MINNEAPOLIS, MINN. – Indoor tanning is a significant contributor to the U.S. skin cancer epidemic and represents a 100% preventable source of exposure to these cancers. Understanding exactly who is using indoor tanning – and why – can provide insight and leverage to help change behavior, according to Cindy Firkins Smith, MD, adjunct professor of dermatology at the University of Minnesota, Minneapolis.

Dr. Smith noted that the typical indoor tanning bed user is female and between 17 and 30 years old. Other aspects of her lifestyle may be unhealthy; for example, she may smoke cigarettes, have an unhealthy pattern of alcohol consumption, and make unhealthy food choices (Cancer Causes Control 2006 June. doi:10.1007/s10552-005-0453-9). She also is likely to watch beauty-focused reality TV shows (J Am Acad Dermatol 2013 May. doi:10.1016/j.jaad.2012.09.055) and is likely to objectify her own body, seeing it as something to be viewed and judged (Arch Dermatol 2009 Sep 1. doi:10.1001/archdermatol.2009.190).

©Vidmantas Goldbergas/Thinkstock

Tanning is a behavior that provides relaxation and positive emotions, and she receives support for this behavior from family and friends. “Tanning often starts with mom, which is one reason that parental permission legislation doesn’t work,” she said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Smith said that up to 30 million people tan indoors every year. Rates of tanning for teenage girls are very high: up to 40% of American teenagers use indoor tanning, and 20%-30% of all 18- to 29-year-olds have used a tanning bed in the previous year (Jama Dermatol 2014 April doi: 10.1001/jamadermatol.2013.6896).

The ubiquity of tanning salons contributes to the problem, said Dr. Smith. “More is not better; in the largest U.S. cities, tanning salons outnumber [both] Starbucks and McDonald’s,” she said, noting that studies have shown that both proximity to tanning salons and the low cost of tanning encourage their use (Am J Prev Med. 2009 Mar 36[3]:243-6).

A 2015 study surveyed 125 colleges, finding that 48% had indoor tanning facilities in their campus or off-campus housing. College cash cards were acceptable payment at 14.4% of colleges, and 96% of off-campus housing facilities that offered tanning provided it as a free “perk” to residents (JAMA Dermatol 2015 Jan. doi: 10.1001/jamadermatol.2014.3590).

Further, some data suggest that tanning really can be addictive for some patients. Ultraviolet light exposure has been shown to “light up” pleasure centers in PET-CT studies, and some frequent tanners report relaxation and pleasure from tanning as well as craving and feelings of withdrawal when they miss sessions. Dr. Smith said she does not hesitate to refer teen patients to mental health providers if there are concerns about mood and depression.

Having an understanding of patient motivations to tan can help in getting patients to take steps toward change, said Dr. Smith. “What can we do? We can actually do a lot. We have a lot more influence than we think we do.”

At the level of the individual patient, just opening up a conversation can make a big difference. “We assume we know why teenagers go to a tanning booth. But do we? When you notice a young woman who’s been to a tanning booth, ask why,” using a nonjudgmental approach to begin a dialogue about the near-term and long-term dangers of tanning. A positive approach is key, noted Dr. Smith. “Focusing on the benefits of avoiding UV tanning is more effective than a heavy reliance on scare tactics,” she said. Also, “multiple interventions work better.”

Before-and-after photos of celebrities whose appearance has been affected by photoaging can be effective. Another tactic with a more positive spin is to share images of celebrities who have chosen not to tan and who celebrate their fair skin. These conversations are particularly important at prom time, peak tanning season for many young women, said Dr. Smith. She has a portfolio of photos showing fair-skinned women wearing high-contrast gowns, which she says are more flattering for pale skin than white or nude colors.

For patients who still want that tan look, “Tanning for reasons of appearance can be satisfied with sunless tanners,” said Dr. Smith. The most common ingredient in sunless tanners is dihydroxyacetone (DHA), which was approved in the 1970s for topical use. However, the Food and Drug Administration issued a warning in 2011 about spray tanning, noting that the “industry has not provided safety data to FDA in order for the agency to consider approving it for … ‘misting’ from tanning booths.” The FDA’s specific concern had to do with the unknown safety of ingestion, inhalation, and mucous membrane exposure that can result from spray tanning.

Moving to the legislative and policy level, change can be achieved when stakeholders band together to “ban the tan,” said Dr. Smith. “The best way to do it is with a village. It really takes a lot of people to do this.”

There are solid epidemiologic and economic reasons to focus on the skin cancer epidemic, said Dr. Smith. Skin cancer is now the most common cancer in the United States, and more new cases “are diagnosed each year than breast, prostate, lung, and colon cancers combined,” she said. Of nonmelanoma skin cancers, 90% are thought to be UV-related, and “the vast majority of mutations found in melanoma are caused by UV radiation.”

Skin cancers cost the United States over $8 billion annually, and although promising new immunotherapies are extending the lives of those with melanoma, these treatments cost hundreds of thousands of dollars a year. “This type of treatment is unaffordable for our system,” said Dr. Smith.

Progress is being made, she said, despite industry opposition. Individual states have regulated or banned tanning for minors, and at the federal level, tanning beds are now considered by the FDA to be Class II (moderate-risk) medical devices, a step up from their previous classification as the lowest-risk Class I devices, “The same as a tongue blade,” she said.

Dr. Smith had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

MINNEAPOLIS, MINN. – Indoor tanning is a significant contributor to the U.S. skin cancer epidemic and represents a 100% preventable source of exposure to these cancers. Understanding exactly who is using indoor tanning – and why – can provide insight and leverage to help change behavior, according to Cindy Firkins Smith, MD, adjunct professor of dermatology at the University of Minnesota, Minneapolis.

Dr. Smith noted that the typical indoor tanning bed user is female and between 17 and 30 years old. Other aspects of her lifestyle may be unhealthy; for example, she may smoke cigarettes, have an unhealthy pattern of alcohol consumption, and make unhealthy food choices (Cancer Causes Control 2006 June. doi:10.1007/s10552-005-0453-9). She also is likely to watch beauty-focused reality TV shows (J Am Acad Dermatol 2013 May. doi:10.1016/j.jaad.2012.09.055) and is likely to objectify her own body, seeing it as something to be viewed and judged (Arch Dermatol 2009 Sep 1. doi:10.1001/archdermatol.2009.190).

©Vidmantas Goldbergas/Thinkstock

Tanning is a behavior that provides relaxation and positive emotions, and she receives support for this behavior from family and friends. “Tanning often starts with mom, which is one reason that parental permission legislation doesn’t work,” she said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Smith said that up to 30 million people tan indoors every year. Rates of tanning for teenage girls are very high: up to 40% of American teenagers use indoor tanning, and 20%-30% of all 18- to 29-year-olds have used a tanning bed in the previous year (Jama Dermatol 2014 April doi: 10.1001/jamadermatol.2013.6896).

The ubiquity of tanning salons contributes to the problem, said Dr. Smith. “More is not better; in the largest U.S. cities, tanning salons outnumber [both] Starbucks and McDonald’s,” she said, noting that studies have shown that both proximity to tanning salons and the low cost of tanning encourage their use (Am J Prev Med. 2009 Mar 36[3]:243-6).

A 2015 study surveyed 125 colleges, finding that 48% had indoor tanning facilities in their campus or off-campus housing. College cash cards were acceptable payment at 14.4% of colleges, and 96% of off-campus housing facilities that offered tanning provided it as a free “perk” to residents (JAMA Dermatol 2015 Jan. doi: 10.1001/jamadermatol.2014.3590).

Further, some data suggest that tanning really can be addictive for some patients. Ultraviolet light exposure has been shown to “light up” pleasure centers in PET-CT studies, and some frequent tanners report relaxation and pleasure from tanning as well as craving and feelings of withdrawal when they miss sessions. Dr. Smith said she does not hesitate to refer teen patients to mental health providers if there are concerns about mood and depression.

Having an understanding of patient motivations to tan can help in getting patients to take steps toward change, said Dr. Smith. “What can we do? We can actually do a lot. We have a lot more influence than we think we do.”

At the level of the individual patient, just opening up a conversation can make a big difference. “We assume we know why teenagers go to a tanning booth. But do we? When you notice a young woman who’s been to a tanning booth, ask why,” using a nonjudgmental approach to begin a dialogue about the near-term and long-term dangers of tanning. A positive approach is key, noted Dr. Smith. “Focusing on the benefits of avoiding UV tanning is more effective than a heavy reliance on scare tactics,” she said. Also, “multiple interventions work better.”

Before-and-after photos of celebrities whose appearance has been affected by photoaging can be effective. Another tactic with a more positive spin is to share images of celebrities who have chosen not to tan and who celebrate their fair skin. These conversations are particularly important at prom time, peak tanning season for many young women, said Dr. Smith. She has a portfolio of photos showing fair-skinned women wearing high-contrast gowns, which she says are more flattering for pale skin than white or nude colors.

