You have probably heard that determining the A(ntecedent)s, B(ehavior)s, and C(onsequence)s of a behavior is basic to counseling about oppositionality or aggression. But sorting out the As is especially important to going beyond disciplining a misbehavior to building insight for both parents and children.

Antecedents are of two types: triggers such as actions, words, or feelings that happen just before the behavior, and “setting events” that can occur intermittently hours or even days beforehand and lower the threshold for a trigger to cause a child to act out. Lack of sleep, hunger, or fatigue are common setting events that parents recognize and take into account as in “Oh, he missed his nap” to excuse a tantrum in younger children, but is less often considered or excused in older children in whom self-regulation is expected. Often, behavioral specialists in schools are asked to observe a child to identify the triggers and create a “functional behavioral assessment” based on what is observed.

While a functional behavioral assessment requires observations, invisible antecedents to consider include internal thoughts and feelings (meaning). A child feeling shame from a failed math test the day before may be on edge, then, when called on, may uncharacteristically talk back. The child may regard punishment for this “justified” response as unfair, accelerating anger. Feelings of shame or humiliation for failing one’s own standards (or perceived expectations of others the child cares about) are major setups for eliciting defiance.

Even more subtle are meanings the child creates for situations and people, whether real or imagined. A child’s behavior has meaning for the child and the family and can be initiated or maintained by that meaning. For example, a child may “live down” to what the family thinks of him/her; if you think I am bad, I will act badly.

Children may feel guilty about some real or imagined offense, such as divorce or death they think may be their fault, and act up with the family to elicit punishment as payment. When children feel conflicted in a relationship, such as a late adolescent feeling dependent on their mother when their age expectation is independence, they may act up expecting to be ejected from home when they are unable to gather the courage to voluntarily leave. This acting out may also occur with nonconflicted adults, who are actually safer targets. For example, school is often a safer place to express anger through aggression or bullying than home, the real source of the feelings, because family is the “lifeboat” of food and shelter they dare not upset.

Conflicted relationships may be present in blended families, especially if the ex speaks negatively about the other parent. The child of divorce, feeling himself composed of parts of each parent, has diminished self-esteem and anger on behalf of that side being put down. Marital conflict may set children up to feel they have to take sides to angrily defend the parent of like-gender by being oppositional to the other.

Just as we ponder whether the color blue looks the same to someone else, neurologically based differences in perception may make a child misinterpret or act inflexibly or explode in situations that seem normal to adults. While people joke about “being a little OCD,” for some children the distress caused by a change in routine, a messy room, a delayed bus, or loud music is enough to disrupt their functioning and coping enough to explode. Such hypersensitivity can be part of autism or obsessive compulsive disorder or a subthreshold variant. Children vary by age and individually in their ability to understand language, especially sarcastic humor, and often misinterpret it as insulting, threatening, or scary and act accordingly. While most common in children with autism, those with a language learning disability, intellectual disability, or who have English as a second language, or are anxious or vigilant may also take sarcasm the wrong way. Anxious children also may react aggressively from a “hostile bias attribution” of expecting the worst from others.

Another possible meaning of a behavior is that it is being used by the child to manage their feelings. I have found it useful to remind depressed children and parents that it “feels better to be mad than sad” as a reason for irritability. Anger can also push away a person whose otherwise sympathetic approach might release a collapse into tears the child can’t tolerate or would find embarrassing.

The meaning of a child’s misbehavior also resides in the minds of the adults. In addition to all the categories of meaning just described, a parent may be reminded by the child of someone else for whom the adult has strong or conflicted feelings (“projection”) such as a now-hated ex, a sibling of whom the adult is jealous, or a bully from childhood, thus eliciting a reaction falsely triggered by that connection rather than the actual child. Asking parents whom the child “takes after” may elicit such parental projections based on appearance, behavior, or temperament. Helping them pick a feature of the child to focus on to differentiate him/her can serve as an anchor to remind them to control these reactions. Other useful questions to detect meanings of behavior might include asking the child “What’s up with that?” or “What did that make you think/feel?” We can ask parents “How is that for you?” or “What do you think things will be like in 10 years?” to determine despair, mood disorders, or family discord contributing to maladaptive responses possibly maintaining unwanted behaviors.

Throughout life, putting feelings into words is the main way meanings that are contributing to misbehaviors or parenting dysfunction can be uncovered and shifted. For this, the child or adult must feel emotionally safe to talk with a person who conveys curiosity rather than judgment. Helping families explain that divorce is not the child’s fault; admit they also make mistakes; rebuild conflicted relationships through play or talking; identify hypersensitivities or triggers to avoid; and express confidence that the child is a good person, still young, and sure to do better over time, are all things we pediatricians can do to help sort out the meanings of behaviors.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. 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 pdnews@mdedge.com.

You have probably heard that determining the A(ntecedent)s, B(ehavior)s, and C(onsequence)s of a behavior is basic to counseling about oppositionality or aggression. But sorting out the As is especially important to going beyond disciplining a misbehavior to building insight for both parents and children.

Antecedents are of two types: triggers such as actions, words, or feelings that happen just before the behavior, and “setting events” that can occur intermittently hours or even days beforehand and lower the threshold for a trigger to cause a child to act out. Lack of sleep, hunger, or fatigue are common setting events that parents recognize and take into account as in “Oh, he missed his nap” to excuse a tantrum in younger children, but is less often considered or excused in older children in whom self-regulation is expected. Often, behavioral specialists in schools are asked to observe a child to identify the triggers and create a “functional behavioral assessment” based on what is observed.

While a functional behavioral assessment requires observations, invisible antecedents to consider include internal thoughts and feelings (meaning). A child feeling shame from a failed math test the day before may be on edge, then, when called on, may uncharacteristically talk back. The child may regard punishment for this “justified” response as unfair, accelerating anger. Feelings of shame or humiliation for failing one’s own standards (or perceived expectations of others the child cares about) are major setups for eliciting defiance.

Even more subtle are meanings the child creates for situations and people, whether real or imagined. A child’s behavior has meaning for the child and the family and can be initiated or maintained by that meaning. For example, a child may “live down” to what the family thinks of him/her; if you think I am bad, I will act badly.

Children may feel guilty about some real or imagined offense, such as divorce or death they think may be their fault, and act up with the family to elicit punishment as payment. When children feel conflicted in a relationship, such as a late adolescent feeling dependent on their mother when their age expectation is independence, they may act up expecting to be ejected from home when they are unable to gather the courage to voluntarily leave. This acting out may also occur with nonconflicted adults, who are actually safer targets. For example, school is often a safer place to express anger through aggression or bullying than home, the real source of the feelings, because family is the “lifeboat” of food and shelter they dare not upset.

