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Texas’ tasty heart cake and Gotham’s coronavirus robot
Make dialysis great again!
Now, you’re probably thinking that Mr. Nelson tried to bring in his dog or some other animal, and that’s surely an issue of hygiene. But no, Mr. Gibson wasn’t bringing in a dog or cat, or even a squirrel or turkey, but a president.
Specifically, Mr. Nelson’s emotional support was one President Donald J. Trump.
Okay, it wasn’t actually Mr. Trump himself, but a life-sized (bigly?) cardboard cutout of the president smiling and offering two thumbs up. This, um, unusual choice was based on the president’s signing of an executive order in July 2019 launching an initiative promoting kidney disease awareness.
Mr. Nelson had previously been bringing in smaller images of the president. But when he brought in the large cutout – made by his son – a social worker at the center told him that the president couldn’t stay, adding that “this is not a Trump rally,” according to Mr. Nelson.
Naturally, this has caused quite a rift. Mr. Nelson feels that his freedom of expression and speech has been violated, and Fresenius says they can’t allow a support item so big because of those pesky health and safety regulations. Typical doctors.
The actual President Trump has yet to respond to this odd situation, but no doubt he’ll offer Fresenius a hearty “you’re fired!”
Your friendly neighborhood pandemic robot
Robots, of course!
A shiny new robot in Times Square not only can recognize symptoms of the coronavirus, it also can provide information to promote prevention and stop the spread. And if you look like a tourist, it’ll try to sell you half-priced tickets for a Big Apple bus tour. Move over, smartphones; having a robot analyze my symptoms sounds way more fun than frantically googling them.
The “Promobot” was designed with a friendly face and welcoming smile – that’s how you know the robot isn’t a local.
Interested users can interact with the Promobot’s iPad, which has a questionnaire regarding signs and symptoms of the coronavirus. Promobot doesn’t actually physically detect the virus (it’s a robot, not a blood test), but the questionnaire asks about general symptoms of coronavirus. At the end, the robot gives advice on how to proceed if the answers indicate the virus is present (hopefully without any panic-inducing fanfare).
Ah, New York: Where even the robots are friendlier than the residents.
Beating? No. Delicious? Yes
No, it’s a cake!
Heart!
Cake!
Wait, you’re both right. It’s two treats in one! It’s a heart and a cake. It’s the cake that looks like a heart.
Seriously, it really looks like a heart. It looks like it should still be beating. We’re talking anatomically correct and glistening with just-pulled-from-the-body freshness.
This latest wonder of the baking world comes from Crabby Cakes in Portland, Tex., just across the Nueces Bay Causeway from Corpus Christi. Just get on West Broadway Avenue from the I-181 frontage road, then make a right onto Wildcat Drive and a left at Maple Drive.
Crabby Cakes owner Jessica Wolfe is a big fan of horror movies and has even visited some of the sites where scenes were shot for “The Texas Chain Saw Massacre.” She told the Dallas Morning News that she “was trying to do something different for Valentine’s Day, cake-wise.”
She posted a video of the cake on the bakery’s Facebook page and it went viral, gobbling up over a million views in less than a week, the Morning News reported. Each cake costs $70 and will feed about five people, but the bakery cannot ship them out of state.
Among the cake-generated surprises was the attention she got from the health care industry. “Nurses, doctor’s offices, and graduates want the hearts,” Ms. Wolfe told the Morning News. “But they also want livers, kidneys, and lungs.”
Let’s just hope there aren’t any transplant surgeons calling.
Make dialysis great again!
Now, you’re probably thinking that Mr. Nelson tried to bring in his dog or some other animal, and that’s surely an issue of hygiene. But no, Mr. Gibson wasn’t bringing in a dog or cat, or even a squirrel or turkey, but a president.
Specifically, Mr. Nelson’s emotional support was one President Donald J. Trump.
Okay, it wasn’t actually Mr. Trump himself, but a life-sized (bigly?) cardboard cutout of the president smiling and offering two thumbs up. This, um, unusual choice was based on the president’s signing of an executive order in July 2019 launching an initiative promoting kidney disease awareness.
Mr. Nelson had previously been bringing in smaller images of the president. But when he brought in the large cutout – made by his son – a social worker at the center told him that the president couldn’t stay, adding that “this is not a Trump rally,” according to Mr. Nelson.
Naturally, this has caused quite a rift. Mr. Nelson feels that his freedom of expression and speech has been violated, and Fresenius says they can’t allow a support item so big because of those pesky health and safety regulations. Typical doctors.
The actual President Trump has yet to respond to this odd situation, but no doubt he’ll offer Fresenius a hearty “you’re fired!”
Your friendly neighborhood pandemic robot
Robots, of course!
A shiny new robot in Times Square not only can recognize symptoms of the coronavirus, it also can provide information to promote prevention and stop the spread. And if you look like a tourist, it’ll try to sell you half-priced tickets for a Big Apple bus tour. Move over, smartphones; having a robot analyze my symptoms sounds way more fun than frantically googling them.
The “Promobot” was designed with a friendly face and welcoming smile – that’s how you know the robot isn’t a local.
Interested users can interact with the Promobot’s iPad, which has a questionnaire regarding signs and symptoms of the coronavirus. Promobot doesn’t actually physically detect the virus (it’s a robot, not a blood test), but the questionnaire asks about general symptoms of coronavirus. At the end, the robot gives advice on how to proceed if the answers indicate the virus is present (hopefully without any panic-inducing fanfare).
Ah, New York: Where even the robots are friendlier than the residents.
Beating? No. Delicious? Yes
No, it’s a cake!
Heart!
Cake!
Wait, you’re both right. It’s two treats in one! It’s a heart and a cake. It’s the cake that looks like a heart.
Seriously, it really looks like a heart. It looks like it should still be beating. We’re talking anatomically correct and glistening with just-pulled-from-the-body freshness.
This latest wonder of the baking world comes from Crabby Cakes in Portland, Tex., just across the Nueces Bay Causeway from Corpus Christi. Just get on West Broadway Avenue from the I-181 frontage road, then make a right onto Wildcat Drive and a left at Maple Drive.
Crabby Cakes owner Jessica Wolfe is a big fan of horror movies and has even visited some of the sites where scenes were shot for “The Texas Chain Saw Massacre.” She told the Dallas Morning News that she “was trying to do something different for Valentine’s Day, cake-wise.”
She posted a video of the cake on the bakery’s Facebook page and it went viral, gobbling up over a million views in less than a week, the Morning News reported. Each cake costs $70 and will feed about five people, but the bakery cannot ship them out of state.
Among the cake-generated surprises was the attention she got from the health care industry. “Nurses, doctor’s offices, and graduates want the hearts,” Ms. Wolfe told the Morning News. “But they also want livers, kidneys, and lungs.”
Let’s just hope there aren’t any transplant surgeons calling.
Make dialysis great again!
Now, you’re probably thinking that Mr. Nelson tried to bring in his dog or some other animal, and that’s surely an issue of hygiene. But no, Mr. Gibson wasn’t bringing in a dog or cat, or even a squirrel or turkey, but a president.
Specifically, Mr. Nelson’s emotional support was one President Donald J. Trump.
Okay, it wasn’t actually Mr. Trump himself, but a life-sized (bigly?) cardboard cutout of the president smiling and offering two thumbs up. This, um, unusual choice was based on the president’s signing of an executive order in July 2019 launching an initiative promoting kidney disease awareness.
Mr. Nelson had previously been bringing in smaller images of the president. But when he brought in the large cutout – made by his son – a social worker at the center told him that the president couldn’t stay, adding that “this is not a Trump rally,” according to Mr. Nelson.
Naturally, this has caused quite a rift. Mr. Nelson feels that his freedom of expression and speech has been violated, and Fresenius says they can’t allow a support item so big because of those pesky health and safety regulations. Typical doctors.
The actual President Trump has yet to respond to this odd situation, but no doubt he’ll offer Fresenius a hearty “you’re fired!”
Your friendly neighborhood pandemic robot
Robots, of course!
A shiny new robot in Times Square not only can recognize symptoms of the coronavirus, it also can provide information to promote prevention and stop the spread. And if you look like a tourist, it’ll try to sell you half-priced tickets for a Big Apple bus tour. Move over, smartphones; having a robot analyze my symptoms sounds way more fun than frantically googling them.
The “Promobot” was designed with a friendly face and welcoming smile – that’s how you know the robot isn’t a local.
Interested users can interact with the Promobot’s iPad, which has a questionnaire regarding signs and symptoms of the coronavirus. Promobot doesn’t actually physically detect the virus (it’s a robot, not a blood test), but the questionnaire asks about general symptoms of coronavirus. At the end, the robot gives advice on how to proceed if the answers indicate the virus is present (hopefully without any panic-inducing fanfare).
Ah, New York: Where even the robots are friendlier than the residents.
Beating? No. Delicious? Yes
No, it’s a cake!
Heart!
Cake!
Wait, you’re both right. It’s two treats in one! It’s a heart and a cake. It’s the cake that looks like a heart.
Seriously, it really looks like a heart. It looks like it should still be beating. We’re talking anatomically correct and glistening with just-pulled-from-the-body freshness.
This latest wonder of the baking world comes from Crabby Cakes in Portland, Tex., just across the Nueces Bay Causeway from Corpus Christi. Just get on West Broadway Avenue from the I-181 frontage road, then make a right onto Wildcat Drive and a left at Maple Drive.
Crabby Cakes owner Jessica Wolfe is a big fan of horror movies and has even visited some of the sites where scenes were shot for “The Texas Chain Saw Massacre.” She told the Dallas Morning News that she “was trying to do something different for Valentine’s Day, cake-wise.”
She posted a video of the cake on the bakery’s Facebook page and it went viral, gobbling up over a million views in less than a week, the Morning News reported. Each cake costs $70 and will feed about five people, but the bakery cannot ship them out of state.
