PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

PHILADELPHIA – Galcanezumab reduces weekly attack frequency in patients with episodic cluster headache, according to study results presented at the annual meeting of the American Academy of Neurology. The treatment has a similar safety profile in this patient population as it has among people with episodic or chronic migraine, said the researchers.

Calcitonin gene-related peptide (CGRP) has an important role in the pathogenesis of cluster headache. Galcanezumab (Emgality)is a humanized monoclonal antibody that binds to CGRP. Eli Lilly & Co. developed the molecule as a treatment for migraine. Cluster headache is characterized by recurrent unilateral headache attacks accompanied by autonomic symptoms. The most common acute treatments for cluster headache are sumatriptan (Imitrex) and high-flow oxygen, but some patients do not respond to these therapies.

David W. Dodick, MD, director of the headache, sports neurology, and concussion programs at Mayo Clinic in Phoenix, and colleagues conducted a trial to evaluate the efficacy and safety of galcanezumab in patients with episodic cluster headache.

After screening, participants underwent a prospective baseline diary phase for 7 consecutive days. The investigators subsequently randomized patients in equal groups to galcanezumab (300 mg subcutaneously) or placebo. Treatment was administered subcutaneously once monthly. The double-blind treatment period lasted for 8 weeks, and a washout period followed. The trial’s primary endpoint was the overall mean change from baseline in weekly cluster headache attack frequency during weeks 1-3, as recorded in patient diaries. The main secondary endpoint was the proportion of patients who had a reduction in weekly cluster headache attack frequency of 50% or more at week 3.

In all, 49 patients were randomized to galcanezumab, and 57 were randomized to placebo. Mean age was 45-47 years. Between 82% and 84% of patients were male. The mean number of weekly cluster headache attacks at baseline was approximately 17.5 in both groups.

During weeks 1-3, the mean change in weekly attack frequency was −8.7 in the galcanezumab group and −5.2 for controls. The difference between groups was statistically significant. The percentage of participants with a reduction in weekly attack frequency of at least 50% at week 3 was 76% for galcanezumab versus 57% for placebo. The between-group differences in these endpoints were statistically significant.

The discontinuation rate was 8% (4 participants) in the galcanezumab group and 21% (12 participants) in the placebo group. Eight participants (14%) in the placebo group discontinued treatment because of lack of efficacy, compared with one participant (2%) in the galcanezumab group. The researchers observed no clinically meaningful differences between treatment groups on tolerability or safety parameters except for a greater incidence of injection-site pain with galcanezumab versus placebo (8.2% vs. 0%).

Eli Lilly and Co. sponsored the study. Dr. Dodick has a consulting relationship with the company.

[email protected]

SOURCE: Bardos JN et al. AAN 2019, Abstract 02.004.

“Maximal” application of four different sunscreen formulations resulted in plasma concentrations of ingredients that exceeded the Food and Drug Administration’s threshold for waiving nonclinical toxicology studies for sunscreens, in a phase 1 randomized controlled study of 24 healthy volunteers.

Wavebreakmedia Ltd/Thinkstock

In the open-label study, 24 people (mean age 35.5 years) were randomized to one of four commercially available sunscreens (two sprays, one lotion, or one cream formulation); 2 mg of sunscreen per 1 cm² was applied to 75% of their body surface four times a day for 4 days (described as “maximal use conditions consistent with current sunscreen labeling”), and 30 blood samples were collected over 7 days.

The primary outcome was the maximum plasma concentration of avobenzone, from days 1-7; secondary outcomes were maximum plasma concentrations of sunscreen ingredients oxybenzone, octocrylene, and ecamsule over the same period of time.

All but one participant completed the study. “All four sunscreen active ingredients tested resulted in exposures exceeding 0.5 ng/mL,” reported Murali Matta, PhD, of the FDA’s Center for Drug Evaluation and Research, and coauthors. “The clinical effect of plasma concentrations exceeding 0.5 ng/mL is unknown, necessitating further research,” they added.

According to the study, FDA sunscreen guidance and the proposed rule for over-the-counter sunscreen monograph, nonclinical toxicology studies, such as carcinogenicity and reproductive studies, “may be waived if results of an adequately conducted human pharmacokinetic maximal usage trial show a steady state blood level less than 0.5 ng/mL and an adequately conducted toxicology assessment does not reveal any potential safety concerns.”

The results of this study “do not indicate that individuals should refrain from the use of sunscreen,” the authors concluded, adding that the “systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings.” The study was published in JAMA.

In an accompanying editorial, former FDA commissioner Robert Califf, MD, professor of cardiology, Duke University, Durham, N.C., and JAMA Dermatology Editor Kanade Shinkai, MD, PhD, of the department of dermatology, University of California, San Francisco, noted that “the demonstration of systemic absorption well above the FDA guideline does not mean these ingredients are unsafe” (JAMA. 2019 May 6. doi: 10.1001/jama.2019.5528). But, they added, the results “raise many important questions about sunscreen and the process by which the sunscreen industry, clinicians, specialty organizations, and regulatory agencies evaluate the benefits and risks of this topical OTC medication. First and foremost, it is essential to determine whether systemic absorption of sunscreen poses risks to human health. Second, the effects of different sunscreen formulations, clinical characteristics (that is, skin type, age, presence of skin diseases that disrupt the skin barrier), physical activity level, and exposure to sun and water on systemic sunscreen levels require further study.”

