New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

jevans@mdedge.com

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

jevans@mdedge.com

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

New evidence provides estimates of the pregnancy rates for American women with multiple sclerosis (MS), their complication rates, and the rates of relapse and disease-modifying drug treatment during different phases before and after pregnancy.

The two new studies, conducted by Maria K. Houtchens, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues involved retrospective mining of U.S. commercial health plan data in the IQVIA Real-World Data Adjudicated Claims–U.S. database between Jan. 1, 2006, and June 30, 2015.

The mean age of pregnant women in the nine annual cohorts during that period was just over 32 years for those with MS and just over 29 years for those without. The percentage of women without MS who had a pregnancy-related claim in the database declined from 8.83% in 2006 to 7.75% in 2014 after adjusting for age, region, payer, and Charlson Comorbidity Index score, whereas the percentage increased in women with MS during the same period, from 7.91% to 9.47%. The investigators matched 2,115 women with MS and 2,115 without MS who had live births for a variety of variables and found that women with MS had higher rates of premature labor (31.4% vs. 27.4%; P = .005), infection in pregnancy (13.3% vs. 10.9%; P = .016), maternal cardiovascular disease (3.0% vs. 1.9%; P = .028), anemia or acquired coagulation disorder (2.5% vs. 1.3%; P = .007), neurologic complications in pregnancy (1.6% vs. 0.6%; P = .005), and sexually transmitted diseases in pregnancy (0.4% vs. 0%; P = .045). During labor and delivery, women with MS who had a live birth more often had a claim for acquired damage to the fetus (27.8% vs. 23.5%; P = .002) and congenital fetal malformations (13.2% vs. 10.3%; P = .004) than did women without MS.

In the second study, Dr. Houtchens and two coauthors from the first study of the database reported on a set of 2,158 women who had a live birth during the study period and had 1 year of continuous insurance eligibility before and after pregnancy. The odds for having an MS relapse declined during pregnancy (odds ratio, 0.623; 95% confidence interval, 0.521-0.744), rose during the 6-week postpartum puerperium (OR, 1.710; 95% CI, 1.358-2.152), and leveled off during the last three postpartum quarters to remain at a higher level than before pregnancy (OR, 1.216; 95% CI, 1.052-1.406). Disease-modifying drug treatment followed the same pattern with 20% using it before pregnancy, dropping to about 2% in the second trimester, and peaking in about a quarter of all patients 9-12 months post partum.

jevans@mdedge.com

SOURCES: Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006382; Houtchens MK et al. Neurology. 2018 Sep 28. doi: 10.1212/WNL.0000000000006384.

Endometriosis patients experiencing infertility can benefit from assisted reproductive technology (ART) at a young age, but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.

©ktsimage/iStockphoto.com

Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.

In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.

Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.

“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.

They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).

The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.

The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.

SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.

Endometriosis patients experiencing infertility can benefit from assisted reproductive technology (ART) at a young age, but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.

©ktsimage/iStockphoto.com

Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.

In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.

Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.

“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.

They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).

The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.

The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.

SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.

Endometriosis patients experiencing infertility can benefit from assisted reproductive technology (ART) at a young age, but non-ART infertility treatment is less likely to succeed in the endometriosis population, according to data from approximately 1,800 women with infertility.

©ktsimage/iStockphoto.com

Moderate to severe endometriosis had a negative impact on the outcome of ART, but “the efficacy of non-ART treatment in patients with endometriosis remains elusive” wrote Wataru Isono of the University of Tokyo, and colleagues.

In a study published in the Journal of Obstetrics & Gynaecology Research, the investigators sought to determine the impact of endometriosis severity on the effectiveness of non-ART treatment. They calculated the cumulative live birth rates for women treated with ART and non-ART.

Overall, 49% of the 894 ART patients and 22% of the 1,358 non-ART patients gave birth after treatment. The birth rate remained more than twice as high among ART patients across all age groups, but declined among ART patients starting at 35 years of age and declined sharply as patients reached 40 years of age.

“The most important aspect of this study was that we determined the limitations of non-ART and sought to identify optimal management methods, as non-ART can be a more cost-effective treatment than ART in certain circumstances,” the researchers noted.

They then focused on 288 patients with advanced endometriosis, defined as stage III or IV according to the revised American Society for Reproductive Medicine score. Notably, the presence of moderate to severe endometriosis had a significant effect on the outcomes of non-ART patients in their 30s, but ART was effective in this age group in a multivariate analysis. The cumulative live birth rate in advanced endometriosis patients was significantly lower than in those without the condition who underwent non-ART treatment (10% vs. 25%). However, cumulative live birth rates after ART were not significantly different among advanced endometriosis patients, compared with patients without advanced endometriosis (45% vs. 51%).

The study was limited by several factors including the inability to analyze the varied types of infertility treatment, Dr. Isono and associates noted. However, “our results may provide infertility patients with accurate information regarding their expected probabilities of achieving a live birth and may help them select the optimal treatment based on their classification according to various risk factors,” they said.

The researchers had no financial conflicts to disclose. The study was supported by the Japan Society for the Promotion of Sciences; Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; the Japan Agency for Medical Research and Development; and the Ministry of Health, Labor and Welfare.

SOURCE: Isono W et al. J Obstet Gynaecol Res. 2018. doi: 10.1111/jog.13826.

MONTEREY, CALIF. – It’s only found in 2%-3% of allergy cases. So why was propylene glycol (PG) declared the Allergen of the Year for 2018 by the North American Contact Dermatitis Society? Because, a dermatologist told colleagues, it’s so common.

“If you’re allergic to it, it’s tough to stay away from it,” said Joseph F. Fowler Jr., MD, clinical professor of dermatology at the University of Louisville (Ky.) in a presentation about contact dermatitis at the annual Coastal Dermatology Symposium.

Indeed, the synthetic compound PG is found in skin care products and cosmetics, coated pills, topical medications such as corticosteroids, foods (including bread, food coloring, and such flavorings as vanilla extracts). “It’s in every topical acne product I know of,” and is even in brake fluid and so-called nontoxic antifreeze, he said. (Propylene glycol shouldn’t be confused with the poisonous toxin ethylene glycol, which also is found in antifreeze.)

Patients can be tested for allergy to PG, Dr. Fowler pointed out, but it’s important to understand that it can trigger an irritation reaction that can be mistaken for an allergic reaction.

Dr. Fowler offered the following tips related to contact dermatitis and allergens. Be aware that metals, topical antibiotics, fragrances, and preservatives are most likely to cause allergic contact dermatitis. According to 2016 figures on allergen prevalence from the North American Contact Dermatitis Group (NACDG), allergy to the metal nickel is the most common (16%); followed by neomycin (9%); fragrance mix I, a mixture of fragrances used in allergen testing (9%); bacitracin (8%); and myroxylon, also known as balsam of Peru, which is used for a variety of purposes in food, medicines, and fragrances (7%).

These are followed by the metal cobalt (6%); the preservatives quaternium 15 and formaldehyde (both 6%); para-phenylenediamine, also known as PPD, which is used in hair dye (5%); and the fragrance mix II (5%), another mix of fragrances used in allergen testing.

Dr. Fowler cautioned that nickel can trigger an intense body-wide allergic reaction in children with atopic dermatitis. “In this situation, it’s really good to be compulsive and tell parents to absolutely keep that person away from nickel as much as humanly possible,” he said.

Keep an eye out for allergens that aren’t on the NACDG list, which includes 70 items. According to Dr. Fowler, more than 20% of his patients were positive to allergens not on the NACDG list.

Contact dermatitis is as common in children as in adults and can even be more common in children. An Italian study published in 2012 found that 70% of children aged 1-15 years tested via patch test were allergic to at least one allergen, a number that’s similar in adults (Dermatitis. 2012 Nov-Dec;23[6]:275-80). There are wide disparities in reported levels of children who are allergic to nickel, cobalt, and myroxylon, Dr. Fowler said.

The T.R.U.E. Test patch test system has value, compared with standard patch tests, but beware of its limitations, he advised. T.R.U.E. is easy to use and requires no prep time, he said, but the number of allergens is limited. By contrast, his clinic mostly uses the Finn Chambers on Scanpor tape system, which can test for many more allergens and is cheaper if used at least 5-10 times a month.

He cautioned that T.R.U.E. could miss the cause of contact dermatitis as often as 39% of the time, as demonstrated in one study of children undergoing patch testing (Arch Dermatol. 2008 Oct;144[10]:1329-36). However, he said, the T.R.U.E test has value in detecting allergies to nickel, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and neomycin (J Am Acad Dermatol. 2001 Dec;45[6]:836-9).

Consider patch testing in a child with eczema if the eczema is not in normal atopic areas, it spreads beyond normal areas, it doesn’t respond to usual treatments, or it begins later than 5 years of age.

And, Dr. Fowler added, it’s fine to perform patch testing on patients who are taking antihistamines, tumor necrosis factor–alpha inhibitors, NSAIDs, or methotrexate.

Dr. Fowler disclosed consulting for IntraDerm, serving on speakers bureaus for SmartPractice and Regeneron/Sanofi, and serving as an investigator for companies that include AbbVie, Allergan, Bayer, Dow, Galderma, Johnson & Johnson, Eli Lilly, Merck, Regeneron, SmartPractice, and Valeant (now Bausch).

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

 

MONTEREY, CALIF. – It’s only found in 2%-3% of allergy cases. So why was propylene glycol (PG) declared the Allergen of the Year for 2018 by the North American Contact Dermatitis Society? Because, a dermatologist told colleagues, it’s so common.

“If you’re allergic to it, it’s tough to stay away from it,” said Joseph F. Fowler Jr., MD, clinical professor of dermatology at the University of Louisville (Ky.) in a presentation about contact dermatitis at the annual Coastal Dermatology Symposium.

Indeed, the synthetic compound PG is found in skin care products and cosmetics, coated pills, topical medications such as corticosteroids, foods (including bread, food coloring, and such flavorings as vanilla extracts). “It’s in every topical acne product I know of,” and is even in brake fluid and so-called nontoxic antifreeze, he said. (Propylene glycol shouldn’t be confused with the poisonous toxin ethylene glycol, which also is found in antifreeze.)

Patients can be tested for allergy to PG, Dr. Fowler pointed out, but it’s important to understand that it can trigger an irritation reaction that can be mistaken for an allergic reaction.

Dr. Fowler offered the following tips related to contact dermatitis and allergens. Be aware that metals, topical antibiotics, fragrances, and preservatives are most likely to cause allergic contact dermatitis. According to 2016 figures on allergen prevalence from the North American Contact Dermatitis Group (NACDG), allergy to the metal nickel is the most common (16%); followed by neomycin (9%); fragrance mix I, a mixture of fragrances used in allergen testing (9%); bacitracin (8%); and myroxylon, also known as balsam of Peru, which is used for a variety of purposes in food, medicines, and fragrances (7%).

These are followed by the metal cobalt (6%); the preservatives quaternium 15 and formaldehyde (both 6%); para-phenylenediamine, also known as PPD, which is used in hair dye (5%); and the fragrance mix II (5%), another mix of fragrances used in allergen testing.

Dr. Fowler cautioned that nickel can trigger an intense body-wide allergic reaction in children with atopic dermatitis. “In this situation, it’s really good to be compulsive and tell parents to absolutely keep that person away from nickel as much as humanly possible,” he said.

Keep an eye out for allergens that aren’t on the NACDG list, which includes 70 items. According to Dr. Fowler, more than 20% of his patients were positive to allergens not on the NACDG list.

Contact dermatitis is as common in children as in adults and can even be more common in children. An Italian study published in 2012 found that 70% of children aged 1-15 years tested via patch test were allergic to at least one allergen, a number that’s similar in adults (Dermatitis. 2012 Nov-Dec;23[6]:275-80). There are wide disparities in reported levels of children who are allergic to nickel, cobalt, and myroxylon, Dr. Fowler said.

The T.R.U.E. Test patch test system has value, compared with standard patch tests, but beware of its limitations, he advised. T.R.U.E. is easy to use and requires no prep time, he said, but the number of allergens is limited. By contrast, his clinic mostly uses the Finn Chambers on Scanpor tape system, which can test for many more allergens and is cheaper if used at least 5-10 times a month.

He cautioned that T.R.U.E. could miss the cause of contact dermatitis as often as 39% of the time, as demonstrated in one study of children undergoing patch testing (Arch Dermatol. 2008 Oct;144[10]:1329-36). However, he said, the T.R.U.E test has value in detecting allergies to nickel, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and neomycin (J Am Acad Dermatol. 2001 Dec;45[6]:836-9).

Consider patch testing in a child with eczema if the eczema is not in normal atopic areas, it spreads beyond normal areas, it doesn’t respond to usual treatments, or it begins later than 5 years of age.

And, Dr. Fowler added, it’s fine to perform patch testing on patients who are taking antihistamines, tumor necrosis factor–alpha inhibitors, NSAIDs, or methotrexate.

Dr. Fowler disclosed consulting for IntraDerm, serving on speakers bureaus for SmartPractice and Regeneron/Sanofi, and serving as an investigator for companies that include AbbVie, Allergan, Bayer, Dow, Galderma, Johnson & Johnson, Eli Lilly, Merck, Regeneron, SmartPractice, and Valeant (now Bausch).

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

 

MONTEREY, CALIF. – It’s only found in 2%-3% of allergy cases. So why was propylene glycol (PG) declared the Allergen of the Year for 2018 by the North American Contact Dermatitis Society? Because, a dermatologist told colleagues, it’s so common.

“If you’re allergic to it, it’s tough to stay away from it,” said Joseph F. Fowler Jr., MD, clinical professor of dermatology at the University of Louisville (Ky.) in a presentation about contact dermatitis at the annual Coastal Dermatology Symposium.

Indeed, the synthetic compound PG is found in skin care products and cosmetics, coated pills, topical medications such as corticosteroids, foods (including bread, food coloring, and such flavorings as vanilla extracts). “It’s in every topical acne product I know of,” and is even in brake fluid and so-called nontoxic antifreeze, he said. (Propylene glycol shouldn’t be confused with the poisonous toxin ethylene glycol, which also is found in antifreeze.)

Patients can be tested for allergy to PG, Dr. Fowler pointed out, but it’s important to understand that it can trigger an irritation reaction that can be mistaken for an allergic reaction.

Dr. Fowler offered the following tips related to contact dermatitis and allergens. Be aware that metals, topical antibiotics, fragrances, and preservatives are most likely to cause allergic contact dermatitis. According to 2016 figures on allergen prevalence from the North American Contact Dermatitis Group (NACDG), allergy to the metal nickel is the most common (16%); followed by neomycin (9%); fragrance mix I, a mixture of fragrances used in allergen testing (9%); bacitracin (8%); and myroxylon, also known as balsam of Peru, which is used for a variety of purposes in food, medicines, and fragrances (7%).

These are followed by the metal cobalt (6%); the preservatives quaternium 15 and formaldehyde (both 6%); para-phenylenediamine, also known as PPD, which is used in hair dye (5%); and the fragrance mix II (5%), another mix of fragrances used in allergen testing.

Dr. Fowler cautioned that nickel can trigger an intense body-wide allergic reaction in children with atopic dermatitis. “In this situation, it’s really good to be compulsive and tell parents to absolutely keep that person away from nickel as much as humanly possible,” he said.

Keep an eye out for allergens that aren’t on the NACDG list, which includes 70 items. According to Dr. Fowler, more than 20% of his patients were positive to allergens not on the NACDG list.

Contact dermatitis is as common in children as in adults and can even be more common in children. An Italian study published in 2012 found that 70% of children aged 1-15 years tested via patch test were allergic to at least one allergen, a number that’s similar in adults (Dermatitis. 2012 Nov-Dec;23[6]:275-80). There are wide disparities in reported levels of children who are allergic to nickel, cobalt, and myroxylon, Dr. Fowler said.

