In January, I purchased the newly published second edition of “The Anthropology of Childhood: Cherubs, Chattel, Changelings,” by David F. Lancy (New York: Cambridge University Press, 2015), hoping it would provide me with some food for thought on the cold, dark winter nights. When the crocuses sprouted in April, I had slogged only halfway through its 533 pages (of which 104 are a list of references) and set it aside.

It has the heft of college text, but it is really more of a heavily referenced opinion piece. The author is an emeritus professor of anthropology at Utah State University, Logan, and his primary message is that how we value our children and how we choose to raise them here in North America should not be considered a benchmark against which to judge the way other societies treat their children. To emphasize his contention that we should not consider ourselves the norm, he refers to us as part of the WEIRD world (Western, Educated, Industrialized, Rich, Democracies).

Nearly every page includes at least one observation by an anthropologist that illustrates how different we are from many other societies. Not everyone values young children as cherubs the way we do. In some cultures, children are barely tolerated until they are old enough to contribute to the group. In some cultures, they are treated as no more than chattel.

While we believe that parents, certainly mothers, should play a critical role in the raising of children, there are many societies in which mothers are considered essential only for birthing and providing nutrition until the child is weaned. Children are left to be raised by other members of the society. Often, it is older siblings or cousins who assume the role we associate with parenthood.

The diversity of attitudes and child-rearing practices that Professor Lancy lays out in his tome is fascinating, even shocking at times, but after a few hundred pages one gets the message. But what I and every other parent want to know is if there is a common thread in these diverse cultures that can help us define the “natural” or the “best” or the “correct” way to parent our children. This question is particularly vexing for us in the WEIRD as we have become more heterogeneous, diverse, and multicultural. Most new millennium parents have no cultural tradition to fall back on, or if they have one it is likely to be very different from their partner in parenting. The result is that many parents find themselves on a constant, anxiety-driven search for the proper way to raise their child.

It’s not entirely clear to me how he arrives at it, but Professor Lancy offers his opinion on how we WEIRDs should raise our children. He feels we are taking the job of parenting far too seriously, and as a result, are meddling in a process that is best left to play out on its own. He observes, as do I, that children learn best by doing and imitating, not by being taught. Parents, specifically “involved” parents, are not a necessary requirement of successful child rearing. This message may come as an ego-busting shock to some parents. On the other hand, it should be liberating and guilt assuaging for parents whose careers and lifestyles limit the time they can spend with their children.

While I agree with Professor Lancy’s observation that much of the parenting that is done our society is unnecessary, and even at times counterproductive, the problem is that our society doesn’t offer many alternatives that provide the children an environment in which they can learn by doing and imitating. For example, grouping child care and preschool by age isolates young children from older children who can provide powerful role models for skill development. Unrealistic parental and provider fears about injury build barriers that rob children of opportunities to learn and grow.

The fact that here in the WEIRD families tend to have low birth rates makes it unlikely that parents will back off from overfocusing on their children. However, with help from knowledgeable and experienced experts in child health and behavior – pediatricians – there may be hope that some parents can learn to step back and let their children learn and develop in a more natural way.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at pdnews@frontlinemedcom.com.

In January, I purchased the newly published second edition of “The Anthropology of Childhood: Cherubs, Chattel, Changelings,” by David F. Lancy (New York: Cambridge University Press, 2015), hoping it would provide me with some food for thought on the cold, dark winter nights. When the crocuses sprouted in April, I had slogged only halfway through its 533 pages (of which 104 are a list of references) and set it aside.

It has the heft of college text, but it is really more of a heavily referenced opinion piece. The author is an emeritus professor of anthropology at Utah State University, Logan, and his primary message is that how we value our children and how we choose to raise them here in North America should not be considered a benchmark against which to judge the way other societies treat their children. To emphasize his contention that we should not consider ourselves the norm, he refers to us as part of the WEIRD world (Western, Educated, Industrialized, Rich, Democracies).

Nearly every page includes at least one observation by an anthropologist that illustrates how different we are from many other societies. Not everyone values young children as cherubs the way we do. In some cultures, children are barely tolerated until they are old enough to contribute to the group. In some cultures, they are treated as no more than chattel.

While we believe that parents, certainly mothers, should play a critical role in the raising of children, there are many societies in which mothers are considered essential only for birthing and providing nutrition until the child is weaned. Children are left to be raised by other members of the society. Often, it is older siblings or cousins who assume the role we associate with parenthood.

The diversity of attitudes and child-rearing practices that Professor Lancy lays out in his tome is fascinating, even shocking at times, but after a few hundred pages one gets the message. But what I and every other parent want to know is if there is a common thread in these diverse cultures that can help us define the “natural” or the “best” or the “correct” way to parent our children. This question is particularly vexing for us in the WEIRD as we have become more heterogeneous, diverse, and multicultural. Most new millennium parents have no cultural tradition to fall back on, or if they have one it is likely to be very different from their partner in parenting. The result is that many parents find themselves on a constant, anxiety-driven search for the proper way to raise their child.

It’s not entirely clear to me how he arrives at it, but Professor Lancy offers his opinion on how we WEIRDs should raise our children. He feels we are taking the job of parenting far too seriously, and as a result, are meddling in a process that is best left to play out on its own. He observes, as do I, that children learn best by doing and imitating, not by being taught. Parents, specifically “involved” parents, are not a necessary requirement of successful child rearing. This message may come as an ego-busting shock to some parents. On the other hand, it should be liberating and guilt assuaging for parents whose careers and lifestyles limit the time they can spend with their children.

While I agree with Professor Lancy’s observation that much of the parenting that is done our society is unnecessary, and even at times counterproductive, the problem is that our society doesn’t offer many alternatives that provide the children an environment in which they can learn by doing and imitating. For example, grouping child care and preschool by age isolates young children from older children who can provide powerful role models for skill development. Unrealistic parental and provider fears about injury build barriers that rob children of opportunities to learn and grow.

The fact that here in the WEIRD families tend to have low birth rates makes it unlikely that parents will back off from overfocusing on their children. However, with help from knowledgeable and experienced experts in child health and behavior – pediatricians – there may be hope that some parents can learn to step back and let their children learn and develop in a more natural way.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at pdnews@frontlinemedcom.com.

In January, I purchased the newly published second edition of “The Anthropology of Childhood: Cherubs, Chattel, Changelings,” by David F. Lancy (New York: Cambridge University Press, 2015), hoping it would provide me with some food for thought on the cold, dark winter nights. When the crocuses sprouted in April, I had slogged only halfway through its 533 pages (of which 104 are a list of references) and set it aside.

It has the heft of college text, but it is really more of a heavily referenced opinion piece. The author is an emeritus professor of anthropology at Utah State University, Logan, and his primary message is that how we value our children and how we choose to raise them here in North America should not be considered a benchmark against which to judge the way other societies treat their children. To emphasize his contention that we should not consider ourselves the norm, he refers to us as part of the WEIRD world (Western, Educated, Industrialized, Rich, Democracies).

Nearly every page includes at least one observation by an anthropologist that illustrates how different we are from many other societies. Not everyone values young children as cherubs the way we do. In some cultures, children are barely tolerated until they are old enough to contribute to the group. In some cultures, they are treated as no more than chattel.

While we believe that parents, certainly mothers, should play a critical role in the raising of children, there are many societies in which mothers are considered essential only for birthing and providing nutrition until the child is weaned. Children are left to be raised by other members of the society. Often, it is older siblings or cousins who assume the role we associate with parenthood.