Among the cake-generated surprises was the attention she got from the health care industry. “Nurses, doctor’s offices, and graduates want the hearts,” Ms. Wolfe told the Morning News. “But they also want livers, kidneys, and lungs.”
Let’s just hope there aren’t any transplant surgeons calling.
Play it as it lies: Handling lying by kids
“Not my son!” your patient’s parent rants. “If he lies to me, he will regret it for a long time.” While your first reaction may be to agree that a child lying to a parent crosses a kind of moral line in the sand, lying is a far more nuanced part of parenting worth a deeper understanding.
In order to lie, a child has to develop cognitive and social understanding. Typically developing children look to see what is interesting to others, called “joint attention,” at around 12-18 months. Failure to do this is one of the early signs of autism reflecting atypical social understanding. At around 3.5 years, children may attempt to deceive if they have broken a rule. The study demonstrating this may sound a lot like home: Children are left alone with a tempting toy but told not to touch it. Although they do touch it while the adult is out of sight, they say rather sweetly (and eventually convincingly) that they did not, even though the toy was clearly moved! While boys generally have more behavior problems, girls and children with better verbal skills achieve deceit at an earlier age, some as young as 2 years. At this stage, children become aware that the adult can’t know exactly what they know. If the parent shows high emotion to what they consider a lie, this can be a topic for testing! Children with ADHD often lack the inhibition needed for early mastery of deception, and children with autism later or not at all. They don’t see the social point to lying nor can they fake a facial expression. They have a case of intractable honesty!
The inability to refrain from telling the truth can result in social rejection, for example when a child rats on a peer for a trivial misdeed in class. Even though he is speaking the truth and “following the (teacher’s) rules,” he did not see that the cost of breaking the (peer) social rules was more important. By age 6 years, children typically figure out that what another person thinks may not be true – their belief may be incorrect or a “false belief.” This understanding is called Theory of Mind, missing or delayed in autism. Only 40% of high-functioning children with autism passed false belief testing at ages 6- to 13-years-old, compared with 95% of typical age-matched peers (Physiol Behav. 2010 Jun 1;100[3]:268-76). The percentage of children on the spectrum understanding false beliefs more closely matched that of preschoolers (39%). At a later age and given extra time to think, some children with autism can do better at this kind of perspective taking, but many continue having difficulty understanding thoughts of others, especially social expectations or motivations (such as flirting, status seeking, and making an excuse) even as adults. This can impair social relationships even when desire to fit in and IQ are otherwise high.
On the other hand, ADHD is a common condition in which “lying” comes from saying the first thing that comes to mind even if the child knows otherwise. A wise parent of one of my patients with ADHD told me about her “30 second rule” where she would give her child that extra time and walk away briefly to “be sure that is what you wanted to say,” with praise rather than give a consequence for changing the story to the truth. This is an important concept we pediatricians need to know: Punishing lying in children tends to result in more, not less, lying and more sneakiness. Instead, parents need to be advised to recall the origins of the word discipline as being “to teach.”
When children lie there are four basic scenarios: They may not know the rules, they may know but have something they want more, they may be impulsive, or they may have developed an attitude of seeking to con the adults whom they feel are mean as a way to have some power in the relationship and get back at them. Clearly, we do not want to push children to this fourth resort by harsh reactions to lying. We have seen particular difficulty with harsh reactions to lying in parents from strong, rule-oriented careers such as police officers, military, and ministers. Asking “How would your parent have handled this?” often will reveal reasons for their tough but backfiring stance.
Lying can work to get what one wants and nearly all children try it. As with other new milestones, children practice this “skill,” much to parents’ dismay. Parents generally can tell if children are lying; they see it on their faces, hear the story from siblings, or see evidence of what happened. Lying provides an important opportunity for the adult to stop, take some breaths, touch the child, and empathize: “It is hard to admit a mistake. I know you did not mean to do it. But you are young, and I know that you are good and honest inside, and will get stronger and braver at telling the truth as you get older. Will you promise to try harder?” In some cases a consequence may be appropriate, for example if something was broken. Usually, simply empathizing and focusing on the expectation for improvement will increase the child’s desire to please the parents rather than get back at them. Actual rewards for honesty improve truth telling by 1.5 times if the reward is big enough.
But it is important to recognize that we all make split second tactical decisions about our actions based on how safe we feel in the situation and our knowledge of social rules and costs. Children over time need to learn that it is safe to tell the truth among family members and that they will not be harshly dealt with. It is a subtle task, but important to learn that deception is a tool that can be important used judiciously when required socially (I have a curfew) or in dangerous situations (I did not see the thug), but can undermine relationships and should not be used with your allies (family and friends).
But parenting involves lying also, which can be a model for the child. Sarcasm is a peculiar form of problematic adult lying. The adults say the opposite or an exaggeration of what they really mean, usually with a smirk or other nonverbal cue to their intent. This is confusing, if not infuriating, to immature children or those who do not understand this twisted communication. It is best to avoid sarcasm with children, or at least be sure to explain it so the children gain understanding over time.
Parents need to “lie” to their children to some extent to reassure and allow for development of confidence. What adult hasn’t said “It’s going to be all right” about a looming storm, car crash, or illness, when actually there is uncertainty. Children count on adults to keep them safe emotionally and physically from things they can’t yet handle. To move forward developmentally, children need adults to be brave leaders, even when the adults don’t feel confident. Some parents think their children must know the “truth” in every instance. Those children are often painfully anxious and overwhelmed.
There is plenty of time for more facts later when the child has the thinking and emotional power to handle the truth.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
“Not my son!” your patient’s parent rants. “If he lies to me, he will regret it for a long time.” While your first reaction may be to agree that a child lying to a parent crosses a kind of moral line in the sand, lying is a far more nuanced part of parenting worth a deeper understanding.
In order to lie, a child has to develop cognitive and social understanding. Typically developing children look to see what is interesting to others, called “joint attention,” at around 12-18 months. Failure to do this is one of the early signs of autism reflecting atypical social understanding. At around 3.5 years, children may attempt to deceive if they have broken a rule. The study demonstrating this may sound a lot like home: Children are left alone with a tempting toy but told not to touch it. Although they do touch it while the adult is out of sight, they say rather sweetly (and eventually convincingly) that they did not, even though the toy was clearly moved! While boys generally have more behavior problems, girls and children with better verbal skills achieve deceit at an earlier age, some as young as 2 years. At this stage, children become aware that the adult can’t know exactly what they know. If the parent shows high emotion to what they consider a lie, this can be a topic for testing! Children with ADHD often lack the inhibition needed for early mastery of deception, and children with autism later or not at all. They don’t see the social point to lying nor can they fake a facial expression. They have a case of intractable honesty!
The inability to refrain from telling the truth can result in social rejection, for example when a child rats on a peer for a trivial misdeed in class. Even though he is speaking the truth and “following the (teacher’s) rules,” he did not see that the cost of breaking the (peer) social rules was more important. By age 6 years, children typically figure out that what another person thinks may not be true – their belief may be incorrect or a “false belief.” This understanding is called Theory of Mind, missing or delayed in autism. Only 40% of high-functioning children with autism passed false belief testing at ages 6- to 13-years-old, compared with 95% of typical age-matched peers (Physiol Behav. 2010 Jun 1;100[3]:268-76). The percentage of children on the spectrum understanding false beliefs more closely matched that of preschoolers (39%). At a later age and given extra time to think, some children with autism can do better at this kind of perspective taking, but many continue having difficulty understanding thoughts of others, especially social expectations or motivations (such as flirting, status seeking, and making an excuse) even as adults. This can impair social relationships even when desire to fit in and IQ are otherwise high.
On the other hand, ADHD is a common condition in which “lying” comes from saying the first thing that comes to mind even if the child knows otherwise. A wise parent of one of my patients with ADHD told me about her “30 second rule” where she would give her child that extra time and walk away briefly to “be sure that is what you wanted to say,” with praise rather than give a consequence for changing the story to the truth. This is an important concept we pediatricians need to know: Punishing lying in children tends to result in more, not less, lying and more sneakiness. Instead, parents need to be advised to recall the origins of the word discipline as being “to teach.”
When children lie there are four basic scenarios: They may not know the rules, they may know but have something they want more, they may be impulsive, or they may have developed an attitude of seeking to con the adults whom they feel are mean as a way to have some power in the relationship and get back at them. Clearly, we do not want to push children to this fourth resort by harsh reactions to lying. We have seen particular difficulty with harsh reactions to lying in parents from strong, rule-oriented careers such as police officers, military, and ministers. Asking “How would your parent have handled this?” often will reveal reasons for their tough but backfiring stance.
Lying can work to get what one wants and nearly all children try it. As with other new milestones, children practice this “skill,” much to parents’ dismay. Parents generally can tell if children are lying; they see it on their faces, hear the story from siblings, or see evidence of what happened. Lying provides an important opportunity for the adult to stop, take some breaths, touch the child, and empathize: “It is hard to admit a mistake. I know you did not mean to do it. But you are young, and I know that you are good and honest inside, and will get stronger and braver at telling the truth as you get older. Will you promise to try harder?” In some cases a consequence may be appropriate, for example if something was broken. Usually, simply empathizing and focusing on the expectation for improvement will increase the child’s desire to please the parents rather than get back at them. Actual rewards for honesty improve truth telling by 1.5 times if the reward is big enough.
But it is important to recognize that we all make split second tactical decisions about our actions based on how safe we feel in the situation and our knowledge of social rules and costs. Children over time need to learn that it is safe to tell the truth among family members and that they will not be harshly dealt with. It is a subtle task, but important to learn that deception is a tool that can be important used judiciously when required socially (I have a curfew) or in dangerous situations (I did not see the thug), but can undermine relationships and should not be used with your allies (family and friends).
But parenting involves lying also, which can be a model for the child. Sarcasm is a peculiar form of problematic adult lying. The adults say the opposite or an exaggeration of what they really mean, usually with a smirk or other nonverbal cue to their intent. This is confusing, if not infuriating, to immature children or those who do not understand this twisted communication. It is best to avoid sarcasm with children, or at least be sure to explain it so the children gain understanding over time.