The T.R.U.E. Test patch test system has value, compared with standard patch tests, but beware of its limitations, he advised. T.R.U.E. is easy to use and requires no prep time, he said, but the number of allergens is limited. By contrast, his clinic mostly uses the Finn Chambers on Scanpor tape system, which can test for many more allergens and is cheaper if used at least 5-10 times a month.

He cautioned that T.R.U.E. could miss the cause of contact dermatitis as often as 39% of the time, as demonstrated in one study of children undergoing patch testing (Arch Dermatol. 2008 Oct;144[10]:1329-36). However, he said, the T.R.U.E test has value in detecting allergies to nickel, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and neomycin (J Am Acad Dermatol. 2001 Dec;45[6]:836-9).

Consider patch testing in a child with eczema if the eczema is not in normal atopic areas, it spreads beyond normal areas, it doesn’t respond to usual treatments, or it begins later than 5 years of age.

And, Dr. Fowler added, it’s fine to perform patch testing on patients who are taking antihistamines, tumor necrosis factor–alpha inhibitors, NSAIDs, or methotrexate.

Dr. Fowler disclosed consulting for IntraDerm, serving on speakers bureaus for SmartPractice and Regeneron/Sanofi, and serving as an investigator for companies that include AbbVie, Allergan, Bayer, Dow, Galderma, Johnson & Johnson, Eli Lilly, Merck, Regeneron, SmartPractice, and Valeant (now Bausch).

The meeting was jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are both owned by Frontline Medical Communications.

 

Neither age nor previous hormone therapy had statistically significant associations with the effect of intravaginal prasterone on dyspareunia severity, according to a new subgroup analysis of clinical trial data. In a trend that did not reach statistical significance, though, women who were further away from menopause reported numerically smaller improvements in dyspareunia, compared with baseline values, said David F. Archer, MD.

“This was an unexpected finding,” he said in an interview.

In a subgroup analysis of data from two clinical trials of intravaginal prasterone (Intrarosa), Dr. Archer and his colleagues sought to investigate whether age, time since menopause, or any previous use of hormone replacement therapy influenced prasterone’s efficacy in treating dyspareunia.

Dr. Archer and his collaborators pooled data from two prospective, randomized, double-blind, placebo-controlled trials (NCT02013544 and NCT01256684) of intravaginal prasterone dosed at 0.50%, 6.5 mg once daily for 12 weeks; he presented the subgroup analyses at the annual meeting of the North American Menopause Society in San Diego.

For each subgroup, Dr. Archer, a professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and his coinvestigators compared the mean differences in dyspareunia severity score of women who received prasterone and those who received placebo.

All subgroup analyses used the endpoint of improvement in moderate to severe dyspareunia or whether dyspareunia was the most bothersome symptoms for the women participating in the study. The investigators began by looking at the subgroup of 460 women who were 56 years and older at baseline and compared them with the 180 younger participants.

The 283 older participants who received prasterone saw a decrease of 0.36 points in a dyspareunia severity score versus a 0.44 point decrease for the 123 women aged 55 and younger who received prasterone, a nonsignificant difference between subgroups. The decrease compared with placebo-takers was significant in both cases, however (P = .0003 and P =.0031, respectively).

Looking at time since menopause, Dr. Archer and his collaborators divided participants into 33 individuals who were 1 or 2 years post menopause, 86 women who were 3-5 years post menopause, and 521 women who had experienced menopause at least 6 years before study baseline.

In this analysis, 22 of the earliest postmenopause women received prasterone, seeing a 1.59 point drop in dyspareunia severity. For the 59 women in the prasterone study arms who were 3-5 year past menopause, the decrease from baseline was 0.59 points. Finally, among the 325 women who received prasterone and experienced menopause 6 or more years ago, the decrease was 0.27 points.

Although there was a numeric difference in the change in dyspareunia score severity among these groups, the differences were not statistically significant, said Dr. Archer. Again, though, those who took prasterone had a significant reduction in dyspareunia severity scores when compared with those taking placebo (P less than .0001, P = .0136, and P = .0024, respectively).

In the prasterone study arms, 184 had previously used hormone therapy, and 222 had not. After 12 weeks of intravaginal prasterone, there was no statistically significant difference between the two subgroups, with a decreases in dyspareunia severity scores of 0.45 and 0.32, respectively. The decreases in severity scores when compared with those among women who took placebo were again statistically significant for both subgroups, however (P = .0002 and P = .0057, respectively).

Prasterone is a steroid that is also known as dehydroepiandrosterone (DHEA) and is an endogenous hormone that is a precursor for estrogens and androgens. Prasterone’s mechanism of action to reduce vulvar and vaginal atrophy is not completely understood, according to the Food and Drug Administration.

“The nonstatistically significant smaller effect on dyspareunia observed when treatment is initiated after a longer period after menopause suggests that a longer treatment period could be needed to achieve optimal benefit and that treatment of dyspareunia should be initiated as early as possible after menopause,” said Dr. Archer.

Dr. Archer reported grant support from and consulting relationships with several pharmaceutical companies, including Endoceutics, the producer of Intrarosa intravaginal prasterone.

koakes@mdedge.com

Neither age nor previous hormone therapy had statistically significant associations with the effect of intravaginal prasterone on dyspareunia severity, according to a new subgroup analysis of clinical trial data. In a trend that did not reach statistical significance, though, women who were further away from menopause reported numerically smaller improvements in dyspareunia, compared with baseline values, said David F. Archer, MD.

“This was an unexpected finding,” he said in an interview.

In a subgroup analysis of data from two clinical trials of intravaginal prasterone (Intrarosa), Dr. Archer and his colleagues sought to investigate whether age, time since menopause, or any previous use of hormone replacement therapy influenced prasterone’s efficacy in treating dyspareunia.

Dr. Archer and his collaborators pooled data from two prospective, randomized, double-blind, placebo-controlled trials (NCT02013544 and NCT01256684) of intravaginal prasterone dosed at 0.50%, 6.5 mg once daily for 12 weeks; he presented the subgroup analyses at the annual meeting of the North American Menopause Society in San Diego.

For each subgroup, Dr. Archer, a professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and his coinvestigators compared the mean differences in dyspareunia severity score of women who received prasterone and those who received placebo.

All subgroup analyses used the endpoint of improvement in moderate to severe dyspareunia or whether dyspareunia was the most bothersome symptoms for the women participating in the study. The investigators began by looking at the subgroup of 460 women who were 56 years and older at baseline and compared them with the 180 younger participants.

The 283 older participants who received prasterone saw a decrease of 0.36 points in a dyspareunia severity score versus a 0.44 point decrease for the 123 women aged 55 and younger who received prasterone, a nonsignificant difference between subgroups. The decrease compared with placebo-takers was significant in both cases, however (P = .0003 and P =.0031, respectively).

Looking at time since menopause, Dr. Archer and his collaborators divided participants into 33 individuals who were 1 or 2 years post menopause, 86 women who were 3-5 years post menopause, and 521 women who had experienced menopause at least 6 years before study baseline.

In this analysis, 22 of the earliest postmenopause women received prasterone, seeing a 1.59 point drop in dyspareunia severity. For the 59 women in the prasterone study arms who were 3-5 year past menopause, the decrease from baseline was 0.59 points. Finally, among the 325 women who received prasterone and experienced menopause 6 or more years ago, the decrease was 0.27 points.

Although there was a numeric difference in the change in dyspareunia score severity among these groups, the differences were not statistically significant, said Dr. Archer. Again, though, those who took prasterone had a significant reduction in dyspareunia severity scores when compared with those taking placebo (P less than .0001, P = .0136, and P = .0024, respectively).

In the prasterone study arms, 184 had previously used hormone therapy, and 222 had not. After 12 weeks of intravaginal prasterone, there was no statistically significant difference between the two subgroups, with a decreases in dyspareunia severity scores of 0.45 and 0.32, respectively. The decreases in severity scores when compared with those among women who took placebo were again statistically significant for both subgroups, however (P = .0002 and P = .0057, respectively).

Prasterone is a steroid that is also known as dehydroepiandrosterone (DHEA) and is an endogenous hormone that is a precursor for estrogens and androgens. Prasterone’s mechanism of action to reduce vulvar and vaginal atrophy is not completely understood, according to the Food and Drug Administration.

“The nonstatistically significant smaller effect on dyspareunia observed when treatment is initiated after a longer period after menopause suggests that a longer treatment period could be needed to achieve optimal benefit and that treatment of dyspareunia should be initiated as early as possible after menopause,” said Dr. Archer.

Dr. Archer reported grant support from and consulting relationships with several pharmaceutical companies, including Endoceutics, the producer of Intrarosa intravaginal prasterone.

koakes@mdedge.com

Neither age nor previous hormone therapy had statistically significant associations with the effect of intravaginal prasterone on dyspareunia severity, according to a new subgroup analysis of clinical trial data. In a trend that did not reach statistical significance, though, women who were further away from menopause reported numerically smaller improvements in dyspareunia, compared with baseline values, said David F. Archer, MD.

“This was an unexpected finding,” he said in an interview.

In a subgroup analysis of data from two clinical trials of intravaginal prasterone (Intrarosa), Dr. Archer and his colleagues sought to investigate whether age, time since menopause, or any previous use of hormone replacement therapy influenced prasterone’s efficacy in treating dyspareunia.

Dr. Archer and his collaborators pooled data from two prospective, randomized, double-blind, placebo-controlled trials (NCT02013544 and NCT01256684) of intravaginal prasterone dosed at 0.50%, 6.5 mg once daily for 12 weeks; he presented the subgroup analyses at the annual meeting of the North American Menopause Society in San Diego.

For each subgroup, Dr. Archer, a professor of obstetrics and gynecology at Eastern Virginia Medical School, Norfolk, and his coinvestigators compared the mean differences in dyspareunia severity score of women who received prasterone and those who received placebo.

All subgroup analyses used the endpoint of improvement in moderate to severe dyspareunia or whether dyspareunia was the most bothersome symptoms for the women participating in the study. The investigators began by looking at the subgroup of 460 women who were 56 years and older at baseline and compared them with the 180 younger participants.

The 283 older participants who received prasterone saw a decrease of 0.36 points in a dyspareunia severity score versus a 0.44 point decrease for the 123 women aged 55 and younger who received prasterone, a nonsignificant difference between subgroups. The decrease compared with placebo-takers was significant in both cases, however (P = .0003 and P =.0031, respectively).

Looking at time since menopause, Dr. Archer and his collaborators divided participants into 33 individuals who were 1 or 2 years post menopause, 86 women who were 3-5 years post menopause, and 521 women who had experienced menopause at least 6 years before study baseline.

In this analysis, 22 of the earliest postmenopause women received prasterone, seeing a 1.59 point drop in dyspareunia severity. For the 59 women in the prasterone study arms who were 3-5 year past menopause, the decrease from baseline was 0.59 points. Finally, among the 325 women who received prasterone and experienced menopause 6 or more years ago, the decrease was 0.27 points.

Although there was a numeric difference in the change in dyspareunia score severity among these groups, the differences were not statistically significant, said Dr. Archer. Again, though, those who took prasterone had a significant reduction in dyspareunia severity scores when compared with those taking placebo (P less than .0001, P = .0136, and P = .0024, respectively).

In the prasterone study arms, 184 had previously used hormone therapy, and 222 had not. After 12 weeks of intravaginal prasterone, there was no statistically significant difference between the two subgroups, with a decreases in dyspareunia severity scores of 0.45 and 0.32, respectively. The decreases in severity scores when compared with those among women who took placebo were again statistically significant for both subgroups, however (P = .0002 and P = .0057, respectively).

Prasterone is a steroid that is also known as dehydroepiandrosterone (DHEA) and is an endogenous hormone that is a precursor for estrogens and androgens. Prasterone’s mechanism of action to reduce vulvar and vaginal atrophy is not completely understood, according to the Food and Drug Administration.

“The nonstatistically significant smaller effect on dyspareunia observed when treatment is initiated after a longer period after menopause suggests that a longer treatment period could be needed to achieve optimal benefit and that treatment of dyspareunia should be initiated as early as possible after menopause,” said Dr. Archer.

Dr. Archer reported grant support from and consulting relationships with several pharmaceutical companies, including Endoceutics, the producer of Intrarosa intravaginal prasterone.

koakes@mdedge.com

Recent research has pointed to a role for measuring neurofilament light (Nf-L) chain levels to predict disease severity in multiple sclerosis (MS). Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.

A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.

Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.

Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.

dfulton@mdedge.com

Recent research has pointed to a role for measuring neurofilament light (Nf-L) chain levels to predict disease severity in multiple sclerosis (MS). Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.

A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.

Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.

Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.

dfulton@mdedge.com

Recent research has pointed to a role for measuring neurofilament light (Nf-L) chain levels to predict disease severity in multiple sclerosis (MS). Several papers presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis in Berlin will describe new developments on the topic.

A highlighted session on the congress’s last day explores recent development in progressive MS. While much of the research on using Nf-L as a biomarker focuses on relapsing remitting MS, researchers from University Hospital, Basel, Switzerland, and Novartis used data from placebo-controlled, phase 3 trials of fingolimod (INFORMS) and siponimod (EXPAND) to learn how to use biomarkers to track brain atrophy in patients with primary and secondary progressive MS. Hear the results from lead researcher Jens Kuhle, MD, in Hall A at 10:30 a.m. (local time) on Friday, Oct. 12.

Nf-L also is being looked at as a way to suss out treatment failure. Researchers with the Swiss MS Cohort Study will present their study of Nf-L as a biomarker of suboptimal treatment response in patients with relapsing remitting MS on established disease-modifying therapy. Their findings will be presented by Özguer Yaldizli, MD, also of University Hospital, also in Hall A, at 8:30 a.m. (local time) on Friday, Oct. 12.

Follow #ECTRIMS2018 on Twitter to see live highlights and perspective from researchers and meeting attendees.

dfulton@mdedge.com

In the drug-pricing battle, progressive lawmakers such as Sen. Bernie Sanders (I-Vt.) and patients’ rights activists rarely find themselves in step with the health industry’s big players.

But in a twist, these usually at-odds actors are championing similar tactics to tame prescription drug prices.

The strategies involve repurposing two obscure and rarely deployed workarounds in patent law that, in different ways, empower the federal government to take back patents and license them to other companies. The first is known as “march-in rights.” The second is generally referred to as Section 1498 because of its location in the U.S. Code.

Sanders has in recent years pointed to these steps as useful tools in the drug-pricing debate.

As an indicator of how high the stakes have become, these ideas also are finding traction among some major health industry players – most notably, two large trade groups that represent health plans and the “middlemen” companies that negotiate drug coverage.

“It used to be the case that everyone played nicely with one another, and now as prices have gone up, the knives have come out,” said Jacob S. Sherkow, a law professor at New York University who focuses on intellectual property and the pharmaceutical industry.

The push for march-in rights gained momentum this past summer, when activists launched a campaign challenging the patent for Truvada (emtricitabine/tenofovir), the HIV treatment by Gilead Sciences that has been shown to reduce the risks of contracting HIV when taken daily as a preventive.

Initially, patient advocates focused mainly on shaming insurance companies into providing better coverage of that pill, also known as pre-exposure prophylaxis, or PrEP, because it is taken before someone is exposed to the virus. But they soon found themselves targeting a frustration that insurance companies happened to share: the drug’s list price.

James Krellenstein, cofounder of the PrEP4All Collaboration, an advocacy group, was part of that campaign. Health plans had put barriers in place to limit access to the drug, he said. But they, too, were worried about Truvada’s escalating price.

“You can’t scale up to a level you need to unless we deal with the pricing problem,” he said.

Now, as insurers signal they might adopt an approach similar to that of the campaign, he voiced skepticism. On the one hand, the support could benefit their cause. At the same time, “they have their interests, and that’s not the interests of public health,” Mr. Krellenstein said.