The diversity of attitudes and child-rearing practices that Professor Lancy lays out in his tome is fascinating, even shocking at times, but after a few hundred pages one gets the message. But what I and every other parent want to know is if there is a common thread in these diverse cultures that can help us define the “natural” or the “best” or the “correct” way to parent our children. This question is particularly vexing for us in the WEIRD as we have become more heterogeneous, diverse, and multicultural. Most new millennium parents have no cultural tradition to fall back on, or if they have one it is likely to be very different from their partner in parenting. The result is that many parents find themselves on a constant, anxiety-driven search for the proper way to raise their child.

It’s not entirely clear to me how he arrives at it, but Professor Lancy offers his opinion on how we WEIRDs should raise our children. He feels we are taking the job of parenting far too seriously, and as a result, are meddling in a process that is best left to play out on its own. He observes, as do I, that children learn best by doing and imitating, not by being taught. Parents, specifically “involved” parents, are not a necessary requirement of successful child rearing. This message may come as an ego-busting shock to some parents. On the other hand, it should be liberating and guilt assuaging for parents whose careers and lifestyles limit the time they can spend with their children.

While I agree with Professor Lancy’s observation that much of the parenting that is done our society is unnecessary, and even at times counterproductive, the problem is that our society doesn’t offer many alternatives that provide the children an environment in which they can learn by doing and imitating. For example, grouping child care and preschool by age isolates young children from older children who can provide powerful role models for skill development. Unrealistic parental and provider fears about injury build barriers that rob children of opportunities to learn and grow.

The fact that here in the WEIRD families tend to have low birth rates makes it unlikely that parents will back off from overfocusing on their children. However, with help from knowledgeable and experienced experts in child health and behavior – pediatricians – there may be hope that some parents can learn to step back and let their children learn and develop in a more natural way.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Coping with a Picky Eater.” Email him at pdnews@frontlinemedcom.com.

Patients with stroke and sleep apnea may have worse memory and executive function than individuals with sleep apnea alone, stroke alone, or neither diagnosis, according to research presented at the 67th Annual Meeting of the American Academy of Neurology. To read the full article, go to Neurology Reviews.

Patients with stroke and sleep apnea may have worse memory and executive function than individuals with sleep apnea alone, stroke alone, or neither diagnosis, according to research presented at the 67th Annual Meeting of the American Academy of Neurology. To read the full article, go to Neurology Reviews.

Patients with stroke and sleep apnea may have worse memory and executive function than individuals with sleep apnea alone, stroke alone, or neither diagnosis, according to research presented at the 67th Annual Meeting of the American Academy of Neurology. To read the full article, go to Neurology Reviews.

The Centers for Disease Control and Prevention’s A Guide to Comprehensive Hepatitis C Testing and Counseling focuses on identifying hepatitis C infection in adults born between 1945 and 1965. The guide, which is available at http://www.cdc.gov/hepatitis/resources/professionals/pdfs/counselingandtestingpc.pdf, explains why these patients need to be tested, covers testing recommendations, and describes how to counsel patients about the results. (Sample scripts are included.)

The Centers for Disease Control and Prevention’s A Guide to Comprehensive Hepatitis C Testing and Counseling focuses on identifying hepatitis C infection in adults born between 1945 and 1965. The guide, which is available at http://www.cdc.gov/hepatitis/resources/professionals/pdfs/counselingandtestingpc.pdf, explains why these patients need to be tested, covers testing recommendations, and describes how to counsel patients about the results. (Sample scripts are included.)

The Centers for Disease Control and Prevention’s A Guide to Comprehensive Hepatitis C Testing and Counseling focuses on identifying hepatitis C infection in adults born between 1945 and 1965. The guide, which is available at http://www.cdc.gov/hepatitis/resources/professionals/pdfs/counselingandtestingpc.pdf, explains why these patients need to be tested, covers testing recommendations, and describes how to counsel patients about the results. (Sample scripts are included.)

Reducing morbidity and mortality is the focus of medicine, and much of our day is spent focusing on this, but how much do we as pediatricians address on the leading cause of death in teens? Motor vehicle accidents are the leading cause of death among 15- to 20-year-olds. In 2011, about 2,650 teens in the United States aged 16-19 years were killed and almost 292,000 were treated in emergency departments for injuries suffered in motor vehicle crashes, according to the Centers for Disease Control and Prevention^. In 2010, the American Academy of Pediatrics reaffirmed its statement that was published on teen drivers in 2006, which encouraged pediatricians to be active participants in the education and lobbying for laws that promote of safe driving.

It may appear to be out of the scope of treatment to educate on safe driving, but the reality is that many parents are unaware of the risk factors that contribute to unsafe driving, as well the conditions that can be managed to improve their driving ability.

The major risk factors for increased injury among teens are immaturity, which leads to increased risk taking; inexperience; and distractions. Immaturity is the leading risk factor, clearly demonstrated in the number of crashes involving 16-year-old drivers, which is two times greater when compared with 17-year-olds and three times greater when compared with 25- to 29-year-olds.

Although distracted driving is not a problem limited to just teens, that compounded with inexperience certainly explains why they account for 14% of fatal accidents despite being only 6% of drivers. It has been statistically shown that the greater the number of teens in a vehicle, the more likely they are to have an accident. Talking on the phone also increases the risk of an accident, but “hands-free” driving shows little improvement in risk. Texting and driving is the leading cause of death among teens, accounting for 3,000 deaths annually according to a study by Cohen Children’s Medical Center, in New Hyde Park, N.Y., which surpasses drinking and driving; www.teendriversource.org reports the statistics on teen driving and stated that brain activity needed for driving is reduced by 37%. Many teens self-report texting and driving and “near accidents.”

Attention-deficit/hyperactivity disorder (ADHD) also has been shown to put teen drivers at increased risk. Teens with ADHD show two to four times the increased risk of crashes.Psychostimulants have been shown to significantly improve their attention during driving, and long-acting methylphenidate has been shown to more effective, even for nighttime driving, over the short-acting methylphenidate (Pediatrics 2006;118:2570-81).

Fairly recent changes in laws and driver education has shown significant improvement in accident rates. Graduated driver laws started in 1996, and now is the law in every state. The minimum requirements include a learner’s permit of 2 months of longer, night restriction, and passenger restriction; states vary in their requirements. Optimally, graduated driver laws include a three-phase program that starts with the learner’s permit, vision screen, and driver’s test. Phase two is supervised driving, which also requires 6 months of no violations, 12 months of no crashes, and the road test. Phase three is a full license without restrictions.

Analysis of this program by state showed a significant reduction in crashes among the 15- to 19-year-olds. The reduction was mostly attributed to the restriction in nighttime driving, restricted number of passengers, and the extend period of supervised driving. In 1997, Florida’s first full year of its graduated driver law system, there was a 9% reduction in fatal and injury crashes for 15- to 17-year-olds, compared with 1995. All of these are important teaching points for parents; the National Highway Traffic Safety Administration is an excellent resource for statistics on the distracted driver to encourage teens to put the phones down.

Motor vehicle accidents are the No. 1 cause of death for teens, according to the Centers for Disease Control and Prevention. If our role as a pediatrician is to prevent morbidity and mortality, then we must play an active role in educating our patients on seriousness of safe driving. Just as we promote vaccines for the prevention of illness, we must promote the rules of the road to prevent an early and avoidable death.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at pdnews@frontlinemedcom.com.