For patients who still want that tan look, “Tanning for reasons of appearance can be satisfied with sunless tanners,” said Dr. Smith. The most common ingredient in sunless tanners is dihydroxyacetone (DHA), which was approved in the 1970s for topical use. However, the Food and Drug Administration issued a warning in 2011 about spray tanning, noting that the “industry has not provided safety data to FDA in order for the agency to consider approving it for … ‘misting’ from tanning booths.” The FDA’s specific concern had to do with the unknown safety of ingestion, inhalation, and mucous membrane exposure that can result from spray tanning.

Moving to the legislative and policy level, change can be achieved when stakeholders band together to “ban the tan,” said Dr. Smith. “The best way to do it is with a village. It really takes a lot of people to do this.”

There are solid epidemiologic and economic reasons to focus on the skin cancer epidemic, said Dr. Smith. Skin cancer is now the most common cancer in the United States, and more new cases “are diagnosed each year than breast, prostate, lung, and colon cancers combined,” she said. Of nonmelanoma skin cancers, 90% are thought to be UV-related, and “the vast majority of mutations found in melanoma are caused by UV radiation.”

Skin cancers cost the United States over $8 billion annually, and although promising new immunotherapies are extending the lives of those with melanoma, these treatments cost hundreds of thousands of dollars a year. “This type of treatment is unaffordable for our system,” said Dr. Smith.

Progress is being made, she said, despite industry opposition. Individual states have regulated or banned tanning for minors, and at the federal level, tanning beds are now considered by the FDA to be Class II (moderate-risk) medical devices, a step up from their previous classification as the lowest-risk Class I devices, “The same as a tongue blade,” she said.

Dr. Smith had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

MINNEAPOLIS, MINN. – Indoor tanning is a significant contributor to the U.S. skin cancer epidemic and represents a 100% preventable source of exposure to these cancers. Understanding exactly who is using indoor tanning – and why – can provide insight and leverage to help change behavior, according to Cindy Firkins Smith, MD, adjunct professor of dermatology at the University of Minnesota, Minneapolis.

Dr. Smith noted that the typical indoor tanning bed user is female and between 17 and 30 years old. Other aspects of her lifestyle may be unhealthy; for example, she may smoke cigarettes, have an unhealthy pattern of alcohol consumption, and make unhealthy food choices (Cancer Causes Control 2006 June. doi:10.1007/s10552-005-0453-9). She also is likely to watch beauty-focused reality TV shows (J Am Acad Dermatol 2013 May. doi:10.1016/j.jaad.2012.09.055) and is likely to objectify her own body, seeing it as something to be viewed and judged (Arch Dermatol 2009 Sep 1. doi:10.1001/archdermatol.2009.190).

©Vidmantas Goldbergas/Thinkstock

Tanning is a behavior that provides relaxation and positive emotions, and she receives support for this behavior from family and friends. “Tanning often starts with mom, which is one reason that parental permission legislation doesn’t work,” she said at the annual meeting of the Society for Pediatric Dermatology.

Dr. Smith said that up to 30 million people tan indoors every year. Rates of tanning for teenage girls are very high: up to 40% of American teenagers use indoor tanning, and 20%-30% of all 18- to 29-year-olds have used a tanning bed in the previous year (Jama Dermatol 2014 April doi: 10.1001/jamadermatol.2013.6896).

The ubiquity of tanning salons contributes to the problem, said Dr. Smith. “More is not better; in the largest U.S. cities, tanning salons outnumber [both] Starbucks and McDonald’s,” she said, noting that studies have shown that both proximity to tanning salons and the low cost of tanning encourage their use (Am J Prev Med. 2009 Mar 36[3]:243-6).

A 2015 study surveyed 125 colleges, finding that 48% had indoor tanning facilities in their campus or off-campus housing. College cash cards were acceptable payment at 14.4% of colleges, and 96% of off-campus housing facilities that offered tanning provided it as a free “perk” to residents (JAMA Dermatol 2015 Jan. doi: 10.1001/jamadermatol.2014.3590).

Further, some data suggest that tanning really can be addictive for some patients. Ultraviolet light exposure has been shown to “light up” pleasure centers in PET-CT studies, and some frequent tanners report relaxation and pleasure from tanning as well as craving and feelings of withdrawal when they miss sessions. Dr. Smith said she does not hesitate to refer teen patients to mental health providers if there are concerns about mood and depression.

Having an understanding of patient motivations to tan can help in getting patients to take steps toward change, said Dr. Smith. “What can we do? We can actually do a lot. We have a lot more influence than we think we do.”

At the level of the individual patient, just opening up a conversation can make a big difference. “We assume we know why teenagers go to a tanning booth. But do we? When you notice a young woman who’s been to a tanning booth, ask why,” using a nonjudgmental approach to begin a dialogue about the near-term and long-term dangers of tanning. A positive approach is key, noted Dr. Smith. “Focusing on the benefits of avoiding UV tanning is more effective than a heavy reliance on scare tactics,” she said. Also, “multiple interventions work better.”

Before-and-after photos of celebrities whose appearance has been affected by photoaging can be effective. Another tactic with a more positive spin is to share images of celebrities who have chosen not to tan and who celebrate their fair skin. These conversations are particularly important at prom time, peak tanning season for many young women, said Dr. Smith. She has a portfolio of photos showing fair-skinned women wearing high-contrast gowns, which she says are more flattering for pale skin than white or nude colors.

For patients who still want that tan look, “Tanning for reasons of appearance can be satisfied with sunless tanners,” said Dr. Smith. The most common ingredient in sunless tanners is dihydroxyacetone (DHA), which was approved in the 1970s for topical use. However, the Food and Drug Administration issued a warning in 2011 about spray tanning, noting that the “industry has not provided safety data to FDA in order for the agency to consider approving it for … ‘misting’ from tanning booths.” The FDA’s specific concern had to do with the unknown safety of ingestion, inhalation, and mucous membrane exposure that can result from spray tanning.

Moving to the legislative and policy level, change can be achieved when stakeholders band together to “ban the tan,” said Dr. Smith. “The best way to do it is with a village. It really takes a lot of people to do this.”

There are solid epidemiologic and economic reasons to focus on the skin cancer epidemic, said Dr. Smith. Skin cancer is now the most common cancer in the United States, and more new cases “are diagnosed each year than breast, prostate, lung, and colon cancers combined,” she said. Of nonmelanoma skin cancers, 90% are thought to be UV-related, and “the vast majority of mutations found in melanoma are caused by UV radiation.”

Skin cancers cost the United States over $8 billion annually, and although promising new immunotherapies are extending the lives of those with melanoma, these treatments cost hundreds of thousands of dollars a year. “This type of treatment is unaffordable for our system,” said Dr. Smith.

Progress is being made, she said, despite industry opposition. Individual states have regulated or banned tanning for minors, and at the federal level, tanning beds are now considered by the FDA to be Class II (moderate-risk) medical devices, a step up from their previous classification as the lowest-risk Class I devices, “The same as a tongue blade,” she said.

Dr. Smith had no relevant financial disclosures.

[email protected]

On Twitter @karioakes

Talk about sex with patients and their families, and have ongoing, age-appropriate discussions over the course of a patient’s development, urges an updated clinical report from the American Academy of Pediatrics.

Citing gaps in school-based sexuality education programs nationally, the report calls on you to do more to ensure patients have adequate information about preventing teen pregnancy, HIV, and other sexually transmitted diseases.

The report will be seen as good news by pediatricians and others, lead author and chairperson of the AAP Committee on Adolescence, Cora Collette Breuner, MD, said in an interview.

“Pediatricians, parents, and school administrators have been asking for this updated information,” Dr. Breuner said. “Pediatricians want more clarification, more resources, and more evidence for what they are already doing.”

The report, Sexuality Education for Children and Adolescents, is published online and is free to the general public. It is the AAP’s first update on sexuality education since 2001, and includes lists of resources specifically for clinicians, parents, and schools.

“We found that only one out of three adolescent patients receive any information on sexuality from their pediatrician, and if they did, the conversation lasted less than 40 seconds,” Dr. Breuner said, citing a review of health maintenance visits. Dr. Breuneris also a professor of adolescent medicine at the Seattle Children’s Hospital.

Even if less than a minute is all that you have to devote to discussing sexual health with a patient, Dr. Breuner said it’s well worth it, in part because it can help prevent teens from turning to often unreliable sources of information on the Internet, and because it can help fill the gap for teens whose families don’t want to address the topic, or whose schools do not offer programs to address it.

“The conversations should cover a range of aspects of sexual health, including healthy sexual development, interpersonal and consensual relationships, affection, intimacy, and body image,” Dr. Breuner said. “The research shows that just talking about abstinence is not enough.”

Such conversations also should address sexual anatomy and reproduction, sexually transmitted infections, sexual orientation, gender identity, abstinence, contraception, and reproductive rights and responsibilities, according to the report.

The report cites a meta-analysis finding that parents who were trained on how to effectively communicate about sex with their adolescents had better conversations on the subject than parents who were not. Such conversations correlated with a delay in teen sexual debut and an increased use of contraception and condoms.