Parents need to “lie” to their children to some extent to reassure and allow for development of confidence. What adult hasn’t said “It’s going to be all right” about a looming storm, car crash, or illness, when actually there is uncertainty. Children count on adults to keep them safe emotionally and physically from things they can’t yet handle. To move forward developmentally, children need adults to be brave leaders, even when the adults don’t feel confident. Some parents think their children must know the “truth” in every instance. Those children are often painfully anxious and overwhelmed.
There is plenty of time for more facts later when the child has the thinking and emotional power to handle the truth.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
“Not my son!” your patient’s parent rants. “If he lies to me, he will regret it for a long time.” While your first reaction may be to agree that a child lying to a parent crosses a kind of moral line in the sand, lying is a far more nuanced part of parenting worth a deeper understanding.
In order to lie, a child has to develop cognitive and social understanding. Typically developing children look to see what is interesting to others, called “joint attention,” at around 12-18 months. Failure to do this is one of the early signs of autism reflecting atypical social understanding. At around 3.5 years, children may attempt to deceive if they have broken a rule. The study demonstrating this may sound a lot like home: Children are left alone with a tempting toy but told not to touch it. Although they do touch it while the adult is out of sight, they say rather sweetly (and eventually convincingly) that they did not, even though the toy was clearly moved! While boys generally have more behavior problems, girls and children with better verbal skills achieve deceit at an earlier age, some as young as 2 years. At this stage, children become aware that the adult can’t know exactly what they know. If the parent shows high emotion to what they consider a lie, this can be a topic for testing! Children with ADHD often lack the inhibition needed for early mastery of deception, and children with autism later or not at all. They don’t see the social point to lying nor can they fake a facial expression. They have a case of intractable honesty!
The inability to refrain from telling the truth can result in social rejection, for example when a child rats on a peer for a trivial misdeed in class. Even though he is speaking the truth and “following the (teacher’s) rules,” he did not see that the cost of breaking the (peer) social rules was more important. By age 6 years, children typically figure out that what another person thinks may not be true – their belief may be incorrect or a “false belief.” This understanding is called Theory of Mind, missing or delayed in autism. Only 40% of high-functioning children with autism passed false belief testing at ages 6- to 13-years-old, compared with 95% of typical age-matched peers (Physiol Behav. 2010 Jun 1;100[3]:268-76). The percentage of children on the spectrum understanding false beliefs more closely matched that of preschoolers (39%). At a later age and given extra time to think, some children with autism can do better at this kind of perspective taking, but many continue having difficulty understanding thoughts of others, especially social expectations or motivations (such as flirting, status seeking, and making an excuse) even as adults. This can impair social relationships even when desire to fit in and IQ are otherwise high.
On the other hand, ADHD is a common condition in which “lying” comes from saying the first thing that comes to mind even if the child knows otherwise. A wise parent of one of my patients with ADHD told me about her “30 second rule” where she would give her child that extra time and walk away briefly to “be sure that is what you wanted to say,” with praise rather than give a consequence for changing the story to the truth. This is an important concept we pediatricians need to know: Punishing lying in children tends to result in more, not less, lying and more sneakiness. Instead, parents need to be advised to recall the origins of the word discipline as being “to teach.”
When children lie there are four basic scenarios: They may not know the rules, they may know but have something they want more, they may be impulsive, or they may have developed an attitude of seeking to con the adults whom they feel are mean as a way to have some power in the relationship and get back at them. Clearly, we do not want to push children to this fourth resort by harsh reactions to lying. We have seen particular difficulty with harsh reactions to lying in parents from strong, rule-oriented careers such as police officers, military, and ministers. Asking “How would your parent have handled this?” often will reveal reasons for their tough but backfiring stance.
Lying can work to get what one wants and nearly all children try it. As with other new milestones, children practice this “skill,” much to parents’ dismay. Parents generally can tell if children are lying; they see it on their faces, hear the story from siblings, or see evidence of what happened. Lying provides an important opportunity for the adult to stop, take some breaths, touch the child, and empathize: “It is hard to admit a mistake. I know you did not mean to do it. But you are young, and I know that you are good and honest inside, and will get stronger and braver at telling the truth as you get older. Will you promise to try harder?” In some cases a consequence may be appropriate, for example if something was broken. Usually, simply empathizing and focusing on the expectation for improvement will increase the child’s desire to please the parents rather than get back at them. Actual rewards for honesty improve truth telling by 1.5 times if the reward is big enough.
But it is important to recognize that we all make split second tactical decisions about our actions based on how safe we feel in the situation and our knowledge of social rules and costs. Children over time need to learn that it is safe to tell the truth among family members and that they will not be harshly dealt with. It is a subtle task, but important to learn that deception is a tool that can be important used judiciously when required socially (I have a curfew) or in dangerous situations (I did not see the thug), but can undermine relationships and should not be used with your allies (family and friends).
But parenting involves lying also, which can be a model for the child. Sarcasm is a peculiar form of problematic adult lying. The adults say the opposite or an exaggeration of what they really mean, usually with a smirk or other nonverbal cue to their intent. This is confusing, if not infuriating, to immature children or those who do not understand this twisted communication. It is best to avoid sarcasm with children, or at least be sure to explain it so the children gain understanding over time.
Parents need to “lie” to their children to some extent to reassure and allow for development of confidence. What adult hasn’t said “It’s going to be all right” about a looming storm, car crash, or illness, when actually there is uncertainty. Children count on adults to keep them safe emotionally and physically from things they can’t yet handle. To move forward developmentally, children need adults to be brave leaders, even when the adults don’t feel confident. Some parents think their children must know the “truth” in every instance. Those children are often painfully anxious and overwhelmed.
There is plenty of time for more facts later when the child has the thinking and emotional power to handle the truth.
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
FDA approves weekly contraceptive patch Twirla
in women whose body mass index is less than 30 kg/m2 and for whom a combined hormonal contraceptive is appropriate.
Applied weekly to the abdomen, buttock, or upper torso (excluding the breasts), Twirla delivers a 30-mcg daily dose of ethinyl estradiol and 120-mcg daily dose of levonorgestrel.
“Twirla is an important addition to available hormonal contraceptive methods, allowing prescribers to now offer appropriate U.S. women a weekly transdermal option that delivers estrogen levels in line with labeled doses of many commonly prescribed oral contraceptives, David Portman, MD, an obstetrician/gynecologist in Columbus, Ohio, and a primary investigator of the SECURE trial, said in a news release issued by the company.
Twirla was evaluated in “a diverse population providing important data to prescribers and to women seeking contraception. It is vital to expand the full range of contraceptive methods and inform the choices that fit an individual’s family planning needs and lifestyle,” Dr. Portman added.
As part of approval, the FDA will require Agile Therapeutics to conduct a long-term, prospective, observational postmarketing study to assess risks for venous thromboembolism and arterial thromboembolism in new users of Twirla, compared with new users of other combined hormonal contraceptives.
Twirla is contraindicated in women at high risk for arterial or venous thrombotic disease, including women with a BMI equal to or greater than 30 kg/m2; women who have headaches with focal neurologic symptoms or migraine with aura; and women older than 35 years who have any migraine headache.
Twirla also should be avoided in women who have liver tumors, acute viral hepatitis, decompensated cirrhosis, liver disease, or undiagnosed abnormal uterine bleeding. It also should be avoided during pregnancy; in women who currently have or who have history of breast cancer or other estrogen- or progestin-sensitive cancer; in women who are hypersensitivity to any components of Twirla; and in women who use hepatitis C drug combinations containing ombitasvir/paraparesis/ritonavir, with or without dasabuvir.
Because cigarette smoking increases the risk for serious cardiovascular events from combined hormonal contraceptive use, Twirla also is contraindicated in women older than 35 who smoke.
Twirla will contain a boxed warning that will include these risks about cigarette smoking and the serious cardiovascular events, and it will stipulate that Twirla is contraindicated in women with a BMI greater than 30 kg/m2.
This article first appeared on Medscape.com.
in women whose body mass index is less than 30 kg/m2 and for whom a combined hormonal contraceptive is appropriate.
Applied weekly to the abdomen, buttock, or upper torso (excluding the breasts), Twirla delivers a 30-mcg daily dose of ethinyl estradiol and 120-mcg daily dose of levonorgestrel.
“Twirla is an important addition to available hormonal contraceptive methods, allowing prescribers to now offer appropriate U.S. women a weekly transdermal option that delivers estrogen levels in line with labeled doses of many commonly prescribed oral contraceptives, David Portman, MD, an obstetrician/gynecologist in Columbus, Ohio, and a primary investigator of the SECURE trial, said in a news release issued by the company.
Twirla was evaluated in “a diverse population providing important data to prescribers and to women seeking contraception. It is vital to expand the full range of contraceptive methods and inform the choices that fit an individual’s family planning needs and lifestyle,” Dr. Portman added.
As part of approval, the FDA will require Agile Therapeutics to conduct a long-term, prospective, observational postmarketing study to assess risks for venous thromboembolism and arterial thromboembolism in new users of Twirla, compared with new users of other combined hormonal contraceptives.
Twirla is contraindicated in women at high risk for arterial or venous thrombotic disease, including women with a BMI equal to or greater than 30 kg/m2; women who have headaches with focal neurologic symptoms or migraine with aura; and women older than 35 years who have any migraine headache.
Twirla also should be avoided in women who have liver tumors, acute viral hepatitis, decompensated cirrhosis, liver disease, or undiagnosed abnormal uterine bleeding. It also should be avoided during pregnancy; in women who currently have or who have history of breast cancer or other estrogen- or progestin-sensitive cancer; in women who are hypersensitivity to any components of Twirla; and in women who use hepatitis C drug combinations containing ombitasvir/paraparesis/ritonavir, with or without dasabuvir.
Because cigarette smoking increases the risk for serious cardiovascular events from combined hormonal contraceptive use, Twirla also is contraindicated in women older than 35 who smoke.