In a statement, former American Academy of Dermatology President Darrel Rigel, MD, of the department of dermatology, New York University, said that he was concerned that the results were misleading. “We have always known that there is a very small amount of absorption of sunscreens in the bloodstream,” and there are no data that this is a problem, he said, adding: “Tens of millions of people use sunscreens in the U.S. every summer weekend for many years with no incidence. Daily use of a broad-spectrum SPF of at least 30 is the best way to protect yourself from skin cancer. For many people, the chemical formulations cited in the study are the only ones that feel cosmetically elegant enough to wear. Consumers should continue to use their preferred formulation if it means they will actually wear it.”

[email protected]

SOURCE: JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586

“Maximal” application of four different sunscreen formulations resulted in plasma concentrations of ingredients that exceeded the Food and Drug Administration’s threshold for waiving nonclinical toxicology studies for sunscreens, in a phase 1 randomized controlled study of 24 healthy volunteers.

Wavebreakmedia Ltd/Thinkstock

In the open-label study, 24 people (mean age 35.5 years) were randomized to one of four commercially available sunscreens (two sprays, one lotion, or one cream formulation); 2 mg of sunscreen per 1 cm² was applied to 75% of their body surface four times a day for 4 days (described as “maximal use conditions consistent with current sunscreen labeling”), and 30 blood samples were collected over 7 days.

The primary outcome was the maximum plasma concentration of avobenzone, from days 1-7; secondary outcomes were maximum plasma concentrations of sunscreen ingredients oxybenzone, octocrylene, and ecamsule over the same period of time.

All but one participant completed the study. “All four sunscreen active ingredients tested resulted in exposures exceeding 0.5 ng/mL,” reported Murali Matta, PhD, of the FDA’s Center for Drug Evaluation and Research, and coauthors. “The clinical effect of plasma concentrations exceeding 0.5 ng/mL is unknown, necessitating further research,” they added.

According to the study, FDA sunscreen guidance and the proposed rule for over-the-counter sunscreen monograph, nonclinical toxicology studies, such as carcinogenicity and reproductive studies, “may be waived if results of an adequately conducted human pharmacokinetic maximal usage trial show a steady state blood level less than 0.5 ng/mL and an adequately conducted toxicology assessment does not reveal any potential safety concerns.”

The results of this study “do not indicate that individuals should refrain from the use of sunscreen,” the authors concluded, adding that the “systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings.” The study was published in JAMA.

In an accompanying editorial, former FDA commissioner Robert Califf, MD, professor of cardiology, Duke University, Durham, N.C., and JAMA Dermatology Editor Kanade Shinkai, MD, PhD, of the department of dermatology, University of California, San Francisco, noted that “the demonstration of systemic absorption well above the FDA guideline does not mean these ingredients are unsafe” (JAMA. 2019 May 6. doi: 10.1001/jama.2019.5528). But, they added, the results “raise many important questions about sunscreen and the process by which the sunscreen industry, clinicians, specialty organizations, and regulatory agencies evaluate the benefits and risks of this topical OTC medication. First and foremost, it is essential to determine whether systemic absorption of sunscreen poses risks to human health. Second, the effects of different sunscreen formulations, clinical characteristics (that is, skin type, age, presence of skin diseases that disrupt the skin barrier), physical activity level, and exposure to sun and water on systemic sunscreen levels require further study.”

In a statement, former American Academy of Dermatology President Darrel Rigel, MD, of the department of dermatology, New York University, said that he was concerned that the results were misleading. “We have always known that there is a very small amount of absorption of sunscreens in the bloodstream,” and there are no data that this is a problem, he said, adding: “Tens of millions of people use sunscreens in the U.S. every summer weekend for many years with no incidence. Daily use of a broad-spectrum SPF of at least 30 is the best way to protect yourself from skin cancer. For many people, the chemical formulations cited in the study are the only ones that feel cosmetically elegant enough to wear. Consumers should continue to use their preferred formulation if it means they will actually wear it.”

[email protected]

SOURCE: JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586

“Maximal” application of four different sunscreen formulations resulted in plasma concentrations of ingredients that exceeded the Food and Drug Administration’s threshold for waiving nonclinical toxicology studies for sunscreens, in a phase 1 randomized controlled study of 24 healthy volunteers.

Wavebreakmedia Ltd/Thinkstock

In the open-label study, 24 people (mean age 35.5 years) were randomized to one of four commercially available sunscreens (two sprays, one lotion, or one cream formulation); 2 mg of sunscreen per 1 cm² was applied to 75% of their body surface four times a day for 4 days (described as “maximal use conditions consistent with current sunscreen labeling”), and 30 blood samples were collected over 7 days.