Talking with young persons about their sexuality is also a way to help screen them for depression and suicidality, Dr. Breuner said. “These issues can often be uncovered when talking with kids about sexuality, particularly with those who are questioning their sexual identity.”

The report also suggests pediatricians discuss issues of physical, cognitive, and psychosexual development with parents of young children during well visits over time.

Earlier this year, in conjunction with the North American Society of Pediatric and Adolescent Gynecology, the AAP issued its first clinical guidance on addressing sexual health in adolescents with special needs (Pediatrics. 2006. doi: 10.1542/peds.2006-1115).

Neither Dr. Breuner nor the authors of the clinical report had any relevant financial disclosures.

[email protected]

On Twitter @whitneymcknight

Talk about sex with patients and their families, and have ongoing, age-appropriate discussions over the course of a patient’s development, urges an updated clinical report from the American Academy of Pediatrics.

Citing gaps in school-based sexuality education programs nationally, the report calls on you to do more to ensure patients have adequate information about preventing teen pregnancy, HIV, and other sexually transmitted diseases.

The report will be seen as good news by pediatricians and others, lead author and chairperson of the AAP Committee on Adolescence, Cora Collette Breuner, MD, said in an interview.

“Pediatricians, parents, and school administrators have been asking for this updated information,” Dr. Breuner said. “Pediatricians want more clarification, more resources, and more evidence for what they are already doing.”

The report, Sexuality Education for Children and Adolescents, is published online and is free to the general public. It is the AAP’s first update on sexuality education since 2001, and includes lists of resources specifically for clinicians, parents, and schools.

“We found that only one out of three adolescent patients receive any information on sexuality from their pediatrician, and if they did, the conversation lasted less than 40 seconds,” Dr. Breuner said, citing a review of health maintenance visits. Dr. Breuneris also a professor of adolescent medicine at the Seattle Children’s Hospital.

Even if less than a minute is all that you have to devote to discussing sexual health with a patient, Dr. Breuner said it’s well worth it, in part because it can help prevent teens from turning to often unreliable sources of information on the Internet, and because it can help fill the gap for teens whose families don’t want to address the topic, or whose schools do not offer programs to address it.

“The conversations should cover a range of aspects of sexual health, including healthy sexual development, interpersonal and consensual relationships, affection, intimacy, and body image,” Dr. Breuner said. “The research shows that just talking about abstinence is not enough.”

Such conversations also should address sexual anatomy and reproduction, sexually transmitted infections, sexual orientation, gender identity, abstinence, contraception, and reproductive rights and responsibilities, according to the report.

The report cites a meta-analysis finding that parents who were trained on how to effectively communicate about sex with their adolescents had better conversations on the subject than parents who were not. Such conversations correlated with a delay in teen sexual debut and an increased use of contraception and condoms.

Talking with young persons about their sexuality is also a way to help screen them for depression and suicidality, Dr. Breuner said. “These issues can often be uncovered when talking with kids about sexuality, particularly with those who are questioning their sexual identity.”

The report also suggests pediatricians discuss issues of physical, cognitive, and psychosexual development with parents of young children during well visits over time.

Earlier this year, in conjunction with the North American Society of Pediatric and Adolescent Gynecology, the AAP issued its first clinical guidance on addressing sexual health in adolescents with special needs (Pediatrics. 2006. doi: 10.1542/peds.2006-1115).

Neither Dr. Breuner nor the authors of the clinical report had any relevant financial disclosures.

[email protected]

On Twitter @whitneymcknight

Talk about sex with patients and their families, and have ongoing, age-appropriate discussions over the course of a patient’s development, urges an updated clinical report from the American Academy of Pediatrics.

Citing gaps in school-based sexuality education programs nationally, the report calls on you to do more to ensure patients have adequate information about preventing teen pregnancy, HIV, and other sexually transmitted diseases.

The report will be seen as good news by pediatricians and others, lead author and chairperson of the AAP Committee on Adolescence, Cora Collette Breuner, MD, said in an interview.

“Pediatricians, parents, and school administrators have been asking for this updated information,” Dr. Breuner said. “Pediatricians want more clarification, more resources, and more evidence for what they are already doing.”

The report, Sexuality Education for Children and Adolescents, is published online and is free to the general public. It is the AAP’s first update on sexuality education since 2001, and includes lists of resources specifically for clinicians, parents, and schools.

“We found that only one out of three adolescent patients receive any information on sexuality from their pediatrician, and if they did, the conversation lasted less than 40 seconds,” Dr. Breuner said, citing a review of health maintenance visits. Dr. Breuneris also a professor of adolescent medicine at the Seattle Children’s Hospital.

Even if less than a minute is all that you have to devote to discussing sexual health with a patient, Dr. Breuner said it’s well worth it, in part because it can help prevent teens from turning to often unreliable sources of information on the Internet, and because it can help fill the gap for teens whose families don’t want to address the topic, or whose schools do not offer programs to address it.

“The conversations should cover a range of aspects of sexual health, including healthy sexual development, interpersonal and consensual relationships, affection, intimacy, and body image,” Dr. Breuner said. “The research shows that just talking about abstinence is not enough.”

Such conversations also should address sexual anatomy and reproduction, sexually transmitted infections, sexual orientation, gender identity, abstinence, contraception, and reproductive rights and responsibilities, according to the report.

The report cites a meta-analysis finding that parents who were trained on how to effectively communicate about sex with their adolescents had better conversations on the subject than parents who were not. Such conversations correlated with a delay in teen sexual debut and an increased use of contraception and condoms.

Talking with young persons about their sexuality is also a way to help screen them for depression and suicidality, Dr. Breuner said. “These issues can often be uncovered when talking with kids about sexuality, particularly with those who are questioning their sexual identity.”

The report also suggests pediatricians discuss issues of physical, cognitive, and psychosexual development with parents of young children during well visits over time.

Earlier this year, in conjunction with the North American Society of Pediatric and Adolescent Gynecology, the AAP issued its first clinical guidance on addressing sexual health in adolescents with special needs (Pediatrics. 2006. doi: 10.1542/peds.2006-1115).

Neither Dr. Breuner nor the authors of the clinical report had any relevant financial disclosures.

[email protected]

On Twitter @whitneymcknight

Evidence summary

A 2014 systematic review included 8 RCTs in adults (3954 patients) and one RCT in children (669 patients) with influenza and compared time to alleviation of symptoms with oseltamivir and placebo.¹ Symptoms were defined as local (nasal discharge, dry cough, sore throat) and systemic (fever, myalgia, headache, fatigue). Methodology for diagnosis varied by trial.

Oral oseltamivir (75, 150, or 300 mg for 5 to 10 days) reduced time to first alleviation of symptoms by 17 hours (95% confidence interval [CI], 8.4-25 hours) compared with placebo for adults and 29 hours (95% CI, 12-47 hours) for the otherwise healthy children.

The systematic review also included 2 RCTs involving 660 children with chronic asthma who received treatment with oseltamivir. Researchers found no reduction in time to symptom alleviation with the oseltamivir.

Treatment with oseltamivir increased the risk of nausea (number needed to harm [NNH]=28) and vomiting (NNH=22) in adults and the risk of vomiting (NNH=19) in children. Sources of bias included industry sponsorship of all trials, differing placebo components, inadequate recruitment, and use of other medication.

Shorter fever duration?

A 2012 meta-analysis of 6 observational studies (5842 patients) compared the effect of oral oseltamivir with no treatment on duration of signs and symptoms (definition not given) in patients with influenza (method of diagnosis not stated).² Oseltamivir reduced fever duration by 33 hours (95% CI, 21-45 hours) compared with no treatment.

The authors describe the evidence as being of very low quality because of study heterogeneity, lack of control for confounding variables, selection bias, and study sources (many unpublished industry studies).

There’s benefit even with late Tx

A 2014 double-blind RCT, not included in the previously described reviews, of 130 adults and 1070 children with a positive rapid influenza test examined the effect of oseltamivir and placebo on symptom duration.³ Research assistants visited participants at home each day until patients were asymptomatic for 7 consecutive days.

Treatment with oseltamivir reduced symptom duration by a median of one day compared with no treatment (hazard ratio=0.87; 95% CI, 0.79-0.95). This benefit was observed regardless of whether treatment was initiated fewer or more than 48 hours after symptom onset. One notable limitation was failure to control for paracetamol (acetaminophen) usage, a possible confounder for duration of symptoms, such as fever.

Evidence summary

A 2014 systematic review included 8 RCTs in adults (3954 patients) and one RCT in children (669 patients) with influenza and compared time to alleviation of symptoms with oseltamivir and placebo.¹ Symptoms were defined as local (nasal discharge, dry cough, sore throat) and systemic (fever, myalgia, headache, fatigue). Methodology for diagnosis varied by trial.

Oral oseltamivir (75, 150, or 300 mg for 5 to 10 days) reduced time to first alleviation of symptoms by 17 hours (95% confidence interval [CI], 8.4-25 hours) compared with placebo for adults and 29 hours (95% CI, 12-47 hours) for the otherwise healthy children.