Conflicted relationships may be present in blended families, especially if the ex speaks negatively about the other parent. The child of divorce, feeling himself composed of parts of each parent, has diminished self-esteem and anger on behalf of that side being put down. Marital conflict may set children up to feel they have to take sides to angrily defend the parent of like-gender by being oppositional to the other.

Just as we ponder whether the color blue looks the same to someone else, neurologically based differences in perception may make a child misinterpret or act inflexibly or explode in situations that seem normal to adults. While people joke about “being a little OCD,” for some children the distress caused by a change in routine, a messy room, a delayed bus, or loud music is enough to disrupt their functioning and coping enough to explode. Such hypersensitivity can be part of autism or obsessive compulsive disorder or a subthreshold variant. Children vary by age and individually in their ability to understand language, especially sarcastic humor, and often misinterpret it as insulting, threatening, or scary and act accordingly. While most common in children with autism, those with a language learning disability, intellectual disability, or who have English as a second language, or are anxious or vigilant may also take sarcasm the wrong way. Anxious children also may react aggressively from a “hostile bias attribution” of expecting the worst from others.

Another possible meaning of a behavior is that it is being used by the child to manage their feelings. I have found it useful to remind depressed children and parents that it “feels better to be mad than sad” as a reason for irritability. Anger can also push away a person whose otherwise sympathetic approach might release a collapse into tears the child can’t tolerate or would find embarrassing.

The meaning of a child’s misbehavior also resides in the minds of the adults. In addition to all the categories of meaning just described, a parent may be reminded by the child of someone else for whom the adult has strong or conflicted feelings (“projection”) such as a now-hated ex, a sibling of whom the adult is jealous, or a bully from childhood, thus eliciting a reaction falsely triggered by that connection rather than the actual child. Asking parents whom the child “takes after” may elicit such parental projections based on appearance, behavior, or temperament. Helping them pick a feature of the child to focus on to differentiate him/her can serve as an anchor to remind them to control these reactions. Other useful questions to detect meanings of behavior might include asking the child “What’s up with that?” or “What did that make you think/feel?” We can ask parents “How is that for you?” or “What do you think things will be like in 10 years?” to determine despair, mood disorders, or family discord contributing to maladaptive responses possibly maintaining unwanted behaviors.

Throughout life, putting feelings into words is the main way meanings that are contributing to misbehaviors or parenting dysfunction can be uncovered and shifted. For this, the child or adult must feel emotionally safe to talk with a person who conveys curiosity rather than judgment. Helping families explain that divorce is not the child’s fault; admit they also make mistakes; rebuild conflicted relationships through play or talking; identify hypersensitivities or triggers to avoid; and express confidence that the child is a good person, still young, and sure to do better over time, are all things we pediatricians can do to help sort out the meanings of behaviors.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. 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 pdnews@mdedge.com.

You have probably heard that determining the A(ntecedent)s, B(ehavior)s, and C(onsequence)s of a behavior is basic to counseling about oppositionality or aggression. But sorting out the As is especially important to going beyond disciplining a misbehavior to building insight for both parents and children.

Antecedents are of two types: triggers such as actions, words, or feelings that happen just before the behavior, and “setting events” that can occur intermittently hours or even days beforehand and lower the threshold for a trigger to cause a child to act out. Lack of sleep, hunger, or fatigue are common setting events that parents recognize and take into account as in “Oh, he missed his nap” to excuse a tantrum in younger children, but is less often considered or excused in older children in whom self-regulation is expected. Often, behavioral specialists in schools are asked to observe a child to identify the triggers and create a “functional behavioral assessment” based on what is observed.

While a functional behavioral assessment requires observations, invisible antecedents to consider include internal thoughts and feelings (meaning). A child feeling shame from a failed math test the day before may be on edge, then, when called on, may uncharacteristically talk back. The child may regard punishment for this “justified” response as unfair, accelerating anger. Feelings of shame or humiliation for failing one’s own standards (or perceived expectations of others the child cares about) are major setups for eliciting defiance.

Even more subtle are meanings the child creates for situations and people, whether real or imagined. A child’s behavior has meaning for the child and the family and can be initiated or maintained by that meaning. For example, a child may “live down” to what the family thinks of him/her; if you think I am bad, I will act badly.

Children may feel guilty about some real or imagined offense, such as divorce or death they think may be their fault, and act up with the family to elicit punishment as payment. When children feel conflicted in a relationship, such as a late adolescent feeling dependent on their mother when their age expectation is independence, they may act up expecting to be ejected from home when they are unable to gather the courage to voluntarily leave. This acting out may also occur with nonconflicted adults, who are actually safer targets. For example, school is often a safer place to express anger through aggression or bullying than home, the real source of the feelings, because family is the “lifeboat” of food and shelter they dare not upset.

Conflicted relationships may be present in blended families, especially if the ex speaks negatively about the other parent. The child of divorce, feeling himself composed of parts of each parent, has diminished self-esteem and anger on behalf of that side being put down. Marital conflict may set children up to feel they have to take sides to angrily defend the parent of like-gender by being oppositional to the other.

Just as we ponder whether the color blue looks the same to someone else, neurologically based differences in perception may make a child misinterpret or act inflexibly or explode in situations that seem normal to adults. While people joke about “being a little OCD,” for some children the distress caused by a change in routine, a messy room, a delayed bus, or loud music is enough to disrupt their functioning and coping enough to explode. Such hypersensitivity can be part of autism or obsessive compulsive disorder or a subthreshold variant. Children vary by age and individually in their ability to understand language, especially sarcastic humor, and often misinterpret it as insulting, threatening, or scary and act accordingly. While most common in children with autism, those with a language learning disability, intellectual disability, or who have English as a second language, or are anxious or vigilant may also take sarcasm the wrong way. Anxious children also may react aggressively from a “hostile bias attribution” of expecting the worst from others.

Another possible meaning of a behavior is that it is being used by the child to manage their feelings. I have found it useful to remind depressed children and parents that it “feels better to be mad than sad” as a reason for irritability. Anger can also push away a person whose otherwise sympathetic approach might release a collapse into tears the child can’t tolerate or would find embarrassing.

The meaning of a child’s misbehavior also resides in the minds of the adults. In addition to all the categories of meaning just described, a parent may be reminded by the child of someone else for whom the adult has strong or conflicted feelings (“projection”) such as a now-hated ex, a sibling of whom the adult is jealous, or a bully from childhood, thus eliciting a reaction falsely triggered by that connection rather than the actual child. Asking parents whom the child “takes after” may elicit such parental projections based on appearance, behavior, or temperament. Helping them pick a feature of the child to focus on to differentiate him/her can serve as an anchor to remind them to control these reactions. Other useful questions to detect meanings of behavior might include asking the child “What’s up with that?” or “What did that make you think/feel?” We can ask parents “How is that for you?” or “What do you think things will be like in 10 years?” to determine despair, mood disorders, or family discord contributing to maladaptive responses possibly maintaining unwanted behaviors.