Still, in Washington, the influence of groups like America’s Health Insurance Plans (AHIP), which is the largest trade association for health insurers, and the Pharmaceutical Care Management Association (PCMA), which represents those middlemen companies known as pharmacy benefit managers (PBMs), could add political credibility to these long-shot ideas.

President Trump has said curbing prescription drug costs is a high priority. But, as congressional action seems increasingly unlikely, these two approaches offer another possible path forward.

They are “already part of a law that is intact. ... An option the administration can take now,” said Walid Gellad, MD, MPH, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

AHIP says the Department of Health & Human Services should lean on a federal statute that lets the government take over drug patents and grant them to other manufacturers, as long as it adequately compensates the original patent holder.

Meanwhile, PCMA is pressing the administration to use the march-in rights championed by HIV activists. Provided under the 1980 Bayh-Dole Act, they empower the government to rescind a drug’s patent and let other companies develop versions of it. This applies only if government funding helped develop the drug, and it can be invoked only in specific circumstances, including a threat to public health or safety.

“Everybody is feeling the heat, and I think that is the reason you’re seeing this interest in using the tools that exist,” said Amy Kapczynski, a professor at Yale Law School who has written extensively about drug patents.

But opposition is strong among drugmakers.

“Policies should spur competition and new innovations to meet patient needs not disincentivize them such as the use of 1498 and march-in could do,” said Priscilla VanderVeer, a spokeswoman for the Pharmaceutical Researchers and Manufacturers of America, or PhRMA, a trade and lobbying group.

Gilead, which manufactures Truvada, has a similar stance.

“We believe that there is no rationale or precedent for the government to exercise march-in or other [intellectual property] rights related to Truvada for PrEP,” said Ryan McKeel, a spokesman for Gilead. The company’s other efforts to make the drug “available for health and safety needs,” he added, “clearly satisfy” the company’s legal requirements.

And the potential for march-in authority is still theoretical. It has never been used, despite at least five petitions to the National Institutes of Health, three of which cited high drug prices.

Section 1498 was used to negotiate lower drug prices in the 1960s and 1970s, but has since faded. In 2001, during the nation’s anthrax scare, HHS threatened to invoke it to procure more of the antibiotic used to treat the deadly bacterial disease, according to contemporaneous reports. Last year, Louisiana’s health secretary unsuccessfully tried to use it to ease the toll pricey hepatitis C medications exerted on the state’s Medicaid program.

NIH Director Francis Collins, MD, PhD, remains skeptical, repeatedly saying that a drug’s price doesn’t constitute a health or safety concern within the agency’s jurisdiction.

HHS Secretary Alex M. Azar II, speaking at a June Senate hearing, described march-in, also known as “compulsory licensing,” as a “socialist” approach.

But health plans and other payers, increasingly squeezed by fast-climbing prices, are undeterred – touting this kind of intervention as a “market-based solution.”

“The trends of drug prices in this country suggest that we all collectively need to find new approaches – including new approaches that are available under existing law – to try to change this trend,” said Mark Hamelburg, AHIP’s senior vice president of federal programs.

Kaiser Permanente, the health system and insurance provider, called for leveraging Section 1498 in a public comment submitted to HHS about its strategy to bring down drug prices. In a similar filing, Humana, a major insurer, pointed to “existing law [that] allows for actions around patents,” singling out march-in rights.

Humana did not respond to requests for comment. Both PCMA and Kaiser Permanente declined to comment beyond their statements. (Kaiser Health News is not affiliated with Kaiser Permanente.)

Nonetheless, experts say there are serious sticking points.

Neither of these legal provisions would be a sweeping solution. And both require administration buy-in.

“They’re only as effective as the government’s willingness to pursue them,” said Robin Feldman, a law professor at the University of California-Hastings.

Simply taking a patent doesn’t bring down prices, either. There are other ways manufacturers gain favorable market positioning for specific drugs, said Rachel Sachs, an associate law professor at Washington University in St. Louis who tracks drug-pricing laws.

And creating an opening for generics is only one step. Another drugmaker would still need to create a competing product, gain approval, and make it available. Then, theoretically, market competition can kick in.

Finally, there’s no guarantee such savings would benefit consumers, argued Nicholson Price, an assistant professor at the University of Michigan Law School. Insurance plans or PBMs could simply bargain greater discounts on drugs and pocket the money. (AHIP says any savings should be passed on.)

That’s the fundamental question, Mr. Krellenstein said.

“Is this going to be more armor in the fighting [between payers and drug companies]?” he said. “Or is it actually going to be a dramatic reform that actually results in real changes, that actually makes it easier for Americans to access the medications they need?”
 

KHN’s coverage of prescription drug development, costs, and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In the drug-pricing battle, progressive lawmakers such as Sen. Bernie Sanders (I-Vt.) and patients’ rights activists rarely find themselves in step with the health industry’s big players.

But in a twist, these usually at-odds actors are championing similar tactics to tame prescription drug prices.

The strategies involve repurposing two obscure and rarely deployed workarounds in patent law that, in different ways, empower the federal government to take back patents and license them to other companies. The first is known as “march-in rights.” The second is generally referred to as Section 1498 because of its location in the U.S. Code.

Sanders has in recent years pointed to these steps as useful tools in the drug-pricing debate.

As an indicator of how high the stakes have become, these ideas also are finding traction among some major health industry players – most notably, two large trade groups that represent health plans and the “middlemen” companies that negotiate drug coverage.

“It used to be the case that everyone played nicely with one another, and now as prices have gone up, the knives have come out,” said Jacob S. Sherkow, a law professor at New York University who focuses on intellectual property and the pharmaceutical industry.

The push for march-in rights gained momentum this past summer, when activists launched a campaign challenging the patent for Truvada (emtricitabine/tenofovir), the HIV treatment by Gilead Sciences that has been shown to reduce the risks of contracting HIV when taken daily as a preventive.

Initially, patient advocates focused mainly on shaming insurance companies into providing better coverage of that pill, also known as pre-exposure prophylaxis, or PrEP, because it is taken before someone is exposed to the virus. But they soon found themselves targeting a frustration that insurance companies happened to share: the drug’s list price.

James Krellenstein, cofounder of the PrEP4All Collaboration, an advocacy group, was part of that campaign. Health plans had put barriers in place to limit access to the drug, he said. But they, too, were worried about Truvada’s escalating price.

“You can’t scale up to a level you need to unless we deal with the pricing problem,” he said.

Now, as insurers signal they might adopt an approach similar to that of the campaign, he voiced skepticism. On the one hand, the support could benefit their cause. At the same time, “they have their interests, and that’s not the interests of public health,” Mr. Krellenstein said.

Still, in Washington, the influence of groups like America’s Health Insurance Plans (AHIP), which is the largest trade association for health insurers, and the Pharmaceutical Care Management Association (PCMA), which represents those middlemen companies known as pharmacy benefit managers (PBMs), could add political credibility to these long-shot ideas.

President Trump has said curbing prescription drug costs is a high priority. But, as congressional action seems increasingly unlikely, these two approaches offer another possible path forward.

They are “already part of a law that is intact. ... An option the administration can take now,” said Walid Gellad, MD, MPH, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

AHIP says the Department of Health & Human Services should lean on a federal statute that lets the government take over drug patents and grant them to other manufacturers, as long as it adequately compensates the original patent holder.

Meanwhile, PCMA is pressing the administration to use the march-in rights championed by HIV activists. Provided under the 1980 Bayh-Dole Act, they empower the government to rescind a drug’s patent and let other companies develop versions of it. This applies only if government funding helped develop the drug, and it can be invoked only in specific circumstances, including a threat to public health or safety.

“Everybody is feeling the heat, and I think that is the reason you’re seeing this interest in using the tools that exist,” said Amy Kapczynski, a professor at Yale Law School who has written extensively about drug patents.

But opposition is strong among drugmakers.

“Policies should spur competition and new innovations to meet patient needs not disincentivize them such as the use of 1498 and march-in could do,” said Priscilla VanderVeer, a spokeswoman for the Pharmaceutical Researchers and Manufacturers of America, or PhRMA, a trade and lobbying group.

Gilead, which manufactures Truvada, has a similar stance.

“We believe that there is no rationale or precedent for the government to exercise march-in or other [intellectual property] rights related to Truvada for PrEP,” said Ryan McKeel, a spokesman for Gilead. The company’s other efforts to make the drug “available for health and safety needs,” he added, “clearly satisfy” the company’s legal requirements.

And the potential for march-in authority is still theoretical. It has never been used, despite at least five petitions to the National Institutes of Health, three of which cited high drug prices.

Section 1498 was used to negotiate lower drug prices in the 1960s and 1970s, but has since faded. In 2001, during the nation’s anthrax scare, HHS threatened to invoke it to procure more of the antibiotic used to treat the deadly bacterial disease, according to contemporaneous reports. Last year, Louisiana’s health secretary unsuccessfully tried to use it to ease the toll pricey hepatitis C medications exerted on the state’s Medicaid program.

NIH Director Francis Collins, MD, PhD, remains skeptical, repeatedly saying that a drug’s price doesn’t constitute a health or safety concern within the agency’s jurisdiction.

HHS Secretary Alex M. Azar II, speaking at a June Senate hearing, described march-in, also known as “compulsory licensing,” as a “socialist” approach.

But health plans and other payers, increasingly squeezed by fast-climbing prices, are undeterred – touting this kind of intervention as a “market-based solution.”

“The trends of drug prices in this country suggest that we all collectively need to find new approaches – including new approaches that are available under existing law – to try to change this trend,” said Mark Hamelburg, AHIP’s senior vice president of federal programs.

Kaiser Permanente, the health system and insurance provider, called for leveraging Section 1498 in a public comment submitted to HHS about its strategy to bring down drug prices. In a similar filing, Humana, a major insurer, pointed to “existing law [that] allows for actions around patents,” singling out march-in rights.

Humana did not respond to requests for comment. Both PCMA and Kaiser Permanente declined to comment beyond their statements. (Kaiser Health News is not affiliated with Kaiser Permanente.)

Nonetheless, experts say there are serious sticking points.

Neither of these legal provisions would be a sweeping solution. And both require administration buy-in.

“They’re only as effective as the government’s willingness to pursue them,” said Robin Feldman, a law professor at the University of California-Hastings.

Simply taking a patent doesn’t bring down prices, either. There are other ways manufacturers gain favorable market positioning for specific drugs, said Rachel Sachs, an associate law professor at Washington University in St. Louis who tracks drug-pricing laws.

And creating an opening for generics is only one step. Another drugmaker would still need to create a competing product, gain approval, and make it available. Then, theoretically, market competition can kick in.

Finally, there’s no guarantee such savings would benefit consumers, argued Nicholson Price, an assistant professor at the University of Michigan Law School. Insurance plans or PBMs could simply bargain greater discounts on drugs and pocket the money. (AHIP says any savings should be passed on.)

That’s the fundamental question, Mr. Krellenstein said.

“Is this going to be more armor in the fighting [between payers and drug companies]?” he said. “Or is it actually going to be a dramatic reform that actually results in real changes, that actually makes it easier for Americans to access the medications they need?”
 

KHN’s coverage of prescription drug development, costs, and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

In the drug-pricing battle, progressive lawmakers such as Sen. Bernie Sanders (I-Vt.) and patients’ rights activists rarely find themselves in step with the health industry’s big players.

But in a twist, these usually at-odds actors are championing similar tactics to tame prescription drug prices.

The strategies involve repurposing two obscure and rarely deployed workarounds in patent law that, in different ways, empower the federal government to take back patents and license them to other companies. The first is known as “march-in rights.” The second is generally referred to as Section 1498 because of its location in the U.S. Code.

Sanders has in recent years pointed to these steps as useful tools in the drug-pricing debate.

As an indicator of how high the stakes have become, these ideas also are finding traction among some major health industry players – most notably, two large trade groups that represent health plans and the “middlemen” companies that negotiate drug coverage.

“It used to be the case that everyone played nicely with one another, and now as prices have gone up, the knives have come out,” said Jacob S. Sherkow, a law professor at New York University who focuses on intellectual property and the pharmaceutical industry.

The push for march-in rights gained momentum this past summer, when activists launched a campaign challenging the patent for Truvada (emtricitabine/tenofovir), the HIV treatment by Gilead Sciences that has been shown to reduce the risks of contracting HIV when taken daily as a preventive.

Initially, patient advocates focused mainly on shaming insurance companies into providing better coverage of that pill, also known as pre-exposure prophylaxis, or PrEP, because it is taken before someone is exposed to the virus. But they soon found themselves targeting a frustration that insurance companies happened to share: the drug’s list price.

James Krellenstein, cofounder of the PrEP4All Collaboration, an advocacy group, was part of that campaign. Health plans had put barriers in place to limit access to the drug, he said. But they, too, were worried about Truvada’s escalating price.

“You can’t scale up to a level you need to unless we deal with the pricing problem,” he said.

Now, as insurers signal they might adopt an approach similar to that of the campaign, he voiced skepticism. On the one hand, the support could benefit their cause. At the same time, “they have their interests, and that’s not the interests of public health,” Mr. Krellenstein said.

Still, in Washington, the influence of groups like America’s Health Insurance Plans (AHIP), which is the largest trade association for health insurers, and the Pharmaceutical Care Management Association (PCMA), which represents those middlemen companies known as pharmacy benefit managers (PBMs), could add political credibility to these long-shot ideas.

President Trump has said curbing prescription drug costs is a high priority. But, as congressional action seems increasingly unlikely, these two approaches offer another possible path forward.

They are “already part of a law that is intact. ... An option the administration can take now,” said Walid Gellad, MD, MPH, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh.

AHIP says the Department of Health & Human Services should lean on a federal statute that lets the government take over drug patents and grant them to other manufacturers, as long as it adequately compensates the original patent holder.

Meanwhile, PCMA is pressing the administration to use the march-in rights championed by HIV activists. Provided under the 1980 Bayh-Dole Act, they empower the government to rescind a drug’s patent and let other companies develop versions of it. This applies only if government funding helped develop the drug, and it can be invoked only in specific circumstances, including a threat to public health or safety.

“Everybody is feeling the heat, and I think that is the reason you’re seeing this interest in using the tools that exist,” said Amy Kapczynski, a professor at Yale Law School who has written extensively about drug patents.

But opposition is strong among drugmakers.

“Policies should spur competition and new innovations to meet patient needs not disincentivize them such as the use of 1498 and march-in could do,” said Priscilla VanderVeer, a spokeswoman for the Pharmaceutical Researchers and Manufacturers of America, or PhRMA, a trade and lobbying group.

Gilead, which manufactures Truvada, has a similar stance.

“We believe that there is no rationale or precedent for the government to exercise march-in or other [intellectual property] rights related to Truvada for PrEP,” said Ryan McKeel, a spokesman for Gilead. The company’s other efforts to make the drug “available for health and safety needs,” he added, “clearly satisfy” the company’s legal requirements.

And the potential for march-in authority is still theoretical. It has never been used, despite at least five petitions to the National Institutes of Health, three of which cited high drug prices.

Section 1498 was used to negotiate lower drug prices in the 1960s and 1970s, but has since faded. In 2001, during the nation’s anthrax scare, HHS threatened to invoke it to procure more of the antibiotic used to treat the deadly bacterial disease, according to contemporaneous reports. Last year, Louisiana’s health secretary unsuccessfully tried to use it to ease the toll pricey hepatitis C medications exerted on the state’s Medicaid program.

NIH Director Francis Collins, MD, PhD, remains skeptical, repeatedly saying that a drug’s price doesn’t constitute a health or safety concern within the agency’s jurisdiction.

HHS Secretary Alex M. Azar II, speaking at a June Senate hearing, described march-in, also known as “compulsory licensing,” as a “socialist” approach.