The systematic review also included 2 RCTs involving 660 children with chronic asthma who received treatment with oseltamivir. Researchers found no reduction in time to symptom alleviation with the oseltamivir.

Treatment with oseltamivir increased the risk of nausea (number needed to harm [NNH]=28) and vomiting (NNH=22) in adults and the risk of vomiting (NNH=19) in children. Sources of bias included industry sponsorship of all trials, differing placebo components, inadequate recruitment, and use of other medication.

Shorter fever duration?

A 2012 meta-analysis of 6 observational studies (5842 patients) compared the effect of oral oseltamivir with no treatment on duration of signs and symptoms (definition not given) in patients with influenza (method of diagnosis not stated).² Oseltamivir reduced fever duration by 33 hours (95% CI, 21-45 hours) compared with no treatment.

The authors describe the evidence as being of very low quality because of study heterogeneity, lack of control for confounding variables, selection bias, and study sources (many unpublished industry studies).

There’s benefit even with late Tx

A 2014 double-blind RCT, not included in the previously described reviews, of 130 adults and 1070 children with a positive rapid influenza test examined the effect of oseltamivir and placebo on symptom duration.³ Research assistants visited participants at home each day until patients were asymptomatic for 7 consecutive days.

Treatment with oseltamivir reduced symptom duration by a median of one day compared with no treatment (hazard ratio=0.87; 95% CI, 0.79-0.95). This benefit was observed regardless of whether treatment was initiated fewer or more than 48 hours after symptom onset. One notable limitation was failure to control for paracetamol (acetaminophen) usage, a possible confounder for duration of symptoms, such as fever.

Evidence summary

A 2014 systematic review included 8 RCTs in adults (3954 patients) and one RCT in children (669 patients) with influenza and compared time to alleviation of symptoms with oseltamivir and placebo.¹ Symptoms were defined as local (nasal discharge, dry cough, sore throat) and systemic (fever, myalgia, headache, fatigue). Methodology for diagnosis varied by trial.

Oral oseltamivir (75, 150, or 300 mg for 5 to 10 days) reduced time to first alleviation of symptoms by 17 hours (95% confidence interval [CI], 8.4-25 hours) compared with placebo for adults and 29 hours (95% CI, 12-47 hours) for the otherwise healthy children.

The systematic review also included 2 RCTs involving 660 children with chronic asthma who received treatment with oseltamivir. Researchers found no reduction in time to symptom alleviation with the oseltamivir.

Treatment with oseltamivir increased the risk of nausea (number needed to harm [NNH]=28) and vomiting (NNH=22) in adults and the risk of vomiting (NNH=19) in children. Sources of bias included industry sponsorship of all trials, differing placebo components, inadequate recruitment, and use of other medication.

Shorter fever duration?

A 2012 meta-analysis of 6 observational studies (5842 patients) compared the effect of oral oseltamivir with no treatment on duration of signs and symptoms (definition not given) in patients with influenza (method of diagnosis not stated).² Oseltamivir reduced fever duration by 33 hours (95% CI, 21-45 hours) compared with no treatment.

The authors describe the evidence as being of very low quality because of study heterogeneity, lack of control for confounding variables, selection bias, and study sources (many unpublished industry studies).

There’s benefit even with late Tx

A 2014 double-blind RCT, not included in the previously described reviews, of 130 adults and 1070 children with a positive rapid influenza test examined the effect of oseltamivir and placebo on symptom duration.³ Research assistants visited participants at home each day until patients were asymptomatic for 7 consecutive days.

Treatment with oseltamivir reduced symptom duration by a median of one day compared with no treatment (hazard ratio=0.87; 95% CI, 0.79-0.95). This benefit was observed regardless of whether treatment was initiated fewer or more than 48 hours after symptom onset. One notable limitation was failure to control for paracetamol (acetaminophen) usage, a possible confounder for duration of symptoms, such as fever.

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

Cancer patient receiving

chemotherapy

Photo by Rhoda Baer

Malignant and non-malignant blood disorders cost 31 European countries a total of €23 billion in 2012, according to a pair of papers published in The Lancet Haematology.

Healthcare costs accounted for €16 billion of the total costs, with €7 billion for hospital inpatient care and €4 billion for medications.

Informal care (from friends and relatives) cost €1.6 billion, productivity losses due to mortality cost €2.5 billion, and morbidity cost €3 billion.

Researchers determined these figures by analyzing data from international health organizations (WHO and EUROSTAT), as well as national ministries of health and statistical institutes.

The team estimated the economic burden of malignant and non-malignant blood disorders in 2012 for all 28 countries in the European Union (EU), as well as Iceland, Norway, and Switzerland.

The costs considered were healthcare costs (primary care, accident and emergency care, hospital inpatient and outpatient care, and drugs), informal care costs (from friends and relatives), and productivity losses (due to premature death and people being unable to work due to illness).

Malignant blood disorders

In one paper, the researchers noted that the total economic cost of blood cancers to the 31 countries studied was €12 billion in 2012. Healthcare costs measured €7.3 billion (62% of total costs), productivity losses cost €3.6 billion (30%), and informal care cost €1 billion (8%).

In the 28 EU countries, blood cancers represented 8% of the total cancer costs (€143 billion), meaning that blood cancers are the fourth most expensive type of cancer after lung (15%), breast (12%), and colorectal (10%) cancers.

When considering healthcare costs alone, blood cancers were second only to breast cancers (12% vs 13% of healthcare costs for all cancers).

In 2012, blood cancers cost, on average, €14,674 per patient in the EU (€15,126 in all 31 countries), which is almost 2 times higher than the average cost per patient across all cancers (€7929 in the EU).

The researchers said this difference may be due to the longer length of hospital stay observed for patients with blood cancers (14 days, on average, compared to 8 days across all cancers).

Another potential reason is that blood cancers are increasingly treated with complex, long-term treatments (including stem cell transplants, multi-agent chemotherapy, and radiotherapy) and diagnosed via extensive procedures.

The costs of blood cancers varied widely between the countries studied, but the reasons for this were unclear. For instance, the average healthcare costs in Finland were nearly twice as high as in Belgium (€18,014 vs €9596), despite both countries having similar national income per capita.

Non-malignant blood disorders

In the other paper, the researchers said the total economic cost of non-malignant blood disorders to the 31 countries studied was €11 billion in 2012. Healthcare costs accounted for €8 billion (75% of total costs), productivity losses for €2 billion (19%), and informal care for €618 million (6%).

Averaged across the population studied, non-malignant blood disorders represented an annual healthcare cost of €159 per 10 citizens.

“Non-malignant blood disorders cost the European economy nearly as much as all blood cancers combined,” said Jose Leal, DPhil, of the University of Oxford in the UK.

“We found wide differences in the cost of treating blood disorders in different countries, likely linked to the significant differences in the access and delivery of care for patients with blood disorders. Our findings suggest there is a need to harmonize care of blood disorders across Europe in a cost-effective way.”

An EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

The European Commission (EC) has granted orphan drug designation for CMD-003 (baltaleucel-T) as a treatment for nasal type extranodal NK/T-cell lymphoma and post-transplant lymphoproliferative disorder.

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with Epstein-Barr virus (EBV).

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine, with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About orphan designation

Orphan designation from the EC provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

CMD-003 also has orphan designation from the US Food and Drug Administration to treat all EBV-associated non-Hodgkin lymphomas.

CMD-003-related research

CMD-003 is currently under investigation in a phase 2 trial, CITADEL, for the treatment of advanced NK/T-cell lymphoma.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

An EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

The European Commission (EC) has granted orphan drug designation for CMD-003 (baltaleucel-T) as a treatment for nasal type extranodal NK/T-cell lymphoma and post-transplant lymphoproliferative disorder.

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with Epstein-Barr virus (EBV).

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine, with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About orphan designation

Orphan designation from the EC provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

CMD-003 also has orphan designation from the US Food and Drug Administration to treat all EBV-associated non-Hodgkin lymphomas.

CMD-003-related research

CMD-003 is currently under investigation in a phase 2 trial, CITADEL, for the treatment of advanced NK/T-cell lymphoma.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

An EBV-infected cell (green/red)

among uninfected cells (blue)

Image courtesy of

Benjamin Chaigne-Delalande

The European Commission (EC) has granted orphan drug designation for CMD-003 (baltaleucel-T) as a treatment for nasal type extranodal NK/T-cell lymphoma and post-transplant lymphoproliferative disorder.

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with Epstein-Barr virus (EBV).

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine, with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About orphan designation

Orphan designation from the EC provides regulatory and financial incentives for companies to develop and market therapies that treat a life-threatening or chronically debilitating condition affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity in the European Union if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

CMD-003 also has orphan designation from the US Food and Drug Administration to treat all EBV-associated non-Hodgkin lymphomas.