Twirla will contain a boxed warning that will include these risks about cigarette smoking and the serious cardiovascular events, and it will stipulate that Twirla is contraindicated in women with a BMI greater than 30 kg/m2.
This article first appeared on Medscape.com.
in women whose body mass index is less than 30 kg/m2 and for whom a combined hormonal contraceptive is appropriate.
Applied weekly to the abdomen, buttock, or upper torso (excluding the breasts), Twirla delivers a 30-mcg daily dose of ethinyl estradiol and 120-mcg daily dose of levonorgestrel.
“Twirla is an important addition to available hormonal contraceptive methods, allowing prescribers to now offer appropriate U.S. women a weekly transdermal option that delivers estrogen levels in line with labeled doses of many commonly prescribed oral contraceptives, David Portman, MD, an obstetrician/gynecologist in Columbus, Ohio, and a primary investigator of the SECURE trial, said in a news release issued by the company.
Twirla was evaluated in “a diverse population providing important data to prescribers and to women seeking contraception. It is vital to expand the full range of contraceptive methods and inform the choices that fit an individual’s family planning needs and lifestyle,” Dr. Portman added.
As part of approval, the FDA will require Agile Therapeutics to conduct a long-term, prospective, observational postmarketing study to assess risks for venous thromboembolism and arterial thromboembolism in new users of Twirla, compared with new users of other combined hormonal contraceptives.
Twirla is contraindicated in women at high risk for arterial or venous thrombotic disease, including women with a BMI equal to or greater than 30 kg/m2; women who have headaches with focal neurologic symptoms or migraine with aura; and women older than 35 years who have any migraine headache.
Twirla also should be avoided in women who have liver tumors, acute viral hepatitis, decompensated cirrhosis, liver disease, or undiagnosed abnormal uterine bleeding. It also should be avoided during pregnancy; in women who currently have or who have history of breast cancer or other estrogen- or progestin-sensitive cancer; in women who are hypersensitivity to any components of Twirla; and in women who use hepatitis C drug combinations containing ombitasvir/paraparesis/ritonavir, with or without dasabuvir.
Because cigarette smoking increases the risk for serious cardiovascular events from combined hormonal contraceptive use, Twirla also is contraindicated in women older than 35 who smoke.
Twirla will contain a boxed warning that will include these risks about cigarette smoking and the serious cardiovascular events, and it will stipulate that Twirla is contraindicated in women with a BMI greater than 30 kg/m2.
This article first appeared on Medscape.com.
Synovial biopsy findings drive precision medicine for RA closer to the clinic
Researchers are mining the synovium for potential treasure: robust markers to bring precision medicine to the rheumatoid arthritis (RA) arena. The signs, according to a number of recent reports, point toward a gold strike via synovial tissue biopsy.
“I have no doubt about that – I am very confident that this concept of going straight to the tissue and using functional genomics will help us stratify our patients and will be a predictive model for patients with respect to therapy,” Harris R. Perlman, PhD, the Mabel Greene Myers Professor of Medicine and chief of the division of rheumatology at Northwestern University, Chicago, said in an interview.
Dr. Perlman is the principle investigator for the REASON (Rheumatoid Arthritis Synovial Tissue Network) study, and in a 2018 report on the network’s efforts to train participants across the United States in ultrasound-guided joint biopsy techniques and to collect and analyze synovial tissue samples submitted by the six participating centers, he and the coinvestigators explained why a precision approach can’t come soon enough.
“Currently, the standard of care for RA is to prescribe biologic therapy through a costly and time‐consuming trial‐and‐error process. Therefore, the utility of a biomarker to identify how a patient will respond to a particular therapy cannot be overstated,” they wrote (Arthritis Rheumatol. 2018 Jun;70[6]:841-54).
Since that REASON report was published, efforts by the investigators and others, such as those involved with the Accelerating Medicines Partnership (AMP) in RA and Lupus Network, to identify such biomarkers have continued to yield encouraging results.
In fact, data from the phase 4 R4-RA (Response, Relapse and Resistance to Rituximab Therapy in patients with RA) trial – the first randomized, controlled, biopsy-driven trial in RA – were reported in November 2019 at the annual meeting of the American College of Rheumatology. R4-RA demonstrated that patients with B cell–poor RA identified on synovial tissue biopsy (STB) responded better to tocilizumab (Actemra) than to rituximab (Rituxan), whereas those with B cell–rich RA on STB did not, Constantino Pitzalis, MD, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London said, noting that the findings could have “massive implications” for RA management and outcomes.
Numerous treatments exist for RA, but methods for determining which to use for a given patient are sorely lacking and the field of rheumatology lags behind others, like oncology, in bringing individualized medicine to the clinic, he explained.
Why STB?
Despite extensive efforts, blood testing has failed to yield markers sufficient for guiding RA treatment, and although the synovium has long been considered a potentially better source of information to guide treatment given the damage it sustains from RA, biopsies have generally been accessible only during arthroscopic or joint replacement surgery in patients with severe disease, which doesn’t reflect the population of patients who could benefit from early intervention, Dr. Perlman and colleagues explained in their 2018 report.
Musculoskeletal ultrasound (US) technology, however, has advanced dramatically over the past decade, is available and used by rheumatologists in clinical practice, and has brought US-guided joint biopsies to the forefront of research. Such techniques have been used in Europe for years, and as a result, an extensive catalog of literature supports the safety, feasibility, and tolerability of the approach.
A recent study in Portugal by Romao et al., for example, showed “remarkably high” patient tolerability (70%) with 64 US-guided procedures, including 52 in clinical practice and 12 for research purposes. No major adverse events occurred, and biopsy usefulness was high, with 37% having a direct diagnostic impact and with 100% and 95% positive- and negative-predictive values for infection. Further, synovial tissues were retrieved in 88% of biopsies and a median of 75% of samples were gradable (Arthritis Care Res. 2019 Aug 17. doi: 10.1002/acr.24050).
A 2018 study of 524 synovial biopsies, including 402 performed using US-guided needle biopsy, performed at five centers across Europe similarly demonstrated safety and patient tolerability (RMD Open. 2018;4[2]:e000799. doi: 10.1136/mdopen-2018-000799).
Building on the work in Europe, investigators at Northwestern launched the REASON study, assembling a consortium of academic rheumatology groups across the United States, training participants in minimally invasive US-guided joint biopsy techniques, and collecting and analyzing synovial tissue samples submitted by the participating centers.
Laura B. Hughes, MD, a professor at the University of Alabama at Birmingham and an investigator in both the REASON study and AMP, said in an interview that her experience with patients is similar.
“It has been very, very well tolerated,” she said of the biopsy procedure used in the course of the studies – and that’s despite the time and commitment required, she added, explaining that 12 samples, each requiring a separate injection, are obtained over a 30- to 45-minute visit.
“We’ve had no problems, no complications,” she said, also noting the importance of careful patient selection.
Patients are altruistic; they want to be a part of moving things forward and helping other patients, and they have been more than willing to participate, both she and Dr. Perlman noted.
In fact, the REASON study investigators reported that performance of STB by rheumatologists in the United States is feasible and generates high-quality samples.
Further, the transcriptional profiles of isolated RA synovial macrophages identified from samples submitted by Dr. Hughes and others in the network characterized subpopulations of patients and identified six novel transcriptional modules associated with disease activity and therapy, underscoring the potential for precision medicine in RA.
“We posit that transcriptional signatures in macrophages ... will predict responsiveness to specific nonbiologic and/or biologic therapies,” they wrote, adding that future studies will “entail collection of synovial biopsy specimens from a larger cohort longitudinally, prior to, and following therapy.”
The ongoing National Institutes of Health–funded AMP Network research is also using synovial biopsies, but more for identification of molecular pathways with a focus on potential drug development.
A 2019 report from the AMP investigators described their integrated use of single-cell transcriptomics and mass cytometry to reveal cell states expanded in RA synovia and the mapping of inflammatory mediators to their source cell populations, which may be key mediators of RA pathogenesis.
“We observed upregulation of chemokines (CXCL8, CXCL9, and CXCL13), cytokines (IFNG and IL15), and surface receptors (PDGFRB and SMAMF7) in distinct immune and stromal cell populations, suggesting potential novel targets,” they wrote (Nat Immunol. 2019 Jul;20[7]:928-42).
Next steps
These reports, along with the thousands of papers published over the past few decades describing phenotypic and functional abnormalities in synovial tissue obtained from RA patients undergoing joint replacement surgery or, more recently, via STB early in the course of disease, have provided a wealth of information, Helen Michelle McGettrick, MD, noted in an editorial addressing the potential of STB analysis for “unlocking the hidden secrets to personalized medicine.”
The question, however, is whether they have moved the field closer to “translating this discovery science into new biomarkers or drugs to improve diagnosis or prognosis,” she wrote (Arthritis Res Ther. 2019;21[90]. doi: 10.1186/s13075-019-1871-5).
“Three sides of our square are in place: clinical expertise, technology, and patient willingness,” she said, arguing that the fourth side is “standardization in the handling, evaluation, and interpretation of STB.”
In fact, her editorial focused on a joint consensus of the European League Against Rheumatism Synovitis Study Group and the OMERACT Synovial Tissue Biopsy Group (Arthritis Res Ther. 2018;20[265]. doi: 10.1186/s13075-018-1762-1).
The groups, based on member survey responses, proposed a “consensual set of analysis items” to be used for synovial biopsies in clinical practice and translational research, including matters such as biopsy sampling, histologic criteria, and biopsy interpretation. Their work, according to Dr. McGettrick and the authors themselves, marked a step forward, but provided only a foundation for a standardization framework.
One particular area of synovial research that has received recent attention and which illustrates the need for standardization involves the role of synovial B cells in RA. The R4-RA researchers, in conjunction with the Pathobiology of Early Arthritis Cohort, are working to better define the relationship of synovial B cells to clinical RA phenotypes at various disease stages and drug exposures as a potential source of predictive and prognostic biomarkers, and in an article accepted for publication in Arthritis & Rheumatology, they describe a “robust semiquantitative histological B cell score that closely replicates the quantification of B cells by digital or molecular analyses.”