But health plans and other payers, increasingly squeezed by fast-climbing prices, are undeterred – touting this kind of intervention as a “market-based solution.”

“The trends of drug prices in this country suggest that we all collectively need to find new approaches – including new approaches that are available under existing law – to try to change this trend,” said Mark Hamelburg, AHIP’s senior vice president of federal programs.

Kaiser Permanente, the health system and insurance provider, called for leveraging Section 1498 in a public comment submitted to HHS about its strategy to bring down drug prices. In a similar filing, Humana, a major insurer, pointed to “existing law [that] allows for actions around patents,” singling out march-in rights.

Humana did not respond to requests for comment. Both PCMA and Kaiser Permanente declined to comment beyond their statements. (Kaiser Health News is not affiliated with Kaiser Permanente.)

Nonetheless, experts say there are serious sticking points.

Neither of these legal provisions would be a sweeping solution. And both require administration buy-in.

“They’re only as effective as the government’s willingness to pursue them,” said Robin Feldman, a law professor at the University of California-Hastings.

Simply taking a patent doesn’t bring down prices, either. There are other ways manufacturers gain favorable market positioning for specific drugs, said Rachel Sachs, an associate law professor at Washington University in St. Louis who tracks drug-pricing laws.

And creating an opening for generics is only one step. Another drugmaker would still need to create a competing product, gain approval, and make it available. Then, theoretically, market competition can kick in.

Finally, there’s no guarantee such savings would benefit consumers, argued Nicholson Price, an assistant professor at the University of Michigan Law School. Insurance plans or PBMs could simply bargain greater discounts on drugs and pocket the money. (AHIP says any savings should be passed on.)

That’s the fundamental question, Mr. Krellenstein said.

“Is this going to be more armor in the fighting [between payers and drug companies]?” he said. “Or is it actually going to be a dramatic reform that actually results in real changes, that actually makes it easier for Americans to access the medications they need?”
 

KHN’s coverage of prescription drug development, costs, and pricing is supported in part by the Laura and John Arnold Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

PHOENIX – Opioid use in urologic oncology patients dropped by 46% after one high-volume surgical center introduced changes to order sets and adopted new patient communication strategies, a researcher has reported.

The changes, which promoted opioid-sparing pain regimens, led to a substantial drop in postoperative opioid use with no compromise in pain control, according to Kerri Stevenson, a nurse practitioner with Stanford Health Care.

“Patients can be successfully managed with minimal opioid medication,” Ms. Stevenson said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

However, “it takes a multidisciplinary team for effective change to occur – this cannot be done in silos,” she told attendees at the meeting.

Seeking to reduce their reliance on opioids to manage postoperative pain, Ms. Stevenson and her colleagues set out to reduce opioid use by 50%, from a baseline morphine equivalent daily dose (MEDD) of 95.1 in June to September 2017 to a target of 47.5 by March 2018.

The actual MEDD at the end of the quality improvement project was 51.5, a 46% reduction that was just shy of that goal, she reported.

Factors fueling opioid use included patient expectations that they would be used and the belief that adjunct medications were not as effective as opioids, Dr. Stevenson found in a team survey.

“We decided to target those,” she said. “Our key drivers were really focused on appropriate prescriptions, increasing patient and provider awareness, standardizing our pathways, and setting expectations.”

To tackle the problem, they revised EMR order sets to default to selection of adjunct medications, educated providers, and introduced new patient communication strategies.

Instead of asking “Would you like me to bring you some oxycodone?” providers would instead start by asking about the patient’s current pain control medications and whether they were working well. When prescribed, opioids should be started at lower doses and escalated only if needed.

“Once we started our interventions, we noticed an immediate effect,” Ms. Stevenson.

The decreases were consistent across a range of surgery types. For example, the MEDD dropped to 55.1 with robotic prostatectomy, a procedure with a 1-day admission and very small incisions, and to 50.6 for open radical cystectomy, which involves a large incision and a stay of approximately 4 days, she said.

To address concerns that they might just be undertreating patients, investigators looked retrospectively at pain scores. They saw no differences pre- and post intervention in pain or anxiety scores within the first 24-48 hours post procedure, Ms. Stevenson reported.

Ms. Stevenson had no disclosures related to the presentation. Coauthor Jay Bakul Shah, MD of Stanford Health Care reported a consulting or advisory role with Pacira Pharmaceuticals.

SOURCE: Stevenson K et al. Quality Care Symposium, Abstract 269.

PHOENIX – Opioid use in urologic oncology patients dropped by 46% after one high-volume surgical center introduced changes to order sets and adopted new patient communication strategies, a researcher has reported.

The changes, which promoted opioid-sparing pain regimens, led to a substantial drop in postoperative opioid use with no compromise in pain control, according to Kerri Stevenson, a nurse practitioner with Stanford Health Care.

“Patients can be successfully managed with minimal opioid medication,” Ms. Stevenson said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

However, “it takes a multidisciplinary team for effective change to occur – this cannot be done in silos,” she told attendees at the meeting.

Seeking to reduce their reliance on opioids to manage postoperative pain, Ms. Stevenson and her colleagues set out to reduce opioid use by 50%, from a baseline morphine equivalent daily dose (MEDD) of 95.1 in June to September 2017 to a target of 47.5 by March 2018.

The actual MEDD at the end of the quality improvement project was 51.5, a 46% reduction that was just shy of that goal, she reported.

Factors fueling opioid use included patient expectations that they would be used and the belief that adjunct medications were not as effective as opioids, Dr. Stevenson found in a team survey.

“We decided to target those,” she said. “Our key drivers were really focused on appropriate prescriptions, increasing patient and provider awareness, standardizing our pathways, and setting expectations.”

To tackle the problem, they revised EMR order sets to default to selection of adjunct medications, educated providers, and introduced new patient communication strategies.

Instead of asking “Would you like me to bring you some oxycodone?” providers would instead start by asking about the patient’s current pain control medications and whether they were working well. When prescribed, opioids should be started at lower doses and escalated only if needed.

“Once we started our interventions, we noticed an immediate effect,” Ms. Stevenson.

The decreases were consistent across a range of surgery types. For example, the MEDD dropped to 55.1 with robotic prostatectomy, a procedure with a 1-day admission and very small incisions, and to 50.6 for open radical cystectomy, which involves a large incision and a stay of approximately 4 days, she said.

To address concerns that they might just be undertreating patients, investigators looked retrospectively at pain scores. They saw no differences pre- and post intervention in pain or anxiety scores within the first 24-48 hours post procedure, Ms. Stevenson reported.

Ms. Stevenson had no disclosures related to the presentation. Coauthor Jay Bakul Shah, MD of Stanford Health Care reported a consulting or advisory role with Pacira Pharmaceuticals.

SOURCE: Stevenson K et al. Quality Care Symposium, Abstract 269.

PHOENIX – Opioid use in urologic oncology patients dropped by 46% after one high-volume surgical center introduced changes to order sets and adopted new patient communication strategies, a researcher has reported.

The changes, which promoted opioid-sparing pain regimens, led to a substantial drop in postoperative opioid use with no compromise in pain control, according to Kerri Stevenson, a nurse practitioner with Stanford Health Care.

“Patients can be successfully managed with minimal opioid medication,” Ms. Stevenson said at a symposium on quality care sponsored by the American Society of Clinical Oncology.

However, “it takes a multidisciplinary team for effective change to occur – this cannot be done in silos,” she told attendees at the meeting.

Seeking to reduce their reliance on opioids to manage postoperative pain, Ms. Stevenson and her colleagues set out to reduce opioid use by 50%, from a baseline morphine equivalent daily dose (MEDD) of 95.1 in June to September 2017 to a target of 47.5 by March 2018.

The actual MEDD at the end of the quality improvement project was 51.5, a 46% reduction that was just shy of that goal, she reported.

Factors fueling opioid use included patient expectations that they would be used and the belief that adjunct medications were not as effective as opioids, Dr. Stevenson found in a team survey.

“We decided to target those,” she said. “Our key drivers were really focused on appropriate prescriptions, increasing patient and provider awareness, standardizing our pathways, and setting expectations.”

To tackle the problem, they revised EMR order sets to default to selection of adjunct medications, educated providers, and introduced new patient communication strategies.

Instead of asking “Would you like me to bring you some oxycodone?” providers would instead start by asking about the patient’s current pain control medications and whether they were working well. When prescribed, opioids should be started at lower doses and escalated only if needed.

“Once we started our interventions, we noticed an immediate effect,” Ms. Stevenson.

The decreases were consistent across a range of surgery types. For example, the MEDD dropped to 55.1 with robotic prostatectomy, a procedure with a 1-day admission and very small incisions, and to 50.6 for open radical cystectomy, which involves a large incision and a stay of approximately 4 days, she said.

To address concerns that they might just be undertreating patients, investigators looked retrospectively at pain scores. They saw no differences pre- and post intervention in pain or anxiety scores within the first 24-48 hours post procedure, Ms. Stevenson reported.

Ms. Stevenson had no disclosures related to the presentation. Coauthor Jay Bakul Shah, MD of Stanford Health Care reported a consulting or advisory role with Pacira Pharmaceuticals.

SOURCE: Stevenson K et al. Quality Care Symposium, Abstract 269.

ABSTRACT

Soccer requires significant physical conditioning and endurance, as well as the physicality required for contact play. In order to keep athletes safe, it is important that coaches, medical staff, and the players themselves are educated on the most common dangers to their health that they may encounter on a soccer pitch. This article aims to review the current literature and recommendations on concussion, cardiovascular considerations, and heat-related illness as they relate to competitive soccer, with a goal of educating all those who help to keep athletes healthy and competing to their full potential.  

Continue to: Soccer is one of the most popular sports...

Soccer is one of the most popular sports in the modern world and requires significant physical conditioning and endurance, as well as the physicality required for contact play. This article covers the topics of concussion, cardiovascular considerations, and heat-related illness as they relate to competitive soccer players. We provide a review of the prevention, recognition, and management required to keep athletes safe on the soccer pitch, both in practice and in competitive play.

HEAD

With an estimated 1.6 to 3.8 million sports-related mild traumatic brain injuries (ie, concussions) occurring annually in the United States,¹ there has been an appropriate increase in the focus on prevention and treatment of these injuries. For more than a decade the spotlight has been on concussions that occur in American football, but other sports have also had to examine the prevalence of concussions in their sport. This is certainly true for soccer.

There has been a steady increase in soccer participation in the United States. From 1973 to 2014 there was a 4-fold increase in high school boys and a 35-fold increase in high school girls playing soccer.² Currently, there are more than 3.7 million youth who play on teams under the supervision of the US Soccer Federation, the sport’s national governing body.³ With the growth of the sport, there has also been an intensified focus on injury prevention in soccer players, including concussive brain injuries.

A recent study examined injury rates in high school soccer players and noted that concussion is the second most common injury (17.9%), after ligament sprains (29.7%).⁴ The overall injury rate was 2.06 per 1000 athletic exposures (AEs [defined as participation in practice or game play]), but higher in games (4.42 per 1000 AEs) than during practices (1.05 per 1000 AEs). The overall concussion rate was 0.36 per 1000 AEs.⁴

Most concussions (54.8%) resulted in missing play between 1 to 3 weeks, but a sizeable portion of the athletes (14.9%) were out of play for more than 3 weeks. Additionally, 10.7% of all medical disqualifications were due to concussive injuries. Khodaee and colleagues⁴ found no statistically significant difference in concussion rates between male and female soccer players over the 9-year period of time that they examined, however previous studies have found higher rates in female athletes.⁵

In soccer, as in other sports, there is a concern about both the adequate recognition of concussions during practice and play and the underreporting of concussions by athletes. The US Soccer Federation has taken a proactive stance on addressing concussion in youth soccer by developing the “Recognize to Recover” program.⁶ Recognize to Recover is the US Soccer Federation’s “comprehensive player health and safety program aimed at promoting safe play and reducing injuries in soccer players of all ages.” The website provides an educational video geared toward players, along with links to concussion assessment tools, the US Soccer Federation Concussion Protocol, and US Soccer Federation-Centers for Disease Control fact sheets for athletes, parents, and coaches.⁶

Continue to: A challenge for all sports...

 

 

A challenge for all sports is allowing adequate evaluation of a suspected concussion by properly trained healthcare professionals. The 2017 Berlin Concussion in Sport Group position paper stated, “when a concussion is suspected, the athlete should be removed from the sporting environment and a multimodal assessment should be conducted in standardized fashion (eg, Sport Concussion Assessment Tool- 5th edition). Sporting bodies should allow adequate time to conduct this evaluation.”⁷ However, the International Federation of Football Association (FIFA) rules limit substitutions to 3 over the course of the game, which can make a thorough evaluation of players difficult as trainers and coaches are under increased pressure to quickly determine whether to use one of their valuable substitutions. Fortunately, the National Collegiate Athletic Association (NCAA) soccer has mitigated this issue by allowing unlimited substitutions during matches, and high school teams generally follow similar rules.

One of the goals of any safety education program is not only to raise the awareness of the signs and symptoms of concussion by all those involved in the sport, but also to increase the number of athletes who self-report their symptoms and decrease those who hide any possible concussions. A study found that a majority (58.6%) of middle school soccer players continued to play while experiencing concussion symptoms.⁵ However, in a very recent (not yet published) study, 92% of US Soccer Federation players reported that they did seek out a medical evaluation for their concussion.⁸ This is certainly a positive sign and further research needs to clarify what methods of education or training will maintain this level of self-reporting in soccer players.

There has also been an increased focus on understanding the mechanism of injury of concussions. In soccer, concussions can occur from player-to-player contact, contact with the player surface, contact with playing apparatus (eg, goal posts) and non-contact mechanisms. While there has been a focus on concussions from heading the ball, player-to-player contact is the most common cause of concussions. A 2017 study of 7- to 12-year-old soccer players in 4 European countries found that about 1 out of 10 concussions were caused by heading the ball.⁹ Comstock and colleageues¹⁰ found slightly higher numbers, roughly 25% to 30% (depending on gender), but 70% to 78% (again depending on gender) of those were caused by player-to-player contact rather than contact with the ball.

To date there has not been any meta-analytic review evaluating the cognitive and physical symptoms associated with heading in soccer. A recent review paper stated that the “current evidence seems insufficient to support a ban of heading in children’s football (soccer).”¹⁰ However, in December 2015 the US Soccer Federation included age-specific heading limitations. Players ages 10 years and under “shall not engage in heading, either in practices or in games” and players age 11 years and 12 years should have “limited heading in practice; maximum of 30 minutes of heading training per week, with no more than 15-20 headers per player, per week.”¹¹ US Soccer Federation officials acknowledged the limitations in the current science regarding heading in young soccer players but chose to err on the side of caution until further empirical evidence regarding the risks associated with repetitive heading is available.

The US Soccer Federation is also exploring other ways to reduce the incidence rate of concussions, including ensuring that the age-appropriate sized ball is used in practice and play, possible rule changes, evaluation of different playing surfaces, and equipment usage. To date, there is no strong evidence to support the use of mouth guards or helmets to reduce concussions in soccer. Additionally, the current data about the value of head impact sensors in soccer has not supported its widespread use.

Continue to: Finally, the issue of the prevalence...

 

 

Finally, the issue of the prevalence of chronic traumatic encephalopathy (CTE) in soccer players is beyond the scope of this article. The expert opinion from the 2017 US Soccer Federation, Major League Soccer (MLS), and National Women’s Soccer League (NWSL) conference concluded, “At present, no data exist that support that soccer participation is a risk factor for the development of neurodegenerative disease. Similarly, at this time, consistent with evidence discussed in the Berlin Concussion in Sport Group (CISG) Consensus Conference, our review suggests no causal relationship has been demonstrated between soccer and CTE pathology.”¹²

The more we know about concussions, both in general and those sustained during soccer play, the better we are able to diagnose and manage these injuries in our athletes. An important step is creating evidence-based protocols that evolve as our knowledge of concussions does as well. In April 2017, the US Soccer Federation, MLS, and the NWSL held a joint summit entitled, “Head Injury in Soccer: From Science to the Field” to address the current evidence-based science of concussions in soccer.⁸ An article discussing the findings of this meeting is forthcoming and will undoubtedly guide further development of concussion protocols for soccer players of all ages.

