n=123) were in CP-e, and 5% (n=56) were in accelerated phase (AP, 10% to 19% blasts).
CP-e patients had similar clinical characteristics as patients in AP. Both groups had higher white blood cell counts; lower hemoglobin and platelets; and more frequent splenomegaly, systemic symptoms, and presence of abnormal and unfavorable karyotype than CP patients.
Among the 1030 treated patients, ruxolitinib was used in 30% (n=328), including 28% of CP patients (n=289), 27% of CP-e patients (n=33), and 11% of AP patients (n=6). The median treatment duration was about 22 months in the CP and CP-e groups.
After a median follow-up of 27 months, half the patients studied had died.
“Patients in the [CP-e] group had similar OS as those in AP, which was inferior to patients in CP,” Dr Masarova said.
The median OS was 48 months for the entire cohort, 56 months in the CP group, 34 months in the CP-e group, and 23 months in the AP group.
One-year OS rates were 86% for the CP group, 73% for the CP-e group, and 65% for the AP group. Five-year OS rates were 46%, 24%, and 21%, respectively.
CP and CP-e patients had superior OS if they had received ruxolitinib.
Among CP patients, the median OS was 61 months in those who received ruxolitinib and 54 months in those who did not (hazard ratio=0.85, P=0.002).
Among CP-e patients, the median OS was 54 months in those who received ruxolitinib and 27 months in those who did not (hazard ratio=0.50, P=0.001).
Ruxolitinib had no impact on OS in AP patients, which was 23 months with or without the drug. However, Dr Masarova noted that the AP patient numbers were small.
Progression to AML occurred in 9% of patients overall (n=139), 9% in the CP group, 20% in the CP-e group, and 39% in the AP group.
Ruxolitinib had no impact on the rate of AML progression, which was 9% in CP patients, with and without the drug.
In CP-e patients, AML progression occurred in 22% of those who received ruxolitinib and 18% of those who did not.
“The [CP-e] patients are similar to AP patients, with adverse clinical characteristics, inferior OS, and a 20% to 40% AML rate,” Dr Masarova said. “Ruxolitinib improves survival of [CP-e] patients, which is similar to CP patients on the drug.”
CP-e patients should be considered a high-risk population, she said, adding “we need to find new, better treatments for these patients.”
Dr Masarova had no disclosures. 
ATLANTA—A new study suggests the JAK2 inhibitor ruxolitinib has the potential to significantly improve survival in patients who have chronic phase (CP) myelofibrosis (MF), with or without elevated blasts.
In this retrospective study, researchers found evidence to suggest that MF patients in CP with elevated blasts (CP-e) should be considered a high-risk group.
However, ruxolitinib significantly improved overall survival (OS) in CP-e patients—who had 5% to 9% blasts in the bone marrow or peripheral blood—and in patients with CP and less than 5% blasts.
On the other hand, ruxolitinib had no impact on the rate of progression to acute myeloid leukemia (AML) in CP or CP-e patients.
Lucia Masarova, MD, of The University of Texas MD Anderson Cancer Center in Houston, presented these findings at the 2017 ASH Annual Meeting (abstract 201).
Clinical characteristics of MF CP-e patients are not well described, and the outcome of available therapy in this population is largely unknown. Therefore, Dr Masarova and her colleagues set out to evaluate the effects of ruxolitinib on CP-e patients.
The team conducted a retrospective chart review of 1199 MF patients, 832 with primary MF, 169 with post-essential thrombocythemia MF, and 198 with post-polycythemia vera MF. About two-thirds of the patients were newly diagnosed.
The majority of patients (85%, n=1020) were in CP with less than 5% blasts, 10% (n=123) were in CP-e, and 5% (n=56) were in accelerated phase (AP, 10% to 19% blasts).
CP-e patients had similar clinical characteristics as patients in AP. Both groups had higher white blood cell counts; lower hemoglobin and platelets; and more frequent splenomegaly, systemic symptoms, and presence of abnormal and unfavorable karyotype than CP patients.
Among the 1030 treated patients, ruxolitinib was used in 30% (n=328), including 28% of CP patients (n=289), 27% of CP-e patients (n=33), and 11% of AP patients (n=6). The median treatment duration was about 22 months in the CP and CP-e groups.
After a median follow-up of 27 months, half the patients studied had died.
“Patients in the [CP-e] group had similar OS as those in AP, which was inferior to patients in CP,” Dr Masarova said.
The median OS was 48 months for the entire cohort, 56 months in the CP group, 34 months in the CP-e group, and 23 months in the AP group.