In their study of 329 patients, they demonstrated an ongoing B cell–rich synovitis more prevalent in patients with established RA who had inadequate response to tumor necrosis factor inhibitor therapy than in those with early RA (47.4% vs. 35%), but which does not appear to be captured by standard clinimetric assessment (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41184).
“Overall, our study confirms the relevance of synovial B cells in RA and suggests that the classification of patients into B cell–rich/–poor can contribute to patient stratification,” they concluded.
In a related editorial, Dana E. Orange, MD, and Laura T. Donlin, PhD, of the Hospital for Special Surgery, New York, note that previously discrepant findings with respect to the value of B cell infiltrate scores for predicting RA treatment response may relate to the lack of a standardized scoring system (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41185).
Together, these emerging findings are “advancing our understanding of the transcriptional and cellular characteristics of the synovium in RA,” they wrote, concluding that incorporation of synovial assessments into clinical management of patients is “the next step in empowering clinicians to apply advances in molecular immunology to better tailor treatment decisions.”
Indeed, an important goal is empowering rheumatologists to become adept in obtaining synovial biopsies in clinical practice, much like gastroenterologists collect tissue for biopsy via colonoscopy, Dr. Pitzalis said in an interview following his R4-RA presentation at the ACR meeting.
Dr. Hughes predicts that a subset will embrace the concept, but not all rheumatologists are interested and not all use musculoskeletal US in their practice.
“It requires a lot of training, there is a credentialing exam, and it’s not necessary for practicing rheumatology, but there is a lot of growth,” she said, noting that training is being promoted through the ACR and other organizations, and Europeans who are well-versed in US-guided STB have served as mentors. “It’s been a nice collaboration, and I think it’s just going to push the field forward ... it really is exciting – I think synovial biopsies will yield a lot of information and really, hopefully, help us target therapy and find new therapeutic targets that we haven’t even thought of.”
However, Dr. Pitzalis stressed that there remains much work to do.
“It’s important to understand this is early data and will require validation in larger and target-driven and biopsy-driven treatment clinical trials,” he said of the R4-RA findings.
Those efforts are underway; the REASON study, for example, is moving forward, having recently been awarded a National Institutes of Health Research Project Grant, Dr. Perlman said, explaining that the latest goal is to determine whether the transcription modules the investigators have identified to date can be predictive of treatment response.
He expects to report outcomes at ACR 2020, and noted that preliminary findings suggest that “we can tell, by 4 weeks, which patients will respond or not.”
Dr. Pitzalis and his colleagues are also working on their “next set of trials,” which are using biopsies for treatment allocation (B cell–poor patients get one drug, B cell–rich patients, another, for example), and he, too said he expects to have additional data to present at ACR 2020.
“If we are to demonstrate clinical utility, I think rheumatology will be ready to implement this methodology in clinical practice,” he said.
The authors interviewed for this article reported having no relevant financial disclosures.
Researchers are mining the synovium for potential treasure: robust markers to bring precision medicine to the rheumatoid arthritis (RA) arena. The signs, according to a number of recent reports, point toward a gold strike via synovial tissue biopsy.
“I have no doubt about that – I am very confident that this concept of going straight to the tissue and using functional genomics will help us stratify our patients and will be a predictive model for patients with respect to therapy,” Harris R. Perlman, PhD, the Mabel Greene Myers Professor of Medicine and chief of the division of rheumatology at Northwestern University, Chicago, said in an interview.
Dr. Perlman is the principle investigator for the REASON (Rheumatoid Arthritis Synovial Tissue Network) study, and in a 2018 report on the network’s efforts to train participants across the United States in ultrasound-guided joint biopsy techniques and to collect and analyze synovial tissue samples submitted by the six participating centers, he and the coinvestigators explained why a precision approach can’t come soon enough.
“Currently, the standard of care for RA is to prescribe biologic therapy through a costly and time‐consuming trial‐and‐error process. Therefore, the utility of a biomarker to identify how a patient will respond to a particular therapy cannot be overstated,” they wrote (Arthritis Rheumatol. 2018 Jun;70[6]:841-54).
Since that REASON report was published, efforts by the investigators and others, such as those involved with the Accelerating Medicines Partnership (AMP) in RA and Lupus Network, to identify such biomarkers have continued to yield encouraging results.
In fact, data from the phase 4 R4-RA (Response, Relapse and Resistance to Rituximab Therapy in patients with RA) trial – the first randomized, controlled, biopsy-driven trial in RA – were reported in November 2019 at the annual meeting of the American College of Rheumatology. R4-RA demonstrated that patients with B cell–poor RA identified on synovial tissue biopsy (STB) responded better to tocilizumab (Actemra) than to rituximab (Rituxan), whereas those with B cell–rich RA on STB did not, Constantino Pitzalis, MD, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London said, noting that the findings could have “massive implications” for RA management and outcomes.
Numerous treatments exist for RA, but methods for determining which to use for a given patient are sorely lacking and the field of rheumatology lags behind others, like oncology, in bringing individualized medicine to the clinic, he explained.
Why STB?
Despite extensive efforts, blood testing has failed to yield markers sufficient for guiding RA treatment, and although the synovium has long been considered a potentially better source of information to guide treatment given the damage it sustains from RA, biopsies have generally been accessible only during arthroscopic or joint replacement surgery in patients with severe disease, which doesn’t reflect the population of patients who could benefit from early intervention, Dr. Perlman and colleagues explained in their 2018 report.
Musculoskeletal ultrasound (US) technology, however, has advanced dramatically over the past decade, is available and used by rheumatologists in clinical practice, and has brought US-guided joint biopsies to the forefront of research. Such techniques have been used in Europe for years, and as a result, an extensive catalog of literature supports the safety, feasibility, and tolerability of the approach.
A recent study in Portugal by Romao et al., for example, showed “remarkably high” patient tolerability (70%) with 64 US-guided procedures, including 52 in clinical practice and 12 for research purposes. No major adverse events occurred, and biopsy usefulness was high, with 37% having a direct diagnostic impact and with 100% and 95% positive- and negative-predictive values for infection. Further, synovial tissues were retrieved in 88% of biopsies and a median of 75% of samples were gradable (Arthritis Care Res. 2019 Aug 17. doi: 10.1002/acr.24050).
A 2018 study of 524 synovial biopsies, including 402 performed using US-guided needle biopsy, performed at five centers across Europe similarly demonstrated safety and patient tolerability (RMD Open. 2018;4[2]:e000799. doi: 10.1136/mdopen-2018-000799).
Building on the work in Europe, investigators at Northwestern launched the REASON study, assembling a consortium of academic rheumatology groups across the United States, training participants in minimally invasive US-guided joint biopsy techniques, and collecting and analyzing synovial tissue samples submitted by the participating centers.
Laura B. Hughes, MD, a professor at the University of Alabama at Birmingham and an investigator in both the REASON study and AMP, said in an interview that her experience with patients is similar.
“It has been very, very well tolerated,” she said of the biopsy procedure used in the course of the studies – and that’s despite the time and commitment required, she added, explaining that 12 samples, each requiring a separate injection, are obtained over a 30- to 45-minute visit.
“We’ve had no problems, no complications,” she said, also noting the importance of careful patient selection.
Patients are altruistic; they want to be a part of moving things forward and helping other patients, and they have been more than willing to participate, both she and Dr. Perlman noted.
In fact, the REASON study investigators reported that performance of STB by rheumatologists in the United States is feasible and generates high-quality samples.
Further, the transcriptional profiles of isolated RA synovial macrophages identified from samples submitted by Dr. Hughes and others in the network characterized subpopulations of patients and identified six novel transcriptional modules associated with disease activity and therapy, underscoring the potential for precision medicine in RA.
“We posit that transcriptional signatures in macrophages ... will predict responsiveness to specific nonbiologic and/or biologic therapies,” they wrote, adding that future studies will “entail collection of synovial biopsy specimens from a larger cohort longitudinally, prior to, and following therapy.”
The ongoing National Institutes of Health–funded AMP Network research is also using synovial biopsies, but more for identification of molecular pathways with a focus on potential drug development.
A 2019 report from the AMP investigators described their integrated use of single-cell transcriptomics and mass cytometry to reveal cell states expanded in RA synovia and the mapping of inflammatory mediators to their source cell populations, which may be key mediators of RA pathogenesis.
“We observed upregulation of chemokines (CXCL8, CXCL9, and CXCL13), cytokines (IFNG and IL15), and surface receptors (PDGFRB and SMAMF7) in distinct immune and stromal cell populations, suggesting potential novel targets,” they wrote (Nat Immunol. 2019 Jul;20[7]:928-42).
Next steps
These reports, along with the thousands of papers published over the past few decades describing phenotypic and functional abnormalities in synovial tissue obtained from RA patients undergoing joint replacement surgery or, more recently, via STB early in the course of disease, have provided a wealth of information, Helen Michelle McGettrick, MD, noted in an editorial addressing the potential of STB analysis for “unlocking the hidden secrets to personalized medicine.”
The question, however, is whether they have moved the field closer to “translating this discovery science into new biomarkers or drugs to improve diagnosis or prognosis,” she wrote (Arthritis Res Ther. 2019;21[90]. doi: 10.1186/s13075-019-1871-5).
“Three sides of our square are in place: clinical expertise, technology, and patient willingness,” she said, arguing that the fourth side is “standardization in the handling, evaluation, and interpretation of STB.”
In fact, her editorial focused on a joint consensus of the European League Against Rheumatism Synovitis Study Group and the OMERACT Synovial Tissue Biopsy Group (Arthritis Res Ther. 2018;20[265]. doi: 10.1186/s13075-018-1762-1).