Throughout life, putting feelings into words is the main way meanings that are contributing to misbehaviors or parenting dysfunction can be uncovered and shifted. For this, the child or adult must feel emotionally safe to talk with a person who conveys curiosity rather than judgment. Helping families explain that divorce is not the child’s fault; admit they also make mistakes; rebuild conflicted relationships through play or talking; identify hypersensitivities or triggers to avoid; and express confidence that the child is a good person, still young, and sure to do better over time, are all things we pediatricians can do to help sort out the meanings of behaviors.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS. 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 pdnews@mdedge.com.

Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.

The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.

To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.

Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).

Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.

Questions about antibody levels remain difficult to answer

“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”

“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”

Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.

“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”

Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”

As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”

The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.

Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.

The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.

To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.

Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).

Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.

Questions about antibody levels remain difficult to answer

“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”

“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”

Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.

“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”

Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”

As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”

The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.

Patients who are being treated with Janus kinase (JAK) inhibitors overall show a high immune response rate to COVID-19 vaccination, one that matches the rates seen in patients on other immunosuppressants, a new study has found.

The patients taking a JAK inhibitor who are most at risk of a diminished response may be those on upadacitinib (Rinvoq) and anyone 65 years or older, wrote Raphaèle Seror, MD, PhD, of Paris-Saclay (France) University and coauthors. The study was published in The Lancet Rheumatology.

To gauge the effectiveness of COVID-19 vaccines in this subset of immunosuppressed patients, the researchers analyzed 113 participants in the MAJIK-SFR Registry, a multicenter study of French patients with rheumatoid or psoriatic arthritis. The participants were treated at 13 centers throughout France; their mean age was 61.8 years (standard deviation, 12.5), and 72% were female. A total of 56 were taking baricitinib (Olumiant), 30 were taking tofacitinib (Xeljanz), and 27 were taking upadacitinib.

Serologic assessment was performed an average of 8.7 weeks (SD, 5.2) after the last dose of vaccine. The overall response rate – defined as the proportion of patients with detectable anti-spike antibodies per manufacturer’s cutoff values – was 88% (100 of 113). The nonresponse rate was higher with upadacitinib (7 of 27 patients, 26%) than with baricitinib (5 of 56, 9%) or tofacitinib (1 of 30, 3%). The only nonresponders who were not age 65 or older were four of the seven who received upadacitinib. The interval between the last vaccine dose and serologic assessment was somewhat longer in nonresponders (11.3 weeks) than in responders (8.3 weeks).

Earlier this year, the American College of Rheumatology recommended withholding JAK inhibitors for 1 week after each vaccine dose because of “concern related to the effects of this medication class on interferon signaling that may result in a diminished vaccine response Only two patients in the study had treatment with JAK inhibitors stopped before or after vaccination.

Questions about antibody levels remain difficult to answer

“This study does further confirm a big point,” said Alfred Kim, MD, PhD, of Washington University, St. Louis, in an interview. “Most people on any sort of immunosuppression, with rare exceptions, can mount responses to COVID-19 vaccination.”

“What level of response is going to be sufficient, of course, is not clear,” he added. “Even though most people generate responses, at the population level those responses seem lower than those in nonimmunosuppressed people. Particularly for those on upadacitinib, which is lower than patients on the other JAK inhibitors. Is that problematic? We don’t know yet.”

Dr. Kim, who was part of a separate, earlier study that assessed vaccine response in patients with chronic inflammatory disease who were being treated with immunosuppressive medications, noted that many of the questions patients are asking about their antibody levels cannot yet be answered.

“It’s kind of the Wild West of serologic testing out there right now,” he said. “Even though we’re recommending that people still don’t check their antibody levels because their results are largely inactionable, everyone is still getting them anyway. But each of these tests are slightly different, and the results and the interpretation are further clouded because of those slight performance differences between each platform.”

Dr. Kim highlighted the number of different tests as one of this study’s notable limitations: 11 different assays were used to determine patients’ immune responses. “The authors made the argument that these tests are FDA approved, and that’s true, but that doesn’t necessarily mean much. Approval does translate to technical reliability but not to comparisons between the tests.”

As for next steps, both the authors and Dr. Kim recognized the need for a prospective trial. “To do a vaccine effectiveness–type study and show clinical protection against either infection or hospitalization – those are going to take a while, simply because of the nature of how many people you need for each of these studies,” he said. “Time will tell whether or not the data that are being presented here will translate literally into protective outcomes downstream.”

The MAJIK Registry is supported by the French Rheumatology Society. The authors acknowledged numerous potential conflicts of interest, including receiving consulting fees, research support, and honoraria from various pharmaceutical companies.

Background: Many health care facilities have instituted universal masking policies for health care workers while also systematically testing any symptomatic health care workers. There is a paucity of data examining the effectiveness of universal masking policies in reducing COVID positivity among health care workers.

This study is limited by the retrospective cohort, nonrandomized design. Potential confounders include other infection-control measures such as limiting elective procedures, social distancing, and increasing masking in the general population. It is also unclear that a symptomatic testing database is generalizable to the asymptomatic spread of SARS-CoV-2 among health care workers.

Bottom line: Universal masking policy for health care workers appears to decrease the COVID-positive test rates among symptomatic health care workers.

Citation: Wang X et al. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA. 2020;324(7):703-4.

Dr. Ouyang is a hospitalist and chief of the hospitalist section at the Lexington (Ky.) VA Health Care System.

Background: Many health care facilities have instituted universal masking policies for health care workers while also systematically testing any symptomatic health care workers. There is a paucity of data examining the effectiveness of universal masking policies in reducing COVID positivity among health care workers.

This study is limited by the retrospective cohort, nonrandomized design. Potential confounders include other infection-control measures such as limiting elective procedures, social distancing, and increasing masking in the general population. It is also unclear that a symptomatic testing database is generalizable to the asymptomatic spread of SARS-CoV-2 among health care workers.

Bottom line: Universal masking policy for health care workers appears to decrease the COVID-positive test rates among symptomatic health care workers.

Citation: Wang X et al. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA. 2020;324(7):703-4.

Dr. Ouyang is a hospitalist and chief of the hospitalist section at the Lexington (Ky.) VA Health Care System.