One-year OS rates were 86% for the CP group, 73% for the CP-e group, and 65% for the AP group. Five-year OS rates were 46%, 24%, and 21%, respectively.
CP and CP-e patients had superior OS if they had received ruxolitinib.
Among CP patients, the median OS was 61 months in those who received ruxolitinib and 54 months in those who did not (hazard ratio=0.85, P=0.002).
Among CP-e patients, the median OS was 54 months in those who received ruxolitinib and 27 months in those who did not (hazard ratio=0.50, P=0.001).
Ruxolitinib had no impact on OS in AP patients, which was 23 months with or without the drug. However, Dr Masarova noted that the AP patient numbers were small.
Progression to AML occurred in 9% of patients overall (n=139), 9% in the CP group, 20% in the CP-e group, and 39% in the AP group.
Ruxolitinib had no impact on the rate of AML progression, which was 9% in CP patients, with and without the drug.
In CP-e patients, AML progression occurred in 22% of those who received ruxolitinib and 18% of those who did not.
“The [CP-e] patients are similar to AP patients, with adverse clinical characteristics, inferior OS, and a 20% to 40% AML rate,” Dr Masarova said. “Ruxolitinib improves survival of [CP-e] patients, which is similar to CP patients on the drug.”
CP-e patients should be considered a high-risk population, she said, adding “we need to find new, better treatments for these patients.”
Dr Masarova had no disclosures.
ATLANTA—A new study suggests the JAK2 inhibitor ruxolitinib has the potential to significantly improve survival in patients who have chronic phase (CP) myelofibrosis (MF), with or without elevated blasts.
In this retrospective study, researchers found evidence to suggest that MF patients in CP with elevated blasts (CP-e) should be considered a high-risk group.
However, ruxolitinib significantly improved overall survival (OS) in CP-e patients—who had 5% to 9% blasts in the bone marrow or peripheral blood—and in patients with CP and less than 5% blasts.
On the other hand, ruxolitinib had no impact on the rate of progression to acute myeloid leukemia (AML) in CP or CP-e patients.
Lucia Masarova, MD, of The University of Texas MD Anderson Cancer Center in Houston, presented these findings at the 2017 ASH Annual Meeting (abstract 201).
Clinical characteristics of MF CP-e patients are not well described, and the outcome of available therapy in this population is largely unknown. Therefore, Dr Masarova and her colleagues set out to evaluate the effects of ruxolitinib on CP-e patients.
The team conducted a retrospective chart review of 1199 MF patients, 832 with primary MF, 169 with post-essential thrombocythemia MF, and 198 with post-polycythemia vera MF. About two-thirds of the patients were newly diagnosed.
The majority of patients (85%, n=1020) were in CP with less than 5% blasts, 10% (n=123) were in CP-e, and 5% (n=56) were in accelerated phase (AP, 10% to 19% blasts).
CP-e patients had similar clinical characteristics as patients in AP. Both groups had higher white blood cell counts; lower hemoglobin and platelets; and more frequent splenomegaly, systemic symptoms, and presence of abnormal and unfavorable karyotype than CP patients.
Among the 1030 treated patients, ruxolitinib was used in 30% (n=328), including 28% of CP patients (n=289), 27% of CP-e patients (n=33), and 11% of AP patients (n=6). The median treatment duration was about 22 months in the CP and CP-e groups.
After a median follow-up of 27 months, half the patients studied had died.
“Patients in the [CP-e] group had similar OS as those in AP, which was inferior to patients in CP,” Dr Masarova said.
The median OS was 48 months for the entire cohort, 56 months in the CP group, 34 months in the CP-e group, and 23 months in the AP group.
One-year OS rates were 86% for the CP group, 73% for the CP-e group, and 65% for the AP group. Five-year OS rates were 46%, 24%, and 21%, respectively.
CP and CP-e patients had superior OS if they had received ruxolitinib.
Among CP patients, the median OS was 61 months in those who received ruxolitinib and 54 months in those who did not (hazard ratio=0.85, P=0.002).
Among CP-e patients, the median OS was 54 months in those who received ruxolitinib and 27 months in those who did not (hazard ratio=0.50, P=0.001).
Ruxolitinib had no impact on OS in AP patients, which was 23 months with or without the drug. However, Dr Masarova noted that the AP patient numbers were small.
Progression to AML occurred in 9% of patients overall (n=139), 9% in the CP group, 20% in the CP-e group, and 39% in the AP group.
Ruxolitinib had no impact on the rate of AML progression, which was 9% in CP patients, with and without the drug.