The primary outcome was the maximum plasma concentration of avobenzone, from days 1-7; secondary outcomes were maximum plasma concentrations of sunscreen ingredients oxybenzone, octocrylene, and ecamsule over the same period of time.

All but one participant completed the study. “All four sunscreen active ingredients tested resulted in exposures exceeding 0.5 ng/mL,” reported Murali Matta, PhD, of the FDA’s Center for Drug Evaluation and Research, and coauthors. “The clinical effect of plasma concentrations exceeding 0.5 ng/mL is unknown, necessitating further research,” they added.

According to the study, FDA sunscreen guidance and the proposed rule for over-the-counter sunscreen monograph, nonclinical toxicology studies, such as carcinogenicity and reproductive studies, “may be waived if results of an adequately conducted human pharmacokinetic maximal usage trial show a steady state blood level less than 0.5 ng/mL and an adequately conducted toxicology assessment does not reveal any potential safety concerns.”

The results of this study “do not indicate that individuals should refrain from the use of sunscreen,” the authors concluded, adding that the “systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings.” The study was published in JAMA.

In an accompanying editorial, former FDA commissioner Robert Califf, MD, professor of cardiology, Duke University, Durham, N.C., and JAMA Dermatology Editor Kanade Shinkai, MD, PhD, of the department of dermatology, University of California, San Francisco, noted that “the demonstration of systemic absorption well above the FDA guideline does not mean these ingredients are unsafe” (JAMA. 2019 May 6. doi: 10.1001/jama.2019.5528). But, they added, the results “raise many important questions about sunscreen and the process by which the sunscreen industry, clinicians, specialty organizations, and regulatory agencies evaluate the benefits and risks of this topical OTC medication. First and foremost, it is essential to determine whether systemic absorption of sunscreen poses risks to human health. Second, the effects of different sunscreen formulations, clinical characteristics (that is, skin type, age, presence of skin diseases that disrupt the skin barrier), physical activity level, and exposure to sun and water on systemic sunscreen levels require further study.”

In a statement, former American Academy of Dermatology President Darrel Rigel, MD, of the department of dermatology, New York University, said that he was concerned that the results were misleading. “We have always known that there is a very small amount of absorption of sunscreens in the bloodstream,” and there are no data that this is a problem, he said, adding: “Tens of millions of people use sunscreens in the U.S. every summer weekend for many years with no incidence. Daily use of a broad-spectrum SPF of at least 30 is the best way to protect yourself from skin cancer. For many people, the chemical formulations cited in the study are the only ones that feel cosmetically elegant enough to wear. Consumers should continue to use their preferred formulation if it means they will actually wear it.”

[email protected]

SOURCE: JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586

NASHVILLE, TENN. – The unintended pregnancy rate is declining after years of hovering at close to 50%.

While the rates among women of color remain high – currently at 58 and 79 per 1,000 women aged 15-44 years for Hispanic and black women, respectively – they have declined from 79 and 92 per 1,000 Hispanic and black women in that age group in 2008, and the overall rate is now at about 45%, Eve Espey, MD, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Considering the scope and number of women affected by unplanned pregnancy, this is actually a huge public health achievement,” said Dr. Espey, professor and chair of the department of obstetrics & gynecology at the University of New Mexico, Albuquerque.

The declines in unintended pregnancies are largely attributable to “better and more consistent use of contraceptives, and, interestingly, increased abstinence,” she noted, adding that “another enormous determinant of this decrease in unintended pregnancy is the use of long-acting reversible contraception [LARC].” About 2% of women used contraceptives in 2002, and now, based on the latest cycle of data from 2015-2017, 16% of women use contraceptives.

In this video interview, Dr. Espey discusses the main points of her talk entitled “Contraceptives: What you need to know in 2019,” including:

• The importance of “following reproductive justice–based principles and counseling” when it comes to prescribing contraceptives.
• The latest data showing that certain LARC methods remain safe and effective beyond their approved duration of use.
• Trends with respect to tubal ligation and salpingectomy.
• The value of the Centers for Disease Control and Prevention’s U.S. Medical Eligibility Criteria (MEC) for evidence-based guidance on selecting contraceptives based on patients’ individual needs.

“[MEC] is something every ob.gyn. should consider using,” she said, noting that access is available through a free app. “As our patients are more complex and have more comorbidities, it’s particularly helpful for matching up patients and their conditions with recommendations for specific contraceptive methods.”

Dr. Espey reported having no financial disclosures.

[email protected]

NASHVILLE, TENN. – The unintended pregnancy rate is declining after years of hovering at close to 50%.

While the rates among women of color remain high – currently at 58 and 79 per 1,000 women aged 15-44 years for Hispanic and black women, respectively – they have declined from 79 and 92 per 1,000 Hispanic and black women in that age group in 2008, and the overall rate is now at about 45%, Eve Espey, MD, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Considering the scope and number of women affected by unplanned pregnancy, this is actually a huge public health achievement,” said Dr. Espey, professor and chair of the department of obstetrics & gynecology at the University of New Mexico, Albuquerque.