Reducing morbidity and mortality is the focus of medicine, and much of our day is spent focusing on this, but how much do we as pediatricians address on the leading cause of death in teens? Motor vehicle accidents are the leading cause of death among 15- to 20-year-olds. In 2011, about 2,650 teens in the United States aged 16-19 years were killed and almost 292,000 were treated in emergency departments for injuries suffered in motor vehicle crashes, according to the Centers for Disease Control and Prevention^. In 2010, the American Academy of Pediatrics reaffirmed its statement that was published on teen drivers in 2006, which encouraged pediatricians to be active participants in the education and lobbying for laws that promote of safe driving.

It may appear to be out of the scope of treatment to educate on safe driving, but the reality is that many parents are unaware of the risk factors that contribute to unsafe driving, as well the conditions that can be managed to improve their driving ability.

The major risk factors for increased injury among teens are immaturity, which leads to increased risk taking; inexperience; and distractions. Immaturity is the leading risk factor, clearly demonstrated in the number of crashes involving 16-year-old drivers, which is two times greater when compared with 17-year-olds and three times greater when compared with 25- to 29-year-olds.

Although distracted driving is not a problem limited to just teens, that compounded with inexperience certainly explains why they account for 14% of fatal accidents despite being only 6% of drivers. It has been statistically shown that the greater the number of teens in a vehicle, the more likely they are to have an accident. Talking on the phone also increases the risk of an accident, but “hands-free” driving shows little improvement in risk. Texting and driving is the leading cause of death among teens, accounting for 3,000 deaths annually according to a study by Cohen Children’s Medical Center, in New Hyde Park, N.Y., which surpasses drinking and driving; www.teendriversource.org reports the statistics on teen driving and stated that brain activity needed for driving is reduced by 37%. Many teens self-report texting and driving and “near accidents.”

Attention-deficit/hyperactivity disorder (ADHD) also has been shown to put teen drivers at increased risk. Teens with ADHD show two to four times the increased risk of crashes.Psychostimulants have been shown to significantly improve their attention during driving, and long-acting methylphenidate has been shown to more effective, even for nighttime driving, over the short-acting methylphenidate (Pediatrics 2006;118:2570-81).

Fairly recent changes in laws and driver education has shown significant improvement in accident rates. Graduated driver laws started in 1996, and now is the law in every state. The minimum requirements include a learner’s permit of 2 months of longer, night restriction, and passenger restriction; states vary in their requirements. Optimally, graduated driver laws include a three-phase program that starts with the learner’s permit, vision screen, and driver’s test. Phase two is supervised driving, which also requires 6 months of no violations, 12 months of no crashes, and the road test. Phase three is a full license without restrictions.

Analysis of this program by state showed a significant reduction in crashes among the 15- to 19-year-olds. The reduction was mostly attributed to the restriction in nighttime driving, restricted number of passengers, and the extend period of supervised driving. In 1997, Florida’s first full year of its graduated driver law system, there was a 9% reduction in fatal and injury crashes for 15- to 17-year-olds, compared with 1995. All of these are important teaching points for parents; the National Highway Traffic Safety Administration is an excellent resource for statistics on the distracted driver to encourage teens to put the phones down.

Motor vehicle accidents are the No. 1 cause of death for teens, according to the Centers for Disease Control and Prevention. If our role as a pediatrician is to prevent morbidity and mortality, then we must play an active role in educating our patients on seriousness of safe driving. Just as we promote vaccines for the prevention of illness, we must promote the rules of the road to prevent an early and avoidable death.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at pdnews@frontlinemedcom.com.

Reducing morbidity and mortality is the focus of medicine, and much of our day is spent focusing on this, but how much do we as pediatricians address on the leading cause of death in teens? Motor vehicle accidents are the leading cause of death among 15- to 20-year-olds. In 2011, about 2,650 teens in the United States aged 16-19 years were killed and almost 292,000 were treated in emergency departments for injuries suffered in motor vehicle crashes, according to the Centers for Disease Control and Prevention^. In 2010, the American Academy of Pediatrics reaffirmed its statement that was published on teen drivers in 2006, which encouraged pediatricians to be active participants in the education and lobbying for laws that promote of safe driving.

It may appear to be out of the scope of treatment to educate on safe driving, but the reality is that many parents are unaware of the risk factors that contribute to unsafe driving, as well the conditions that can be managed to improve their driving ability.

The major risk factors for increased injury among teens are immaturity, which leads to increased risk taking; inexperience; and distractions. Immaturity is the leading risk factor, clearly demonstrated in the number of crashes involving 16-year-old drivers, which is two times greater when compared with 17-year-olds and three times greater when compared with 25- to 29-year-olds.

Although distracted driving is not a problem limited to just teens, that compounded with inexperience certainly explains why they account for 14% of fatal accidents despite being only 6% of drivers. It has been statistically shown that the greater the number of teens in a vehicle, the more likely they are to have an accident. Talking on the phone also increases the risk of an accident, but “hands-free” driving shows little improvement in risk. Texting and driving is the leading cause of death among teens, accounting for 3,000 deaths annually according to a study by Cohen Children’s Medical Center, in New Hyde Park, N.Y., which surpasses drinking and driving; www.teendriversource.org reports the statistics on teen driving and stated that brain activity needed for driving is reduced by 37%. Many teens self-report texting and driving and “near accidents.”

Attention-deficit/hyperactivity disorder (ADHD) also has been shown to put teen drivers at increased risk. Teens with ADHD show two to four times the increased risk of crashes.Psychostimulants have been shown to significantly improve their attention during driving, and long-acting methylphenidate has been shown to more effective, even for nighttime driving, over the short-acting methylphenidate (Pediatrics 2006;118:2570-81).

Fairly recent changes in laws and driver education has shown significant improvement in accident rates. Graduated driver laws started in 1996, and now is the law in every state. The minimum requirements include a learner’s permit of 2 months of longer, night restriction, and passenger restriction; states vary in their requirements. Optimally, graduated driver laws include a three-phase program that starts with the learner’s permit, vision screen, and driver’s test. Phase two is supervised driving, which also requires 6 months of no violations, 12 months of no crashes, and the road test. Phase three is a full license without restrictions.

Analysis of this program by state showed a significant reduction in crashes among the 15- to 19-year-olds. The reduction was mostly attributed to the restriction in nighttime driving, restricted number of passengers, and the extend period of supervised driving. In 1997, Florida’s first full year of its graduated driver law system, there was a 9% reduction in fatal and injury crashes for 15- to 17-year-olds, compared with 1995. All of these are important teaching points for parents; the National Highway Traffic Safety Administration is an excellent resource for statistics on the distracted driver to encourage teens to put the phones down.

Motor vehicle accidents are the No. 1 cause of death for teens, according to the Centers for Disease Control and Prevention. If our role as a pediatrician is to prevent morbidity and mortality, then we must play an active role in educating our patients on seriousness of safe driving. Just as we promote vaccines for the prevention of illness, we must promote the rules of the road to prevent an early and avoidable death.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at pdnews@frontlinemedcom.com.

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(Reuters Health) - Patients with hypertension who regularly take non-steroidal anti-inflammatory drugs (NSAIDs) may increase their risk of developing chronic kidney disease, a study from Taiwan suggests.