In CP-e patients, AML progression occurred in 22% of those who received ruxolitinib and 18% of those who did not.
“The [CP-e] patients are similar to AP patients, with adverse clinical characteristics, inferior OS, and a 20% to 40% AML rate,” Dr Masarova said. “Ruxolitinib improves survival of [CP-e] patients, which is similar to CP patients on the drug.”
CP-e patients should be considered a high-risk population, she said, adding “we need to find new, better treatments for these patients.”
Dr Masarova had no disclosures.
Counseling parents may curb nonmedical vaccine exemptions
Nonmedical vaccine exemptions for children in Washington State decreased by 40% after the implementation of a law requiring parent counseling and a signed form from a medical provider, based on data from a regression analysis of kindergarten students during time periods before and after the law took effect.
The Washington State Senate Bill 5005 (SB5005), implemented in 2011, requires parents seeking exemptions to file a certificate of exemption (COE) signed by a Washington-licensed health care provider. It documents that the parents have discussed “the benefits and risks of immunizations” with the provider, the researchers wrote.
The researchers examined the effect of the parent counseling and signature requirement on exemption rates by reviewing data on kindergarten students.
Overall, the significant relative decrease of 40% translated to a significant absolute reduction of 2.9% in immunization exemption rates, and vaccine coverage increased or remained the same across all vaccines required for school. The greatest decline in exemption rates occurred in geographic areas with historically high rates before the bill was passed, the researchers said.
Based on the Washington findings, “states in the United States and jurisdictions in other countries should consider adding parental counseling as a requirement for obtaining exemptions to vaccination requirements,” they concluded.
Dr. Omer had no financial conflicts to disclose. One of the coauthors disclosed ties to vaccine manufacturers, and another’s organization had such ties. The study was supported by the Robert Wood Johnson Foundation.
Restoring community immunity requires diligence on the part of medical professionals, policymakers, and parents, wrote California state senator Richard J. Pan, MD, MPH, in an accompanying editorial.
Laws requiring that children be vaccinated before starting school are designed to protect the vaccinated children and the community at large, wrote Dr. Pan, but the passage of certain laws resulted in nonmedical exemptions that can reduce the effectiveness of childhood vaccinations on community health. In the past, parents rarely chose nonmedical exemptions because they recognized the dangers of diseases such as polio and measles and acknowledged the safety and effectiveness of the vaccines to protect against them, said Dr. Pan.
“However, some saw the opportunity to exploit these circumstances for personal gain by spreading vaccine misinformation over the Internet and social media to fuel parental anxiety and promote sales of their supplements and books, leading to increased use of nonmedical exemptions,” he said.
In Dr. Pan’s view, community immunity can be restored by creating stricter policies for vaccination and eliminating nonmedical exemptions. He authored a bill in California to abolish these exemptions, and the vaccination rate was 96% among kindergartners in California during the first year the policy was in place.
But antivaccine groups are well organized. One study found that “half of all Twitter posts about vaccines contain antivaccine beliefs. Just this year [2017] in Minnesota, antivaccine groups targeted a community, causing a significant drop in vaccination rates. The resulting measles outbreak exposed more than 8,000 people, sickened 79 (of which 73 were less than 10 years old), and hospitalized 22,” Dr. Pan said.
Pediatricians and other child health advocates must continue to work to address medical exemptions as well and to define the standards for what constitutes a medical exemption, Dr. Pan said. By educating and working with parents, legislators, and other health care professionals, “pediatricians need to build the political will to pass effective vaccine policy,” he said.
Dr. Pan is a California state senator in Sacramento. He had no financial conflicts to disclose. He commented in an editorial accompanying the study by Omer et al. (Pediatrics. 2017 Dec 18;141[1]:e20173449).
Restoring community immunity requires diligence on the part of medical professionals, policymakers, and parents, wrote California state senator Richard J. Pan, MD, MPH, in an accompanying editorial.
Laws requiring that children be vaccinated before starting school are designed to protect the vaccinated children and the community at large, wrote Dr. Pan, but the passage of certain laws resulted in nonmedical exemptions that can reduce the effectiveness of childhood vaccinations on community health. In the past, parents rarely chose nonmedical exemptions because they recognized the dangers of diseases such as polio and measles and acknowledged the safety and effectiveness of the vaccines to protect against them, said Dr. Pan.
“However, some saw the opportunity to exploit these circumstances for personal gain by spreading vaccine misinformation over the Internet and social media to fuel parental anxiety and promote sales of their supplements and books, leading to increased use of nonmedical exemptions,” he said.