Background: Many health care facilities have instituted universal masking policies for health care workers while also systematically testing any symptomatic health care workers. There is a paucity of data examining the effectiveness of universal masking policies in reducing COVID positivity among health care workers.

This study is limited by the retrospective cohort, nonrandomized design. Potential confounders include other infection-control measures such as limiting elective procedures, social distancing, and increasing masking in the general population. It is also unclear that a symptomatic testing database is generalizable to the asymptomatic spread of SARS-CoV-2 among health care workers.

Bottom line: Universal masking policy for health care workers appears to decrease the COVID-positive test rates among symptomatic health care workers.

Citation: Wang X et al. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA. 2020;324(7):703-4.

Dr. Ouyang is a hospitalist and chief of the hospitalist section at the Lexington (Ky.) VA Health Care System.

For women with breast cancer who undergo mastectomy and opt for implant-based breast reconstruction (IBBR), the use of a mesh device does not appear to offer any advantage over conventional techniques.

A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.

“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.

It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”

The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”

Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.

The study was published online October 1 in JAMA Network Open.
 

Any advantage to using mesh device?

Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.

However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.

The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.

The primary endpoint was the number of repeat surgeries at 2 years.

At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).

Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.

For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.

The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.

Some questions remain

Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”

Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.

However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”

But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”

The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For women with breast cancer who undergo mastectomy and opt for implant-based breast reconstruction (IBBR), the use of a mesh device does not appear to offer any advantage over conventional techniques.

A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.

“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.

It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”

The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”

Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.

The study was published online October 1 in JAMA Network Open.
 

Any advantage to using mesh device?

Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.

However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.

The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.

The primary endpoint was the number of repeat surgeries at 2 years.

At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).

Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.

For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.

The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.

Some questions remain

Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”

Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.

However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”

But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”

The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For women with breast cancer who undergo mastectomy and opt for implant-based breast reconstruction (IBBR), the use of a mesh device does not appear to offer any advantage over conventional techniques.

A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.

“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.

It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”

The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”

Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.

The study was published online October 1 in JAMA Network Open.
 

Any advantage to using mesh device?

Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.

However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.

The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.

The primary endpoint was the number of repeat surgeries at 2 years.

At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).

Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.

For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.

The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.

Some questions remain

Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”

Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.

However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”

But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”

The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with ulcerative colitis (UC) who are in remission from their disease lack luminal signals capable of inducing macrophage hyporesponsiveness, which may contribute to a patient’s persistent vulnerability to relapse, according to a new study.

“Together with the distinct fecal metabolomic profile of UC patients in remission, our data suggest that UC patients may lack the signals required for proper macrophage education, rendering them vulnerable to relapse,” wrote study authors Lujain Maasfeh, PhD, of the University of Gothenburg (Sweden) and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

Macrophages found in the lamina propria play a role in sustaining intestinal homeostasis. Through education by local signals, intestinal macrophages adopt a hyporesponsive phenotype and tolerogenic nature and are replenished constantly from monocytes. In patients with UC who are in remission, however, the lack of proper macrophage maturation may result in gut inflammation.

Current evidence has yet to define fully the immunomodulating determinants in the education of intestinal macrophages; however, Dr. Maasfeh and associates wrote that “intestinal microbiota and microbiota-derived metabolites increasingly are recognized for their role in imprinting tissue-specific features of intestinal macrophages.”

The researchers added that previous evidence has established that patients with UC demonstrate dysbiosis, which may impact maturation of intestinal macrophages. As such, the hyporesponsive state of intestinal lamina propria macrophages induced by the microbiota may be lost in patients with UC who are in remission, ultimately resulting in disease relapse.

To gauge the effects of fecal luminal factors on macrophage phenotype and function, the researchers extracted fecal supernatants (FS) from the fecal samples of 10 healthy volunteers and 17 patients with UC who were in remission. Following maturation of monocytes to macrophages in the presence of granulocyte-macrophage colony-stimulating factor without and with FS, the researchers assessed macrophage phenotype and function. The investigators also used gas chromatography and mass spectrometry to analyze fecal metabolomic profiles.

In healthy donors, fecal luminal factors effectively downregulated Toll-like receptor signaling, cytokine signaling, as well as antigen presentation in macrophages. In contrast, the fecal luminal factors in patients with UC demonstrated less potency in their ability to induce lipopolysaccharide hyporesponsiveness. An immune pathway scoring analysis also showed a consistently higher reaction potential among UC remission FS-treated macrophages vs. healthy FS-treated macrophages.

While FS treatment did not seem to affect the phagocytic and bactericidal abilities of macrophages, the researchers observed that the healthy FS-treated macrophages better suppressed a cluster of differentiation 4⁺ T-cell activation as well as interferon gamma secretion vs. FS-treated macrophages from patients with UC in remission. The FS-treated macrophages in the UC remission population also featured less potency in their ability to suppress CD4+ T-cell activation and cytokine secretion.

The authors acknowledged a few limitations, including the small sample size and the effects from using in vitro system.

“Identification of the factors involved in intestinal macrophage education is important to maintain/reestablish gut homeostasis in patients with UC,” they concluded.

The study received financial support from Swedish Research Council-Medicine, in addition to funding from a Region Västra Götaland ALF-agreement, the Knut och Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine at the University of Gothenburg, Ruth and Richard Julin’s foundation, Adlerbertska Foundation, Wilhelm and Martina Lundgren Foundation, and Apotekare Hedberg’s Foundation. The authors disclose no conflicts.

Patients with ulcerative colitis (UC) who are in remission from their disease lack luminal signals capable of inducing macrophage hyporesponsiveness, which may contribute to a patient’s persistent vulnerability to relapse, according to a new study.

“Together with the distinct fecal metabolomic profile of UC patients in remission, our data suggest that UC patients may lack the signals required for proper macrophage education, rendering them vulnerable to relapse,” wrote study authors Lujain Maasfeh, PhD, of the University of Gothenburg (Sweden) and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

Macrophages found in the lamina propria play a role in sustaining intestinal homeostasis. Through education by local signals, intestinal macrophages adopt a hyporesponsive phenotype and tolerogenic nature and are replenished constantly from monocytes. In patients with UC who are in remission, however, the lack of proper macrophage maturation may result in gut inflammation.

Current evidence has yet to define fully the immunomodulating determinants in the education of intestinal macrophages; however, Dr. Maasfeh and associates wrote that “intestinal microbiota and microbiota-derived metabolites increasingly are recognized for their role in imprinting tissue-specific features of intestinal macrophages.”

The researchers added that previous evidence has established that patients with UC demonstrate dysbiosis, which may impact maturation of intestinal macrophages. As such, the hyporesponsive state of intestinal lamina propria macrophages induced by the microbiota may be lost in patients with UC who are in remission, ultimately resulting in disease relapse.