The researchers examined data on more than 30,000 people with hypertension and found that those who'd been taking NSAIDs for at least three months were 32% more likely to have chronic kidney disease than participants who didn't use NSAIDs.

In addition, participants who typically took NSAIDs more than once a day had a 23% greater risk of developing chronic kidney disease than people who didn't use the pills.

Even if patients used NSAIDs for less than three months, they still had an 18% higher risk of developing chronic kidney disease, the study found.

"Our results suggest that NSAID duration plays a role in chronic kidney disease among subjects with hypertension," said senior study author Hui-Ju Tsai, a scientist at the Institute of Population Health Sciences, National Health Research Institutes in Zhunan.

"Physicians should exercise caution when administering NSAIDs to people with hypertension and closely monitor renal function," Tsai said by email.

One shortcoming of the study is a lack of blood test data to confirm the severity of kidney disease, the authors noted online July 13 in Hypertension. It's also possible that some patients with kidney disease weren't identified due to a lack of clinical or laboratory data.

In addition, the study only tracked prescription NSAID use. In Taiwan, the vast majority of people taking these drugs get prescriptions because the cost is much lower than it would be for over-the-counter versions of the drugs, the authors point out.

While past research has suggested that kidney damage linked to NSAIDs might be reversed if the drugs are stopped, the current study points to the possibility that long-term use of these painkillers might lead to permanently impaired renal function, said Dr. Liffert Vogt, a nephrologist at Academic Medical Center at the University of Amsterdam in The Netherlands.

NSAIDs can cause the kidney to retain salts and water, prompting a rise in blood pressure and potentially making medications to lower hypertension ineffective, Vogt, who wasn't involved in the study, said by email.

"When a patient is already treated with a blood pressure lowering drug, NSAIDs should be avoided," Vogt said. "The negative effects of NSAIDs on the kidneys can be explained by their effects on blood pressure control."

(Reuters Health) - Patients with hypertension who regularly take non-steroidal anti-inflammatory drugs (NSAIDs) may increase their risk of developing chronic kidney disease, a study from Taiwan suggests.

The researchers examined data on more than 30,000 people with hypertension and found that those who'd been taking NSAIDs for at least three months were 32% more likely to have chronic kidney disease than participants who didn't use NSAIDs.

In addition, participants who typically took NSAIDs more than once a day had a 23% greater risk of developing chronic kidney disease than people who didn't use the pills.

Even if patients used NSAIDs for less than three months, they still had an 18% higher risk of developing chronic kidney disease, the study found.

"Our results suggest that NSAID duration plays a role in chronic kidney disease among subjects with hypertension," said senior study author Hui-Ju Tsai, a scientist at the Institute of Population Health Sciences, National Health Research Institutes in Zhunan.

"Physicians should exercise caution when administering NSAIDs to people with hypertension and closely monitor renal function," Tsai said by email.

One shortcoming of the study is a lack of blood test data to confirm the severity of kidney disease, the authors noted online July 13 in Hypertension. It's also possible that some patients with kidney disease weren't identified due to a lack of clinical or laboratory data.

In addition, the study only tracked prescription NSAID use. In Taiwan, the vast majority of people taking these drugs get prescriptions because the cost is much lower than it would be for over-the-counter versions of the drugs, the authors point out.

While past research has suggested that kidney damage linked to NSAIDs might be reversed if the drugs are stopped, the current study points to the possibility that long-term use of these painkillers might lead to permanently impaired renal function, said Dr. Liffert Vogt, a nephrologist at Academic Medical Center at the University of Amsterdam in The Netherlands.

NSAIDs can cause the kidney to retain salts and water, prompting a rise in blood pressure and potentially making medications to lower hypertension ineffective, Vogt, who wasn't involved in the study, said by email.

"When a patient is already treated with a blood pressure lowering drug, NSAIDs should be avoided," Vogt said. "The negative effects of NSAIDs on the kidneys can be explained by their effects on blood pressure control."

(Reuters Health) - Patients with hypertension who regularly take non-steroidal anti-inflammatory drugs (NSAIDs) may increase their risk of developing chronic kidney disease, a study from Taiwan suggests.

The researchers examined data on more than 30,000 people with hypertension and found that those who'd been taking NSAIDs for at least three months were 32% more likely to have chronic kidney disease than participants who didn't use NSAIDs.

In addition, participants who typically took NSAIDs more than once a day had a 23% greater risk of developing chronic kidney disease than people who didn't use the pills.

Even if patients used NSAIDs for less than three months, they still had an 18% higher risk of developing chronic kidney disease, the study found.

"Our results suggest that NSAID duration plays a role in chronic kidney disease among subjects with hypertension," said senior study author Hui-Ju Tsai, a scientist at the Institute of Population Health Sciences, National Health Research Institutes in Zhunan.

"Physicians should exercise caution when administering NSAIDs to people with hypertension and closely monitor renal function," Tsai said by email.

One shortcoming of the study is a lack of blood test data to confirm the severity of kidney disease, the authors noted online July 13 in Hypertension. It's also possible that some patients with kidney disease weren't identified due to a lack of clinical or laboratory data.

In addition, the study only tracked prescription NSAID use. In Taiwan, the vast majority of people taking these drugs get prescriptions because the cost is much lower than it would be for over-the-counter versions of the drugs, the authors point out.

While past research has suggested that kidney damage linked to NSAIDs might be reversed if the drugs are stopped, the current study points to the possibility that long-term use of these painkillers might lead to permanently impaired renal function, said Dr. Liffert Vogt, a nephrologist at Academic Medical Center at the University of Amsterdam in The Netherlands.

NSAIDs can cause the kidney to retain salts and water, prompting a rise in blood pressure and potentially making medications to lower hypertension ineffective, Vogt, who wasn't involved in the study, said by email.

"When a patient is already treated with a blood pressure lowering drug, NSAIDs should be avoided," Vogt said. "The negative effects of NSAIDs on the kidneys can be explained by their effects on blood pressure control."

Drs. Pate and Engel presented a hot topic in pediatric hospital medicine, sparking fruitful conversation about current evidence, identified gaps, and controversies regarding the management of febrile infants with urinary tract infections. After the American Academy of Pediatrics published the updated clinical guideline in 2011, controversies about radioimaging, duration of treatment, and pursuit of laboratory evaluations arose. These controversies continue today, and value and gold standard tests are now being questioned. Should urine culture truly be the gold standard to define a UTI?

The current evidence (applying to 2 month-2 years) in a nutshell includes:

• Oral and parental antibiotics are equally efficacious,
• Duration of treatment is a wide range of 7-14 days,
• Positive UA indicating inflammation/infection and a culture >50,000 uropathogens/ml is needed to make the diagnosis, and
• Febrile infants with first UTI should get a renal ultrasound; only if the ultrasound is abnormal should patients get a Voiding Cystourethrogram (VCUG).

Since the guideline was published in 2011, there has been continued disagreement between pediatricians and pediatric urologists. When thinking about high-value care, what value is added by doing the renal ultrasound and/or VCUG? The research over the last couple of years shows that although there is concern that UTIs lead to renal scarring and chronic kidney disease, in the absence of structural kidney abnormalities, recurrent UTIs cause at most 0.3% of chronic kidney disease. The takehome point from the 2014 RIVUR study is:

• The treatment group had significantly higher rates of resistance organisms (63% ppx 19% placebo).
• The NNT with prophylaxis in children with VUR is 9 children for 2 years to prevent 1 UTI, or 6570 days of antibiotics to prevent one 7-14 day course.