In Dr. Pan’s view, community immunity can be restored by creating stricter policies for vaccination and eliminating nonmedical exemptions. He authored a bill in California to abolish these exemptions, and the vaccination rate was 96% among kindergartners in California during the first year the policy was in place.
But antivaccine groups are well organized. One study found that “half of all Twitter posts about vaccines contain antivaccine beliefs. Just this year [2017] in Minnesota, antivaccine groups targeted a community, causing a significant drop in vaccination rates. The resulting measles outbreak exposed more than 8,000 people, sickened 79 (of which 73 were less than 10 years old), and hospitalized 22,” Dr. Pan said.
Pediatricians and other child health advocates must continue to work to address medical exemptions as well and to define the standards for what constitutes a medical exemption, Dr. Pan said. By educating and working with parents, legislators, and other health care professionals, “pediatricians need to build the political will to pass effective vaccine policy,” he said.
Dr. Pan is a California state senator in Sacramento. He had no financial conflicts to disclose. He commented in an editorial accompanying the study by Omer et al. (Pediatrics. 2017 Dec 18;141[1]:e20173449).
Restoring community immunity requires diligence on the part of medical professionals, policymakers, and parents, wrote California state senator Richard J. Pan, MD, MPH, in an accompanying editorial.
Laws requiring that children be vaccinated before starting school are designed to protect the vaccinated children and the community at large, wrote Dr. Pan, but the passage of certain laws resulted in nonmedical exemptions that can reduce the effectiveness of childhood vaccinations on community health. In the past, parents rarely chose nonmedical exemptions because they recognized the dangers of diseases such as polio and measles and acknowledged the safety and effectiveness of the vaccines to protect against them, said Dr. Pan.
“However, some saw the opportunity to exploit these circumstances for personal gain by spreading vaccine misinformation over the Internet and social media to fuel parental anxiety and promote sales of their supplements and books, leading to increased use of nonmedical exemptions,” he said.
In Dr. Pan’s view, community immunity can be restored by creating stricter policies for vaccination and eliminating nonmedical exemptions. He authored a bill in California to abolish these exemptions, and the vaccination rate was 96% among kindergartners in California during the first year the policy was in place.
But antivaccine groups are well organized. One study found that “half of all Twitter posts about vaccines contain antivaccine beliefs. Just this year [2017] in Minnesota, antivaccine groups targeted a community, causing a significant drop in vaccination rates. The resulting measles outbreak exposed more than 8,000 people, sickened 79 (of which 73 were less than 10 years old), and hospitalized 22,” Dr. Pan said.
Pediatricians and other child health advocates must continue to work to address medical exemptions as well and to define the standards for what constitutes a medical exemption, Dr. Pan said. By educating and working with parents, legislators, and other health care professionals, “pediatricians need to build the political will to pass effective vaccine policy,” he said.
Dr. Pan is a California state senator in Sacramento. He had no financial conflicts to disclose. He commented in an editorial accompanying the study by Omer et al. (Pediatrics. 2017 Dec 18;141[1]:e20173449).
Nonmedical vaccine exemptions for children in Washington State decreased by 40% after the implementation of a law requiring parent counseling and a signed form from a medical provider, based on data from a regression analysis of kindergarten students during time periods before and after the law took effect.
The Washington State Senate Bill 5005 (SB5005), implemented in 2011, requires parents seeking exemptions to file a certificate of exemption (COE) signed by a Washington-licensed health care provider. It documents that the parents have discussed “the benefits and risks of immunizations” with the provider, the researchers wrote.
The researchers examined the effect of the parent counseling and signature requirement on exemption rates by reviewing data on kindergarten students.
Overall, the significant relative decrease of 40% translated to a significant absolute reduction of 2.9% in immunization exemption rates, and vaccine coverage increased or remained the same across all vaccines required for school. The greatest decline in exemption rates occurred in geographic areas with historically high rates before the bill was passed, the researchers said.
Based on the Washington findings, “states in the United States and jurisdictions in other countries should consider adding parental counseling as a requirement for obtaining exemptions to vaccination requirements,” they concluded.
Dr. Omer had no financial conflicts to disclose. One of the coauthors disclosed ties to vaccine manufacturers, and another’s organization had such ties. The study was supported by the Robert Wood Johnson Foundation.
Nonmedical vaccine exemptions for children in Washington State decreased by 40% after the implementation of a law requiring parent counseling and a signed form from a medical provider, based on data from a regression analysis of kindergarten students during time periods before and after the law took effect.