To gauge the effects of fecal luminal factors on macrophage phenotype and function, the researchers extracted fecal supernatants (FS) from the fecal samples of 10 healthy volunteers and 17 patients with UC who were in remission. Following maturation of monocytes to macrophages in the presence of granulocyte-macrophage colony-stimulating factor without and with FS, the researchers assessed macrophage phenotype and function. The investigators also used gas chromatography and mass spectrometry to analyze fecal metabolomic profiles.

In healthy donors, fecal luminal factors effectively downregulated Toll-like receptor signaling, cytokine signaling, as well as antigen presentation in macrophages. In contrast, the fecal luminal factors in patients with UC demonstrated less potency in their ability to induce lipopolysaccharide hyporesponsiveness. An immune pathway scoring analysis also showed a consistently higher reaction potential among UC remission FS-treated macrophages vs. healthy FS-treated macrophages.

While FS treatment did not seem to affect the phagocytic and bactericidal abilities of macrophages, the researchers observed that the healthy FS-treated macrophages better suppressed a cluster of differentiation 4⁺ T-cell activation as well as interferon gamma secretion vs. FS-treated macrophages from patients with UC in remission. The FS-treated macrophages in the UC remission population also featured less potency in their ability to suppress CD4+ T-cell activation and cytokine secretion.

The authors acknowledged a few limitations, including the small sample size and the effects from using in vitro system.

“Identification of the factors involved in intestinal macrophage education is important to maintain/reestablish gut homeostasis in patients with UC,” they concluded.

The study received financial support from Swedish Research Council-Medicine, in addition to funding from a Region Västra Götaland ALF-agreement, the Knut och Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine at the University of Gothenburg, Ruth and Richard Julin’s foundation, Adlerbertska Foundation, Wilhelm and Martina Lundgren Foundation, and Apotekare Hedberg’s Foundation. The authors disclose no conflicts.

Patients with ulcerative colitis (UC) who are in remission from their disease lack luminal signals capable of inducing macrophage hyporesponsiveness, which may contribute to a patient’s persistent vulnerability to relapse, according to a new study.

“Together with the distinct fecal metabolomic profile of UC patients in remission, our data suggest that UC patients may lack the signals required for proper macrophage education, rendering them vulnerable to relapse,” wrote study authors Lujain Maasfeh, PhD, of the University of Gothenburg (Sweden) and colleagues in Cellular and Molecular Gastroenterology and Hepatology.

Macrophages found in the lamina propria play a role in sustaining intestinal homeostasis. Through education by local signals, intestinal macrophages adopt a hyporesponsive phenotype and tolerogenic nature and are replenished constantly from monocytes. In patients with UC who are in remission, however, the lack of proper macrophage maturation may result in gut inflammation.

Current evidence has yet to define fully the immunomodulating determinants in the education of intestinal macrophages; however, Dr. Maasfeh and associates wrote that “intestinal microbiota and microbiota-derived metabolites increasingly are recognized for their role in imprinting tissue-specific features of intestinal macrophages.”

The researchers added that previous evidence has established that patients with UC demonstrate dysbiosis, which may impact maturation of intestinal macrophages. As such, the hyporesponsive state of intestinal lamina propria macrophages induced by the microbiota may be lost in patients with UC who are in remission, ultimately resulting in disease relapse.

To gauge the effects of fecal luminal factors on macrophage phenotype and function, the researchers extracted fecal supernatants (FS) from the fecal samples of 10 healthy volunteers and 17 patients with UC who were in remission. Following maturation of monocytes to macrophages in the presence of granulocyte-macrophage colony-stimulating factor without and with FS, the researchers assessed macrophage phenotype and function. The investigators also used gas chromatography and mass spectrometry to analyze fecal metabolomic profiles.

In healthy donors, fecal luminal factors effectively downregulated Toll-like receptor signaling, cytokine signaling, as well as antigen presentation in macrophages. In contrast, the fecal luminal factors in patients with UC demonstrated less potency in their ability to induce lipopolysaccharide hyporesponsiveness. An immune pathway scoring analysis also showed a consistently higher reaction potential among UC remission FS-treated macrophages vs. healthy FS-treated macrophages.

While FS treatment did not seem to affect the phagocytic and bactericidal abilities of macrophages, the researchers observed that the healthy FS-treated macrophages better suppressed a cluster of differentiation 4⁺ T-cell activation as well as interferon gamma secretion vs. FS-treated macrophages from patients with UC in remission. The FS-treated macrophages in the UC remission population also featured less potency in their ability to suppress CD4+ T-cell activation and cytokine secretion.

The authors acknowledged a few limitations, including the small sample size and the effects from using in vitro system.

“Identification of the factors involved in intestinal macrophage education is important to maintain/reestablish gut homeostasis in patients with UC,” they concluded.

The study received financial support from Swedish Research Council-Medicine, in addition to funding from a Region Västra Götaland ALF-agreement, the Knut och Alice Wallenberg Foundation Wallenberg Centre for Molecular and Translational Medicine at the University of Gothenburg, Ruth and Richard Julin’s foundation, Adlerbertska Foundation, Wilhelm and Martina Lundgren Foundation, and Apotekare Hedberg’s Foundation. The authors disclose no conflicts.

Updated milestones for professional development aim to help specialists in gastroenterology and transplant hepatology achieve knowledge, skills, and attitudes that will help them establish their own practices.

The new version, Milestones 2.0, represents the latest milestones created by the Accreditation Council for Graduate Medical Education, including six core competencies developed initially in 1999: Patient care (PC), medical knowledge (MK), interpersonal and communication skills (ICS), professionalism (PROF), systems-based practice (SBP), and practice-based learning and improvement (PBLI).

In 2013, the Oversight Working Network, working with gastroenterology societies, developed a companion document of 13 entrustable professional activities (EPAs) aimed at gastroenterologists: These include management of various individual disorders such as liver or pancreatic diseases, performance of specific diagnostic procedures, and managing patient adverse events and nutritional status.

Milestones 1.0 encountered some resistance from the graduate education community. Too many of the milestones were deemed to be too vague or were described using language that was too complex. Some viewed the milestones as burdensome, and a review suggested hundreds of different ways to describe ICS and PROF, leading to confusion.

In an effort to improve matters, the ACGME made some changes. The first involved standardizing milestones used for ICS, PROF, SBP, and PBLI so that they could be used across disciplines. They also developed PC and MK milestones tailored to each specialty.