CMD-003-related research

CMD-003 is currently under investigation in a phase 2 trial, CITADEL, for the treatment of advanced NK/T-cell lymphoma.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

Vial of heparin

Results of an observational study support early initiation of venous thromboembolism (VTE) prophylaxis in patients with severe traumatic brain injury (sTBI).

The research suggests that starting anticoagulant therapy within 72 hours of hospital arrival significantly lowers the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with sTBI, without increasing the risk of bleeding complications or death.

These results were published in the Journal of the American College of Surgeons.

“Physicians have traditionally been hesitant to initiate pharmacological blood clot prophylaxis early in patients with severe brain injuries because, while thinning the blood might prevent PE and DVT, it might also increase the risk of complications related to worsening intracranial hemorrhage,” said study author James P. Byrne, MD, of the University of Toronto in Ontario, Canada.

“We performed this study because there wasn’t clear evidence that starting prophylaxis early actually prevented blood clots, or whether this benefit would outweigh the risk of complications from intracranial hemorrhage. Current evidence-based guidelines don’t address the optimal timing for starting prophylaxis in patients with severe TBI.”

The researchers looked at data on 3634 adult patients with sTBI who were treated at 186 trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program. The patients received VTE prophylaxis with either low-molecular-weight heparin or unfractionated heparin between 2012 and 2014.

The researchers divided patients into 2 groups: early prophylaxis (started within 72 hours of hospital arrival) or late prophylaxis (started after 72 hours). The primary outcomes were PE or DVT. The secondary outcomes were late neurosurgical interventions (performed after 72 hours) and in-hospital death.

The team used propensity-score matching to emulate the design of a randomized, controlled trial and minimize selection bias. This method took into account a large set of patient baseline and injury factors, and yielded a cohort of 2468 patients. Outcomes were then compared between early and late prophylaxis groups.

Results

The researchers found that early VTE prophylaxis was associated with significantly lower rates of PE (adjusted odds ratio [aOR]=0.48; 95% CI 0.25–0.91) and DVT (aOR=0.51; 95% CI 0.36–0.72) than late prophylaxis.

“No previous study has shown that patients who receive early prophylaxis have lower rates of pulmonary embolism, which is important because this complication is a potentially fatal one,” Dr Byrne noted.

“We also found that trauma centers that most frequently used early prophylaxis in their patients had significantly lower rates of deep vein thrombosis, compared with counterparts where fewer patients received early prophylaxis, with no difference in rates of late neurosurgical intervention or mortality.”

Specifically, there was no significant difference between early prophylaxis and late prophylaxis groups with respect to rates of in-hospital mortality (aOR=1.10; 95% CI 0.84–1.45) or late neurosurgical interventions, including craniotomy/craniectomy (aOR=0.86; 95% CI 0.53–1.40) and intracranial monitor (aOR=0.76; 95% CI 0.37–1.58).

The researchers said this is the largest study to date comparing the effectiveness and safety of early versus late VTE prophylaxis in patients with sTBI.

A limitation of this study was the fact that statistical methods could not account for confounding factors that were not measured in the study dataset. One such factor was changes in patterns of intracranial hemorrhage on head CT scan, which would influence physician decision-making.

“The takeaway message is that early prophylaxis really does matter in patients with severe traumatic brain injury, in terms of reducing a patient’s risk of pulmonary embolism or deep vein thrombosis,” Dr Byrne said.

“Our findings suggest that this is possible without increasing the risk of the most feared complications, such as the need to take a patient to the operating room to evacuate intracranial hemorrhage or death. In other words, it’s possible to prevent PE or DVT with early prophylaxis, without putting patients at risk of bad outcomes, and we should be striving to achieve this.”

Vial of heparin

Results of an observational study support early initiation of venous thromboembolism (VTE) prophylaxis in patients with severe traumatic brain injury (sTBI).

The research suggests that starting anticoagulant therapy within 72 hours of hospital arrival significantly lowers the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with sTBI, without increasing the risk of bleeding complications or death.

These results were published in the Journal of the American College of Surgeons.

“Physicians have traditionally been hesitant to initiate pharmacological blood clot prophylaxis early in patients with severe brain injuries because, while thinning the blood might prevent PE and DVT, it might also increase the risk of complications related to worsening intracranial hemorrhage,” said study author James P. Byrne, MD, of the University of Toronto in Ontario, Canada.

“We performed this study because there wasn’t clear evidence that starting prophylaxis early actually prevented blood clots, or whether this benefit would outweigh the risk of complications from intracranial hemorrhage. Current evidence-based guidelines don’t address the optimal timing for starting prophylaxis in patients with severe TBI.”

The researchers looked at data on 3634 adult patients with sTBI who were treated at 186 trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program. The patients received VTE prophylaxis with either low-molecular-weight heparin or unfractionated heparin between 2012 and 2014.

The researchers divided patients into 2 groups: early prophylaxis (started within 72 hours of hospital arrival) or late prophylaxis (started after 72 hours). The primary outcomes were PE or DVT. The secondary outcomes were late neurosurgical interventions (performed after 72 hours) and in-hospital death.

The team used propensity-score matching to emulate the design of a randomized, controlled trial and minimize selection bias. This method took into account a large set of patient baseline and injury factors, and yielded a cohort of 2468 patients. Outcomes were then compared between early and late prophylaxis groups.

Results

The researchers found that early VTE prophylaxis was associated with significantly lower rates of PE (adjusted odds ratio [aOR]=0.48; 95% CI 0.25–0.91) and DVT (aOR=0.51; 95% CI 0.36–0.72) than late prophylaxis.

“No previous study has shown that patients who receive early prophylaxis have lower rates of pulmonary embolism, which is important because this complication is a potentially fatal one,” Dr Byrne noted.

“We also found that trauma centers that most frequently used early prophylaxis in their patients had significantly lower rates of deep vein thrombosis, compared with counterparts where fewer patients received early prophylaxis, with no difference in rates of late neurosurgical intervention or mortality.”

Specifically, there was no significant difference between early prophylaxis and late prophylaxis groups with respect to rates of in-hospital mortality (aOR=1.10; 95% CI 0.84–1.45) or late neurosurgical interventions, including craniotomy/craniectomy (aOR=0.86; 95% CI 0.53–1.40) and intracranial monitor (aOR=0.76; 95% CI 0.37–1.58).

The researchers said this is the largest study to date comparing the effectiveness and safety of early versus late VTE prophylaxis in patients with sTBI.

A limitation of this study was the fact that statistical methods could not account for confounding factors that were not measured in the study dataset. One such factor was changes in patterns of intracranial hemorrhage on head CT scan, which would influence physician decision-making.

“The takeaway message is that early prophylaxis really does matter in patients with severe traumatic brain injury, in terms of reducing a patient’s risk of pulmonary embolism or deep vein thrombosis,” Dr Byrne said.

“Our findings suggest that this is possible without increasing the risk of the most feared complications, such as the need to take a patient to the operating room to evacuate intracranial hemorrhage or death. In other words, it’s possible to prevent PE or DVT with early prophylaxis, without putting patients at risk of bad outcomes, and we should be striving to achieve this.”

Vial of heparin

Results of an observational study support early initiation of venous thromboembolism (VTE) prophylaxis in patients with severe traumatic brain injury (sTBI).

The research suggests that starting anticoagulant therapy within 72 hours of hospital arrival significantly lowers the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with sTBI, without increasing the risk of bleeding complications or death.

These results were published in the Journal of the American College of Surgeons.

“Physicians have traditionally been hesitant to initiate pharmacological blood clot prophylaxis early in patients with severe brain injuries because, while thinning the blood might prevent PE and DVT, it might also increase the risk of complications related to worsening intracranial hemorrhage,” said study author James P. Byrne, MD, of the University of Toronto in Ontario, Canada.

“We performed this study because there wasn’t clear evidence that starting prophylaxis early actually prevented blood clots, or whether this benefit would outweigh the risk of complications from intracranial hemorrhage. Current evidence-based guidelines don’t address the optimal timing for starting prophylaxis in patients with severe TBI.”

The researchers looked at data on 3634 adult patients with sTBI who were treated at 186 trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program. The patients received VTE prophylaxis with either low-molecular-weight heparin or unfractionated heparin between 2012 and 2014.

The researchers divided patients into 2 groups: early prophylaxis (started within 72 hours of hospital arrival) or late prophylaxis (started after 72 hours). The primary outcomes were PE or DVT. The secondary outcomes were late neurosurgical interventions (performed after 72 hours) and in-hospital death.

The team used propensity-score matching to emulate the design of a randomized, controlled trial and minimize selection bias. This method took into account a large set of patient baseline and injury factors, and yielded a cohort of 2468 patients. Outcomes were then compared between early and late prophylaxis groups.

Results

The researchers found that early VTE prophylaxis was associated with significantly lower rates of PE (adjusted odds ratio [aOR]=0.48; 95% CI 0.25–0.91) and DVT (aOR=0.51; 95% CI 0.36–0.72) than late prophylaxis.