The Washington State Senate Bill 5005 (SB5005), implemented in 2011, requires parents seeking exemptions to file a certificate of exemption (COE) signed by a Washington-licensed health care provider. It documents that the parents have discussed “the benefits and risks of immunizations” with the provider, the researchers wrote.
The researchers examined the effect of the parent counseling and signature requirement on exemption rates by reviewing data on kindergarten students.
Overall, the significant relative decrease of 40% translated to a significant absolute reduction of 2.9% in immunization exemption rates, and vaccine coverage increased or remained the same across all vaccines required for school. The greatest decline in exemption rates occurred in geographic areas with historically high rates before the bill was passed, the researchers said.
Based on the Washington findings, “states in the United States and jurisdictions in other countries should consider adding parental counseling as a requirement for obtaining exemptions to vaccination requirements,” they concluded.
Dr. Omer had no financial conflicts to disclose. One of the coauthors disclosed ties to vaccine manufacturers, and another’s organization had such ties. The study was supported by the Robert Wood Johnson Foundation.
FROM PEDIATRICS
Key clinical point:
Major finding: After the implementation of SB5005 in Washington State, the rate of exemptions decreased by 40%.
Data source: The data come from a regression analysis of immunization coverage and exemption rates in Washington State for the school years 1997-1998 through 2013-2014.
Disclosures: Dr. Omer had no financial conflicts to disclose. One of the coauthors disclosed ties to vaccine manufacturers, and another’s organization had such ties. The study was supported by the Robert Wood Johnson Foundation.
Source: Omer SB et al. Pediatrics. 2018;141(1):e20172364.
Diagnosing & Treating Neuromyelitis Optica Spectrum Disorder
Q) How do you know if a neurologic symptom is due to a relapse of neuromyelitis optica spectrum disorder? And how should a confirmed relapse be treated?
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, relapsing autoimmune disease of the central nervous system (CNS) that targets the optic nerves and spinal cord, leading to blindness and paralysis.1,2 Whereas multiple sclerosis (MS) is characterized by demyelination, NMOSD is associated with astrocytic damage and tissue necrosis.3 Because longitudinally extensive inflammatory lesions are typical with NMOSD, permanent CNS damage is common with each relapse.4
Health care providers first need to determine whether a patient with NMOSD who presents with new or worsening symptoms is having a relapse. A relapse is caused by a breach of the blood-brain barrier by the peripheral immune system, which leads to inflammation and damage to the CNS.5 This causes neurologic symptoms that depend on the anatomic location. Once damage has occurred, symptoms may result either from a new relapse in the same location as a previous inflammatory event or from a pseudorelapse.6
Pseudorelapses are triggered by a systemic metabolic imbalance; they exacerbate symptoms from previous CNS damage. Differentiating between a true relapse and a pseudorelapse can be a diagnostic challenge for even the most seasoned of health care providers. Kessler et al retrospectively examined which clinical factors can distinguish relapses from pseudorelapses.6 Their findings suggest that while clinical examination alone may be effective in events involving vision loss, MRI may be necessary when signs and symptoms are attributable to a spinal cord lesion.
In fact, they found that the degree of clinical worsening in patients with spinal cord symptoms caused by a pseudorelapse was similar to that of a true relapse. The most common causes of pseudorelapse included infection, dysautonomia, metabolic abnormalities, and changes to medication regimens. Interestingly, the presence of infection did not rule out a relapse, as patients experiencing relapses were equally likely as those with pseudorelapse to have a urinary tract infection. The authors concluded, based on their data, that an MRI is warranted to verify a relapse in patients who experience worsening of symptoms localized to the spinal cord but is not necessary to rule out a pseudorelapse of optic neu
In contrast to MS, a progressive phase is not believed to be associated with NMOSD.7 Instead, accrual of disability occurs with each relapse. The majority of patients with NMOSD do not return to baseline following an untreated relapse, making it especially important that patients receive adequate acute treatment to mitigate the damage.8
Currently, there are no medications approved by the FDA for the acute or preventive treatment of NMOSD. However, off-label use of immunotherapies, including rituximab, mycophenolate mofetil, azathioprine, prednisone, methotrexate, tocilizumab, and mitoxantrone, have been studied for relapse prevention.2 In addition, there are three ongoing phase III trials investigating eculizumab (C5 complement inhibitor), inebilizumab (CD19 monoclonal antibody), and SA237 (IL6R blocker); results from these studies could potentially widen the landscape of immunotherapy use in NMOSD.2
Less investigation into appropriate acute treatment of new relapses has been conducted, however, leaving clinicians and patients uncertain about how to manage a new inflammatory event. Traditionally, firstline treatment for acute NMOSD relapses has been the same as for MS relapses—high-dose methylprednisolone. However, due to the severity of NMOSD relapses and the relative lack of response to steroids alone, methylprednisolone is commonly followed by plasma exchange (PLEX).2
Most data to guide clinical decision-making suggest that patients with NMOSD relapses recover better when PLEX is added to steroid treatment. Abboud et al found that 65% of patients who received both PLEX and methylprednisolone recovered to their prerelapse baseline, compared to 35% of those who received methylprednisolone alone.9 These findings were supported by a larger retrospective investigation by Kleiter et al, which found improved recovery with treatment escalation in their cohort.8 These data support the recommendation to use PLEX as an adjunct therapy in acute relapses—particularly in relapses with severe presentations.