The groups, based on member survey responses, proposed a “consensual set of analysis items” to be used for synovial biopsies in clinical practice and translational research, including matters such as biopsy sampling, histologic criteria, and biopsy interpretation. Their work, according to Dr. McGettrick and the authors themselves, marked a step forward, but provided only a foundation for a standardization framework.
One particular area of synovial research that has received recent attention and which illustrates the need for standardization involves the role of synovial B cells in RA. The R4-RA researchers, in conjunction with the Pathobiology of Early Arthritis Cohort, are working to better define the relationship of synovial B cells to clinical RA phenotypes at various disease stages and drug exposures as a potential source of predictive and prognostic biomarkers, and in an article accepted for publication in Arthritis & Rheumatology, they describe a “robust semiquantitative histological B cell score that closely replicates the quantification of B cells by digital or molecular analyses.”
In their study of 329 patients, they demonstrated an ongoing B cell–rich synovitis more prevalent in patients with established RA who had inadequate response to tumor necrosis factor inhibitor therapy than in those with early RA (47.4% vs. 35%), but which does not appear to be captured by standard clinimetric assessment (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41184).
“Overall, our study confirms the relevance of synovial B cells in RA and suggests that the classification of patients into B cell–rich/–poor can contribute to patient stratification,” they concluded.
In a related editorial, Dana E. Orange, MD, and Laura T. Donlin, PhD, of the Hospital for Special Surgery, New York, note that previously discrepant findings with respect to the value of B cell infiltrate scores for predicting RA treatment response may relate to the lack of a standardized scoring system (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41185).
Together, these emerging findings are “advancing our understanding of the transcriptional and cellular characteristics of the synovium in RA,” they wrote, concluding that incorporation of synovial assessments into clinical management of patients is “the next step in empowering clinicians to apply advances in molecular immunology to better tailor treatment decisions.”
Indeed, an important goal is empowering rheumatologists to become adept in obtaining synovial biopsies in clinical practice, much like gastroenterologists collect tissue for biopsy via colonoscopy, Dr. Pitzalis said in an interview following his R4-RA presentation at the ACR meeting.
Dr. Hughes predicts that a subset will embrace the concept, but not all rheumatologists are interested and not all use musculoskeletal US in their practice.
“It requires a lot of training, there is a credentialing exam, and it’s not necessary for practicing rheumatology, but there is a lot of growth,” she said, noting that training is being promoted through the ACR and other organizations, and Europeans who are well-versed in US-guided STB have served as mentors. “It’s been a nice collaboration, and I think it’s just going to push the field forward ... it really is exciting – I think synovial biopsies will yield a lot of information and really, hopefully, help us target therapy and find new therapeutic targets that we haven’t even thought of.”
However, Dr. Pitzalis stressed that there remains much work to do.
“It’s important to understand this is early data and will require validation in larger and target-driven and biopsy-driven treatment clinical trials,” he said of the R4-RA findings.
Those efforts are underway; the REASON study, for example, is moving forward, having recently been awarded a National Institutes of Health Research Project Grant, Dr. Perlman said, explaining that the latest goal is to determine whether the transcription modules the investigators have identified to date can be predictive of treatment response.
He expects to report outcomes at ACR 2020, and noted that preliminary findings suggest that “we can tell, by 4 weeks, which patients will respond or not.”
Dr. Pitzalis and his colleagues are also working on their “next set of trials,” which are using biopsies for treatment allocation (B cell–poor patients get one drug, B cell–rich patients, another, for example), and he, too said he expects to have additional data to present at ACR 2020.
“If we are to demonstrate clinical utility, I think rheumatology will be ready to implement this methodology in clinical practice,” he said.
The authors interviewed for this article reported having no relevant financial disclosures.
Researchers are mining the synovium for potential treasure: robust markers to bring precision medicine to the rheumatoid arthritis (RA) arena. The signs, according to a number of recent reports, point toward a gold strike via synovial tissue biopsy.
“I have no doubt about that – I am very confident that this concept of going straight to the tissue and using functional genomics will help us stratify our patients and will be a predictive model for patients with respect to therapy,” Harris R. Perlman, PhD, the Mabel Greene Myers Professor of Medicine and chief of the division of rheumatology at Northwestern University, Chicago, said in an interview.
Dr. Perlman is the principle investigator for the REASON (Rheumatoid Arthritis Synovial Tissue Network) study, and in a 2018 report on the network’s efforts to train participants across the United States in ultrasound-guided joint biopsy techniques and to collect and analyze synovial tissue samples submitted by the six participating centers, he and the coinvestigators explained why a precision approach can’t come soon enough.
“Currently, the standard of care for RA is to prescribe biologic therapy through a costly and time‐consuming trial‐and‐error process. Therefore, the utility of a biomarker to identify how a patient will respond to a particular therapy cannot be overstated,” they wrote (Arthritis Rheumatol. 2018 Jun;70[6]:841-54).
Since that REASON report was published, efforts by the investigators and others, such as those involved with the Accelerating Medicines Partnership (AMP) in RA and Lupus Network, to identify such biomarkers have continued to yield encouraging results.
In fact, data from the phase 4 R4-RA (Response, Relapse and Resistance to Rituximab Therapy in patients with RA) trial – the first randomized, controlled, biopsy-driven trial in RA – were reported in November 2019 at the annual meeting of the American College of Rheumatology. R4-RA demonstrated that patients with B cell–poor RA identified on synovial tissue biopsy (STB) responded better to tocilizumab (Actemra) than to rituximab (Rituxan), whereas those with B cell–rich RA on STB did not, Constantino Pitzalis, MD, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London said, noting that the findings could have “massive implications” for RA management and outcomes.
Numerous treatments exist for RA, but methods for determining which to use for a given patient are sorely lacking and the field of rheumatology lags behind others, like oncology, in bringing individualized medicine to the clinic, he explained.
Why STB?
Despite extensive efforts, blood testing has failed to yield markers sufficient for guiding RA treatment, and although the synovium has long been considered a potentially better source of information to guide treatment given the damage it sustains from RA, biopsies have generally been accessible only during arthroscopic or joint replacement surgery in patients with severe disease, which doesn’t reflect the population of patients who could benefit from early intervention, Dr. Perlman and colleagues explained in their 2018 report.
Musculoskeletal ultrasound (US) technology, however, has advanced dramatically over the past decade, is available and used by rheumatologists in clinical practice, and has brought US-guided joint biopsies to the forefront of research. Such techniques have been used in Europe for years, and as a result, an extensive catalog of literature supports the safety, feasibility, and tolerability of the approach.
A recent study in Portugal by Romao et al., for example, showed “remarkably high” patient tolerability (70%) with 64 US-guided procedures, including 52 in clinical practice and 12 for research purposes. No major adverse events occurred, and biopsy usefulness was high, with 37% having a direct diagnostic impact and with 100% and 95% positive- and negative-predictive values for infection. Further, synovial tissues were retrieved in 88% of biopsies and a median of 75% of samples were gradable (Arthritis Care Res. 2019 Aug 17. doi: 10.1002/acr.24050).
A 2018 study of 524 synovial biopsies, including 402 performed using US-guided needle biopsy, performed at five centers across Europe similarly demonstrated safety and patient tolerability (RMD Open. 2018;4[2]:e000799. doi: 10.1136/mdopen-2018-000799).
Building on the work in Europe, investigators at Northwestern launched the REASON study, assembling a consortium of academic rheumatology groups across the United States, training participants in minimally invasive US-guided joint biopsy techniques, and collecting and analyzing synovial tissue samples submitted by the participating centers.
Laura B. Hughes, MD, a professor at the University of Alabama at Birmingham and an investigator in both the REASON study and AMP, said in an interview that her experience with patients is similar.
“It has been very, very well tolerated,” she said of the biopsy procedure used in the course of the studies – and that’s despite the time and commitment required, she added, explaining that 12 samples, each requiring a separate injection, are obtained over a 30- to 45-minute visit.
“We’ve had no problems, no complications,” she said, also noting the importance of careful patient selection.
Patients are altruistic; they want to be a part of moving things forward and helping other patients, and they have been more than willing to participate, both she and Dr. Perlman noted.
In fact, the REASON study investigators reported that performance of STB by rheumatologists in the United States is feasible and generates high-quality samples.
Further, the transcriptional profiles of isolated RA synovial macrophages identified from samples submitted by Dr. Hughes and others in the network characterized subpopulations of patients and identified six novel transcriptional modules associated with disease activity and therapy, underscoring the potential for precision medicine in RA.
“We posit that transcriptional signatures in macrophages ... will predict responsiveness to specific nonbiologic and/or biologic therapies,” they wrote, adding that future studies will “entail collection of synovial biopsy specimens from a larger cohort longitudinally, prior to, and following therapy.”
The ongoing National Institutes of Health–funded AMP Network research is also using synovial biopsies, but more for identification of molecular pathways with a focus on potential drug development.
A 2019 report from the AMP investigators described their integrated use of single-cell transcriptomics and mass cytometry to reveal cell states expanded in RA synovia and the mapping of inflammatory mediators to their source cell populations, which may be key mediators of RA pathogenesis.
“We observed upregulation of chemokines (CXCL8, CXCL9, and CXCL13), cytokines (IFNG and IL15), and surface receptors (PDGFRB and SMAMF7) in distinct immune and stromal cell populations, suggesting potential novel targets,” they wrote (Nat Immunol. 2019 Jul;20[7]:928-42).
Next steps
These reports, along with the thousands of papers published over the past few decades describing phenotypic and functional abnormalities in synovial tissue obtained from RA patients undergoing joint replacement surgery or, more recently, via STB early in the course of disease, have provided a wealth of information, Helen Michelle McGettrick, MD, noted in an editorial addressing the potential of STB analysis for “unlocking the hidden secrets to personalized medicine.”
The question, however, is whether they have moved the field closer to “translating this discovery science into new biomarkers or drugs to improve diagnosis or prognosis,” she wrote (Arthritis Res Ther. 2019;21[90]. doi: 10.1186/s13075-019-1871-5).