In the latest article on the topic, appearing in Gastroenterology, the authors led by Brijen J. Shah, MD, of the Icahn School of Medicine at Mount Sinai, New York, outlined a second group of changes, which included development of specialty-specific milestones aimed at gastroenterology and transplant hepatology.
 

Development

The new set of milestones includes 17 for gastroenterology and 16 for transplant hepatology.

There are four PC milestones, which include taking a history and conducting patient examinations, patient management, and two more related to cognitive and technical components of procedures. The MK milestones include competency in gastrointestinal and liver diseases (MK1) and medical reasoning (MK2). These milestones are different from the internal medicine milestones met by graduating residents. MK1 includes specialty-specific disorders and diagnostic, therapeutic, and pharmacologic options for treatment or prevention. MK2 encompasses differential diagnoses and how cognitive bias can influence decision-making, a new concept introduced in Milestones 2.0.

Because the skills represented in the four other core milestones (ICS, PROF, SBP, and PBLI) are “common across specialties,” the authors drafted subcompetencies for these four areas with “harmonized” language for use by every specialty. These harmonized milestones were then tailored for each specialty. An important change occurred with SBP because transplant hepatology poses unique challenges in this domain. They ultimately split SBP into two, with SBP1 focusing on unique liver transplant regulatory requirements and SBP2 covering organ allocation and Model for End-Stage Liver Disease (MELD) score exceptions.
 

Public response

The researchers sought out comment on the updated milestones from program directors and coordinators, and published on the ACGME website, and members of the working group also shared it with faculty, fellows, and specialty societies. Overall, 48 respondents assessed “whether the updated milestone provided a realistic measure of knowledge, skills, and behavior; whether it discriminated between different levels of competency; whether the respondent knew how to assess the milestone effectively; and whether the Supplemental Guide was a useful resource in understanding the milestone.” They rated each on a scale of 1 (strongly disagree) to 4 (strongly agree). They could also provide free-text comments.

Respondents agreed that milestones realistically measure progression (mean, 3.49), could distinguish levels of competency (mean, 3.41), could be used accurately (mean, 3.43), and were explained well by the supplemental guide (mean, 3.42). No trends that suggested a need for additional action were found in the free-text comments.
 

Role of milestones

The milestones can be used to develop learning objectives, which in turn can be worked into clinical rotations and learning activities. For instance, the inpatient consult rotation could be used to address the SBP2 (organ allocation/MELD score exemptions), SBP3 (the physician’s role in the health care system), PBLI1 (evidence-based medicine), and some of the PC (patient care) milestones.

The milestones should not be used as an assessment method by supervisors, the authors cautioned, but rather should be used by the Clinical Competency Committee to assess trainees at various time points. The committee may combine milestones with direct observation, chart-simulated recall, multiple evaluations, and other factors to determine a trainee’s progress.

An institution’s program directors can use the milestones to adjust curriculum development and ensure that any gaps are filled. Milestones can be used at multiple times throughout training: When trainees repeat rotations, they can be used to determine year-to-year progress. Trainees who are not progressing adequately may be identified earlier on, then offered supplemental learning opportunities. On the other hand, trainees who exceed expectations may be offered additional opportunities.

Trainees can also use milestones in self-directed learning, though they should work with the program director and clinical faculty to identify gaps in their learning as well as any deficiencies.

The authors have no relevant financial disclosures.

Updated milestones for professional development aim to help specialists in gastroenterology and transplant hepatology achieve knowledge, skills, and attitudes that will help them establish their own practices.

The new version, Milestones 2.0, represents the latest milestones created by the Accreditation Council for Graduate Medical Education, including six core competencies developed initially in 1999: Patient care (PC), medical knowledge (MK), interpersonal and communication skills (ICS), professionalism (PROF), systems-based practice (SBP), and practice-based learning and improvement (PBLI).

In 2013, the Oversight Working Network, working with gastroenterology societies, developed a companion document of 13 entrustable professional activities (EPAs) aimed at gastroenterologists: These include management of various individual disorders such as liver or pancreatic diseases, performance of specific diagnostic procedures, and managing patient adverse events and nutritional status.

Milestones 1.0 encountered some resistance from the graduate education community. Too many of the milestones were deemed to be too vague or were described using language that was too complex. Some viewed the milestones as burdensome, and a review suggested hundreds of different ways to describe ICS and PROF, leading to confusion.

In an effort to improve matters, the ACGME made some changes. The first involved standardizing milestones used for ICS, PROF, SBP, and PBLI so that they could be used across disciplines. They also developed PC and MK milestones tailored to each specialty.

In the latest article on the topic, appearing in Gastroenterology, the authors led by Brijen J. Shah, MD, of the Icahn School of Medicine at Mount Sinai, New York, outlined a second group of changes, which included development of specialty-specific milestones aimed at gastroenterology and transplant hepatology.
 

Development

The new set of milestones includes 17 for gastroenterology and 16 for transplant hepatology.

There are four PC milestones, which include taking a history and conducting patient examinations, patient management, and two more related to cognitive and technical components of procedures. The MK milestones include competency in gastrointestinal and liver diseases (MK1) and medical reasoning (MK2). These milestones are different from the internal medicine milestones met by graduating residents. MK1 includes specialty-specific disorders and diagnostic, therapeutic, and pharmacologic options for treatment or prevention. MK2 encompasses differential diagnoses and how cognitive bias can influence decision-making, a new concept introduced in Milestones 2.0.

Because the skills represented in the four other core milestones (ICS, PROF, SBP, and PBLI) are “common across specialties,” the authors drafted subcompetencies for these four areas with “harmonized” language for use by every specialty. These harmonized milestones were then tailored for each specialty. An important change occurred with SBP because transplant hepatology poses unique challenges in this domain. They ultimately split SBP into two, with SBP1 focusing on unique liver transplant regulatory requirements and SBP2 covering organ allocation and Model for End-Stage Liver Disease (MELD) score exceptions.
 

Public response

The researchers sought out comment on the updated milestones from program directors and coordinators, and published on the ACGME website, and members of the working group also shared it with faculty, fellows, and specialty societies. Overall, 48 respondents assessed “whether the updated milestone provided a realistic measure of knowledge, skills, and behavior; whether it discriminated between different levels of competency; whether the respondent knew how to assess the milestone effectively; and whether the Supplemental Guide was a useful resource in understanding the milestone.” They rated each on a scale of 1 (strongly disagree) to 4 (strongly agree). They could also provide free-text comments.

Respondents agreed that milestones realistically measure progression (mean, 3.49), could distinguish levels of competency (mean, 3.41), could be used accurately (mean, 3.43), and were explained well by the supplemental guide (mean, 3.42). No trends that suggested a need for additional action were found in the free-text comments.
 