Because diagnosis and treatment of relapses involve many factors, ranging from accrual of disability, long-term immunotherapy decisions, and medical costs, diligence in provider decision-making is essential when caring for patients with NMOSD. -MAM
Maureen A. Mealy, BSN, MSCN
Neuromyelitis Optica Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, PhD candidate at Johns Hopkins School of Nursing in Baltimore
1. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114.
2. Kessler RA, Mealy MA, Levy M. Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic. Curr Treat Options Neurol. 2016;18(1):2.
3. Popescu BF, Lucchinetti CF. Immunopathology: autoimmune glial diseases and differentiation from multiple sclerosis. Handb Clin Neurol. 2016;133:95-106.
4. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.
5. Orman G, Wang KY, Pekcevik Y, et al. Enhancing brain lesions during acute optic neuritis and/or longitudinally extensive transverse myelitis may portend a higher relapse rate in neuromyelitis optica spectrum disorders. Am J Neuroradiol. 2017;38(5):949-953.
6. Kessler RA, Mealy MA, Levy M. Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e269.
7. Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68(8):603-605.
8. Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206-216.
9. Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016;22(2):185-192.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Denise R. Bruen, MSN, APRN-BC, MSCN, who is with the University of Virginia in Charlottesville, and Maureen A. Mealy, BSN, MSCN, who is Neuromyelitis Optica Clinical Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, and PhD candidate at Johns Hopkins School of Nursing in Baltimore.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Denise R. Bruen, MSN, APRN-BC, MSCN, who is with the University of Virginia in Charlottesville, and Maureen A. Mealy, BSN, MSCN, who is Neuromyelitis Optica Clinical Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, and PhD candidate at Johns Hopkins School of Nursing in Baltimore.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Denise R. Bruen, MSN, APRN-BC, MSCN, who is with the University of Virginia in Charlottesville, and Maureen A. Mealy, BSN, MSCN, who is Neuromyelitis Optica Clinical Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, and PhD candidate at Johns Hopkins School of Nursing in Baltimore.
Q) How do you know if a neurologic symptom is due to a relapse of neuromyelitis optica spectrum disorder? And how should a confirmed relapse be treated?
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, relapsing autoimmune disease of the central nervous system (CNS) that targets the optic nerves and spinal cord, leading to blindness and paralysis.1,2 Whereas multiple sclerosis (MS) is characterized by demyelination, NMOSD is associated with astrocytic damage and tissue necrosis.3 Because longitudinally extensive inflammatory lesions are typical with NMOSD, permanent CNS damage is common with each relapse.4
Health care providers first need to determine whether a patient with NMOSD who presents with new or worsening symptoms is having a relapse. A relapse is caused by a breach of the blood-brain barrier by the peripheral immune system, which leads to inflammation and damage to the CNS.5 This causes neurologic symptoms that depend on the anatomic location. Once damage has occurred, symptoms may result either from a new relapse in the same location as a previous inflammatory event or from a pseudorelapse.6
Pseudorelapses are triggered by a systemic metabolic imbalance; they exacerbate symptoms from previous CNS damage. Differentiating between a true relapse and a pseudorelapse can be a diagnostic challenge for even the most seasoned of health care providers. Kessler et al retrospectively examined which clinical factors can distinguish relapses from pseudorelapses.6 Their findings suggest that while clinical examination alone may be effective in events involving vision loss, MRI may be necessary when signs and symptoms are attributable to a spinal cord lesion.