HEART

The physiologic demands of soccer place considerable stress on the cardiovascular system. Participation in training and competition is characterized by a combination of aerobic and anaerobic physiology with the typical athlete covering approximately 10 km over the course of the 90-minute match. The primary role of the heart and blood vessels is to supply the exercising skeletal muscle with oxygen and energy substrate and to clear the byproducts of metabolism. Among healthy athletes without cardiovascular disease, these processes are typically well tolerated and may be associated with beneficial cardiovascular adaptations over time. However, competitive soccer players are not completely immune to cardiovascular disease. Athletes across the age and competition spectrum may develop symptoms suggestive of underlying cardiovascular disease during play including exertional chest pain, inappropriate shortness of breath, palpitations, and syncope. These athletes require timely clinical evaluation. In extremely rare but high visibility cases, competitive soccer players may succumb to cardiac arrest on the pitch, underscoring the need for comprehensive emergency action plans (EAPs). We provide the practicing clinician with an overview of cardiovascular issues relevant to the competitive soccer athlete.

CARDIOVASCULAR ADAPTATIONS TO SPORT

The pressure (ie, repetitive surges in systemic blood pressure) and volume (ie, sustained increases in high cardiac output) challenges inherent in soccer participation place stress on the cardiovascular system. Healthy athletes across the age spectrum typically tolerate the hemodynamic stressors of participation without issues. Athletes that engage in training and competition over months to years often develop beneficial adaptations of the cardiovascular system that enhance on-field performance and contribute to optimal long-term health. Detailed discussion of how the heart and blood vessels respond to exercise training is beyond the scope of this article, but the interested reader is referred to several prior publications.^13,14 In brief, the heart of the healthy soccer athlete demonstrates the balanced mild chamber dilation and wall thickening characteristic of left ventricular eccentric remodeling. This form of exercise-induced cardiac remodeling facilitates maintenance of high stroke volume during exercise with minimal increases in cardiac work. In parallel, routine aerobic exercise training confers favorable changes in the systemic arterial system, which leads to reductions in age-associated ventricular stiffening and maintenance of healthy low blood pressure. It must be emphasized that the healthy heart muscle dilation and thickening that develop in response to sports participation, regardless of age, ethnicity, or gender, are relatively mild and should not be confused with common forms of heart muscle disease that may be seen in athletes at risk for adverse outcomes. In some situations, consultation with an extreme sports cardiologist may be required to differentiate exercise-induced remodeling from over heart muscle pathology.¹⁵

Continue to: THE SYMPTOMATIC ATHLETE...

 

 

THE SYMPTOMATIC ATHLETE

Any athlete presenting with symptoms suggestive of underlying cardiovascular disease should be withheld from training and competition until a comprehensive clinical evaluation has been completed. Common manifestations of underlying heart disease that occur in soccer players include exertional chest pain/pressure/tightness, shortness of breath that is out of proportion to workload, palpitations or the perception of irregular cardiac activity, and syncope. Chest discomfort, inappropriate shortness of breath, and palpitations that occur during training or competition should be managed with immediate removal from the playing field and prompt medical assessment. In many cases, thorough evaluation will involve collaboration between sports medicine and sports cardiology providers. Evaluations must be individualized on a case-by-case basis as tailored to the athlete’s presenting chief complaint and prior medical history. Most of these assessments will include a detailed medical history and physical examination, a 12-lead electrocardiogram (ECG), provocative exercise testing in a controlled environment, noninvasive cardiac imaging, and in some cases ambulatory rhythm monitoring. Uniformly, the athlete should be withheld from further training and competition until high-risk cardiovascular disease has been excluded. We refer the interested reader to a comprehensive discussion of symptom-based assessment of the athlete with suspected cardiovascular disease.¹⁶

Syncope (sudden and abrupt loss of consciousness with spontaneous neurologic recovery) is common among trained athletes. The vast majority of syncope is caused by “neurocardiogenic” mechanisms and carries a benign prognosis. Benign neurally-mediated syncope most often occurs outside of training and competition among athletes with heightened vagal tone and a predisposed susceptibility to triggers including pain, anxiety, emotional stimulation, and sudden postural change. Athletes who experience neurally-mediated syncope outside of training and competition routinely report a pre-event prodrome or aura that permits them to lower themselves to the ground, thereby avoiding injury. A distinct, but similarly benign and common, form of neurally-mediated fainting is post-exertional syncope. Here, fainting occurs within seconds of abrupt termination of exercise due to a rapid reduction cardiac preload and corollary cerebral blood supply. When either form of neurally-mediated syncope is suggested by a comprehensive medical history, normal physical examination, and a normal 12- lead ECG, further evaluation is unnecessary. However, the athlete and their coaching staff should be educated about avoidance tactics including hydration, dietary sodium supplementation, and avoidance of abrupt exercise termination as neutrally-mediated syncope tends to be recurrent without such measures. Fainting episodes that occur during training or competition that are not clearly post-exertional should be considered a medical emergency and should prompt comprehensive evaluation by a qualified cardiovascular specialist. Working closely with team physicians and athletic training staff, it is the responsibility of sports cardiologists to exclude potentially life-threatening forms of electrical, muscular, coronary, and valvular heart disease. Ideally, this evaluation should be conducted rapidly to avoid unnecessary delays in return to play.

CARDIAC ARREST AND SUDDEN DEATH

Numerous high-visibility cases of cardiac arrest on the soccer pitch have alerted the sporting community to the potential for these rare and potentially tragic events. Definitive incidence statistics defining the risk of cardiac arrest among soccer players are lacking. Data from the NCAA database suggest a sudden death incidence rate among collegiate male soccer athletes of approximately 1:24,000 athlete years.⁸ Similar data documenting incidence among female athletes and among those at lower (ie, youth level and high school) and higher (ie, professional) levels of play are unavailable. Underlying cardiovascular disease in the forms of heart muscle abnormalities (ie, genetic and acquired cardiomyopathy), coronary artery abnormalities (ie, genetic coronary anomalies and atherosclerotic coronary disease), valvular heart problems (ie, congenitally malformed aortic valves), and primary disturbances of the cardiac electrical system (ie, Wolf-Parkinson-White syndrome, long QT syndrome, etc.) explain a substantial percentage of on-pitch cardiac arrest. However, it is increasingly recognized that a significant minority of sudden cardiac deaths among athletes occur in the absence of attributable cardiovascular abnormality.¹⁷ Such cases, often referred to as “sudden unexplained death,” present unique challenges in the context of pre-participation screening, as they are undetectable and thus unpredictable.

Reduction of cardiac arrest and sudden death may best be accomplished through a combination of focused pre-participation screening and the development and implementation of a comprehensive EAP. Pre-participation involves the performance of a battery of tests prior to training and competition that are geared toward the detection of occult high-risk cardiovascular disease. Recommendations regarding pre-participation screening vary both across and within countries. Current US recommendations call for a focused medical history and physical examination prior to training and competition with consideration of the addition of a 12-lead ECG on a local level based on expertise and available resources.¹⁸ Conversely, current European guidelines including those endorsed by FIFA, suggest routine inclusion of a 12-lead ECG and in some cases, a transthoracic ECG.¹⁹ It must be emphasized that no screening approach has been confirmed to reduce the incidence of sudden death, and the decision to extend screening beyond the medical history and physical examination to include a 12-lead ECG or echocardiogram may come at the cost of increased false positive testing. In practice, decisions about how and when to screen are ideally made at a local level after consideration of medical and financial resources.²⁰

Continue to: Even the most comprehensive approach...

 

 

Even the most comprehensive approach to screening and evaluation of symptomatic athletes will not completely eliminate on-pitch cardiac arrest. Thus, all stakeholders that engage in the oversight of organized soccer must be committed to the development and implementation of an EAP.²¹ Key components of an effective EAP include the training of coaching staff, athletic trainers, and players in basic cardiopulmonary resuscitation, access to and training in the use of automated external defibrillators, and a triage/transport protocol that ensures timely access to advanced cardiac life support. Much like screening, emergency action planning involving these key core components must be developed and tailored locally. In the era of contemporary organized athletics, the absence of an EAP at any level of competition, from youth to professional leagues, is unacceptable. Effective EAPs must be developed, documented, and rehearsed at regular intervals. For the health and safety of competitive soccer players, as well as coaching staff and spectators, these steps are of critical importance.

HEAT

Heat-related illnesses can be serious and, at times, even life threatening. It is important for athletic staff and athletes to be well versed in the prevention, signs and symptoms, and treatment of heat-related illnesses in order to prevent serious and lasting injury. We aim to educate physicians about the prevention, recognition, and management of heat-related injury, and stress the importance of similarly educating athletes and coaching staff.

Exertional heat illnesses most often occur at temperatures >86°F, however they can occur at any temperature with heavy exertion.²² Signs and symptoms can be nonspecific early on, including weakness, fatigue, headache, nausea, and dizziness. Later signs can include imbalance, altered mentation, confusion, and behavior that is out of character such as irritability or aggression.²³ It is easy to see how the later signs can be confused for concussion in the right context. We cover the recognition and treatment of two common and serious heat-related illnesses: heat exhaustion and exertional heat stroke (EHS).

HEAT EXHAUSTION

Heat exhaustion occurs when an athlete cannot continue to exercise due to weakness and fatigue. While the exact mechanism is not well understood, it has been established that the combined effect of heat and dehydration have been proven to decrease exercise capacity and performance to a greater degree than either alone. The heat created by the body during exercise is 15 to 20 times greater than when at rest, and can increase core body temperature by 1°C every 5 minutes if no heat is lost, such as through sweating.²⁴ Additionally, when fluid deficits reach >3% to 5% of total body water, sweat production and skin blood flow decline, blunting the ability for the body to cool itself and causing progressive elevation of core body temperature if the athlete continues exerting him or herself. When fluid deficits reach 6% to 10%, cardiac output, sweat, and muscle blood flow decrease, likely leading to the symptoms seen with heat exhaustion: weakness, profound fatigue, and occasionally confusion and disorientation. Athletes with suspected heat exhaustion should be moved to a cooler area, laid down with legs elevated, and orally rehydrated. If they do not improve with oral rehydration, they may require intravenous fluids. The diagnosis of heat exhaustion hinges on a rectal temperature of <104°F; if >104°F the athlete should be presumed to have heat stroke, which will be addressed in the following paragraphs. Players can be cleared to return to play in mild cases within 24 to 48 hours with gradual increases in exercise intensity.²⁴

EXERTIONAL HEAT STROKE

EHS occurs when the body can no longer regulate the core body temperature and it rises to upwards of 104°F. In EHS, elevated core body temperature is associated with evidence of end organ dysfunction. The most easily identified on the playing field is likely central nervous system dysfunction, including irritability, confusion, irrational behavior, lethargy, dizziness, confusion, and even loss of consciousness. Temperature should be measured with rectal temperature only, as other methods of measurement have been shown to be consistently inaccurate.²² Heat stroke can be confused with exertional hyponatremia, heat exhaustion, or concussion, especially when core body temperature cannot be determined. However, EHS should always be the presumed cause of altered mentation when no rectal temperature is available because rapid cooling is critical to minimizing lasting effects. Morbidity and mortality are directly related to the length of time required to cool the athlete under 40°C (104°F).²⁴ Cooling should be completed on site prior to transport to a medical facility and is best achieved with submersion in an ice bath (ie, a kiddie pool or soaking tub full of ice and water).^22,25 If an ice bath is not available, ice bags should be applied to the neck axilla and groin and exchanged for fresh bags every 2 to 3 minutes.²² Ice bags have been shown to be inferior to whole body cooling, only cooling the athlete .04°C to .08°C/min compared to .15°C to .24°C/min with the ice bath.²⁴ All other tests should be delayed until cooling is achieved, unless they can be completed while cooling the athlete. The athlete can be removed from the ice bath once rectal temperatures reach <101°F to 102°F.²³ If the athlete returns to baseline after cooling, transportation to a medical facility may not be necessary. However, they should refrain from physical activity and heat exposure for at least 7 days and should be evaluated by a physician at that time. If all labs are normal and the athlete is asymptomatic, they can start progressive return to play under the direction of an athletic trainer or a sports medicine physician.²³

Continue to: HEAT-RELATED ILLNESS...

 

 

HEAT-RELATED ILLNESS

It is impossible to predict exactly which athletes will be most at risk for heat-related illness, so it is important to have a high degree of suspicion when environmental conditions are right. Athletes with recent illness, fever, or lack of sleep are at higher risk. Additional intrinsic risk factors include low fitness level, obesity, and inadequate hydration. Athletes who are highly competitive or motivated can be more likely to push through the early signs of illness or be reluctant to report symptoms.²³ Those with a history of exertional heat illness are more at risk for developing it again in the future.²³

The extrinsic risk factors for the development of heat-related illness are much easier to identify and modify in order to keep athletes safe. High temperature and high humidity conditions, heavy sun exposure, and exposure to similar conditions the preceding day put athletes at risk for exertional heat illness. Risks are even greater when the exercise is prolonged or intense with few breaks and access to hydration is limited.²³ Therefore, prevention of exertional heat illness is centered on these external risk factors.

Each team should have a heat policy as part of their EAP aimed at prevention and early recognition of heat-related illness. This policy should be shared with all athletes and coaches. The plan should be centered on acclimatization, activity modification, and early recognition and management as previously discussed. The US Soccer Federation “Recognize to Recover” Heat Guidelines suggest a 3-step process for appropriate activity modification:²²

1. Find the wet bulb globe temperature, either using a wet bulb globe thermometer or the temperature and humidity (Figure 1).

2. Find your regional weather category on the map (Figure 2).

3. Find your alert level and work to rest ratio recommendations (Figure 3).

Scheduled hydration breaks should be given as listed in Figure 3. Breaks of 4 minutes should be given for each 30 minutes of continuous practice or play. In a regulation 90-minute match, a hydration break should be given at 30 and 75 minutes (with half time at 45 minutes) at minimum. Athletes should be educated about where hydration can be accessed, and given unlimited access to hydration even outside of planned breaks.²²

Acclimatization to conditions is another integral part of preventing heat-related illness. It allows the body time to adapt to exercising in heat gradually, with a measured progression of exertion over the course of 10 to 14 days. The “Recognize to Recover” Heat Guidelines also provide guidance on acclimatization, and specifics can be found on the website.¹ Generally speaking, the warmest part of the day, usually between 11 AM and 4 PM, should be avoided for all training sessions, and length of practice and exertion should be gradually increased over 2 weeks.²²

In summary, appropriate acclimatization, hydration, activity modification, and education of athletes and staff are essential for the prevention of heat-related illness. Athletes and staff should understand the signs and symptoms of heat-related illness so that it can be recognized early and treated appropriately. If an athlete is altered in the heat and rectal temperature is >104°F or rectal temperature cannot be obtained, rapid cooling using an ice bath or ice bags is essential to prevent the morbidity and mortality associated with EHS. Above all, teams should have an explicit plan that includes protocols for acclimatization, activity modification, and all necessary equipment to prevent and treat heat-related illnesses should they occur, and ultimately keep athletes safe and healthy.

ABSTRACT

Soccer requires significant physical conditioning and endurance, as well as the physicality required for contact play. In order to keep athletes safe, it is important that coaches, medical staff, and the players themselves are educated on the most common dangers to their health that they may encounter on a soccer pitch. This article aims to review the current literature and recommendations on concussion, cardiovascular considerations, and heat-related illness as they relate to competitive soccer, with a goal of educating all those who help to keep athletes healthy and competing to their full potential.  