The declines in unintended pregnancies are largely attributable to “better and more consistent use of contraceptives, and, interestingly, increased abstinence,” she noted, adding that “another enormous determinant of this decrease in unintended pregnancy is the use of long-acting reversible contraception [LARC].” About 2% of women used contraceptives in 2002, and now, based on the latest cycle of data from 2015-2017, 16% of women use contraceptives.

In this video interview, Dr. Espey discusses the main points of her talk entitled “Contraceptives: What you need to know in 2019,” including:

• The importance of “following reproductive justice–based principles and counseling” when it comes to prescribing contraceptives.
• The latest data showing that certain LARC methods remain safe and effective beyond their approved duration of use.
• Trends with respect to tubal ligation and salpingectomy.
• The value of the Centers for Disease Control and Prevention’s U.S. Medical Eligibility Criteria (MEC) for evidence-based guidance on selecting contraceptives based on patients’ individual needs.

“[MEC] is something every ob.gyn. should consider using,” she said, noting that access is available through a free app. “As our patients are more complex and have more comorbidities, it’s particularly helpful for matching up patients and their conditions with recommendations for specific contraceptive methods.”

Dr. Espey reported having no financial disclosures.

[email protected]

NASHVILLE, TENN. – The unintended pregnancy rate is declining after years of hovering at close to 50%.

While the rates among women of color remain high – currently at 58 and 79 per 1,000 women aged 15-44 years for Hispanic and black women, respectively – they have declined from 79 and 92 per 1,000 Hispanic and black women in that age group in 2008, and the overall rate is now at about 45%, Eve Espey, MD, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

“Considering the scope and number of women affected by unplanned pregnancy, this is actually a huge public health achievement,” said Dr. Espey, professor and chair of the department of obstetrics & gynecology at the University of New Mexico, Albuquerque.

The declines in unintended pregnancies are largely attributable to “better and more consistent use of contraceptives, and, interestingly, increased abstinence,” she noted, adding that “another enormous determinant of this decrease in unintended pregnancy is the use of long-acting reversible contraception [LARC].” About 2% of women used contraceptives in 2002, and now, based on the latest cycle of data from 2015-2017, 16% of women use contraceptives.

In this video interview, Dr. Espey discusses the main points of her talk entitled “Contraceptives: What you need to know in 2019,” including:

• The importance of “following reproductive justice–based principles and counseling” when it comes to prescribing contraceptives.
• The latest data showing that certain LARC methods remain safe and effective beyond their approved duration of use.
• Trends with respect to tubal ligation and salpingectomy.
• The value of the Centers for Disease Control and Prevention’s U.S. Medical Eligibility Criteria (MEC) for evidence-based guidance on selecting contraceptives based on patients’ individual needs.

“[MEC] is something every ob.gyn. should consider using,” she said, noting that access is available through a free app. “As our patients are more complex and have more comorbidities, it’s particularly helpful for matching up patients and their conditions with recommendations for specific contraceptive methods.”

Dr. Espey reported having no financial disclosures.

[email protected]

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

Former athletes with a history of concussion averaged higher levels of total tau in their cerebrospinal fluid than did healthy controls, and those with the highest levels showed signs of reduced cognitive function in a case-control study.

solar22/Thinkstock

Chronic traumatic encephalopathy (CTE) remains a postmortem diagnosis, but “the potential for treating postconcussion degeneration such as CTE depends on being able to detect the in vivo pathology at an early stage to intervene before the disease progresses to an irreversible stage,” wrote Foad Taghdiri, MD, of the University of Toronto and colleagues.

In a study published in Neurology, the researchers measured concentrations of phosphorylated tau181, total tau (t-tau), and beta-amyloid in the cerebrospinal fluid (CSF) of three groups: 22 former professional athletes who had suffered multiple concussions, 5 healthy controls, and 12 individuals diagnosed with Alzheimer’s disease (AD). The average ages of the groups were 56 years, 57 years, and 60 years, respectively. All the athletes were male, and their sports included snowboarding, hockey, and football.

The average t-tau level in the CSF of the athletes was significantly higher than that of controls (349.3 pg/mL vs. 188.8 pg/mL) and significantly lower than that of AD patients (857.0 pg/mL).

Normal CSF t-tau was defined as 300 pg/mL, and 12 former athletes (45%) had high t-tau levels, with an average of 499.3 pg/mL. In this group of high t-tau former athletes, the average score on the Trail Making Test (TMT) Part B was significantly lower than the average score among the 10 former athletes with normal CSF t-tau levels (t scores 45.6 vs. 62.3; P = .017).

In addition, results from MRI scans showed that fractional anisotropy values across all the tracts were significantly lower for those with high CSF t-tau levels, compared with those who had normal CSF t-tau levels (P = .036).

The findings were limited by several factors, including the small sample size, lack of female athletes, and limited ability to compare white matter integrity between high and normal CSF t-tau groups, the researchers noted.