In fact, they found that the degree of clinical worsening in patients with spinal cord symptoms caused by a pseudorelapse was similar to that of a true relapse. The most common causes of pseudorelapse included infection, dysautonomia, metabolic abnormalities, and changes to medication regimens. Interestingly, the presence of infection did not rule out a relapse, as patients experiencing relapses were equally likely as those with pseudorelapse to have a urinary tract infection. The authors concluded, based on their data, that an MRI is warranted to verify a relapse in patients who experience worsening of symptoms localized to the spinal cord but is not necessary to rule out a pseudorelapse of optic neu
In contrast to MS, a progressive phase is not believed to be associated with NMOSD.7 Instead, accrual of disability occurs with each relapse. The majority of patients with NMOSD do not return to baseline following an untreated relapse, making it especially important that patients receive adequate acute treatment to mitigate the damage.8
Currently, there are no medications approved by the FDA for the acute or preventive treatment of NMOSD. However, off-label use of immunotherapies, including rituximab, mycophenolate mofetil, azathioprine, prednisone, methotrexate, tocilizumab, and mitoxantrone, have been studied for relapse prevention.2 In addition, there are three ongoing phase III trials investigating eculizumab (C5 complement inhibitor), inebilizumab (CD19 monoclonal antibody), and SA237 (IL6R blocker); results from these studies could potentially widen the landscape of immunotherapy use in NMOSD.2
Less investigation into appropriate acute treatment of new relapses has been conducted, however, leaving clinicians and patients uncertain about how to manage a new inflammatory event. Traditionally, firstline treatment for acute NMOSD relapses has been the same as for MS relapses—high-dose methylprednisolone. However, due to the severity of NMOSD relapses and the relative lack of response to steroids alone, methylprednisolone is commonly followed by plasma exchange (PLEX).2
Most data to guide clinical decision-making suggest that patients with NMOSD relapses recover better when PLEX is added to steroid treatment. Abboud et al found that 65% of patients who received both PLEX and methylprednisolone recovered to their prerelapse baseline, compared to 35% of those who received methylprednisolone alone.9 These findings were supported by a larger retrospective investigation by Kleiter et al, which found improved recovery with treatment escalation in their cohort.8 These data support the recommendation to use PLEX as an adjunct therapy in acute relapses—particularly in relapses with severe presentations.
Because diagnosis and treatment of relapses involve many factors, ranging from accrual of disability, long-term immunotherapy decisions, and medical costs, diligence in provider decision-making is essential when caring for patients with NMOSD. -MAM
Maureen A. Mealy, BSN, MSCN
Neuromyelitis Optica Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, PhD candidate at Johns Hopkins School of Nursing in Baltimore
Q) How do you know if a neurologic symptom is due to a relapse of neuromyelitis optica spectrum disorder? And how should a confirmed relapse be treated?
Neuromyelitis optica spectrum disorder (NMOSD) is a severe, relapsing autoimmune disease of the central nervous system (CNS) that targets the optic nerves and spinal cord, leading to blindness and paralysis.1,2 Whereas multiple sclerosis (MS) is characterized by demyelination, NMOSD is associated with astrocytic damage and tissue necrosis.3 Because longitudinally extensive inflammatory lesions are typical with NMOSD, permanent CNS damage is common with each relapse.4
Health care providers first need to determine whether a patient with NMOSD who presents with new or worsening symptoms is having a relapse. A relapse is caused by a breach of the blood-brain barrier by the peripheral immune system, which leads to inflammation and damage to the CNS.5 This causes neurologic symptoms that depend on the anatomic location. Once damage has occurred, symptoms may result either from a new relapse in the same location as a previous inflammatory event or from a pseudorelapse.6
Pseudorelapses are triggered by a systemic metabolic imbalance; they exacerbate symptoms from previous CNS damage. Differentiating between a true relapse and a pseudorelapse can be a diagnostic challenge for even the most seasoned of health care providers. Kessler et al retrospectively examined which clinical factors can distinguish relapses from pseudorelapses.6 Their findings suggest that while clinical examination alone may be effective in events involving vision loss, MRI may be necessary when signs and symptoms are attributable to a spinal cord lesion.