The RIVUR study raised more questions:

• Is there a difference in outcome if a child had concurrent bacteremia?

  • There is no significant difference in clinical presentation between an isolated UTI and an infant with bacteremia. Those patients with bacteremia received longer duration of parenteral antibiotics, but the number of days were highly variable and outcomes were excellent overall regardless.

• How accurate is UA in the diagnosis of urinary tract infections in infants less than 3 months of age?

  • Urinalysis in those infants

• Could inflammatory markers accurately identify infants at high risk for more severe disease?

  • Not really.

Guidelines were reviewed, controversies were discussed, and questions were proposed. The session ended with tools to take home to help change hospital practice, and quality-UTI projects metrics were shared, as this is the next AAP VIP project about to launch.

Key Takeaways:

• The guidelines represent a living and dynamic tool that integrates the best evidence we have.
• There is new research evolving and lessons to be learned.

Dr. Hopkins is an academic pediatric hospitalist and instructor at All Children's Hospital Johns Hopkins Medicine, St. Petersburg, Fla.​

Drs. Pate and Engel presented a hot topic in pediatric hospital medicine, sparking fruitful conversation about current evidence, identified gaps, and controversies regarding the management of febrile infants with urinary tract infections. After the American Academy of Pediatrics published the updated clinical guideline in 2011, controversies about radioimaging, duration of treatment, and pursuit of laboratory evaluations arose. These controversies continue today, and value and gold standard tests are now being questioned. Should urine culture truly be the gold standard to define a UTI?

The current evidence (applying to 2 month-2 years) in a nutshell includes:

• Oral and parental antibiotics are equally efficacious,
• Duration of treatment is a wide range of 7-14 days,
• Positive UA indicating inflammation/infection and a culture >50,000 uropathogens/ml is needed to make the diagnosis, and
• Febrile infants with first UTI should get a renal ultrasound; only if the ultrasound is abnormal should patients get a Voiding Cystourethrogram (VCUG).

Since the guideline was published in 2011, there has been continued disagreement between pediatricians and pediatric urologists. When thinking about high-value care, what value is added by doing the renal ultrasound and/or VCUG? The research over the last couple of years shows that although there is concern that UTIs lead to renal scarring and chronic kidney disease, in the absence of structural kidney abnormalities, recurrent UTIs cause at most 0.3% of chronic kidney disease. The takehome point from the 2014 RIVUR study is:

• The treatment group had significantly higher rates of resistance organisms (63% ppx 19% placebo).
• The NNT with prophylaxis in children with VUR is 9 children for 2 years to prevent 1 UTI, or 6570 days of antibiotics to prevent one 7-14 day course.

The RIVUR study raised more questions:

• Is there a difference in outcome if a child had concurrent bacteremia?

  • There is no significant difference in clinical presentation between an isolated UTI and an infant with bacteremia. Those patients with bacteremia received longer duration of parenteral antibiotics, but the number of days were highly variable and outcomes were excellent overall regardless.

• How accurate is UA in the diagnosis of urinary tract infections in infants less than 3 months of age?

  • Urinalysis in those infants

• Could inflammatory markers accurately identify infants at high risk for more severe disease?

  • Not really.

Guidelines were reviewed, controversies were discussed, and questions were proposed. The session ended with tools to take home to help change hospital practice, and quality-UTI projects metrics were shared, as this is the next AAP VIP project about to launch.

Key Takeaways:

• The guidelines represent a living and dynamic tool that integrates the best evidence we have.
• There is new research evolving and lessons to be learned.

Dr. Hopkins is an academic pediatric hospitalist and instructor at All Children's Hospital Johns Hopkins Medicine, St. Petersburg, Fla.​

Drs. Pate and Engel presented a hot topic in pediatric hospital medicine, sparking fruitful conversation about current evidence, identified gaps, and controversies regarding the management of febrile infants with urinary tract infections. After the American Academy of Pediatrics published the updated clinical guideline in 2011, controversies about radioimaging, duration of treatment, and pursuit of laboratory evaluations arose. These controversies continue today, and value and gold standard tests are now being questioned. Should urine culture truly be the gold standard to define a UTI?

The current evidence (applying to 2 month-2 years) in a nutshell includes:

• Oral and parental antibiotics are equally efficacious,
• Duration of treatment is a wide range of 7-14 days,
• Positive UA indicating inflammation/infection and a culture >50,000 uropathogens/ml is needed to make the diagnosis, and
• Febrile infants with first UTI should get a renal ultrasound; only if the ultrasound is abnormal should patients get a Voiding Cystourethrogram (VCUG).

Since the guideline was published in 2011, there has been continued disagreement between pediatricians and pediatric urologists. When thinking about high-value care, what value is added by doing the renal ultrasound and/or VCUG? The research over the last couple of years shows that although there is concern that UTIs lead to renal scarring and chronic kidney disease, in the absence of structural kidney abnormalities, recurrent UTIs cause at most 0.3% of chronic kidney disease. The takehome point from the 2014 RIVUR study is:

• The treatment group had significantly higher rates of resistance organisms (63% ppx 19% placebo).
• The NNT with prophylaxis in children with VUR is 9 children for 2 years to prevent 1 UTI, or 6570 days of antibiotics to prevent one 7-14 day course.

The RIVUR study raised more questions:

• Is there a difference in outcome if a child had concurrent bacteremia?

  • There is no significant difference in clinical presentation between an isolated UTI and an infant with bacteremia. Those patients with bacteremia received longer duration of parenteral antibiotics, but the number of days were highly variable and outcomes were excellent overall regardless.

• How accurate is UA in the diagnosis of urinary tract infections in infants less than 3 months of age?

  • Urinalysis in those infants

• Could inflammatory markers accurately identify infants at high risk for more severe disease?

  • Not really.

Guidelines were reviewed, controversies were discussed, and questions were proposed. The session ended with tools to take home to help change hospital practice, and quality-UTI projects metrics were shared, as this is the next AAP VIP project about to launch.

Key Takeaways:

• The guidelines represent a living and dynamic tool that integrates the best evidence we have.
• There is new research evolving and lessons to be learned.

Dr. Hopkins is an academic pediatric hospitalist and instructor at All Children's Hospital Johns Hopkins Medicine, St. Petersburg, Fla.​

Doctor and patient in hospital

Photo courtesy of the CDC

Imposing financial penalties on hospitals based on the incidence of hospital-acquired venous thromboembolism (VTE) may be unfair, according to researchers.

They argue that pay-for-performance systems should take VTE prevention efforts into account, instead of simply tallying the number of hospital-acquired VTEs.

They say the current system fails to account for VTEs that occur despite appropriate use of preventive therapies.

The researchers expressed this viewpoint and disclosed research supporting it in a letter to JAMA Surgery.

“We have a big problem with current pay-for-performance systems based on ‘numbers-only’ total counts of clots, because even when hospitals do everything they can to prevent venous thromboembolism events, they are still being dinged for patients who develop these clots,” said Elliott R. Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“Our study of patients just at The Johns Hopkins Hospital identifies a need to dramatically re-evaluate the venous thromboembolism outcome and process measures. Nearly half of the venous thromboembolism events identified by the state program in the records we reviewed were not truly preventable because patients received best practice prevention and still developed blood clots.”