However, the results suggest that “multiple concussive or subconcussive events may trigger neurodegeneration to a greater degree than expected on the basis of age alone,” they said. Although the study did not allow for diagnosing the participants with CTE, “we are engaged in longitudinal studies to track neurologic and neuropsychological function, CSF biomarkers, and structural brain changes over time to further assess the delayed effects of multiple concussions on the brain,” the researchers wrote.

The study was funded by the Toronto General and Western Hospital Foundation, PSI Foundation, and the Canadian Institute of Health Research. The researchers had no financial conflicts to disclose.

SOURCE: Taghdiri F et al. Neurology. 2019 May 8. doi: 10.1212/WNL.0000000000007608

NASHVILLE, TENN. – By 2020, millennials will comprise more than a third of individuals in the workplace, and that has important implications for employment, communication, and education, according to Patrice M. Weiss, MD.

Each generation brings a unique set of experiences and expectations. Millennials – or members of “Generation Y,” who comprised 18% of the workforce in 2018 and 0% in 2008 – tend to prefer flexible work hours and communication via technology, she said during a session on navigating generational differences in the workplace during the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

They, along with members of “Generation X” (generally those born between 1962 and 1981) and “Generation Z” (generally those born from 1987 on), tend to be technology savvy, whereas the “Silent Generation” (generally those born between 1925 and 1942) and older members of the “Baby Boomer Generation” (generally those born between 1943 and 1961), may prefer printed communication and phone calls, said Dr. Weiss, chief medical officer at the Carilion Clinic in Roanoke, Va.

“It’s not good, it’s not bad – it’s just the way things are changing,” she said, adding that it’s important to look at the strengths that each generation brings to the workplace.

Importantly, the generational differences also affect patient expectations and therefore should guide physician-patient interactions, she said.

In this video interview, she further discusses how generational differences should be considered in medical practice, and how clinicians can adapt to the changing expectations and different needs of patients from different generations.

“Gen Ys want to communicate with us through technology. They don’t want to pick up the phone and schedule an appointment, they want to be able to go online ... through an app and self-schedule an appointment,” she said. “And they want health care when they want it.

“We as health care providers and health care organizations, we need to meet the needs of each generation ... so what we need to do is really identify what are the needs of all the generations as patients.”

During her presentation, Dr. Weiss further noted that these generational differences present a major challenge with respect to teaching, learning, and communicating.

“Rather than becoming frustrated ... let’s hope that we can ... reach across generations, identify what their strengths are, capitalize on those, and then, as health care providers, be more user and consumer friendly to the generations, particularly the millennials [so] that they have access to us and to information.”

Dr. Weiss said she had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – By 2020, millennials will comprise more than a third of individuals in the workplace, and that has important implications for employment, communication, and education, according to Patrice M. Weiss, MD.

Each generation brings a unique set of experiences and expectations. Millennials – or members of “Generation Y,” who comprised 18% of the workforce in 2018 and 0% in 2008 – tend to prefer flexible work hours and communication via technology, she said during a session on navigating generational differences in the workplace during the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

They, along with members of “Generation X” (generally those born between 1962 and 1981) and “Generation Z” (generally those born from 1987 on), tend to be technology savvy, whereas the “Silent Generation” (generally those born between 1925 and 1942) and older members of the “Baby Boomer Generation” (generally those born between 1943 and 1961), may prefer printed communication and phone calls, said Dr. Weiss, chief medical officer at the Carilion Clinic in Roanoke, Va.

“It’s not good, it’s not bad – it’s just the way things are changing,” she said, adding that it’s important to look at the strengths that each generation brings to the workplace.

Importantly, the generational differences also affect patient expectations and therefore should guide physician-patient interactions, she said.

In this video interview, she further discusses how generational differences should be considered in medical practice, and how clinicians can adapt to the changing expectations and different needs of patients from different generations.

“Gen Ys want to communicate with us through technology. They don’t want to pick up the phone and schedule an appointment, they want to be able to go online ... through an app and self-schedule an appointment,” she said. “And they want health care when they want it.

“We as health care providers and health care organizations, we need to meet the needs of each generation ... so what we need to do is really identify what are the needs of all the generations as patients.”

During her presentation, Dr. Weiss further noted that these generational differences present a major challenge with respect to teaching, learning, and communicating.

“Rather than becoming frustrated ... let’s hope that we can ... reach across generations, identify what their strengths are, capitalize on those, and then, as health care providers, be more user and consumer friendly to the generations, particularly the millennials [so] that they have access to us and to information.”

Dr. Weiss said she had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – By 2020, millennials will comprise more than a third of individuals in the workplace, and that has important implications for employment, communication, and education, according to Patrice M. Weiss, MD.

Each generation brings a unique set of experiences and expectations. Millennials – or members of “Generation Y,” who comprised 18% of the workforce in 2018 and 0% in 2008 – tend to prefer flexible work hours and communication via technology, she said during a session on navigating generational differences in the workplace during the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

They, along with members of “Generation X” (generally those born between 1962 and 1981) and “Generation Z” (generally those born from 1987 on), tend to be technology savvy, whereas the “Silent Generation” (generally those born between 1925 and 1942) and older members of the “Baby Boomer Generation” (generally those born between 1943 and 1961), may prefer printed communication and phone calls, said Dr. Weiss, chief medical officer at the Carilion Clinic in Roanoke, Va.