In fact, they found that the degree of clinical worsening in patients with spinal cord symptoms caused by a pseudorelapse was similar to that of a true relapse. The most common causes of pseudorelapse included infection, dysautonomia, metabolic abnormalities, and changes to medication regimens. Interestingly, the presence of infection did not rule out a relapse, as patients experiencing relapses were equally likely as those with pseudorelapse to have a urinary tract infection. The authors concluded, based on their data, that an MRI is warranted to verify a relapse in patients who experience worsening of symptoms localized to the spinal cord but is not necessary to rule out a pseudorelapse of optic neu
In contrast to MS, a progressive phase is not believed to be associated with NMOSD.7 Instead, accrual of disability occurs with each relapse. The majority of patients with NMOSD do not return to baseline following an untreated relapse, making it especially important that patients receive adequate acute treatment to mitigate the damage.8
Currently, there are no medications approved by the FDA for the acute or preventive treatment of NMOSD. However, off-label use of immunotherapies, including rituximab, mycophenolate mofetil, azathioprine, prednisone, methotrexate, tocilizumab, and mitoxantrone, have been studied for relapse prevention.2 In addition, there are three ongoing phase III trials investigating eculizumab (C5 complement inhibitor), inebilizumab (CD19 monoclonal antibody), and SA237 (IL6R blocker); results from these studies could potentially widen the landscape of immunotherapy use in NMOSD.2
Less investigation into appropriate acute treatment of new relapses has been conducted, however, leaving clinicians and patients uncertain about how to manage a new inflammatory event. Traditionally, firstline treatment for acute NMOSD relapses has been the same as for MS relapses—high-dose methylprednisolone. However, due to the severity of NMOSD relapses and the relative lack of response to steroids alone, methylprednisolone is commonly followed by plasma exchange (PLEX).2
Most data to guide clinical decision-making suggest that patients with NMOSD relapses recover better when PLEX is added to steroid treatment. Abboud et al found that 65% of patients who received both PLEX and methylprednisolone recovered to their prerelapse baseline, compared to 35% of those who received methylprednisolone alone.9 These findings were supported by a larger retrospective investigation by Kleiter et al, which found improved recovery with treatment escalation in their cohort.8 These data support the recommendation to use PLEX as an adjunct therapy in acute relapses—particularly in relapses with severe presentations.
Because diagnosis and treatment of relapses involve many factors, ranging from accrual of disability, long-term immunotherapy decisions, and medical costs, diligence in provider decision-making is essential when caring for patients with NMOSD. -MAM
Maureen A. Mealy, BSN, MSCN
Neuromyelitis Optica Research Program Manager, Senior Research Nurse of the Transverse Myelitis & Multiple Sclerosis Centers, PhD candidate at Johns Hopkins School of Nursing in Baltimore
1. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114.
2. Kessler RA, Mealy MA, Levy M. Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic. Curr Treat Options Neurol. 2016;18(1):2.
3. Popescu BF, Lucchinetti CF. Immunopathology: autoimmune glial diseases and differentiation from multiple sclerosis. Handb Clin Neurol. 2016;133:95-106.
4. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.
5. Orman G, Wang KY, Pekcevik Y, et al. Enhancing brain lesions during acute optic neuritis and/or longitudinally extensive transverse myelitis may portend a higher relapse rate in neuromyelitis optica spectrum disorders. Am J Neuroradiol. 2017;38(5):949-953.
6. Kessler RA, Mealy MA, Levy M. Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e269.
7. Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68(8):603-605.
8. Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206-216.
9. Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016;22(2):185-192.
1. Wingerchuk DM, Hogancamp WF, O’Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic’s syndrome). Neurology. 1999;53(5):1107-1114.
2. Kessler RA, Mealy MA, Levy M. Treatment of neuromyelitis optica spectrum disorder: acute, preventive, and symptomatic. Curr Treat Options Neurol. 2016;18(1):2.
3. Popescu BF, Lucchinetti CF. Immunopathology: autoimmune glial diseases and differentiation from multiple sclerosis. Handb Clin Neurol. 2016;133:95-106.
4. Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: a multicentre study of 175 patients. J Neuroinflammation. 2012;9:14.
5. Orman G, Wang KY, Pekcevik Y, et al. Enhancing brain lesions during acute optic neuritis and/or longitudinally extensive transverse myelitis may portend a higher relapse rate in neuromyelitis optica spectrum disorders. Am J Neuroradiol. 2017;38(5):949-953.
6. Kessler RA, Mealy MA, Levy M. Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(5):e269.
7. Wingerchuk DM, Pittock SJ, Lucchinetti CF, et al. A secondary progressive clinical course is uncommon in neuromyelitis optica. Neurology. 2007;68(8):603-605.
8. Kleiter I, Gahlen A, Borisow N, et al. Neuromyelitis optica: evaluation of 871 attacks and 1,153 treatment courses. Ann Neurol. 2016;79(2):206-216.
9. Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: steroids alone versus steroids plus plasma exchange. Mult Scler. 2016;22(2):185-192.