Role of milestones

The milestones can be used to develop learning objectives, which in turn can be worked into clinical rotations and learning activities. For instance, the inpatient consult rotation could be used to address the SBP2 (organ allocation/MELD score exemptions), SBP3 (the physician’s role in the health care system), PBLI1 (evidence-based medicine), and some of the PC (patient care) milestones.

The milestones should not be used as an assessment method by supervisors, the authors cautioned, but rather should be used by the Clinical Competency Committee to assess trainees at various time points. The committee may combine milestones with direct observation, chart-simulated recall, multiple evaluations, and other factors to determine a trainee’s progress.

An institution’s program directors can use the milestones to adjust curriculum development and ensure that any gaps are filled. Milestones can be used at multiple times throughout training: When trainees repeat rotations, they can be used to determine year-to-year progress. Trainees who are not progressing adequately may be identified earlier on, then offered supplemental learning opportunities. On the other hand, trainees who exceed expectations may be offered additional opportunities.

Trainees can also use milestones in self-directed learning, though they should work with the program director and clinical faculty to identify gaps in their learning as well as any deficiencies.

The authors have no relevant financial disclosures.

Updated milestones for professional development aim to help specialists in gastroenterology and transplant hepatology achieve knowledge, skills, and attitudes that will help them establish their own practices.

The new version, Milestones 2.0, represents the latest milestones created by the Accreditation Council for Graduate Medical Education, including six core competencies developed initially in 1999: Patient care (PC), medical knowledge (MK), interpersonal and communication skills (ICS), professionalism (PROF), systems-based practice (SBP), and practice-based learning and improvement (PBLI).

In 2013, the Oversight Working Network, working with gastroenterology societies, developed a companion document of 13 entrustable professional activities (EPAs) aimed at gastroenterologists: These include management of various individual disorders such as liver or pancreatic diseases, performance of specific diagnostic procedures, and managing patient adverse events and nutritional status.

Milestones 1.0 encountered some resistance from the graduate education community. Too many of the milestones were deemed to be too vague or were described using language that was too complex. Some viewed the milestones as burdensome, and a review suggested hundreds of different ways to describe ICS and PROF, leading to confusion.

In an effort to improve matters, the ACGME made some changes. The first involved standardizing milestones used for ICS, PROF, SBP, and PBLI so that they could be used across disciplines. They also developed PC and MK milestones tailored to each specialty.

In the latest article on the topic, appearing in Gastroenterology, the authors led by Brijen J. Shah, MD, of the Icahn School of Medicine at Mount Sinai, New York, outlined a second group of changes, which included development of specialty-specific milestones aimed at gastroenterology and transplant hepatology.
 

Development

The new set of milestones includes 17 for gastroenterology and 16 for transplant hepatology.

There are four PC milestones, which include taking a history and conducting patient examinations, patient management, and two more related to cognitive and technical components of procedures. The MK milestones include competency in gastrointestinal and liver diseases (MK1) and medical reasoning (MK2). These milestones are different from the internal medicine milestones met by graduating residents. MK1 includes specialty-specific disorders and diagnostic, therapeutic, and pharmacologic options for treatment or prevention. MK2 encompasses differential diagnoses and how cognitive bias can influence decision-making, a new concept introduced in Milestones 2.0.

Because the skills represented in the four other core milestones (ICS, PROF, SBP, and PBLI) are “common across specialties,” the authors drafted subcompetencies for these four areas with “harmonized” language for use by every specialty. These harmonized milestones were then tailored for each specialty. An important change occurred with SBP because transplant hepatology poses unique challenges in this domain. They ultimately split SBP into two, with SBP1 focusing on unique liver transplant regulatory requirements and SBP2 covering organ allocation and Model for End-Stage Liver Disease (MELD) score exceptions.
 

Public response

The researchers sought out comment on the updated milestones from program directors and coordinators, and published on the ACGME website, and members of the working group also shared it with faculty, fellows, and specialty societies. Overall, 48 respondents assessed “whether the updated milestone provided a realistic measure of knowledge, skills, and behavior; whether it discriminated between different levels of competency; whether the respondent knew how to assess the milestone effectively; and whether the Supplemental Guide was a useful resource in understanding the milestone.” They rated each on a scale of 1 (strongly disagree) to 4 (strongly agree). They could also provide free-text comments.

Respondents agreed that milestones realistically measure progression (mean, 3.49), could distinguish levels of competency (mean, 3.41), could be used accurately (mean, 3.43), and were explained well by the supplemental guide (mean, 3.42). No trends that suggested a need for additional action were found in the free-text comments.
 

Role of milestones

The milestones can be used to develop learning objectives, which in turn can be worked into clinical rotations and learning activities. For instance, the inpatient consult rotation could be used to address the SBP2 (organ allocation/MELD score exemptions), SBP3 (the physician’s role in the health care system), PBLI1 (evidence-based medicine), and some of the PC (patient care) milestones.

The milestones should not be used as an assessment method by supervisors, the authors cautioned, but rather should be used by the Clinical Competency Committee to assess trainees at various time points. The committee may combine milestones with direct observation, chart-simulated recall, multiple evaluations, and other factors to determine a trainee’s progress.

An institution’s program directors can use the milestones to adjust curriculum development and ensure that any gaps are filled. Milestones can be used at multiple times throughout training: When trainees repeat rotations, they can be used to determine year-to-year progress. Trainees who are not progressing adequately may be identified earlier on, then offered supplemental learning opportunities. On the other hand, trainees who exceed expectations may be offered additional opportunities.

Trainees can also use milestones in self-directed learning, though they should work with the program director and clinical faculty to identify gaps in their learning as well as any deficiencies.

The authors have no relevant financial disclosures.

The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.

The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.

The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.

Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.

The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.

Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.

jevans@mdedge.com

The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.

The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.

The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.

Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.

The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.

Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.

jevans@mdedge.com

The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.

The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.

The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.

Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.

The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.

Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.

jevans@mdedge.com

A new clinical practice update expert review for the diagnosis and management of atrophic gastritis (AG) from the American Gastroenterological Association focuses on cases linked to Helicobacter pylori infection or autoimmunity.

This update addresses a sparsity of guidelines for AG in the United States and should be seen as complementary to the AGA Clinical Practice Guidelines on Management of Gastric Intestinal Metaplasia, according to the authors led by Shailja C. Shah, MD, MPH, of the gastroenterology section at Veterans Affairs San Diego Healthcare System and the division of gastroenterology at the University of California, San Diego.

The 2020 guidelines didn’t specifically discuss diagnosis and management of AG; however, a diagnosis of intestinal metaplasia based on gastric histopathology indicates the presence AG since metaplasia occurs in atrophic mucosa. Nevertheless, AG often goes unmentioned in histopathology reports. Such omissions are important because AG is an important stage in the potential development of gastric cancer.