“It’s not good, it’s not bad – it’s just the way things are changing,” she said, adding that it’s important to look at the strengths that each generation brings to the workplace.

Importantly, the generational differences also affect patient expectations and therefore should guide physician-patient interactions, she said.

In this video interview, she further discusses how generational differences should be considered in medical practice, and how clinicians can adapt to the changing expectations and different needs of patients from different generations.

“Gen Ys want to communicate with us through technology. They don’t want to pick up the phone and schedule an appointment, they want to be able to go online ... through an app and self-schedule an appointment,” she said. “And they want health care when they want it.

“We as health care providers and health care organizations, we need to meet the needs of each generation ... so what we need to do is really identify what are the needs of all the generations as patients.”

During her presentation, Dr. Weiss further noted that these generational differences present a major challenge with respect to teaching, learning, and communicating.

“Rather than becoming frustrated ... let’s hope that we can ... reach across generations, identify what their strengths are, capitalize on those, and then, as health care providers, be more user and consumer friendly to the generations, particularly the millennials [so] that they have access to us and to information.”

Dr. Weiss said she had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – The decision regarding medical versus surgical management of second trimester fetal demise is one that should be shared between the physician and patient, according to Sara W. Prager, MD.

Information transfer between the physician and patient, as opposed to a provider-driven or patient-driven decision-making process, better ensures that “the best possible decision” will be reached, Dr. Prager, director of the family planning division and family planning fellowship at the University of Washington in Seattle, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Engaging the patient in the process – actively involving and supporting her in health care and treatment decision-making activities – is critically important, especially when dealing with pregnancy loss, which involves an acute sense of powerlessness, she said. Patient engagement is essential for respecting her autonomy, enhancing her agency, improving health status, reducing decisional conflict, and improving overall satisfaction.

Shared decision making requires a discussion about how the two approaches compare, particularly with respect to specific complications associated with each, Dr. Prager said, noting that discussion of values also should be encouraged.

Although surgical management is used more often, both approaches are safe and effective, and in the absence of clear contraindications in settings where both medication and a practitioner skilled in dilatation and evacuation are available, patient preference should honored, she said.

In this video interview, Dr. Prager further explains her position. “Using evidence-based medicine to have a shared decision-making process ... is extremely helpful for patients to feel like they have some control in this out-of-control situation where they’re experiencing a pregnancy loss.”

She also discussed how the use of mifepristone plus misoprostol for medical management of second-trimester loss has the potential to improve access.

“This is medication that, because of stigma surrounding abortion, is not always available ... so actually using it for non–abortion-related activities can be a way to help reduce that stigma around the medication itself, and get it into clinical sites, because it really does meaningfully improve management in the second trimester, as well as in the first trimester.”

In fact, the combination can cut nearly in half the amount of time it takes from the start of an induction until the end of the induction process, she said.

Dr. Prager also discussed surgical training resources and how to advocate for patient access to family planning experts who have the appropriate training.

Dr. Prager said she had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – The decision regarding medical versus surgical management of second trimester fetal demise is one that should be shared between the physician and patient, according to Sara W. Prager, MD.

Information transfer between the physician and patient, as opposed to a provider-driven or patient-driven decision-making process, better ensures that “the best possible decision” will be reached, Dr. Prager, director of the family planning division and family planning fellowship at the University of Washington in Seattle, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Engaging the patient in the process – actively involving and supporting her in health care and treatment decision-making activities – is critically important, especially when dealing with pregnancy loss, which involves an acute sense of powerlessness, she said. Patient engagement is essential for respecting her autonomy, enhancing her agency, improving health status, reducing decisional conflict, and improving overall satisfaction.

Shared decision making requires a discussion about how the two approaches compare, particularly with respect to specific complications associated with each, Dr. Prager said, noting that discussion of values also should be encouraged.

Although surgical management is used more often, both approaches are safe and effective, and in the absence of clear contraindications in settings where both medication and a practitioner skilled in dilatation and evacuation are available, patient preference should honored, she said.

In this video interview, Dr. Prager further explains her position. “Using evidence-based medicine to have a shared decision-making process ... is extremely helpful for patients to feel like they have some control in this out-of-control situation where they’re experiencing a pregnancy loss.”

She also discussed how the use of mifepristone plus misoprostol for medical management of second-trimester loss has the potential to improve access.

“This is medication that, because of stigma surrounding abortion, is not always available ... so actually using it for non–abortion-related activities can be a way to help reduce that stigma around the medication itself, and get it into clinical sites, because it really does meaningfully improve management in the second trimester, as well as in the first trimester.”

In fact, the combination can cut nearly in half the amount of time it takes from the start of an induction until the end of the induction process, she said.

Dr. Prager also discussed surgical training resources and how to advocate for patient access to family planning experts who have the appropriate training.

Dr. Prager said she had no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – The decision regarding medical versus surgical management of second trimester fetal demise is one that should be shared between the physician and patient, according to Sara W. Prager, MD.