Continue to: Soccer is one of the most popular sports...

Soccer is one of the most popular sports in the modern world and requires significant physical conditioning and endurance, as well as the physicality required for contact play. This article covers the topics of concussion, cardiovascular considerations, and heat-related illness as they relate to competitive soccer players. We provide a review of the prevention, recognition, and management required to keep athletes safe on the soccer pitch, both in practice and in competitive play.

HEAD

With an estimated 1.6 to 3.8 million sports-related mild traumatic brain injuries (ie, concussions) occurring annually in the United States,¹ there has been an appropriate increase in the focus on prevention and treatment of these injuries. For more than a decade the spotlight has been on concussions that occur in American football, but other sports have also had to examine the prevalence of concussions in their sport. This is certainly true for soccer.

There has been a steady increase in soccer participation in the United States. From 1973 to 2014 there was a 4-fold increase in high school boys and a 35-fold increase in high school girls playing soccer.² Currently, there are more than 3.7 million youth who play on teams under the supervision of the US Soccer Federation, the sport’s national governing body.³ With the growth of the sport, there has also been an intensified focus on injury prevention in soccer players, including concussive brain injuries.

A recent study examined injury rates in high school soccer players and noted that concussion is the second most common injury (17.9%), after ligament sprains (29.7%).⁴ The overall injury rate was 2.06 per 1000 athletic exposures (AEs [defined as participation in practice or game play]), but higher in games (4.42 per 1000 AEs) than during practices (1.05 per 1000 AEs). The overall concussion rate was 0.36 per 1000 AEs.⁴

Most concussions (54.8%) resulted in missing play between 1 to 3 weeks, but a sizeable portion of the athletes (14.9%) were out of play for more than 3 weeks. Additionally, 10.7% of all medical disqualifications were due to concussive injuries. Khodaee and colleagues⁴ found no statistically significant difference in concussion rates between male and female soccer players over the 9-year period of time that they examined, however previous studies have found higher rates in female athletes.⁵

In soccer, as in other sports, there is a concern about both the adequate recognition of concussions during practice and play and the underreporting of concussions by athletes. The US Soccer Federation has taken a proactive stance on addressing concussion in youth soccer by developing the “Recognize to Recover” program.⁶ Recognize to Recover is the US Soccer Federation’s “comprehensive player health and safety program aimed at promoting safe play and reducing injuries in soccer players of all ages.” The website provides an educational video geared toward players, along with links to concussion assessment tools, the US Soccer Federation Concussion Protocol, and US Soccer Federation-Centers for Disease Control fact sheets for athletes, parents, and coaches.⁶

Continue to: A challenge for all sports...

 

 

A challenge for all sports is allowing adequate evaluation of a suspected concussion by properly trained healthcare professionals. The 2017 Berlin Concussion in Sport Group position paper stated, “when a concussion is suspected, the athlete should be removed from the sporting environment and a multimodal assessment should be conducted in standardized fashion (eg, Sport Concussion Assessment Tool- 5th edition). Sporting bodies should allow adequate time to conduct this evaluation.”⁷ However, the International Federation of Football Association (FIFA) rules limit substitutions to 3 over the course of the game, which can make a thorough evaluation of players difficult as trainers and coaches are under increased pressure to quickly determine whether to use one of their valuable substitutions. Fortunately, the National Collegiate Athletic Association (NCAA) soccer has mitigated this issue by allowing unlimited substitutions during matches, and high school teams generally follow similar rules.

One of the goals of any safety education program is not only to raise the awareness of the signs and symptoms of concussion by all those involved in the sport, but also to increase the number of athletes who self-report their symptoms and decrease those who hide any possible concussions. A study found that a majority (58.6%) of middle school soccer players continued to play while experiencing concussion symptoms.⁵ However, in a very recent (not yet published) study, 92% of US Soccer Federation players reported that they did seek out a medical evaluation for their concussion.⁸ This is certainly a positive sign and further research needs to clarify what methods of education or training will maintain this level of self-reporting in soccer players.

There has also been an increased focus on understanding the mechanism of injury of concussions. In soccer, concussions can occur from player-to-player contact, contact with the player surface, contact with playing apparatus (eg, goal posts) and non-contact mechanisms. While there has been a focus on concussions from heading the ball, player-to-player contact is the most common cause of concussions. A 2017 study of 7- to 12-year-old soccer players in 4 European countries found that about 1 out of 10 concussions were caused by heading the ball.⁹ Comstock and colleageues¹⁰ found slightly higher numbers, roughly 25% to 30% (depending on gender), but 70% to 78% (again depending on gender) of those were caused by player-to-player contact rather than contact with the ball.

To date there has not been any meta-analytic review evaluating the cognitive and physical symptoms associated with heading in soccer. A recent review paper stated that the “current evidence seems insufficient to support a ban of heading in children’s football (soccer).”¹⁰ However, in December 2015 the US Soccer Federation included age-specific heading limitations. Players ages 10 years and under “shall not engage in heading, either in practices or in games” and players age 11 years and 12 years should have “limited heading in practice; maximum of 30 minutes of heading training per week, with no more than 15-20 headers per player, per week.”¹¹ US Soccer Federation officials acknowledged the limitations in the current science regarding heading in young soccer players but chose to err on the side of caution until further empirical evidence regarding the risks associated with repetitive heading is available.

The US Soccer Federation is also exploring other ways to reduce the incidence rate of concussions, including ensuring that the age-appropriate sized ball is used in practice and play, possible rule changes, evaluation of different playing surfaces, and equipment usage. To date, there is no strong evidence to support the use of mouth guards or helmets to reduce concussions in soccer. Additionally, the current data about the value of head impact sensors in soccer has not supported its widespread use.

Continue to: Finally, the issue of the prevalence...

 

 

Finally, the issue of the prevalence of chronic traumatic encephalopathy (CTE) in soccer players is beyond the scope of this article. The expert opinion from the 2017 US Soccer Federation, Major League Soccer (MLS), and National Women’s Soccer League (NWSL) conference concluded, “At present, no data exist that support that soccer participation is a risk factor for the development of neurodegenerative disease. Similarly, at this time, consistent with evidence discussed in the Berlin Concussion in Sport Group (CISG) Consensus Conference, our review suggests no causal relationship has been demonstrated between soccer and CTE pathology.”¹²

The more we know about concussions, both in general and those sustained during soccer play, the better we are able to diagnose and manage these injuries in our athletes. An important step is creating evidence-based protocols that evolve as our knowledge of concussions does as well. In April 2017, the US Soccer Federation, MLS, and the NWSL held a joint summit entitled, “Head Injury in Soccer: From Science to the Field” to address the current evidence-based science of concussions in soccer.⁸ An article discussing the findings of this meeting is forthcoming and will undoubtedly guide further development of concussion protocols for soccer players of all ages.

HEART

The physiologic demands of soccer place considerable stress on the cardiovascular system. Participation in training and competition is characterized by a combination of aerobic and anaerobic physiology with the typical athlete covering approximately 10 km over the course of the 90-minute match. The primary role of the heart and blood vessels is to supply the exercising skeletal muscle with oxygen and energy substrate and to clear the byproducts of metabolism. Among healthy athletes without cardiovascular disease, these processes are typically well tolerated and may be associated with beneficial cardiovascular adaptations over time. However, competitive soccer players are not completely immune to cardiovascular disease. Athletes across the age and competition spectrum may develop symptoms suggestive of underlying cardiovascular disease during play including exertional chest pain, inappropriate shortness of breath, palpitations, and syncope. These athletes require timely clinical evaluation. In extremely rare but high visibility cases, competitive soccer players may succumb to cardiac arrest on the pitch, underscoring the need for comprehensive emergency action plans (EAPs). We provide the practicing clinician with an overview of cardiovascular issues relevant to the competitive soccer athlete.

CARDIOVASCULAR ADAPTATIONS TO SPORT

The pressure (ie, repetitive surges in systemic blood pressure) and volume (ie, sustained increases in high cardiac output) challenges inherent in soccer participation place stress on the cardiovascular system. Healthy athletes across the age spectrum typically tolerate the hemodynamic stressors of participation without issues. Athletes that engage in training and competition over months to years often develop beneficial adaptations of the cardiovascular system that enhance on-field performance and contribute to optimal long-term health. Detailed discussion of how the heart and blood vessels respond to exercise training is beyond the scope of this article, but the interested reader is referred to several prior publications.^13,14 In brief, the heart of the healthy soccer athlete demonstrates the balanced mild chamber dilation and wall thickening characteristic of left ventricular eccentric remodeling. This form of exercise-induced cardiac remodeling facilitates maintenance of high stroke volume during exercise with minimal increases in cardiac work. In parallel, routine aerobic exercise training confers favorable changes in the systemic arterial system, which leads to reductions in age-associated ventricular stiffening and maintenance of healthy low blood pressure. It must be emphasized that the healthy heart muscle dilation and thickening that develop in response to sports participation, regardless of age, ethnicity, or gender, are relatively mild and should not be confused with common forms of heart muscle disease that may be seen in athletes at risk for adverse outcomes. In some situations, consultation with an extreme sports cardiologist may be required to differentiate exercise-induced remodeling from over heart muscle pathology.¹⁵

Continue to: THE SYMPTOMATIC ATHLETE...

 

 

THE SYMPTOMATIC ATHLETE

Any athlete presenting with symptoms suggestive of underlying cardiovascular disease should be withheld from training and competition until a comprehensive clinical evaluation has been completed. Common manifestations of underlying heart disease that occur in soccer players include exertional chest pain/pressure/tightness, shortness of breath that is out of proportion to workload, palpitations or the perception of irregular cardiac activity, and syncope. Chest discomfort, inappropriate shortness of breath, and palpitations that occur during training or competition should be managed with immediate removal from the playing field and prompt medical assessment. In many cases, thorough evaluation will involve collaboration between sports medicine and sports cardiology providers. Evaluations must be individualized on a case-by-case basis as tailored to the athlete’s presenting chief complaint and prior medical history. Most of these assessments will include a detailed medical history and physical examination, a 12-lead electrocardiogram (ECG), provocative exercise testing in a controlled environment, noninvasive cardiac imaging, and in some cases ambulatory rhythm monitoring. Uniformly, the athlete should be withheld from further training and competition until high-risk cardiovascular disease has been excluded. We refer the interested reader to a comprehensive discussion of symptom-based assessment of the athlete with suspected cardiovascular disease.¹⁶

Syncope (sudden and abrupt loss of consciousness with spontaneous neurologic recovery) is common among trained athletes. The vast majority of syncope is caused by “neurocardiogenic” mechanisms and carries a benign prognosis. Benign neurally-mediated syncope most often occurs outside of training and competition among athletes with heightened vagal tone and a predisposed susceptibility to triggers including pain, anxiety, emotional stimulation, and sudden postural change. Athletes who experience neurally-mediated syncope outside of training and competition routinely report a pre-event prodrome or aura that permits them to lower themselves to the ground, thereby avoiding injury. A distinct, but similarly benign and common, form of neurally-mediated fainting is post-exertional syncope. Here, fainting occurs within seconds of abrupt termination of exercise due to a rapid reduction cardiac preload and corollary cerebral blood supply. When either form of neurally-mediated syncope is suggested by a comprehensive medical history, normal physical examination, and a normal 12- lead ECG, further evaluation is unnecessary. However, the athlete and their coaching staff should be educated about avoidance tactics including hydration, dietary sodium supplementation, and avoidance of abrupt exercise termination as neutrally-mediated syncope tends to be recurrent without such measures. Fainting episodes that occur during training or competition that are not clearly post-exertional should be considered a medical emergency and should prompt comprehensive evaluation by a qualified cardiovascular specialist. Working closely with team physicians and athletic training staff, it is the responsibility of sports cardiologists to exclude potentially life-threatening forms of electrical, muscular, coronary, and valvular heart disease. Ideally, this evaluation should be conducted rapidly to avoid unnecessary delays in return to play.

CARDIAC ARREST AND SUDDEN DEATH

Numerous high-visibility cases of cardiac arrest on the soccer pitch have alerted the sporting community to the potential for these rare and potentially tragic events. Definitive incidence statistics defining the risk of cardiac arrest among soccer players are lacking. Data from the NCAA database suggest a sudden death incidence rate among collegiate male soccer athletes of approximately 1:24,000 athlete years.⁸ Similar data documenting incidence among female athletes and among those at lower (ie, youth level and high school) and higher (ie, professional) levels of play are unavailable. Underlying cardiovascular disease in the forms of heart muscle abnormalities (ie, genetic and acquired cardiomyopathy), coronary artery abnormalities (ie, genetic coronary anomalies and atherosclerotic coronary disease), valvular heart problems (ie, congenitally malformed aortic valves), and primary disturbances of the cardiac electrical system (ie, Wolf-Parkinson-White syndrome, long QT syndrome, etc.) explain a substantial percentage of on-pitch cardiac arrest. However, it is increasingly recognized that a significant minority of sudden cardiac deaths among athletes occur in the absence of attributable cardiovascular abnormality.¹⁷ Such cases, often referred to as “sudden unexplained death,” present unique challenges in the context of pre-participation screening, as they are undetectable and thus unpredictable.

Reduction of cardiac arrest and sudden death may best be accomplished through a combination of focused pre-participation screening and the development and implementation of a comprehensive EAP. Pre-participation involves the performance of a battery of tests prior to training and competition that are geared toward the detection of occult high-risk cardiovascular disease. Recommendations regarding pre-participation screening vary both across and within countries. Current US recommendations call for a focused medical history and physical examination prior to training and competition with consideration of the addition of a 12-lead ECG on a local level based on expertise and available resources.¹⁸ Conversely, current European guidelines including those endorsed by FIFA, suggest routine inclusion of a 12-lead ECG and in some cases, a transthoracic ECG.¹⁹ It must be emphasized that no screening approach has been confirmed to reduce the incidence of sudden death, and the decision to extend screening beyond the medical history and physical examination to include a 12-lead ECG or echocardiogram may come at the cost of increased false positive testing. In practice, decisions about how and when to screen are ideally made at a local level after consideration of medical and financial resources.²⁰

Continue to: Even the most comprehensive approach...

 

 

Even the most comprehensive approach to screening and evaluation of symptomatic athletes will not completely eliminate on-pitch cardiac arrest. Thus, all stakeholders that engage in the oversight of organized soccer must be committed to the development and implementation of an EAP.²¹ Key components of an effective EAP include the training of coaching staff, athletic trainers, and players in basic cardiopulmonary resuscitation, access to and training in the use of automated external defibrillators, and a triage/transport protocol that ensures timely access to advanced cardiac life support. Much like screening, emergency action planning involving these key core components must be developed and tailored locally. In the era of contemporary organized athletics, the absence of an EAP at any level of competition, from youth to professional leagues, is unacceptable. Effective EAPs must be developed, documented, and rehearsed at regular intervals. For the health and safety of competitive soccer players, as well as coaching staff and spectators, these steps are of critical importance.

HEAT

Heat-related illnesses can be serious and, at times, even life threatening. It is important for athletic staff and athletes to be well versed in the prevention, signs and symptoms, and treatment of heat-related illnesses in order to prevent serious and lasting injury. We aim to educate physicians about the prevention, recognition, and management of heat-related injury, and stress the importance of similarly educating athletes and coaching staff.

Exertional heat illnesses most often occur at temperatures >86°F, however they can occur at any temperature with heavy exertion.²² Signs and symptoms can be nonspecific early on, including weakness, fatigue, headache, nausea, and dizziness. Later signs can include imbalance, altered mentation, confusion, and behavior that is out of character such as irritability or aggression.²³ It is easy to see how the later signs can be confused for concussion in the right context. We cover the recognition and treatment of two common and serious heat-related illnesses: heat exhaustion and exertional heat stroke (EHS).