“Three sides of our square are in place: clinical expertise, technology, and patient willingness,” she said, arguing that the fourth side is “standardization in the handling, evaluation, and interpretation of STB.”
In fact, her editorial focused on a joint consensus of the European League Against Rheumatism Synovitis Study Group and the OMERACT Synovial Tissue Biopsy Group (Arthritis Res Ther. 2018;20[265]. doi: 10.1186/s13075-018-1762-1).
The groups, based on member survey responses, proposed a “consensual set of analysis items” to be used for synovial biopsies in clinical practice and translational research, including matters such as biopsy sampling, histologic criteria, and biopsy interpretation. Their work, according to Dr. McGettrick and the authors themselves, marked a step forward, but provided only a foundation for a standardization framework.
One particular area of synovial research that has received recent attention and which illustrates the need for standardization involves the role of synovial B cells in RA. The R4-RA researchers, in conjunction with the Pathobiology of Early Arthritis Cohort, are working to better define the relationship of synovial B cells to clinical RA phenotypes at various disease stages and drug exposures as a potential source of predictive and prognostic biomarkers, and in an article accepted for publication in Arthritis & Rheumatology, they describe a “robust semiquantitative histological B cell score that closely replicates the quantification of B cells by digital or molecular analyses.”
In their study of 329 patients, they demonstrated an ongoing B cell–rich synovitis more prevalent in patients with established RA who had inadequate response to tumor necrosis factor inhibitor therapy than in those with early RA (47.4% vs. 35%), but which does not appear to be captured by standard clinimetric assessment (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41184).
“Overall, our study confirms the relevance of synovial B cells in RA and suggests that the classification of patients into B cell–rich/–poor can contribute to patient stratification,” they concluded.
In a related editorial, Dana E. Orange, MD, and Laura T. Donlin, PhD, of the Hospital for Special Surgery, New York, note that previously discrepant findings with respect to the value of B cell infiltrate scores for predicting RA treatment response may relate to the lack of a standardized scoring system (Arthritis Rheumatol. 2019 Nov 29. doi: 10.1002/art.41185).
Together, these emerging findings are “advancing our understanding of the transcriptional and cellular characteristics of the synovium in RA,” they wrote, concluding that incorporation of synovial assessments into clinical management of patients is “the next step in empowering clinicians to apply advances in molecular immunology to better tailor treatment decisions.”
Indeed, an important goal is empowering rheumatologists to become adept in obtaining synovial biopsies in clinical practice, much like gastroenterologists collect tissue for biopsy via colonoscopy, Dr. Pitzalis said in an interview following his R4-RA presentation at the ACR meeting.
Dr. Hughes predicts that a subset will embrace the concept, but not all rheumatologists are interested and not all use musculoskeletal US in their practice.
“It requires a lot of training, there is a credentialing exam, and it’s not necessary for practicing rheumatology, but there is a lot of growth,” she said, noting that training is being promoted through the ACR and other organizations, and Europeans who are well-versed in US-guided STB have served as mentors. “It’s been a nice collaboration, and I think it’s just going to push the field forward ... it really is exciting – I think synovial biopsies will yield a lot of information and really, hopefully, help us target therapy and find new therapeutic targets that we haven’t even thought of.”
However, Dr. Pitzalis stressed that there remains much work to do.
“It’s important to understand this is early data and will require validation in larger and target-driven and biopsy-driven treatment clinical trials,” he said of the R4-RA findings.
Those efforts are underway; the REASON study, for example, is moving forward, having recently been awarded a National Institutes of Health Research Project Grant, Dr. Perlman said, explaining that the latest goal is to determine whether the transcription modules the investigators have identified to date can be predictive of treatment response.
He expects to report outcomes at ACR 2020, and noted that preliminary findings suggest that “we can tell, by 4 weeks, which patients will respond or not.”
Dr. Pitzalis and his colleagues are also working on their “next set of trials,” which are using biopsies for treatment allocation (B cell–poor patients get one drug, B cell–rich patients, another, for example), and he, too said he expects to have additional data to present at ACR 2020.
“If we are to demonstrate clinical utility, I think rheumatology will be ready to implement this methodology in clinical practice,” he said.
The authors interviewed for this article reported having no relevant financial disclosures.
Episodic Migraines Not Linked to Subsequent Sleep Disturbances
Key clinical point: Occurrence of headache is not associated with subsequent sleep period characterized by shorter sleep duration, higher sleep disruption, or poorer sleep quality in adults with episodic migraine.
Major finding: The average nightly objective sleep duration, efficiency, and wake after sleep onset (WASO) were 7.3±1.2 hours, 89.5%±3.3%, and 44.8±17.0 minutes, respectively. Objective sleep duration was 7.3 (95% confidence interval, 1.5-13.0) minutes longer on nights after a headache day vs. nights on headache-free days. Actigraphically assessed sleep efficiency and WASO did not differ on nights after headache days vs. headache-free days.
Study details: A prospective cohort study of 98 adults (mean age, 35 years, with an average of five migraine headaches/month) with episodic migraine who provided 4,406 days of data; actigraphic sleep data were assessed for six weeks.
Disclosures: This study was funded by grants from the National Institute of Neurological Disorders and Stroke and the American Sleep Medicine Foundation and received financial contributions from Harvard University and its affiliated academic healthcare centers. Dr. Bertisch reported receiving research support from Merck, Sharpe & Dohme, ApniMed and Lockheed Martin and served as a consultant for Verily.
Citation: Vgontzas A et al. Sleep. 2020 Jan 13. doi: 10.1093/sleep/zsaa001.
Key clinical point: Occurrence of headache is not associated with subsequent sleep period characterized by shorter sleep duration, higher sleep disruption, or poorer sleep quality in adults with episodic migraine.
Major finding: The average nightly objective sleep duration, efficiency, and wake after sleep onset (WASO) were 7.3±1.2 hours, 89.5%±3.3%, and 44.8±17.0 minutes, respectively. Objective sleep duration was 7.3 (95% confidence interval, 1.5-13.0) minutes longer on nights after a headache day vs. nights on headache-free days. Actigraphically assessed sleep efficiency and WASO did not differ on nights after headache days vs. headache-free days.
Study details: A prospective cohort study of 98 adults (mean age, 35 years, with an average of five migraine headaches/month) with episodic migraine who provided 4,406 days of data; actigraphic sleep data were assessed for six weeks.
Disclosures: This study was funded by grants from the National Institute of Neurological Disorders and Stroke and the American Sleep Medicine Foundation and received financial contributions from Harvard University and its affiliated academic healthcare centers. Dr. Bertisch reported receiving research support from Merck, Sharpe & Dohme, ApniMed and Lockheed Martin and served as a consultant for Verily.
Citation: Vgontzas A et al. Sleep. 2020 Jan 13. doi: 10.1093/sleep/zsaa001.
Key clinical point: Occurrence of headache is not associated with subsequent sleep period characterized by shorter sleep duration, higher sleep disruption, or poorer sleep quality in adults with episodic migraine.
Major finding: The average nightly objective sleep duration, efficiency, and wake after sleep onset (WASO) were 7.3±1.2 hours, 89.5%±3.3%, and 44.8±17.0 minutes, respectively. Objective sleep duration was 7.3 (95% confidence interval, 1.5-13.0) minutes longer on nights after a headache day vs. nights on headache-free days. Actigraphically assessed sleep efficiency and WASO did not differ on nights after headache days vs. headache-free days.
Study details: A prospective cohort study of 98 adults (mean age, 35 years, with an average of five migraine headaches/month) with episodic migraine who provided 4,406 days of data; actigraphic sleep data were assessed for six weeks.
Disclosures: This study was funded by grants from the National Institute of Neurological Disorders and Stroke and the American Sleep Medicine Foundation and received financial contributions from Harvard University and its affiliated academic healthcare centers. Dr. Bertisch reported receiving research support from Merck, Sharpe & Dohme, ApniMed and Lockheed Martin and served as a consultant for Verily.
Citation: Vgontzas A et al. Sleep. 2020 Jan 13. doi: 10.1093/sleep/zsaa001.
Migraine: What Are the Risk Factors for Flunarizine-Induced Parkinsonism?
Key clinical point: In patients with migraine, flunarizine (Fz)-induced parkinsonism (FIP) is associated with older age, history of comorbidities, exposure to high dose of Fz, and longer duration of exposure to Fz.
Major finding: In patients aged 45-64 years and 65 years or older, FIP risk was 3.18 and 4.89 times, respectively, higher in the Fz-treated group than in the controls. Compared with control group, the risk for FIP in those with comorbidities, annual cumulative Fz dose ≥445 mg, and Fz use for ≥60 days was 4.54-, 7.69-, and 8.49-fold, respectively, higher than in the control group.
Study details: A population-based study used data from Taiwan’s National Health Insurance Research Database and included 6,470 patients with migraine who were divided into two groups, based on their exposure (n=3,235) or non-exposure to Fz (n=3,235).
Disclosures: This study was supported by grants from the Taiwan Ministry of Health and Welfare Clinical Trial Center; China Medical University Hospital; Academia Sinica Stroke Biosignature Project; MOST Clinical Trial Consortium for Stroke; Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. The authors declared no conflict of interest.
Citation: Lin W et al. Front Pharmacol. 2019 Dec 19. doi: 10.3389/fphar.2019.01495.
Key clinical point: In patients with migraine, flunarizine (Fz)-induced parkinsonism (FIP) is associated with older age, history of comorbidities, exposure to high dose of Fz, and longer duration of exposure to Fz.
Major finding: In patients aged 45-64 years and 65 years or older, FIP risk was 3.18 and 4.89 times, respectively, higher in the Fz-treated group than in the controls. Compared with control group, the risk for FIP in those with comorbidities, annual cumulative Fz dose ≥445 mg, and Fz use for ≥60 days was 4.54-, 7.69-, and 8.49-fold, respectively, higher than in the control group.
Study details: A population-based study used data from Taiwan’s National Health Insurance Research Database and included 6,470 patients with migraine who were divided into two groups, based on their exposure (n=3,235) or non-exposure to Fz (n=3,235).