“No previous study has shown that patients who receive early prophylaxis have lower rates of pulmonary embolism, which is important because this complication is a potentially fatal one,” Dr Byrne noted.

“We also found that trauma centers that most frequently used early prophylaxis in their patients had significantly lower rates of deep vein thrombosis, compared with counterparts where fewer patients received early prophylaxis, with no difference in rates of late neurosurgical intervention or mortality.”

Specifically, there was no significant difference between early prophylaxis and late prophylaxis groups with respect to rates of in-hospital mortality (aOR=1.10; 95% CI 0.84–1.45) or late neurosurgical interventions, including craniotomy/craniectomy (aOR=0.86; 95% CI 0.53–1.40) and intracranial monitor (aOR=0.76; 95% CI 0.37–1.58).

The researchers said this is the largest study to date comparing the effectiveness and safety of early versus late VTE prophylaxis in patients with sTBI.

A limitation of this study was the fact that statistical methods could not account for confounding factors that were not measured in the study dataset. One such factor was changes in patterns of intracranial hemorrhage on head CT scan, which would influence physician decision-making.

“The takeaway message is that early prophylaxis really does matter in patients with severe traumatic brain injury, in terms of reducing a patient’s risk of pulmonary embolism or deep vein thrombosis,” Dr Byrne said.

“Our findings suggest that this is possible without increasing the risk of the most feared complications, such as the need to take a patient to the operating room to evacuate intracranial hemorrhage or death. In other words, it’s possible to prevent PE or DVT with early prophylaxis, without putting patients at risk of bad outcomes, and we should be striving to achieve this.”

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to SPK-9001 for the treatment of hemophilia B.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX.

SPK-9001 is intended to control and prevent bleeding episodes in patients with hemophilia B, without the need for regular infusions.

SPK-9001 is under investigation in an ongoing phase 1/2 trial. The therapy is being developed by Spark Therapeutics and Pfizer Inc.

“We are extremely pleased to have been granted breakthrough therapy designation for SPK-9001, which has shown early promise in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with hemophilia B through a potentially one-time, intravenous administration of a highly optimized gene therapy,” said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to SPK-9001 for the treatment of hemophilia B.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX.

SPK-9001 is intended to control and prevent bleeding episodes in patients with hemophilia B, without the need for regular infusions.

SPK-9001 is under investigation in an ongoing phase 1/2 trial. The therapy is being developed by Spark Therapeutics and Pfizer Inc.

“We are extremely pleased to have been granted breakthrough therapy designation for SPK-9001, which has shown early promise in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with hemophilia B through a potentially one-time, intravenous administration of a highly optimized gene therapy,” said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Red blood cells

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to SPK-9001 for the treatment of hemophilia B.

SPK-9001 is a bio-engineered adeno-associated virus capsid expressing a codon-optimized, high-activity human factor IX variant enabling endogenous production of factor IX.

SPK-9001 is intended to control and prevent bleeding episodes in patients with hemophilia B, without the need for regular infusions.

SPK-9001 is under investigation in an ongoing phase 1/2 trial. The therapy is being developed by Spark Therapeutics and Pfizer Inc.

“We are extremely pleased to have been granted breakthrough therapy designation for SPK-9001, which has shown early promise in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with hemophilia B through a potentially one-time, intravenous administration of a highly optimized gene therapy,” said Jeffrey D. Marrazzo, chief executive officer of Spark Therapeutics.

The FDA’s breakthrough therapy designation is intended to expedite the development and review of new therapies for serious or life-threatening conditions.

To earn the designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Although we reserve the term “PURL” for our popular feature, Priority Updates from the Research Literature, I’m proud to comment on the collection of articles in this issue of JFP, each of which contains important “pearls” of information for family physicians and other primary care clinicians.

Managing sport-related concussion. Revelations about serious head injuries in the National Football League have catalyzed important research regarding the management of sports-related head injuries, and the evidence for diagnosis and treatment is evolving. The article in this issue by Dr. Sprouse and colleagues provides some of the latest information regarding brain changes after concussion straight from the American Academy of Neurology’s 2016 Sports Concussion Conference held in Chicago in July, as well as valuable return-to-play recommendations.

Family medicine ultrasound. Because of advances in technology and reductions in the cost of portable machines, ultrasound use is rapidly moving into family medicine offices. Drs. Steinmetz and Oleskevich provide a no-nonsense review of the current uses of ultrasound in family medicine, leading me to wonder whether ultrasound might become the stethoscope of the future.

This month’s review of the current uses of ultrasound in family medicine made me wonder whether ultrasound might become the stethoscope of the future.

Shortness of breath. Although the diagnosis of shortness of breath is straightforward in many cases, misdiagnosis is not uncommon. Recently, I cared for a new patient who was diagnosed with asthma 15 years ago. Because of fine rales on exam, I suspected the patient’s diagnosis was incorrect. Indeed, he had pulmonary fibrosis, not asthma, and he is doing fine now without his asthma inhalers. Dr. Taggart outlines a thoughtful approach to the evaluation of shortness of breath, one that alerts you to when to suspect something beyond the usual culprits.

Cervical cancer screening. The days of yearly Pap smears for all women are over. Combined screening with cytology and human papillomavirus testing is now recommended at 5-year intervals for women 30 to 65 years of age who are at low risk for cervical cancer. In addition, Dr. Hofmeister reviews recent randomized trials that suggest HPV screening alone may be sufficient for low-risk women.

On-demand HIV prophylaxis. Our PURL for the month discusses an effective prevention strategy—other than condoms—that can be used as needed by people at high risk for human immunodeficiency virus.

We hope you enjoy this PURL—and the other “pearls”—this month. As diagnosis and treatments evolve, JFP will continue to bring you the information you need to provide the best possible care for your patients.

Although we reserve the term “PURL” for our popular feature, Priority Updates from the Research Literature, I’m proud to comment on the collection of articles in this issue of JFP, each of which contains important “pearls” of information for family physicians and other primary care clinicians.

Managing sport-related concussion. Revelations about serious head injuries in the National Football League have catalyzed important research regarding the management of sports-related head injuries, and the evidence for diagnosis and treatment is evolving. The article in this issue by Dr. Sprouse and colleagues provides some of the latest information regarding brain changes after concussion straight from the American Academy of Neurology’s 2016 Sports Concussion Conference held in Chicago in July, as well as valuable return-to-play recommendations.

Family medicine ultrasound. Because of advances in technology and reductions in the cost of portable machines, ultrasound use is rapidly moving into family medicine offices. Drs. Steinmetz and Oleskevich provide a no-nonsense review of the current uses of ultrasound in family medicine, leading me to wonder whether ultrasound might become the stethoscope of the future.

This month’s review of the current uses of ultrasound in family medicine made me wonder whether ultrasound might become the stethoscope of the future.

Shortness of breath. Although the diagnosis of shortness of breath is straightforward in many cases, misdiagnosis is not uncommon. Recently, I cared for a new patient who was diagnosed with asthma 15 years ago. Because of fine rales on exam, I suspected the patient’s diagnosis was incorrect. Indeed, he had pulmonary fibrosis, not asthma, and he is doing fine now without his asthma inhalers. Dr. Taggart outlines a thoughtful approach to the evaluation of shortness of breath, one that alerts you to when to suspect something beyond the usual culprits.

Cervical cancer screening. The days of yearly Pap smears for all women are over. Combined screening with cytology and human papillomavirus testing is now recommended at 5-year intervals for women 30 to 65 years of age who are at low risk for cervical cancer. In addition, Dr. Hofmeister reviews recent randomized trials that suggest HPV screening alone may be sufficient for low-risk women.

On-demand HIV prophylaxis. Our PURL for the month discusses an effective prevention strategy—other than condoms—that can be used as needed by people at high risk for human immunodeficiency virus.

We hope you enjoy this PURL—and the other “pearls”—this month. As diagnosis and treatments evolve, JFP will continue to bring you the information you need to provide the best possible care for your patients.

Although we reserve the term “PURL” for our popular feature, Priority Updates from the Research Literature, I’m proud to comment on the collection of articles in this issue of JFP, each of which contains important “pearls” of information for family physicians and other primary care clinicians.

Managing sport-related concussion. Revelations about serious head injuries in the National Football League have catalyzed important research regarding the management of sports-related head injuries, and the evidence for diagnosis and treatment is evolving. The article in this issue by Dr. Sprouse and colleagues provides some of the latest information regarding brain changes after concussion straight from the American Academy of Neurology’s 2016 Sports Concussion Conference held in Chicago in July, as well as valuable return-to-play recommendations.

Family medicine ultrasound. Because of advances in technology and reductions in the cost of portable machines, ultrasound use is rapidly moving into family medicine offices. Drs. Steinmetz and Oleskevich provide a no-nonsense review of the current uses of ultrasound in family medicine, leading me to wonder whether ultrasound might become the stethoscope of the future.

This month’s review of the current uses of ultrasound in family medicine made me wonder whether ultrasound might become the stethoscope of the future.