HEAT EXHAUSTION

Heat exhaustion occurs when an athlete cannot continue to exercise due to weakness and fatigue. While the exact mechanism is not well understood, it has been established that the combined effect of heat and dehydration have been proven to decrease exercise capacity and performance to a greater degree than either alone. The heat created by the body during exercise is 15 to 20 times greater than when at rest, and can increase core body temperature by 1°C every 5 minutes if no heat is lost, such as through sweating.²⁴ Additionally, when fluid deficits reach >3% to 5% of total body water, sweat production and skin blood flow decline, blunting the ability for the body to cool itself and causing progressive elevation of core body temperature if the athlete continues exerting him or herself. When fluid deficits reach 6% to 10%, cardiac output, sweat, and muscle blood flow decrease, likely leading to the symptoms seen with heat exhaustion: weakness, profound fatigue, and occasionally confusion and disorientation. Athletes with suspected heat exhaustion should be moved to a cooler area, laid down with legs elevated, and orally rehydrated. If they do not improve with oral rehydration, they may require intravenous fluids. The diagnosis of heat exhaustion hinges on a rectal temperature of <104°F; if >104°F the athlete should be presumed to have heat stroke, which will be addressed in the following paragraphs. Players can be cleared to return to play in mild cases within 24 to 48 hours with gradual increases in exercise intensity.²⁴

EXERTIONAL HEAT STROKE

EHS occurs when the body can no longer regulate the core body temperature and it rises to upwards of 104°F. In EHS, elevated core body temperature is associated with evidence of end organ dysfunction. The most easily identified on the playing field is likely central nervous system dysfunction, including irritability, confusion, irrational behavior, lethargy, dizziness, confusion, and even loss of consciousness. Temperature should be measured with rectal temperature only, as other methods of measurement have been shown to be consistently inaccurate.²² Heat stroke can be confused with exertional hyponatremia, heat exhaustion, or concussion, especially when core body temperature cannot be determined. However, EHS should always be the presumed cause of altered mentation when no rectal temperature is available because rapid cooling is critical to minimizing lasting effects. Morbidity and mortality are directly related to the length of time required to cool the athlete under 40°C (104°F).²⁴ Cooling should be completed on site prior to transport to a medical facility and is best achieved with submersion in an ice bath (ie, a kiddie pool or soaking tub full of ice and water).^22,25 If an ice bath is not available, ice bags should be applied to the neck axilla and groin and exchanged for fresh bags every 2 to 3 minutes.²² Ice bags have been shown to be inferior to whole body cooling, only cooling the athlete .04°C to .08°C/min compared to .15°C to .24°C/min with the ice bath.²⁴ All other tests should be delayed until cooling is achieved, unless they can be completed while cooling the athlete. The athlete can be removed from the ice bath once rectal temperatures reach <101°F to 102°F.²³ If the athlete returns to baseline after cooling, transportation to a medical facility may not be necessary. However, they should refrain from physical activity and heat exposure for at least 7 days and should be evaluated by a physician at that time. If all labs are normal and the athlete is asymptomatic, they can start progressive return to play under the direction of an athletic trainer or a sports medicine physician.²³

Continue to: HEAT-RELATED ILLNESS...

 

 

HEAT-RELATED ILLNESS

It is impossible to predict exactly which athletes will be most at risk for heat-related illness, so it is important to have a high degree of suspicion when environmental conditions are right. Athletes with recent illness, fever, or lack of sleep are at higher risk. Additional intrinsic risk factors include low fitness level, obesity, and inadequate hydration. Athletes who are highly competitive or motivated can be more likely to push through the early signs of illness or be reluctant to report symptoms.²³ Those with a history of exertional heat illness are more at risk for developing it again in the future.²³

The extrinsic risk factors for the development of heat-related illness are much easier to identify and modify in order to keep athletes safe. High temperature and high humidity conditions, heavy sun exposure, and exposure to similar conditions the preceding day put athletes at risk for exertional heat illness. Risks are even greater when the exercise is prolonged or intense with few breaks and access to hydration is limited.²³ Therefore, prevention of exertional heat illness is centered on these external risk factors.

Each team should have a heat policy as part of their EAP aimed at prevention and early recognition of heat-related illness. This policy should be shared with all athletes and coaches. The plan should be centered on acclimatization, activity modification, and early recognition and management as previously discussed. The US Soccer Federation “Recognize to Recover” Heat Guidelines suggest a 3-step process for appropriate activity modification:²²

1. Find the wet bulb globe temperature, either using a wet bulb globe thermometer or the temperature and humidity (Figure 1).

2. Find your regional weather category on the map (Figure 2).

3. Find your alert level and work to rest ratio recommendations (Figure 3).

Scheduled hydration breaks should be given as listed in Figure 3. Breaks of 4 minutes should be given for each 30 minutes of continuous practice or play. In a regulation 90-minute match, a hydration break should be given at 30 and 75 minutes (with half time at 45 minutes) at minimum. Athletes should be educated about where hydration can be accessed, and given unlimited access to hydration even outside of planned breaks.²²

Acclimatization to conditions is another integral part of preventing heat-related illness. It allows the body time to adapt to exercising in heat gradually, with a measured progression of exertion over the course of 10 to 14 days. The “Recognize to Recover” Heat Guidelines also provide guidance on acclimatization, and specifics can be found on the website.¹ Generally speaking, the warmest part of the day, usually between 11 AM and 4 PM, should be avoided for all training sessions, and length of practice and exertion should be gradually increased over 2 weeks.²²

In summary, appropriate acclimatization, hydration, activity modification, and education of athletes and staff are essential for the prevention of heat-related illness. Athletes and staff should understand the signs and symptoms of heat-related illness so that it can be recognized early and treated appropriately. If an athlete is altered in the heat and rectal temperature is >104°F or rectal temperature cannot be obtained, rapid cooling using an ice bath or ice bags is essential to prevent the morbidity and mortality associated with EHS. Above all, teams should have an explicit plan that includes protocols for acclimatization, activity modification, and all necessary equipment to prevent and treat heat-related illnesses should they occur, and ultimately keep athletes safe and healthy.

ABSTRACT

Soccer requires significant physical conditioning and endurance, as well as the physicality required for contact play. In order to keep athletes safe, it is important that coaches, medical staff, and the players themselves are educated on the most common dangers to their health that they may encounter on a soccer pitch. This article aims to review the current literature and recommendations on concussion, cardiovascular considerations, and heat-related illness as they relate to competitive soccer, with a goal of educating all those who help to keep athletes healthy and competing to their full potential.  

Continue to: Soccer is one of the most popular sports...

Soccer is one of the most popular sports in the modern world and requires significant physical conditioning and endurance, as well as the physicality required for contact play. This article covers the topics of concussion, cardiovascular considerations, and heat-related illness as they relate to competitive soccer players. We provide a review of the prevention, recognition, and management required to keep athletes safe on the soccer pitch, both in practice and in competitive play.

HEAD

With an estimated 1.6 to 3.8 million sports-related mild traumatic brain injuries (ie, concussions) occurring annually in the United States,¹ there has been an appropriate increase in the focus on prevention and treatment of these injuries. For more than a decade the spotlight has been on concussions that occur in American football, but other sports have also had to examine the prevalence of concussions in their sport. This is certainly true for soccer.

There has been a steady increase in soccer participation in the United States. From 1973 to 2014 there was a 4-fold increase in high school boys and a 35-fold increase in high school girls playing soccer.² Currently, there are more than 3.7 million youth who play on teams under the supervision of the US Soccer Federation, the sport’s national governing body.³ With the growth of the sport, there has also been an intensified focus on injury prevention in soccer players, including concussive brain injuries.

A recent study examined injury rates in high school soccer players and noted that concussion is the second most common injury (17.9%), after ligament sprains (29.7%).⁴ The overall injury rate was 2.06 per 1000 athletic exposures (AEs [defined as participation in practice or game play]), but higher in games (4.42 per 1000 AEs) than during practices (1.05 per 1000 AEs). The overall concussion rate was 0.36 per 1000 AEs.⁴

Most concussions (54.8%) resulted in missing play between 1 to 3 weeks, but a sizeable portion of the athletes (14.9%) were out of play for more than 3 weeks. Additionally, 10.7% of all medical disqualifications were due to concussive injuries. Khodaee and colleagues⁴ found no statistically significant difference in concussion rates between male and female soccer players over the 9-year period of time that they examined, however previous studies have found higher rates in female athletes.⁵

In soccer, as in other sports, there is a concern about both the adequate recognition of concussions during practice and play and the underreporting of concussions by athletes. The US Soccer Federation has taken a proactive stance on addressing concussion in youth soccer by developing the “Recognize to Recover” program.⁶ Recognize to Recover is the US Soccer Federation’s “comprehensive player health and safety program aimed at promoting safe play and reducing injuries in soccer players of all ages.” The website provides an educational video geared toward players, along with links to concussion assessment tools, the US Soccer Federation Concussion Protocol, and US Soccer Federation-Centers for Disease Control fact sheets for athletes, parents, and coaches.⁶

Continue to: A challenge for all sports...

 

 

A challenge for all sports is allowing adequate evaluation of a suspected concussion by properly trained healthcare professionals. The 2017 Berlin Concussion in Sport Group position paper stated, “when a concussion is suspected, the athlete should be removed from the sporting environment and a multimodal assessment should be conducted in standardized fashion (eg, Sport Concussion Assessment Tool- 5th edition). Sporting bodies should allow adequate time to conduct this evaluation.”⁷ However, the International Federation of Football Association (FIFA) rules limit substitutions to 3 over the course of the game, which can make a thorough evaluation of players difficult as trainers and coaches are under increased pressure to quickly determine whether to use one of their valuable substitutions. Fortunately, the National Collegiate Athletic Association (NCAA) soccer has mitigated this issue by allowing unlimited substitutions during matches, and high school teams generally follow similar rules.

One of the goals of any safety education program is not only to raise the awareness of the signs and symptoms of concussion by all those involved in the sport, but also to increase the number of athletes who self-report their symptoms and decrease those who hide any possible concussions. A study found that a majority (58.6%) of middle school soccer players continued to play while experiencing concussion symptoms.⁵ However, in a very recent (not yet published) study, 92% of US Soccer Federation players reported that they did seek out a medical evaluation for their concussion.⁸ This is certainly a positive sign and further research needs to clarify what methods of education or training will maintain this level of self-reporting in soccer players.

There has also been an increased focus on understanding the mechanism of injury of concussions. In soccer, concussions can occur from player-to-player contact, contact with the player surface, contact with playing apparatus (eg, goal posts) and non-contact mechanisms. While there has been a focus on concussions from heading the ball, player-to-player contact is the most common cause of concussions. A 2017 study of 7- to 12-year-old soccer players in 4 European countries found that about 1 out of 10 concussions were caused by heading the ball.⁹ Comstock and colleageues¹⁰ found slightly higher numbers, roughly 25% to 30% (depending on gender), but 70% to 78% (again depending on gender) of those were caused by player-to-player contact rather than contact with the ball.

To date there has not been any meta-analytic review evaluating the cognitive and physical symptoms associated with heading in soccer. A recent review paper stated that the “current evidence seems insufficient to support a ban of heading in children’s football (soccer).”¹⁰ However, in December 2015 the US Soccer Federation included age-specific heading limitations. Players ages 10 years and under “shall not engage in heading, either in practices or in games” and players age 11 years and 12 years should have “limited heading in practice; maximum of 30 minutes of heading training per week, with no more than 15-20 headers per player, per week.”¹¹ US Soccer Federation officials acknowledged the limitations in the current science regarding heading in young soccer players but chose to err on the side of caution until further empirical evidence regarding the risks associated with repetitive heading is available.

The US Soccer Federation is also exploring other ways to reduce the incidence rate of concussions, including ensuring that the age-appropriate sized ball is used in practice and play, possible rule changes, evaluation of different playing surfaces, and equipment usage. To date, there is no strong evidence to support the use of mouth guards or helmets to reduce concussions in soccer. Additionally, the current data about the value of head impact sensors in soccer has not supported its widespread use.

Continue to: Finally, the issue of the prevalence...

 

 

Finally, the issue of the prevalence of chronic traumatic encephalopathy (CTE) in soccer players is beyond the scope of this article. The expert opinion from the 2017 US Soccer Federation, Major League Soccer (MLS), and National Women’s Soccer League (NWSL) conference concluded, “At present, no data exist that support that soccer participation is a risk factor for the development of neurodegenerative disease. Similarly, at this time, consistent with evidence discussed in the Berlin Concussion in Sport Group (CISG) Consensus Conference, our review suggests no causal relationship has been demonstrated between soccer and CTE pathology.”¹²

The more we know about concussions, both in general and those sustained during soccer play, the better we are able to diagnose and manage these injuries in our athletes. An important step is creating evidence-based protocols that evolve as our knowledge of concussions does as well. In April 2017, the US Soccer Federation, MLS, and the NWSL held a joint summit entitled, “Head Injury in Soccer: From Science to the Field” to address the current evidence-based science of concussions in soccer.⁸ An article discussing the findings of this meeting is forthcoming and will undoubtedly guide further development of concussion protocols for soccer players of all ages.

HEART

The physiologic demands of soccer place considerable stress on the cardiovascular system. Participation in training and competition is characterized by a combination of aerobic and anaerobic physiology with the typical athlete covering approximately 10 km over the course of the 90-minute match. The primary role of the heart and blood vessels is to supply the exercising skeletal muscle with oxygen and energy substrate and to clear the byproducts of metabolism. Among healthy athletes without cardiovascular disease, these processes are typically well tolerated and may be associated with beneficial cardiovascular adaptations over time. However, competitive soccer players are not completely immune to cardiovascular disease. Athletes across the age and competition spectrum may develop symptoms suggestive of underlying cardiovascular disease during play including exertional chest pain, inappropriate shortness of breath, palpitations, and syncope. These athletes require timely clinical evaluation. In extremely rare but high visibility cases, competitive soccer players may succumb to cardiac arrest on the pitch, underscoring the need for comprehensive emergency action plans (EAPs). We provide the practicing clinician with an overview of cardiovascular issues relevant to the competitive soccer athlete.

CARDIOVASCULAR ADAPTATIONS TO SPORT

The pressure (ie, repetitive surges in systemic blood pressure) and volume (ie, sustained increases in high cardiac output) challenges inherent in soccer participation place stress on the cardiovascular system. Healthy athletes across the age spectrum typically tolerate the hemodynamic stressors of participation without issues. Athletes that engage in training and competition over months to years often develop beneficial adaptations of the cardiovascular system that enhance on-field performance and contribute to optimal long-term health. Detailed discussion of how the heart and blood vessels respond to exercise training is beyond the scope of this article, but the interested reader is referred to several prior publications.^13,14 In brief, the heart of the healthy soccer athlete demonstrates the balanced mild chamber dilation and wall thickening characteristic of left ventricular eccentric remodeling. This form of exercise-induced cardiac remodeling facilitates maintenance of high stroke volume during exercise with minimal increases in cardiac work. In parallel, routine aerobic exercise training confers favorable changes in the systemic arterial system, which leads to reductions in age-associated ventricular stiffening and maintenance of healthy low blood pressure. It must be emphasized that the healthy heart muscle dilation and thickening that develop in response to sports participation, regardless of age, ethnicity, or gender, are relatively mild and should not be confused with common forms of heart muscle disease that may be seen in athletes at risk for adverse outcomes. In some situations, consultation with an extreme sports cardiologist may be required to differentiate exercise-induced remodeling from over heart muscle pathology.¹⁵

Continue to: THE SYMPTOMATIC ATHLETE...