Dr Haut and his colleagues reviewed case records for 128 patients treated between July 2010 and June 2011 at The Johns Hopkins Hospital and who developed hospital-acquired VTE. All 128 were flagged by the Maryland Hospital Acquired Conditions pay-for-performance program.

The researchers looked for evidence that all of the VTEs could have been prevented. They found that 36 patients (28%) had nonpreventable, catheter-related upper extremity deep vein thrombosis (DVT), leaving 92 patients (72%) with clots that were potentially preventable.

Of those 92 patients, 45 had a DVT, 43 had a pulmonary embolism (PE), and 4 had a DVT and PE.

Seventy-nine of the 92 patients (86%) were prescribed optimal thromboprophylaxis, yet only 43 (47%) received “defect-free care,” the researchers found.

Of the 49 patients (53%) who received suboptimal care, 13 (27%) were not prescribed risk-appropriate anticoagulants, and 36 (73%) missed at least one dose of appropriately prescribed medication.

Dr Haut noted that a team of physicians, nurses, quality care researchers, and pharmacists at Johns Hopkins has been studying VTE prevention for the past decade.

Team members have implemented programs to monitor patients in need of VTE prophylaxis through the hospital’s electronic health record system, and they conducted special training for nurses and patients to stress the importance of taking every dose of prescribed medication.

“We know we’re not going to get the VTE rate to 0, but my goal is to have every single one of these events—when they happen—occur when the patient receives best-practice, defect-free care,” Dr Haut said.

The current VTE care goal set by agencies like the Joint Commission and the Centers for Medicare and Medicaid Services is that one dose of VTE prophylaxis is given to patients within the first day of hospitalization. But Dr Haut said this is not enough.

“To reduce preventable harm, policymakers need to re-evaluate how they penalize hospitals and improve the measures they use to assess VTE prevention performance,” he said. “In addition, clinicians need to ensure that patients receive all prescribed preventive therapies.”

Doctor and patient in hospital

Photo courtesy of the CDC

Imposing financial penalties on hospitals based on the incidence of hospital-acquired venous thromboembolism (VTE) may be unfair, according to researchers.

They argue that pay-for-performance systems should take VTE prevention efforts into account, instead of simply tallying the number of hospital-acquired VTEs.

They say the current system fails to account for VTEs that occur despite appropriate use of preventive therapies.

The researchers expressed this viewpoint and disclosed research supporting it in a letter to JAMA Surgery.

“We have a big problem with current pay-for-performance systems based on ‘numbers-only’ total counts of clots, because even when hospitals do everything they can to prevent venous thromboembolism events, they are still being dinged for patients who develop these clots,” said Elliott R. Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“Our study of patients just at The Johns Hopkins Hospital identifies a need to dramatically re-evaluate the venous thromboembolism outcome and process measures. Nearly half of the venous thromboembolism events identified by the state program in the records we reviewed were not truly preventable because patients received best practice prevention and still developed blood clots.”

Dr Haut and his colleagues reviewed case records for 128 patients treated between July 2010 and June 2011 at The Johns Hopkins Hospital and who developed hospital-acquired VTE. All 128 were flagged by the Maryland Hospital Acquired Conditions pay-for-performance program.

The researchers looked for evidence that all of the VTEs could have been prevented. They found that 36 patients (28%) had nonpreventable, catheter-related upper extremity deep vein thrombosis (DVT), leaving 92 patients (72%) with clots that were potentially preventable.

Of those 92 patients, 45 had a DVT, 43 had a pulmonary embolism (PE), and 4 had a DVT and PE.

Seventy-nine of the 92 patients (86%) were prescribed optimal thromboprophylaxis, yet only 43 (47%) received “defect-free care,” the researchers found.

Of the 49 patients (53%) who received suboptimal care, 13 (27%) were not prescribed risk-appropriate anticoagulants, and 36 (73%) missed at least one dose of appropriately prescribed medication.

Dr Haut noted that a team of physicians, nurses, quality care researchers, and pharmacists at Johns Hopkins has been studying VTE prevention for the past decade.

Team members have implemented programs to monitor patients in need of VTE prophylaxis through the hospital’s electronic health record system, and they conducted special training for nurses and patients to stress the importance of taking every dose of prescribed medication.

“We know we’re not going to get the VTE rate to 0, but my goal is to have every single one of these events—when they happen—occur when the patient receives best-practice, defect-free care,” Dr Haut said.

The current VTE care goal set by agencies like the Joint Commission and the Centers for Medicare and Medicaid Services is that one dose of VTE prophylaxis is given to patients within the first day of hospitalization. But Dr Haut said this is not enough.

“To reduce preventable harm, policymakers need to re-evaluate how they penalize hospitals and improve the measures they use to assess VTE prevention performance,” he said. “In addition, clinicians need to ensure that patients receive all prescribed preventive therapies.”

Doctor and patient in hospital

Photo courtesy of the CDC

Imposing financial penalties on hospitals based on the incidence of hospital-acquired venous thromboembolism (VTE) may be unfair, according to researchers.

They argue that pay-for-performance systems should take VTE prevention efforts into account, instead of simply tallying the number of hospital-acquired VTEs.

They say the current system fails to account for VTEs that occur despite appropriate use of preventive therapies.

The researchers expressed this viewpoint and disclosed research supporting it in a letter to JAMA Surgery.

“We have a big problem with current pay-for-performance systems based on ‘numbers-only’ total counts of clots, because even when hospitals do everything they can to prevent venous thromboembolism events, they are still being dinged for patients who develop these clots,” said Elliott R. Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

“Our study of patients just at The Johns Hopkins Hospital identifies a need to dramatically re-evaluate the venous thromboembolism outcome and process measures. Nearly half of the venous thromboembolism events identified by the state program in the records we reviewed were not truly preventable because patients received best practice prevention and still developed blood clots.”

Dr Haut and his colleagues reviewed case records for 128 patients treated between July 2010 and June 2011 at The Johns Hopkins Hospital and who developed hospital-acquired VTE. All 128 were flagged by the Maryland Hospital Acquired Conditions pay-for-performance program.

The researchers looked for evidence that all of the VTEs could have been prevented. They found that 36 patients (28%) had nonpreventable, catheter-related upper extremity deep vein thrombosis (DVT), leaving 92 patients (72%) with clots that were potentially preventable.

Of those 92 patients, 45 had a DVT, 43 had a pulmonary embolism (PE), and 4 had a DVT and PE.

Seventy-nine of the 92 patients (86%) were prescribed optimal thromboprophylaxis, yet only 43 (47%) received “defect-free care,” the researchers found.

Of the 49 patients (53%) who received suboptimal care, 13 (27%) were not prescribed risk-appropriate anticoagulants, and 36 (73%) missed at least one dose of appropriately prescribed medication.

Dr Haut noted that a team of physicians, nurses, quality care researchers, and pharmacists at Johns Hopkins has been studying VTE prevention for the past decade.

Team members have implemented programs to monitor patients in need of VTE prophylaxis through the hospital’s electronic health record system, and they conducted special training for nurses and patients to stress the importance of taking every dose of prescribed medication.

“We know we’re not going to get the VTE rate to 0, but my goal is to have every single one of these events—when they happen—occur when the patient receives best-practice, defect-free care,” Dr Haut said.

The current VTE care goal set by agencies like the Joint Commission and the Centers for Medicare and Medicaid Services is that one dose of VTE prophylaxis is given to patients within the first day of hospitalization. But Dr Haut said this is not enough.