Shortness of breath. Although the diagnosis of shortness of breath is straightforward in many cases, misdiagnosis is not uncommon. Recently, I cared for a new patient who was diagnosed with asthma 15 years ago. Because of fine rales on exam, I suspected the patient’s diagnosis was incorrect. Indeed, he had pulmonary fibrosis, not asthma, and he is doing fine now without his asthma inhalers. Dr. Taggart outlines a thoughtful approach to the evaluation of shortness of breath, one that alerts you to when to suspect something beyond the usual culprits.

Cervical cancer screening. The days of yearly Pap smears for all women are over. Combined screening with cytology and human papillomavirus testing is now recommended at 5-year intervals for women 30 to 65 years of age who are at low risk for cervical cancer. In addition, Dr. Hofmeister reviews recent randomized trials that suggest HPV screening alone may be sufficient for low-risk women.

On-demand HIV prophylaxis. Our PURL for the month discusses an effective prevention strategy—other than condoms—that can be used as needed by people at high risk for human immunodeficiency virus.

We hope you enjoy this PURL—and the other “pearls”—this month. As diagnosis and treatments evolve, JFP will continue to bring you the information you need to provide the best possible care for your patients.

ILLUSTRATIVE CASE

Your patient is a 31-year-old man who has sex with men. He is sexually active with several different partners. He asks you if there is anything he can do to decrease his risk of becoming infected with human immunodeficiency virus (HIV). Besides recommending condom use, what should you offer him?

In most high-income countries, including the United States, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² Without a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the Centers for Disease Control and Prevention (CDC) began recommending daily use of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) in high-risk individuals, as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT]=46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably because of the difficulty in getting patients to take the medication on a daily basis.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ That is because, until now, there have been no studies demonstrating the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays (IPERGAY) study was a double-blind, multicenter study conducted in France and Canada that assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis was that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk of HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection. The investigators defined high risk as having a history of unprotected anal sex with at least 2 partners in the previous 6 months. Other inclusion criteria included age ≥18 years, and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance <60 mL/min, alanine aminotransferase level >2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. After excluding those who withdrew consent, were lost to follow-up, or who acquired HIV-1 infection, the study participants (199 in the TDF-FTC group and 201 in the placebo group) were randomized to take TDF-FTC or placebo before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. The participants were instructed to take a loading dose of 2 pills of TDF-FTC or placebo with food 2 to 24 hours prior to intercourse, followed by a third pill 24 hours after taking the first 2 pills, and a fourth pill 24 hours after the third pill. If there were multiple consecutive days with episodes of sexual intercourse, participants were to take one pill on each of the days of intercourse, and then the 2 post-exposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the preexposure prophylaxis; otherwise, they were to begin again with 2 pills 2 to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants 4 and 8 weeks after enrollment, and then every 8 weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count and drug levels in plasma, as well as with an at-home, computer-assisted interview completed by each participant prior to each visit.

Participants received counseling from a peer community member and were offered preventative services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took the pills correctly. The participants were followed for a median of 9.3 months. Overall, 72% of the participants took the study drugs (TDF-FTC or placebo), although 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. The study was unblinded after 20 months and is continuing as an open-label study because of the discontinuation of another preexposure prophylaxis study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

We suspect the higher benefit of an on-demand PrEP is likely due to increased compliance with medication use.

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk of contracting HIV without PrEP. The open-label part of the study, iPrex-OLE, completed enrollment and data gathering in November 2013, and the data analysis and results are presently pending.⁹

Eighty-six percent relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with 3 of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group (6.6 infections per 100 person-years) and 2 of the new cases were in the TDF-FTC group (incidence 0.91 per 100 person-years). This translated to a relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group of 86% (95% confidence interval, 40%-98%; P=.002; NNT=17 over 9.3 months).

The 2 study participants in the TDF-FTC group diagnosed with new HIV-1 were found to be non-adherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain and were seen at a greater rate (14% vs 5%, P=.002; number needed to harm=11) in the treatment group than in the placebo group. There were also mild increases in serum creatinine level (seen in 18% of the TDF-FTC group), but only 2 participants had a transient decrease in creatinine clearance to <60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction with on-demand use is nearly double that of daily use

This is the first study to look at on-demand preexposure prophylaxis with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the higher benefit of on-demand PrEP is likely due to increased compliance with medication use.

CAVEATS

Is fewer pills enough to maintain adherence over time?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we will need to wait for the results of the open-label study to fully assess the risks of adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of TDF-FTC, the retail price of which is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Your patient is a 31-year-old man who has sex with men. He is sexually active with several different partners. He asks you if there is anything he can do to decrease his risk of becoming infected with human immunodeficiency virus (HIV). Besides recommending condom use, what should you offer him?

In most high-income countries, including the United States, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² Without a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the Centers for Disease Control and Prevention (CDC) began recommending daily use of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) in high-risk individuals, as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT]=46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably because of the difficulty in getting patients to take the medication on a daily basis.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ That is because, until now, there have been no studies demonstrating the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays (IPERGAY) study was a double-blind, multicenter study conducted in France and Canada that assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis was that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk of HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection. The investigators defined high risk as having a history of unprotected anal sex with at least 2 partners in the previous 6 months. Other inclusion criteria included age ≥18 years, and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance <60 mL/min, alanine aminotransferase level >2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. After excluding those who withdrew consent, were lost to follow-up, or who acquired HIV-1 infection, the study participants (199 in the TDF-FTC group and 201 in the placebo group) were randomized to take TDF-FTC or placebo before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. The participants were instructed to take a loading dose of 2 pills of TDF-FTC or placebo with food 2 to 24 hours prior to intercourse, followed by a third pill 24 hours after taking the first 2 pills, and a fourth pill 24 hours after the third pill. If there were multiple consecutive days with episodes of sexual intercourse, participants were to take one pill on each of the days of intercourse, and then the 2 post-exposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the preexposure prophylaxis; otherwise, they were to begin again with 2 pills 2 to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants 4 and 8 weeks after enrollment, and then every 8 weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count and drug levels in plasma, as well as with an at-home, computer-assisted interview completed by each participant prior to each visit.

Participants received counseling from a peer community member and were offered preventative services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took the pills correctly. The participants were followed for a median of 9.3 months. Overall, 72% of the participants took the study drugs (TDF-FTC or placebo), although 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. The study was unblinded after 20 months and is continuing as an open-label study because of the discontinuation of another preexposure prophylaxis study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

We suspect the higher benefit of an on-demand PrEP is likely due to increased compliance with medication use.

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk of contracting HIV without PrEP. The open-label part of the study, iPrex-OLE, completed enrollment and data gathering in November 2013, and the data analysis and results are presently pending.⁹

Eighty-six percent relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with 3 of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group (6.6 infections per 100 person-years) and 2 of the new cases were in the TDF-FTC group (incidence 0.91 per 100 person-years). This translated to a relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group of 86% (95% confidence interval, 40%-98%; P=.002; NNT=17 over 9.3 months).

The 2 study participants in the TDF-FTC group diagnosed with new HIV-1 were found to be non-adherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain and were seen at a greater rate (14% vs 5%, P=.002; number needed to harm=11) in the treatment group than in the placebo group. There were also mild increases in serum creatinine level (seen in 18% of the TDF-FTC group), but only 2 participants had a transient decrease in creatinine clearance to <60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction with on-demand use is nearly double that of daily use

This is the first study to look at on-demand preexposure prophylaxis with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the higher benefit of on-demand PrEP is likely due to increased compliance with medication use.

CAVEATS

Is fewer pills enough to maintain adherence over time?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we will need to wait for the results of the open-label study to fully assess the risks of adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of TDF-FTC, the retail price of which is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Your patient is a 31-year-old man who has sex with men. He is sexually active with several different partners. He asks you if there is anything he can do to decrease his risk of becoming infected with human immunodeficiency virus (HIV). Besides recommending condom use, what should you offer him?

In most high-income countries, including the United States, HIV-1 infection continues to occur in high-risk groups, especially among men who have sex with men (MSM).² Without a vaccine, condom use has served as the primary method of preventing infection.

In 2014, the Centers for Disease Control and Prevention (CDC) began recommending daily use of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) in high-risk individuals, as a form of preexposure prophylaxis (PrEP).^3-5 This recommendation is based primarily on the Preexposure Prophylaxis Initiative (iPrEx) trial, which showed a relative reduction of 44% (number needed to treat [NNT]=46 over 1.2 years) in the incidence of new HIV-1 infection among men and transgender women who have sex with men when TDF-FTC was used on a daily basis.⁶ However, the effectiveness of this strategy in the real world has not been as high as hoped, presumably because of the difficulty in getting patients to take the medication on a daily basis.^7,8

While it would likely improve adherence rates, the use of prophylaxis in an on-demand manner is not currently recommended.⁵ That is because, until now, there have been no studies demonstrating the effectiveness of PrEP used episodically and taken only around the time of potential exposure.