 

 

THE SYMPTOMATIC ATHLETE

Any athlete presenting with symptoms suggestive of underlying cardiovascular disease should be withheld from training and competition until a comprehensive clinical evaluation has been completed. Common manifestations of underlying heart disease that occur in soccer players include exertional chest pain/pressure/tightness, shortness of breath that is out of proportion to workload, palpitations or the perception of irregular cardiac activity, and syncope. Chest discomfort, inappropriate shortness of breath, and palpitations that occur during training or competition should be managed with immediate removal from the playing field and prompt medical assessment. In many cases, thorough evaluation will involve collaboration between sports medicine and sports cardiology providers. Evaluations must be individualized on a case-by-case basis as tailored to the athlete’s presenting chief complaint and prior medical history. Most of these assessments will include a detailed medical history and physical examination, a 12-lead electrocardiogram (ECG), provocative exercise testing in a controlled environment, noninvasive cardiac imaging, and in some cases ambulatory rhythm monitoring. Uniformly, the athlete should be withheld from further training and competition until high-risk cardiovascular disease has been excluded. We refer the interested reader to a comprehensive discussion of symptom-based assessment of the athlete with suspected cardiovascular disease.¹⁶

Syncope (sudden and abrupt loss of consciousness with spontaneous neurologic recovery) is common among trained athletes. The vast majority of syncope is caused by “neurocardiogenic” mechanisms and carries a benign prognosis. Benign neurally-mediated syncope most often occurs outside of training and competition among athletes with heightened vagal tone and a predisposed susceptibility to triggers including pain, anxiety, emotional stimulation, and sudden postural change. Athletes who experience neurally-mediated syncope outside of training and competition routinely report a pre-event prodrome or aura that permits them to lower themselves to the ground, thereby avoiding injury. A distinct, but similarly benign and common, form of neurally-mediated fainting is post-exertional syncope. Here, fainting occurs within seconds of abrupt termination of exercise due to a rapid reduction cardiac preload and corollary cerebral blood supply. When either form of neurally-mediated syncope is suggested by a comprehensive medical history, normal physical examination, and a normal 12- lead ECG, further evaluation is unnecessary. However, the athlete and their coaching staff should be educated about avoidance tactics including hydration, dietary sodium supplementation, and avoidance of abrupt exercise termination as neutrally-mediated syncope tends to be recurrent without such measures. Fainting episodes that occur during training or competition that are not clearly post-exertional should be considered a medical emergency and should prompt comprehensive evaluation by a qualified cardiovascular specialist. Working closely with team physicians and athletic training staff, it is the responsibility of sports cardiologists to exclude potentially life-threatening forms of electrical, muscular, coronary, and valvular heart disease. Ideally, this evaluation should be conducted rapidly to avoid unnecessary delays in return to play.

CARDIAC ARREST AND SUDDEN DEATH

Numerous high-visibility cases of cardiac arrest on the soccer pitch have alerted the sporting community to the potential for these rare and potentially tragic events. Definitive incidence statistics defining the risk of cardiac arrest among soccer players are lacking. Data from the NCAA database suggest a sudden death incidence rate among collegiate male soccer athletes of approximately 1:24,000 athlete years.⁸ Similar data documenting incidence among female athletes and among those at lower (ie, youth level and high school) and higher (ie, professional) levels of play are unavailable. Underlying cardiovascular disease in the forms of heart muscle abnormalities (ie, genetic and acquired cardiomyopathy), coronary artery abnormalities (ie, genetic coronary anomalies and atherosclerotic coronary disease), valvular heart problems (ie, congenitally malformed aortic valves), and primary disturbances of the cardiac electrical system (ie, Wolf-Parkinson-White syndrome, long QT syndrome, etc.) explain a substantial percentage of on-pitch cardiac arrest. However, it is increasingly recognized that a significant minority of sudden cardiac deaths among athletes occur in the absence of attributable cardiovascular abnormality.¹⁷ Such cases, often referred to as “sudden unexplained death,” present unique challenges in the context of pre-participation screening, as they are undetectable and thus unpredictable.

Reduction of cardiac arrest and sudden death may best be accomplished through a combination of focused pre-participation screening and the development and implementation of a comprehensive EAP. Pre-participation involves the performance of a battery of tests prior to training and competition that are geared toward the detection of occult high-risk cardiovascular disease. Recommendations regarding pre-participation screening vary both across and within countries. Current US recommendations call for a focused medical history and physical examination prior to training and competition with consideration of the addition of a 12-lead ECG on a local level based on expertise and available resources.¹⁸ Conversely, current European guidelines including those endorsed by FIFA, suggest routine inclusion of a 12-lead ECG and in some cases, a transthoracic ECG.¹⁹ It must be emphasized that no screening approach has been confirmed to reduce the incidence of sudden death, and the decision to extend screening beyond the medical history and physical examination to include a 12-lead ECG or echocardiogram may come at the cost of increased false positive testing. In practice, decisions about how and when to screen are ideally made at a local level after consideration of medical and financial resources.²⁰

Continue to: Even the most comprehensive approach...

 

 

Even the most comprehensive approach to screening and evaluation of symptomatic athletes will not completely eliminate on-pitch cardiac arrest. Thus, all stakeholders that engage in the oversight of organized soccer must be committed to the development and implementation of an EAP.²¹ Key components of an effective EAP include the training of coaching staff, athletic trainers, and players in basic cardiopulmonary resuscitation, access to and training in the use of automated external defibrillators, and a triage/transport protocol that ensures timely access to advanced cardiac life support. Much like screening, emergency action planning involving these key core components must be developed and tailored locally. In the era of contemporary organized athletics, the absence of an EAP at any level of competition, from youth to professional leagues, is unacceptable. Effective EAPs must be developed, documented, and rehearsed at regular intervals. For the health and safety of competitive soccer players, as well as coaching staff and spectators, these steps are of critical importance.

HEAT

Heat-related illnesses can be serious and, at times, even life threatening. It is important for athletic staff and athletes to be well versed in the prevention, signs and symptoms, and treatment of heat-related illnesses in order to prevent serious and lasting injury. We aim to educate physicians about the prevention, recognition, and management of heat-related injury, and stress the importance of similarly educating athletes and coaching staff.

Exertional heat illnesses most often occur at temperatures >86°F, however they can occur at any temperature with heavy exertion.²² Signs and symptoms can be nonspecific early on, including weakness, fatigue, headache, nausea, and dizziness. Later signs can include imbalance, altered mentation, confusion, and behavior that is out of character such as irritability or aggression.²³ It is easy to see how the later signs can be confused for concussion in the right context. We cover the recognition and treatment of two common and serious heat-related illnesses: heat exhaustion and exertional heat stroke (EHS).

HEAT EXHAUSTION

Heat exhaustion occurs when an athlete cannot continue to exercise due to weakness and fatigue. While the exact mechanism is not well understood, it has been established that the combined effect of heat and dehydration have been proven to decrease exercise capacity and performance to a greater degree than either alone. The heat created by the body during exercise is 15 to 20 times greater than when at rest, and can increase core body temperature by 1°C every 5 minutes if no heat is lost, such as through sweating.²⁴ Additionally, when fluid deficits reach >3% to 5% of total body water, sweat production and skin blood flow decline, blunting the ability for the body to cool itself and causing progressive elevation of core body temperature if the athlete continues exerting him or herself. When fluid deficits reach 6% to 10%, cardiac output, sweat, and muscle blood flow decrease, likely leading to the symptoms seen with heat exhaustion: weakness, profound fatigue, and occasionally confusion and disorientation. Athletes with suspected heat exhaustion should be moved to a cooler area, laid down with legs elevated, and orally rehydrated. If they do not improve with oral rehydration, they may require intravenous fluids. The diagnosis of heat exhaustion hinges on a rectal temperature of <104°F; if >104°F the athlete should be presumed to have heat stroke, which will be addressed in the following paragraphs. Players can be cleared to return to play in mild cases within 24 to 48 hours with gradual increases in exercise intensity.²⁴

EXERTIONAL HEAT STROKE

EHS occurs when the body can no longer regulate the core body temperature and it rises to upwards of 104°F. In EHS, elevated core body temperature is associated with evidence of end organ dysfunction. The most easily identified on the playing field is likely central nervous system dysfunction, including irritability, confusion, irrational behavior, lethargy, dizziness, confusion, and even loss of consciousness. Temperature should be measured with rectal temperature only, as other methods of measurement have been shown to be consistently inaccurate.²² Heat stroke can be confused with exertional hyponatremia, heat exhaustion, or concussion, especially when core body temperature cannot be determined. However, EHS should always be the presumed cause of altered mentation when no rectal temperature is available because rapid cooling is critical to minimizing lasting effects. Morbidity and mortality are directly related to the length of time required to cool the athlete under 40°C (104°F).²⁴ Cooling should be completed on site prior to transport to a medical facility and is best achieved with submersion in an ice bath (ie, a kiddie pool or soaking tub full of ice and water).^22,25 If an ice bath is not available, ice bags should be applied to the neck axilla and groin and exchanged for fresh bags every 2 to 3 minutes.²² Ice bags have been shown to be inferior to whole body cooling, only cooling the athlete .04°C to .08°C/min compared to .15°C to .24°C/min with the ice bath.²⁴ All other tests should be delayed until cooling is achieved, unless they can be completed while cooling the athlete. The athlete can be removed from the ice bath once rectal temperatures reach <101°F to 102°F.²³ If the athlete returns to baseline after cooling, transportation to a medical facility may not be necessary. However, they should refrain from physical activity and heat exposure for at least 7 days and should be evaluated by a physician at that time. If all labs are normal and the athlete is asymptomatic, they can start progressive return to play under the direction of an athletic trainer or a sports medicine physician.²³

Continue to: HEAT-RELATED ILLNESS...

 

 

HEAT-RELATED ILLNESS

It is impossible to predict exactly which athletes will be most at risk for heat-related illness, so it is important to have a high degree of suspicion when environmental conditions are right. Athletes with recent illness, fever, or lack of sleep are at higher risk. Additional intrinsic risk factors include low fitness level, obesity, and inadequate hydration. Athletes who are highly competitive or motivated can be more likely to push through the early signs of illness or be reluctant to report symptoms.²³ Those with a history of exertional heat illness are more at risk for developing it again in the future.²³

The extrinsic risk factors for the development of heat-related illness are much easier to identify and modify in order to keep athletes safe. High temperature and high humidity conditions, heavy sun exposure, and exposure to similar conditions the preceding day put athletes at risk for exertional heat illness. Risks are even greater when the exercise is prolonged or intense with few breaks and access to hydration is limited.²³ Therefore, prevention of exertional heat illness is centered on these external risk factors.

Each team should have a heat policy as part of their EAP aimed at prevention and early recognition of heat-related illness. This policy should be shared with all athletes and coaches. The plan should be centered on acclimatization, activity modification, and early recognition and management as previously discussed. The US Soccer Federation “Recognize to Recover” Heat Guidelines suggest a 3-step process for appropriate activity modification:²²

1. Find the wet bulb globe temperature, either using a wet bulb globe thermometer or the temperature and humidity (Figure 1).

2. Find your regional weather category on the map (Figure 2).

3. Find your alert level and work to rest ratio recommendations (Figure 3).

Scheduled hydration breaks should be given as listed in Figure 3. Breaks of 4 minutes should be given for each 30 minutes of continuous practice or play. In a regulation 90-minute match, a hydration break should be given at 30 and 75 minutes (with half time at 45 minutes) at minimum. Athletes should be educated about where hydration can be accessed, and given unlimited access to hydration even outside of planned breaks.²²

Acclimatization to conditions is another integral part of preventing heat-related illness. It allows the body time to adapt to exercising in heat gradually, with a measured progression of exertion over the course of 10 to 14 days. The “Recognize to Recover” Heat Guidelines also provide guidance on acclimatization, and specifics can be found on the website.¹ Generally speaking, the warmest part of the day, usually between 11 AM and 4 PM, should be avoided for all training sessions, and length of practice and exertion should be gradually increased over 2 weeks.²²

In summary, appropriate acclimatization, hydration, activity modification, and education of athletes and staff are essential for the prevention of heat-related illness. Athletes and staff should understand the signs and symptoms of heat-related illness so that it can be recognized early and treated appropriately. If an athlete is altered in the heat and rectal temperature is >104°F or rectal temperature cannot be obtained, rapid cooling using an ice bath or ice bags is essential to prevent the morbidity and mortality associated with EHS. Above all, teams should have an explicit plan that includes protocols for acclimatization, activity modification, and all necessary equipment to prevent and treat heat-related illnesses should they occur, and ultimately keep athletes safe and healthy.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

Epacadostat, a highly selective oral inhibitor of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, was well tolerated when combined with pembrolizumab and demonstrated encouraging antitumor activity in multiple types of advanced solid tumors, according to the results of a phase l/ll trial.

Tumors may evade immunosurveillance through upregulation of the IDO1 enzyme, and thus there is a great interest in developing combination therapies that can target various immune evasion pathways to improve therapeutic response and outcomes. In this study, the authors evaluated the investigational agent epacadostat combined with pembrolizumab in 62 patients with advanced solid tumors.

In the dose escalation phase, patents received increasing doses of oral epacadostat (25, 50, 100, or 300 mg) twice per day plus intravenous pembrolizumab 2 mg/kg or 200 mg every 3 weeks. During the safety expansion, epacadostat at 50, 100, or 300 mg was given twice per day, plus pembrolizumab 200 mg every 3 weeks. The maximum tolerated dose of epacadostat in combination with pembrolizumab was not reached.

Objective responses (per Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) occurred in 12 (55%) of 22 patients with melanoma and in patients with non–small-cell lung cancer, renal cell carcinoma, endometrial adenocarcinoma, urothelial carcinoma, and squamous cell carcinoma of the head and neck, reported Tara C. Mitchell, MD, of the Abramson Cancer Center, University of Pennsylvania, Philadelphia, and her colleagues. The report is in the Journal of Clinical Oncology.

The authors observed that there was antitumor activity at all epacadostat doses and in several tumor types. A complete response was achieved by 8 patients (treatment naive melanoma [5 patients] and previously treated for advanced/ metastatic melanoma, endometrial adenocarcinoma [EA], or urothelial carcinoma [UC] [1 patient each]), while 17 patients achieved a partial response (treatment-naive melanoma [6 patients], non–small cell lung cancer [NSCLC] [5 patients], renal cell carcinoma [RCC] and UC [2 patients each], and EA and squamous cell carcinoma of the head and neck [1 patient each]).

Most patients (n = 52, 84%) experienced treatment-related adverse events (TRAEs), the most frequently observed being fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%). Grade 3/4 TRAEs occurred in 24% of patients, and 7 patients (11%) discontinued their treatment because of TRAEs. There were no deaths associated with TRAEs.

“The safety profile observed with epacadostat plus pembrolizumab compares favorably with studies of other combination immunotherapies,” wrote Dr. Mitchell and her colleagues. “Although not powered to evaluate efficacy, the phase I portion of this study showed that epacadostat plus pembrolizumab had encouraging and durable antitumor activity,” they said.

SOURCE: Mitchell TC et al. J Clin Oncol. 2018 Sep 28. doi: 10.1200/JCO.2018.78.9602.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.

SAN FRANCISCO – Influenza season is upon us, and Helen Chu, MD, MPH, is here at ID Week 2018 to talk vaccines, especially for pregnant women.

They are at greater risk for more severe illness, and influenza can lead to adverse outcomes in infants. The good news is that recent studies have shown that flu vaccines are safe and effective in pregnant women.

The bad news is that many women are hesitant to be vaccinated out of concerns over safety, in a trend that reflects broader societal worries over vaccination, said Dr. Chu, of the University of Washington, Seattle. In a video interview at an annual scientific meeting on infectious diseases, Dr. Chu advised steps to ensure that pregnant women are aware of the safety and efficacy of flu vaccines, and the benefits to the infant who acquires immunity through the mother. It’s also a good idea to have vaccine on hand to be able to offer it immediately during an office visit.