Disclosures: This study was supported by grants from the Taiwan Ministry of Health and Welfare Clinical Trial Center; China Medical University Hospital; Academia Sinica Stroke Biosignature Project; MOST Clinical Trial Consortium for Stroke; Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. The authors declared no conflict of interest.
Citation: Lin W et al. Front Pharmacol. 2019 Dec 19. doi: 10.3389/fphar.2019.01495.
Key clinical point: In patients with migraine, flunarizine (Fz)-induced parkinsonism (FIP) is associated with older age, history of comorbidities, exposure to high dose of Fz, and longer duration of exposure to Fz.
Major finding: In patients aged 45-64 years and 65 years or older, FIP risk was 3.18 and 4.89 times, respectively, higher in the Fz-treated group than in the controls. Compared with control group, the risk for FIP in those with comorbidities, annual cumulative Fz dose ≥445 mg, and Fz use for ≥60 days was 4.54-, 7.69-, and 8.49-fold, respectively, higher than in the control group.
Study details: A population-based study used data from Taiwan’s National Health Insurance Research Database and included 6,470 patients with migraine who were divided into two groups, based on their exposure (n=3,235) or non-exposure to Fz (n=3,235).
Disclosures: This study was supported by grants from the Taiwan Ministry of Health and Welfare Clinical Trial Center; China Medical University Hospital; Academia Sinica Stroke Biosignature Project; MOST Clinical Trial Consortium for Stroke; Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. The authors declared no conflict of interest.
Citation: Lin W et al. Front Pharmacol. 2019 Dec 19. doi: 10.3389/fphar.2019.01495.
Migraine: Vitamin D Might Improve Headache Characteristics and Reduce Inflammation
Key clinical point: Vitamin D3 supplementation might improve headache characteristics and protect against inflammation in migraine.
Major finding: Analysis of covariance adjusted for baseline values and confounders showed that vitamin D3 supplemented group had significantly lower headache days, attacks frequency, duration and severity, and reduced analgesics consumption compared with the placebo group
(P less than 0.05). Patients receiving vitamin D3 had a significant reduction in inducible nitric oxide synthase
(P=0.001) and serum levels of interleukin-6 (P=0.055) compared with placebo.
Study details: Study of 80 patients with episodic migraine randomly assigned to a daily dose of vitamin D3 2,000 IU (50 μg) or placebo for 12 weeks.
Disclosures: The study was supported by Tehran University of Medical Sciences & health Services grant. The authors declared no conflict of interest.
Citation: Ghorbani Z et al. Neurol Sci. 2020 Jan 2. doi: 10.1007/s10072-019-04220-8.
Key clinical point: Vitamin D3 supplementation might improve headache characteristics and protect against inflammation in migraine.
Major finding: Analysis of covariance adjusted for baseline values and confounders showed that vitamin D3 supplemented group had significantly lower headache days, attacks frequency, duration and severity, and reduced analgesics consumption compared with the placebo group
(P less than 0.05). Patients receiving vitamin D3 had a significant reduction in inducible nitric oxide synthase
(P=0.001) and serum levels of interleukin-6 (P=0.055) compared with placebo.
Study details: Study of 80 patients with episodic migraine randomly assigned to a daily dose of vitamin D3 2,000 IU (50 μg) or placebo for 12 weeks.
Disclosures: The study was supported by Tehran University of Medical Sciences & health Services grant. The authors declared no conflict of interest.
Citation: Ghorbani Z et al. Neurol Sci. 2020 Jan 2. doi: 10.1007/s10072-019-04220-8.
Key clinical point: Vitamin D3 supplementation might improve headache characteristics and protect against inflammation in migraine.
Major finding: Analysis of covariance adjusted for baseline values and confounders showed that vitamin D3 supplemented group had significantly lower headache days, attacks frequency, duration and severity, and reduced analgesics consumption compared with the placebo group
(P less than 0.05). Patients receiving vitamin D3 had a significant reduction in inducible nitric oxide synthase
(P=0.001) and serum levels of interleukin-6 (P=0.055) compared with placebo.
Study details: Study of 80 patients with episodic migraine randomly assigned to a daily dose of vitamin D3 2,000 IU (50 μg) or placebo for 12 weeks.
Disclosures: The study was supported by Tehran University of Medical Sciences & health Services grant. The authors declared no conflict of interest.
Citation: Ghorbani Z et al. Neurol Sci. 2020 Jan 2. doi: 10.1007/s10072-019-04220-8.
Low Sleep Efficiency Linked to Higher Risk of Migraine
Key clinical point: Sleep fragmentation (defined by low sleep efficiency) is associated with a higher risk of migraine onset on day 1; short sleep duration and low sleep quality are not temporally associated with migraine.
Major finding: Low sleep efficiency was associated with 39% higher odds of headache on day 1. Sleep duration ≤6.5 hours and poor sleep quality were not associated with migraine onset on the day immediately following the sleep period (day 0) and the following day (day 1).
Study details: The data were obtained from a prospective study of 98 adults with episodic migraine.
Disclosures: This study was funded by grants from the National Institute of Neurologic Disorders and Stroke and the American Sleep Medicine Foundation; received financial contributions from Harvard University and its affiliated academic healthcare centers. Dr. Bertisch reported receiving research support from Merck, Sharpe & Dohme and Lockheed Martin and served as a consultant for Verily.
Citation: Bertisch SM et al. Neurology. 2019 Dec 16. doi: 10.1212/WNL.0000000000008740.
Key clinical point: Sleep fragmentation (defined by low sleep efficiency) is associated with a higher risk of migraine onset on day 1; short sleep duration and low sleep quality are not temporally associated with migraine.
Major finding: Low sleep efficiency was associated with 39% higher odds of headache on day 1. Sleep duration ≤6.5 hours and poor sleep quality were not associated with migraine onset on the day immediately following the sleep period (day 0) and the following day (day 1).
Study details: The data were obtained from a prospective study of 98 adults with episodic migraine.
Disclosures: This study was funded by grants from the National Institute of Neurologic Disorders and Stroke and the American Sleep Medicine Foundation; received financial contributions from Harvard University and its affiliated academic healthcare centers. Dr. Bertisch reported receiving research support from Merck, Sharpe & Dohme and Lockheed Martin and served as a consultant for Verily.
Citation: Bertisch SM et al. Neurology. 2019 Dec 16. doi: 10.1212/WNL.0000000000008740.
Key clinical point: Sleep fragmentation (defined by low sleep efficiency) is associated with a higher risk of migraine onset on day 1; short sleep duration and low sleep quality are not temporally associated with migraine.
Major finding: Low sleep efficiency was associated with 39% higher odds of headache on day 1. Sleep duration ≤6.5 hours and poor sleep quality were not associated with migraine onset on the day immediately following the sleep period (day 0) and the following day (day 1).
Study details: The data were obtained from a prospective study of 98 adults with episodic migraine.
Disclosures: This study was funded by grants from the National Institute of Neurologic Disorders and Stroke and the American Sleep Medicine Foundation; received financial contributions from Harvard University and its affiliated academic healthcare centers. Dr. Bertisch reported receiving research support from Merck, Sharpe & Dohme and Lockheed Martin and served as a consultant for Verily.
Citation: Bertisch SM et al. Neurology. 2019 Dec 16. doi: 10.1212/WNL.0000000000008740.
Migraine Linked to Adverse Pregnancy Outcomes
Key clinical point: Pregnant women with a history of migraine are at an increased risk of adverse outcomes, including preeclampsia (PE) and low birth weight (LBW).
Major finding: Women with migraine had a higher risk for PE (odds ratio, 2.07; 95% confidence interval, 1.51-2.85) and LBW (odds ratio, 1.18; 95% confidence interval, 1.03-1.34) compared with women without migraine. No significant association was observed between the history of migraine and preterm birth or small for gestational age.
Study details: A systematic review and meta-analysis of 14 studies.
Disclosures: Authors declared no conflict of interest.
Citation: Aukes AM et al. Obstet Gynecol Surv. 2019 Dec. doi: 10.1097/OGX.0000000000000738.
Key clinical point: Pregnant women with a history of migraine are at an increased risk of adverse outcomes, including preeclampsia (PE) and low birth weight (LBW).
Major finding: Women with migraine had a higher risk for PE (odds ratio, 2.07; 95% confidence interval, 1.51-2.85) and LBW (odds ratio, 1.18; 95% confidence interval, 1.03-1.34) compared with women without migraine. No significant association was observed between the history of migraine and preterm birth or small for gestational age.
Study details: A systematic review and meta-analysis of 14 studies.
Disclosures: Authors declared no conflict of interest.
Citation: Aukes AM et al. Obstet Gynecol Surv. 2019 Dec. doi: 10.1097/OGX.0000000000000738.
Key clinical point: Pregnant women with a history of migraine are at an increased risk of adverse outcomes, including preeclampsia (PE) and low birth weight (LBW).
Major finding: Women with migraine had a higher risk for PE (odds ratio, 2.07; 95% confidence interval, 1.51-2.85) and LBW (odds ratio, 1.18; 95% confidence interval, 1.03-1.34) compared with women without migraine. No significant association was observed between the history of migraine and preterm birth or small for gestational age.
Study details: A systematic review and meta-analysis of 14 studies.
Disclosures: Authors declared no conflict of interest.
Citation: Aukes AM et al. Obstet Gynecol Surv. 2019 Dec. doi: 10.1097/OGX.0000000000000738.
HBV: Surface antigen titer and ALT predict seroconversion
Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.
, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.
While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.
To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.
The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.
Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).
The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).
HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.
The investigators reported no disclosures.
SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.
Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.
, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.
While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.
To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.
The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.
Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).
The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).
HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.
The investigators reported no disclosures.
SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.
Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.
, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.
While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.
To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.
The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.
Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).
The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).
HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.
The investigators reported no disclosures.
SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.
FROM JOURNAL OF CLINICAL GASTROENTEROLOGY