STUDY SUMMARY

Fewer pills improves adherence, reduces HIV infection rates

The Intervention Preventive de l’Exposition aux Risques avec et pour les Gays (IPERGAY) study was a double-blind, multicenter study conducted in France and Canada that assessed the efficacy and safety of prophylaxis with TDF-FTC used in an on-demand fashion by MSM.¹ The study hypothesis was that adherence would be higher if chemoprophylaxis was taken only around the time of intercourse, rather than daily, and that this would further reduce the risk of HIV infection.

The study randomized 414 participants who were considered to be at high risk for acquiring HIV-1 infection. The investigators defined high risk as having a history of unprotected anal sex with at least 2 partners in the previous 6 months. Other inclusion criteria included age ≥18 years, and male or transgender female sex. Exclusion criteria included current HIV infection, hepatitis B or C infection, creatinine clearance <60 mL/min, alanine aminotransferase level >2.5 times the upper limit of normal, and significant glycosuria or proteinuria.

The pill and visit schedule. After excluding those who withdrew consent, were lost to follow-up, or who acquired HIV-1 infection, the study participants (199 in the TDF-FTC group and 201 in the placebo group) were randomized to take TDF-FTC or placebo before and after sexual activity. The dose of TDF-FTC was fixed at 300 mg of TDF and 200 mg of FTC per pill. The participants were instructed to take a loading dose of 2 pills of TDF-FTC or placebo with food 2 to 24 hours prior to intercourse, followed by a third pill 24 hours after taking the first 2 pills, and a fourth pill 24 hours after the third pill. If there were multiple consecutive days with episodes of sexual intercourse, participants were to take one pill on each of the days of intercourse, and then the 2 post-exposure pills. If sexual activity resumed within a week of the prior episode, participants were instructed to take only one pill when resuming the preexposure prophylaxis; otherwise, they were to begin again with 2 pills 2 to 24 hours prior to intercourse and repeat the protocol.

Study coordinators followed participants 4 and 8 weeks after enrollment, and then every 8 weeks subsequently. The investigators tested the participants for HIV-1 and HIV-2 at each visit and assessed adherence by pill count and drug levels in plasma, as well as with an at-home, computer-assisted interview completed by each participant prior to each visit.

Participants received counseling from a peer community member and were offered preventative services and testing for other sexually transmitted infections. They were given free condoms and gel at each visit, as well as enough pills (TDF-FTC or placebo) to cover daily use until their next visit.

Forty-three percent took the pills correctly. The participants were followed for a median of 9.3 months. Overall, 72% of the participants took the study drugs (TDF-FTC or placebo), although 29% took a suboptimal dose. There was no change in the sexual behavior of the participants during the study. The study was unblinded after 20 months and is continuing as an open-label study because of the discontinuation of another preexposure prophylaxis study in the United Kingdom, which showed an NNT of 13 to prevent one new HIV infection per year.³

We suspect the higher benefit of an on-demand PrEP is likely due to increased compliance with medication use.

An independent data and safety monitoring board recommended the unblinding because the placebo group was considered to be at significantly increased risk of contracting HIV without PrEP. The open-label part of the study, iPrex-OLE, completed enrollment and data gathering in November 2013, and the data analysis and results are presently pending.⁹

Eighty-six percent relative reduction in HIV. The primary end-point was the diagnosis of HIV-1 infection, and the results were based on an intention-to-treat analysis. HIV-1 infection was diagnosed in 19 study participants, with 3 of those new cases occurring between the time of randomization and enrollment. Fourteen of the cases were in the placebo group (6.6 infections per 100 person-years) and 2 of the new cases were in the TDF-FTC group (incidence 0.91 per 100 person-years). This translated to a relative reduction in the incidence of new HIV-1 seroconversion in the TDF-FTC group of 86% (95% confidence interval, 40%-98%; P=.002; NNT=17 over 9.3 months).

The 2 study participants in the TDF-FTC group diagnosed with new HIV-1 were found to be non-adherent to the prescribed prophylaxis, as they returned 58 and 60 of the 60 pills administered to them, and no study drugs were found in their plasma samples.

Adverse events included gastrointestinal symptoms of nausea, vomiting, diarrhea, and abdominal pain and were seen at a greater rate (14% vs 5%, P=.002; number needed to harm=11) in the treatment group than in the placebo group. There were also mild increases in serum creatinine level (seen in 18% of the TDF-FTC group), but only 2 participants had a transient decrease in creatinine clearance to <60 mL/min. None of the participants discontinued medications due to renal issues.

WHAT’S NEW

Risk reduction with on-demand use is nearly double that of daily use

This is the first study to look at on-demand preexposure prophylaxis with TDF-FTC to decrease the incidence of HIV-1 infection in high-risk MSM. The risk reduction in this study (86%) was much better than the 44% seen in the prior study that used daily PrEP in this population.⁶ We suspect the higher benefit of on-demand PrEP is likely due to increased compliance with medication use.

CAVEATS

Is fewer pills enough to maintain adherence over time?

The median length of follow-up in the study was 9.3 months. One concern is that adherence may wane over time, decreasing the efficacy of the prophylaxis. Continued efforts to improve compliance with this type of PrEP may be needed to ensure efficacy. Since the study was shortened and reported early, we will need to wait for the results of the open-label study to fully assess the risks of adverse events.

CHALLENGES TO IMPLEMENTATION

Efficacy and convenience come at a cost

The main challenge to implementation could be the cost of TDF-FTC, the retail price of which is about $50 per dose.¹⁰ Insurance coverage for the medication varies.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

At the Vascular Annual Meeting, there’s no need to cart around a lot of paper. Instead, the Mobile App puts all the information you need – abstracts, exhibitor map, schedules and more – within fingertip reach, to keep you more organized than ever.

Quick tips for using the Mobile App:

Courtesy SVS

Create a personal schedule. Bookmark potential sessions in the program tab by clinking the small calendar icon the right for each session of interest. Reminders will pop up 10 minutes before the start time, including session details. The information will be pinned to the top of your activity feed to help you stay organized.

Review abstracts and take notes. The index contains all abstracts with author names and affiliations, presentation time, location, and a link to view the full abstract online. All index information is searchable. Take notes on each abstract within the app and export those notes to an email. Create a list of favorite abstracts by bookmarking those you want to refer to again.

Share. Share your thoughts in the app’s activity feed. Let all your friends know what you’re up to by linking your social media accounts to the app so you can post in the app and your social media feed at the same time!

The VAM Meeting App Is ...

Comprehensive: It includes all meeting content, including abstracts.

Searchable: Quickly locate sessions, abstracts, speakers and more.

Interactive: Network with colleagues, share photos and rate programs.

Visit vsweb.org/mobileapp to download the app.

At the Vascular Annual Meeting, there’s no need to cart around a lot of paper. Instead, the Mobile App puts all the information you need – abstracts, exhibitor map, schedules and more – within fingertip reach, to keep you more organized than ever.

Quick tips for using the Mobile App:

Courtesy SVS

Create a personal schedule. Bookmark potential sessions in the program tab by clinking the small calendar icon the right for each session of interest. Reminders will pop up 10 minutes before the start time, including session details. The information will be pinned to the top of your activity feed to help you stay organized.

Review abstracts and take notes. The index contains all abstracts with author names and affiliations, presentation time, location, and a link to view the full abstract online. All index information is searchable. Take notes on each abstract within the app and export those notes to an email. Create a list of favorite abstracts by bookmarking those you want to refer to again.

Share. Share your thoughts in the app’s activity feed. Let all your friends know what you’re up to by linking your social media accounts to the app so you can post in the app and your social media feed at the same time!

The VAM Meeting App Is ...

Comprehensive: It includes all meeting content, including abstracts.

Searchable: Quickly locate sessions, abstracts, speakers and more.

Interactive: Network with colleagues, share photos and rate programs.

Visit vsweb.org/mobileapp to download the app.

At the Vascular Annual Meeting, there’s no need to cart around a lot of paper. Instead, the Mobile App puts all the information you need – abstracts, exhibitor map, schedules and more – within fingertip reach, to keep you more organized than ever.

Quick tips for using the Mobile App:

Courtesy SVS

Create a personal schedule. Bookmark potential sessions in the program tab by clinking the small calendar icon the right for each session of interest. Reminders will pop up 10 minutes before the start time, including session details. The information will be pinned to the top of your activity feed to help you stay organized.

Review abstracts and take notes. The index contains all abstracts with author names and affiliations, presentation time, location, and a link to view the full abstract online. All index information is searchable. Take notes on each abstract within the app and export those notes to an email. Create a list of favorite abstracts by bookmarking those you want to refer to again.

Share. Share your thoughts in the app’s activity feed. Let all your friends know what you’re up to by linking your social media accounts to the app so you can post in the app and your social media feed at the same time!

The VAM Meeting App Is ...

Comprehensive: It includes all meeting content, including abstracts.

Searchable: Quickly locate sessions, abstracts, speakers and more.

Interactive: Network with colleagues, share photos and rate programs.

Visit vsweb.org/mobileapp to download the app.