Information transfer between the physician and patient, as opposed to a provider-driven or patient-driven decision-making process, better ensures that “the best possible decision” will be reached, Dr. Prager, director of the family planning division and family planning fellowship at the University of Washington in Seattle, said at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Engaging the patient in the process – actively involving and supporting her in health care and treatment decision-making activities – is critically important, especially when dealing with pregnancy loss, which involves an acute sense of powerlessness, she said. Patient engagement is essential for respecting her autonomy, enhancing her agency, improving health status, reducing decisional conflict, and improving overall satisfaction.

Shared decision making requires a discussion about how the two approaches compare, particularly with respect to specific complications associated with each, Dr. Prager said, noting that discussion of values also should be encouraged.

Although surgical management is used more often, both approaches are safe and effective, and in the absence of clear contraindications in settings where both medication and a practitioner skilled in dilatation and evacuation are available, patient preference should honored, she said.

In this video interview, Dr. Prager further explains her position. “Using evidence-based medicine to have a shared decision-making process ... is extremely helpful for patients to feel like they have some control in this out-of-control situation where they’re experiencing a pregnancy loss.”

She also discussed how the use of mifepristone plus misoprostol for medical management of second-trimester loss has the potential to improve access.

“This is medication that, because of stigma surrounding abortion, is not always available ... so actually using it for non–abortion-related activities can be a way to help reduce that stigma around the medication itself, and get it into clinical sites, because it really does meaningfully improve management in the second trimester, as well as in the first trimester.”

In fact, the combination can cut nearly in half the amount of time it takes from the start of an induction until the end of the induction process, she said.

Dr. Prager also discussed surgical training resources and how to advocate for patient access to family planning experts who have the appropriate training.

Dr. Prager said she had no relevant financial disclosures.

[email protected]

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

NASHVILLE, TENN. – Is routine induction of labor in a healthy pregnancy at 39 weeks’ gestation a sensible thing to do? Aaron B. Caughey, MD, PhD, discussed this in a video at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

In a healthy pregnancy, with no medical indications for induction of labor, 39-40 weeks’ gestation is a time when there is a relatively low risk of stillbirth, although the risk is not zero, Dr. Caughey explained. The same is true for neonatal death. This gestational age is a time when there is a low risk for respiratory complications and a low risk for meconium.

“This might be a nice time to have a baby,” said Dr. Caughey, professor and chair of the department of obstetrics and gynecology at Oregon Health & Science University, Portland. “The trade-off is intervention. Don’t you increase the risk of C-sections?”

Actually, numerous retrospective studies have shown that there is either no difference or a decreased rate of C-sections with induction of labor at 39-40 weeks’ gestation, compared with expectant management.

These findings led to a prospective, randomized study by William A. Grobman, MD, and associates for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network called the ARRIVE trial (N Engl J Med. 2018;379:513-23). In that trial, the investigators randomized 3,062 women to induction of labor and 3,044 to expectant management. A significantly lower percentage of women in the induction of labor group underwent C-section than did women randomized to expectant management: 19% vs. 22% (relative risk, 0.84; P less than .001) – that is, 16% fewer C-sections. Also, 36% fewer women in the induction of labor group experienced preeclampsia. No significant differences were found between the two groups in terms of neonatal outcomes.

However, this is just one study, Dr. Caughey noted. What does is mean for a local community hospital? What does it mean for a busy private obstetrics practice?

Watch this video for his answer.



 

NASHVILLE, TENN. – Is routine induction of labor in a healthy pregnancy at 39 weeks’ gestation a sensible thing to do? Aaron B. Caughey, MD, PhD, discussed this in a video at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

In a healthy pregnancy, with no medical indications for induction of labor, 39-40 weeks’ gestation is a time when there is a relatively low risk of stillbirth, although the risk is not zero, Dr. Caughey explained. The same is true for neonatal death. This gestational age is a time when there is a low risk for respiratory complications and a low risk for meconium.

“This might be a nice time to have a baby,” said Dr. Caughey, professor and chair of the department of obstetrics and gynecology at Oregon Health & Science University, Portland. “The trade-off is intervention. Don’t you increase the risk of C-sections?”

Actually, numerous retrospective studies have shown that there is either no difference or a decreased rate of C-sections with induction of labor at 39-40 weeks’ gestation, compared with expectant management.

These findings led to a prospective, randomized study by William A. Grobman, MD, and associates for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network called the ARRIVE trial (N Engl J Med. 2018;379:513-23). In that trial, the investigators randomized 3,062 women to induction of labor and 3,044 to expectant management. A significantly lower percentage of women in the induction of labor group underwent C-section than did women randomized to expectant management: 19% vs. 22% (relative risk, 0.84; P less than .001) – that is, 16% fewer C-sections. Also, 36% fewer women in the induction of labor group experienced preeclampsia. No significant differences were found between the two groups in terms of neonatal outcomes.

However, this is just one study, Dr. Caughey noted. What does is mean for a local community hospital? What does it mean for a busy private obstetrics practice?