“To reduce preventable harm, policymakers need to re-evaluate how they penalize hospitals and improve the measures they use to assess VTE prevention performance,” he said. “In addition, clinicians need to ensure that patients receive all prescribed preventive therapies.”

Aik Choon Tan, PhD

Photo courtesy of the

University of Colorado

Researchers say they have developed a tool that allows us to determine which tyrosine kinase inhibitor (TKI) will be most effective against a certain type of cancer.

The tool, known as the Kinase Addiction Ranker (KAR), predicts the genetic abnormalities that are driving the cancer in any population of cells and chooses the best TKI or combination of TKIs to target these abnormalities.

The researchers described the tool in Bioinformatics.

“A lot of [TKIs] inhibit a lot more than what they’re supposed to inhibit,” said study author Aik Choon Tan, PhD, of the University of Colorado Anschutz Medical Campus in Aurora.

“Maybe drug A was designed to inhibit kinase B, but it also inhibits kinase C and D as well. Our approach centers on exploiting the promiscuity of these drugs, the ‘drug spillover.’”

For each TKI, there is a signature describing the kinases each drug fully or partially inhibits. Dr Tan and his colleagues combined these kinase inhibition signatures with the results of high-throughput screening. They used the Genomics of Drug Sensitivity in Cancer database to determine which TKIs have already proven active against which cancer cell lines.

The result is KAR, which does 2 things. For any cancer cell line, the program ranks the kinases that are most important to the growth of the disease. Then, the program recommends the combination of existing TKIs that is likely to do the most good against the implicated kinases.

Dr Tan and his colleagues tested KAR using samples from 151 leukemia patients and found that, among the kinases analyzed, FLT3 had the highest variance in sensitivity to TKIs.

But EPHA5, EPHA3, and BTK were the kinases most commonly associated with drug sensitivity. They had significant associations in 72%, 58%, and 54% of the patient samples, respectively.

The researchers said the frequency of BTK dependence they observed is interesting given the fact that the BTK inhibitor ibrutinib produced favorable results in a phase 1b/2 trial of patients with chronic lymphocytic leukemia (CLL). The progression-free survival rate at 26 months was 75% in that trial.

Dr Tan and his colleagues said this was consistent with their findings, which showed that 70% of CLL patient data had a significant association between BTK inhibition and drug sensitivity.

The researchers also found that KAR could predict TKI sensitivity in 21 lung cancer cell lines. In addition, the tool was able to recommend a combination of TKIs that hindered proliferation in the lung cancer cell line H1581. KAR suggested ponatinib and the experimental anticancer agent AZD8055, and experiments showed that these drugs synergistically reduced proliferation in H1581.

KAR is available for download on the Tan lab’s website.

Aik Choon Tan, PhD

Photo courtesy of the

University of Colorado

Researchers say they have developed a tool that allows us to determine which tyrosine kinase inhibitor (TKI) will be most effective against a certain type of cancer.

The tool, known as the Kinase Addiction Ranker (KAR), predicts the genetic abnormalities that are driving the cancer in any population of cells and chooses the best TKI or combination of TKIs to target these abnormalities.

The researchers described the tool in Bioinformatics.

“A lot of [TKIs] inhibit a lot more than what they’re supposed to inhibit,” said study author Aik Choon Tan, PhD, of the University of Colorado Anschutz Medical Campus in Aurora.

“Maybe drug A was designed to inhibit kinase B, but it also inhibits kinase C and D as well. Our approach centers on exploiting the promiscuity of these drugs, the ‘drug spillover.’”

For each TKI, there is a signature describing the kinases each drug fully or partially inhibits. Dr Tan and his colleagues combined these kinase inhibition signatures with the results of high-throughput screening. They used the Genomics of Drug Sensitivity in Cancer database to determine which TKIs have already proven active against which cancer cell lines.

The result is KAR, which does 2 things. For any cancer cell line, the program ranks the kinases that are most important to the growth of the disease. Then, the program recommends the combination of existing TKIs that is likely to do the most good against the implicated kinases.

Dr Tan and his colleagues tested KAR using samples from 151 leukemia patients and found that, among the kinases analyzed, FLT3 had the highest variance in sensitivity to TKIs.

But EPHA5, EPHA3, and BTK were the kinases most commonly associated with drug sensitivity. They had significant associations in 72%, 58%, and 54% of the patient samples, respectively.

The researchers said the frequency of BTK dependence they observed is interesting given the fact that the BTK inhibitor ibrutinib produced favorable results in a phase 1b/2 trial of patients with chronic lymphocytic leukemia (CLL). The progression-free survival rate at 26 months was 75% in that trial.

Dr Tan and his colleagues said this was consistent with their findings, which showed that 70% of CLL patient data had a significant association between BTK inhibition and drug sensitivity.

The researchers also found that KAR could predict TKI sensitivity in 21 lung cancer cell lines. In addition, the tool was able to recommend a combination of TKIs that hindered proliferation in the lung cancer cell line H1581. KAR suggested ponatinib and the experimental anticancer agent AZD8055, and experiments showed that these drugs synergistically reduced proliferation in H1581.

KAR is available for download on the Tan lab’s website.

Aik Choon Tan, PhD

Photo courtesy of the

University of Colorado

Researchers say they have developed a tool that allows us to determine which tyrosine kinase inhibitor (TKI) will be most effective against a certain type of cancer.

The tool, known as the Kinase Addiction Ranker (KAR), predicts the genetic abnormalities that are driving the cancer in any population of cells and chooses the best TKI or combination of TKIs to target these abnormalities.

The researchers described the tool in Bioinformatics.

“A lot of [TKIs] inhibit a lot more than what they’re supposed to inhibit,” said study author Aik Choon Tan, PhD, of the University of Colorado Anschutz Medical Campus in Aurora.

“Maybe drug A was designed to inhibit kinase B, but it also inhibits kinase C and D as well. Our approach centers on exploiting the promiscuity of these drugs, the ‘drug spillover.’”

For each TKI, there is a signature describing the kinases each drug fully or partially inhibits. Dr Tan and his colleagues combined these kinase inhibition signatures with the results of high-throughput screening. They used the Genomics of Drug Sensitivity in Cancer database to determine which TKIs have already proven active against which cancer cell lines.

The result is KAR, which does 2 things. For any cancer cell line, the program ranks the kinases that are most important to the growth of the disease. Then, the program recommends the combination of existing TKIs that is likely to do the most good against the implicated kinases.

Dr Tan and his colleagues tested KAR using samples from 151 leukemia patients and found that, among the kinases analyzed, FLT3 had the highest variance in sensitivity to TKIs.

But EPHA5, EPHA3, and BTK were the kinases most commonly associated with drug sensitivity. They had significant associations in 72%, 58%, and 54% of the patient samples, respectively.

The researchers said the frequency of BTK dependence they observed is interesting given the fact that the BTK inhibitor ibrutinib produced favorable results in a phase 1b/2 trial of patients with chronic lymphocytic leukemia (CLL). The progression-free survival rate at 26 months was 75% in that trial.

Dr Tan and his colleagues said this was consistent with their findings, which showed that 70% of CLL patient data had a significant association between BTK inhibition and drug sensitivity.

The researchers also found that KAR could predict TKI sensitivity in 21 lung cancer cell lines. In addition, the tool was able to recommend a combination of TKIs that hindered proliferation in the lung cancer cell line H1581. KAR suggested ponatinib and the experimental anticancer agent AZD8055, and experiments showed that these drugs synergistically reduced proliferation in H1581.

KAR is available for download on the Tan lab’s website.

Micrograph showing CTCL

New research suggests cutaneous T-cell lymphoma (CTCL) is driven by a plethora of genetic mutations.

Investigators conducted a genomic analysis of normal and cancer cells from patients with CTCL and identified mutations in 17 genes that are implicated in CTCL pathogenesis.

They also found that somatic copy number variants (SCNVs) driving CTCL outnumbered somatic single-nucleotide variants (SSNVs) by more than 10 to 1.

The team reported these findings in Nature Genetics.

They performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL cells and matched normal cells. And they identified genes implicated in CTCL pathogenesis by looking for:

• Genes with recurrent SSNVs altering the same amino acid more often than expected by chance
• Genes with SSNVs previously identified as recurrent mutations in other cancers
• Genes having a significantly increased burden of protein-altering SSNVs
• SCNVs that occurred more often than expected by chance.

This revealed mutations in 17 genes that are implicated in CTCL pathogenesis—TP53, ZEB1, ARID1A, DNMT3A, CDKN2A, FAS, NFKB2, CD28, RHOA, PLCG1, STAT5B, BRAF, ATM, CTCF, TNFAIP3, PRKCQ, and IRF4.

The investigators noted that these are genes involved in T-cell activation, apoptosis, NF-κB signaling, chromatin remodeling, and DNA damage response.

The team also discovered “a striking bias” for SCNVs as drivers of CTCL. They identified 12 statistically significant chromosome-arm SCNVs and 36 significant focal SCNVs.

Collectively, these SCNVs occurred 473 times in the CTCL samples analyzed—a mean of 7.5 focal deletions, 1.6 broad deletions, 1.0 focal amplification, and 1.8 broad amplifications per CTCL.

On the other hand, there were 38 SSNVs in CTCL driver genes—1.0 per tumor.

So, according to these data, SCNVs comprise 92% of all driver mutations in CTCL—a mean of 11.8 pathogenic SCNVs vs 1.0 SSNV per CTCL.

“This cancer has a very distinctive biology,” said Jaehyuk Choi, MD, PhD, of the Yale School of Medicine in New Haven, Connecticut.

And decoding this biology has revealed potential treatment approaches, according to Dr Choi and his colleagues.

For example, the presence of mutations activating the NF-κB pathway suggests NF-κB inhibitors such as bortezomib may have therapeutic potential in CTCL, and the presence of CD28 mutations suggests inhibitors such as abatacept may be effective against the disease.

Micrograph showing CTCL

New research suggests cutaneous T-cell lymphoma (CTCL) is driven by a plethora of genetic mutations.

Investigators conducted a genomic analysis of normal and cancer cells from patients with CTCL and identified mutations in 17 genes that are implicated in CTCL pathogenesis.

They also found that somatic copy number variants (SCNVs) driving CTCL outnumbered somatic single-nucleotide variants (SSNVs) by more than 10 to 1.

The team reported these findings in Nature Genetics.

They performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL cells and matched normal cells. And they identified genes implicated in CTCL pathogenesis by looking for:

• Genes with recurrent SSNVs altering the same amino acid more often than expected by chance
• Genes with SSNVs previously identified as recurrent mutations in other cancers
• Genes having a significantly increased burden of protein-altering SSNVs
• SCNVs that occurred more often than expected by chance.

This revealed mutations in 17 genes that are implicated in CTCL pathogenesis—TP53, ZEB1, ARID1A, DNMT3A, CDKN2A, FAS, NFKB2, CD28, RHOA, PLCG1, STAT5B, BRAF, ATM, CTCF, TNFAIP3, PRKCQ, and IRF4.

The investigators noted that these are genes involved in T-cell activation, apoptosis, NF-κB signaling, chromatin remodeling, and DNA damage response.

The team also discovered “a striking bias” for SCNVs as drivers of CTCL. They identified 12 statistically significant chromosome-arm SCNVs and 36 significant focal SCNVs.

Collectively, these SCNVs occurred 473 times in the CTCL samples analyzed—a mean of 7.5 focal deletions, 1.6 broad deletions, 1.0 focal amplification, and 1.8 broad amplifications per CTCL.

On the other hand, there were 38 SSNVs in CTCL driver genes—1.0 per tumor.

So, according to these data, SCNVs comprise 92% of all driver mutations in CTCL—a mean of 11.8 pathogenic SCNVs vs 1.0 SSNV per CTCL.

“This cancer has a very distinctive biology,” said Jaehyuk Choi, MD, PhD, of the Yale School of Medicine in New Haven, Connecticut.

And decoding this biology has revealed potential treatment approaches, according to Dr Choi and his colleagues.

For example, the presence of mutations activating the NF-κB pathway suggests NF-κB inhibitors such as bortezomib may have therapeutic potential in CTCL, and the presence of CD28 mutations suggests inhibitors such as abatacept may be effective against the disease.

Micrograph showing CTCL

New research suggests cutaneous T-cell lymphoma (CTCL) is driven by a plethora of genetic mutations.

Investigators conducted a genomic analysis of normal and cancer cells from patients with CTCL and identified mutations in 17 genes that are implicated in CTCL pathogenesis.

They also found that somatic copy number variants (SCNVs) driving CTCL outnumbered somatic single-nucleotide variants (SSNVs) by more than 10 to 1.

The team reported these findings in Nature Genetics.

They performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL cells and matched normal cells. And they identified genes implicated in CTCL pathogenesis by looking for:

• Genes with recurrent SSNVs altering the same amino acid more often than expected by chance
• Genes with SSNVs previously identified as recurrent mutations in other cancers
• Genes having a significantly increased burden of protein-altering SSNVs
• SCNVs that occurred more often than expected by chance.

This revealed mutations in 17 genes that are implicated in CTCL pathogenesis—TP53, ZEB1, ARID1A, DNMT3A, CDKN2A, FAS, NFKB2, CD28, RHOA, PLCG1, STAT5B, BRAF, ATM, CTCF, TNFAIP3, PRKCQ, and IRF4.

The investigators noted that these are genes involved in T-cell activation, apoptosis, NF-κB signaling, chromatin remodeling, and DNA damage response.

The team also discovered “a striking bias” for SCNVs as drivers of CTCL. They identified 12 statistically significant chromosome-arm SCNVs and 36 significant focal SCNVs.

Collectively, these SCNVs occurred 473 times in the CTCL samples analyzed—a mean of 7.5 focal deletions, 1.6 broad deletions, 1.0 focal amplification, and 1.8 broad amplifications per CTCL.

On the other hand, there were 38 SSNVs in CTCL driver genes—1.0 per tumor.

So, according to these data, SCNVs comprise 92% of all driver mutations in CTCL—a mean of 11.8 pathogenic SCNVs vs 1.0 SSNV per CTCL.

“This cancer has a very distinctive biology,” said Jaehyuk Choi, MD, PhD, of the Yale School of Medicine in New Haven, Connecticut.

And decoding this biology has revealed potential treatment approaches, according to Dr Choi and his colleagues.

For example, the presence of mutations activating the NF-κB pathway suggests NF-κB inhibitors such as bortezomib may have therapeutic potential in CTCL, and the presence of CD28 mutations suggests inhibitors such as abatacept may be effective against the disease.