Watch this video for his answer.



 

NASHVILLE, TENN. – Is routine induction of labor in a healthy pregnancy at 39 weeks’ gestation a sensible thing to do? Aaron B. Caughey, MD, PhD, discussed this in a video at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

In a healthy pregnancy, with no medical indications for induction of labor, 39-40 weeks’ gestation is a time when there is a relatively low risk of stillbirth, although the risk is not zero, Dr. Caughey explained. The same is true for neonatal death. This gestational age is a time when there is a low risk for respiratory complications and a low risk for meconium.

“This might be a nice time to have a baby,” said Dr. Caughey, professor and chair of the department of obstetrics and gynecology at Oregon Health & Science University, Portland. “The trade-off is intervention. Don’t you increase the risk of C-sections?”

Actually, numerous retrospective studies have shown that there is either no difference or a decreased rate of C-sections with induction of labor at 39-40 weeks’ gestation, compared with expectant management.

These findings led to a prospective, randomized study by William A. Grobman, MD, and associates for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network called the ARRIVE trial (N Engl J Med. 2018;379:513-23). In that trial, the investigators randomized 3,062 women to induction of labor and 3,044 to expectant management. A significantly lower percentage of women in the induction of labor group underwent C-section than did women randomized to expectant management: 19% vs. 22% (relative risk, 0.84; P less than .001) – that is, 16% fewer C-sections. Also, 36% fewer women in the induction of labor group experienced preeclampsia. No significant differences were found between the two groups in terms of neonatal outcomes.

However, this is just one study, Dr. Caughey noted. What does is mean for a local community hospital? What does it mean for a busy private obstetrics practice?

Watch this video for his answer.



 

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

[email protected]

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

[email protected]

BALTIMORE – Ultrasound can be a very effective way to track early nodal metastasis in patients with high-stage cutaneous squamous cell carcinomas, and at a fraction of the cost of other imaging modalities.

Bogdanhoda/Thinkstock

The technique shows not only abnormal variations in the shape of nodes, but changes in the core and outer density, and vascular patterns, Emily Ruiz, MD, said at the annual meeting of the American College of Mohs Surgery. And over a 2-year surveillance period, this costs thousands less than radiation-based imaging.

Dr. Ruiz, director of the High-Risk Skin Cancer Clinic at Dana-Farber/Brigham and Women’s Cancer Center, Boston, said the standard imaging technique at that center used to be serial CT scans performed at diagnosis and every 6 months thereafter, for 2 years. But recently, the protocol changed: Ultrasound is now the preferred technique.

“The big problem with CT in this earlier disease, is that it can only identify the nodes that are enlarged, and doesn’t tell us anything about the etiology. Ultrasound, on the other hand, looks at a number of different features of the node.”

Tracking high-risk squamous cell carcinoma patients is a must, she said. “About 4% of people diagnosed with high-risk SCC will develop nodal metastases, and 1.5% of those will die from disease-specific death,” most often from locoregional disease. “So it’s critical to identify nodal diseases early as possible. Earlier identification leads to better outcomes.” Ultrasound simply provides more information about nodal metastasis, Dr. Ruiz added.

Michele G. Sullivan/MDedge News

Cost is another consideration, Dr. Ruiz said. Five CT scans conducted over the recommended 2 years of follow-up will run about $5,000. Five scans with magnetic resonance imaging come in at about $6,500. PET CT is, of course, the most expensive, racking up a national average cost of $28,500 for five scans.

Ultrasound is amazingly inexpensive, Dr. Ruiz said. The national average cost of one scan is around $180, bringing the 2-year cost of five surveillance scans to $900.

Finally, clinicians and patients should consider the potential impact of repeated radiation exposure. “This can really add up over the follow-up period. Because there’s a 10-year latency period for these cancers, this might not be an issue for our older patients, but it really is something to consider in younger ones. “

However, she acknowledged that it’s not a completely rosy picture.

“Ultrasound is very user dependent, but we do think that by putting this in the hands of dermatologists with special training, we can solve this issue. In Europe, ultrasound’s very high sensitivity and specificity, combined with clinical exams, really improves disease detection.”

Unfortunately, at this point, anyone who wants to learn the technique has to go to Europe. “I trained in Germany, where I took a standard 3-day course, did 250 supervised scans, and completed an exam. I realize that’s unrealistic for most people,” she said. But a training protocol is being developed at Brigham and Women’s, under the auspices of the institution’s imaging experts, who felt that 3 days and 250 supervised scans was excessive. The Brigham and Women’s program comprises 8 hours of didactic training and at least 30 supervised scans with at least three abnormalities correctly identified, and will be put into place soon, Dr. Ruiz said.

The biggest obstacle to large-scale adoption of this protocol is data – there are not a lot, at least now.

“We are working on that, too. In conjunction with the Skin Cancer Foundation, we’re launching a prospective study. We want to recruit 80 patients with T2B/T3 cutaneous SCCs. They get both and ultrasound and a CT scan at diagnosis and every 6 months for 2 years,” she said.

[email protected]

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.