AG is believed to result from genetic and environmental factors. The two primary triggers for the condition are H. pylori infection (HpAG) and autoimmunity (AIG). The condition results from chronic inflammation and replacement of normal gastric glandular structures with connective tissue or nonnative epithelium. It can proceed to other precancerous conditions, including gastric intestinal metaplasia and dysplasia. An estimated 15% of the U.S. population has AG, according to the authors, although this prevalence could be higher in populations with higher rates of H. pylori infection. AIG is rare, occurring in 0.5%-2% of the U.S. population.

Among individuals with AG, 0.1%-0.3% per year go on to develop gastric adenocarcinoma, though additional factors could heighten this risk. Furthermore, 0.4%-0.7% per year go on develop type 1 neuroendocrine tumors.

HpAG and AIG have different patterns of mucosal involvement. During diagnosis, the authors advised careful mucosal visualization with air insufflation and mucosal cleansing. High-definition white-light endoscopy is more sensitive than traditional WLE in the identification of premalignant mucosal changes.

AG diagnosis should be confirmed by histopathology. The updated Sydney protocol should be used to obtain biopsies, and serum pepsinogens can be used to identify extensive atrophy, though this testing is not generally available in the United States for clinical use. When histology results are suggestive of AIG, the presence of parietal cell antibodies and intrinsic factor antibodies can contribute to a diagnosis, although the former can be prone to false positives because of H. pylori infection, and the latter has low sensitivity.

Patients identified with AG should be tested for H. pylori and treated for infection, followed by nonserologic testing to confirm treatment success. If H. pylori is present, successful eradication may allow for reversal of AG to normal gastric mucosa; however, patients may have irreversible changes. This could leave them at elevated risk of further progression, though elimination of H. pylori does appear to blunt that risk somewhat.

Neoplastic complications from AG are rare, and the benefits of surveillance among those with AG have not been demonstrated in prospective trials. Observational trials show that severe AG is associated with greater risk of gastric adenocarcinoma, and other factors, such as comorbidities and patient values and priorities, should inform decision-making. When called for, providers should consider surveillance endoscopies every 3 years, though the authors noted that the optimal surveillance interval is unknown. Factors such as the quality of the original endoscopy, family history of gastric cancer, and a history of immigration from regions with high rates of H. pylori infection may impact decisions on surveillance intervals.

AG can lead to iron or vitamin B₁₂ deficiency, so patients with AG, especially those with corpus-predominant AG, should be evaluated for both. AG should also be considered as a differential diagnosis in patients presenting with either deficiency.

A diagnosis of AIG should be accompanied by screening for autoimmune thyroid disease, and type 1 diabetes or Addison’s disease may also be indicated if clinical presentation is consistent.

Because AG is commonly underdiagnosed, the authors advise that gastroenterologists and pathologists should improve coordination to maximize diagnosis of the condition, and they call for comparative clinical trials to improve risk stratification algorithms and surveillance strategies.

The authors disclose no relevant conflicts of interest.

A new clinical practice update expert review for the diagnosis and management of atrophic gastritis (AG) from the American Gastroenterological Association focuses on cases linked to Helicobacter pylori infection or autoimmunity.

This update addresses a sparsity of guidelines for AG in the United States and should be seen as complementary to the AGA Clinical Practice Guidelines on Management of Gastric Intestinal Metaplasia, according to the authors led by Shailja C. Shah, MD, MPH, of the gastroenterology section at Veterans Affairs San Diego Healthcare System and the division of gastroenterology at the University of California, San Diego.

The 2020 guidelines didn’t specifically discuss diagnosis and management of AG; however, a diagnosis of intestinal metaplasia based on gastric histopathology indicates the presence AG since metaplasia occurs in atrophic mucosa. Nevertheless, AG often goes unmentioned in histopathology reports. Such omissions are important because AG is an important stage in the potential development of gastric cancer.

AG is believed to result from genetic and environmental factors. The two primary triggers for the condition are H. pylori infection (HpAG) and autoimmunity (AIG). The condition results from chronic inflammation and replacement of normal gastric glandular structures with connective tissue or nonnative epithelium. It can proceed to other precancerous conditions, including gastric intestinal metaplasia and dysplasia. An estimated 15% of the U.S. population has AG, according to the authors, although this prevalence could be higher in populations with higher rates of H. pylori infection. AIG is rare, occurring in 0.5%-2% of the U.S. population.

Among individuals with AG, 0.1%-0.3% per year go on to develop gastric adenocarcinoma, though additional factors could heighten this risk. Furthermore, 0.4%-0.7% per year go on develop type 1 neuroendocrine tumors.

HpAG and AIG have different patterns of mucosal involvement. During diagnosis, the authors advised careful mucosal visualization with air insufflation and mucosal cleansing. High-definition white-light endoscopy is more sensitive than traditional WLE in the identification of premalignant mucosal changes.

AG diagnosis should be confirmed by histopathology. The updated Sydney protocol should be used to obtain biopsies, and serum pepsinogens can be used to identify extensive atrophy, though this testing is not generally available in the United States for clinical use. When histology results are suggestive of AIG, the presence of parietal cell antibodies and intrinsic factor antibodies can contribute to a diagnosis, although the former can be prone to false positives because of H. pylori infection, and the latter has low sensitivity.

Patients identified with AG should be tested for H. pylori and treated for infection, followed by nonserologic testing to confirm treatment success. If H. pylori is present, successful eradication may allow for reversal of AG to normal gastric mucosa; however, patients may have irreversible changes. This could leave them at elevated risk of further progression, though elimination of H. pylori does appear to blunt that risk somewhat.

Neoplastic complications from AG are rare, and the benefits of surveillance among those with AG have not been demonstrated in prospective trials. Observational trials show that severe AG is associated with greater risk of gastric adenocarcinoma, and other factors, such as comorbidities and patient values and priorities, should inform decision-making. When called for, providers should consider surveillance endoscopies every 3 years, though the authors noted that the optimal surveillance interval is unknown. Factors such as the quality of the original endoscopy, family history of gastric cancer, and a history of immigration from regions with high rates of H. pylori infection may impact decisions on surveillance intervals.

AG can lead to iron or vitamin B₁₂ deficiency, so patients with AG, especially those with corpus-predominant AG, should be evaluated for both. AG should also be considered as a differential diagnosis in patients presenting with either deficiency.

A diagnosis of AIG should be accompanied by screening for autoimmune thyroid disease, and type 1 diabetes or Addison’s disease may also be indicated if clinical presentation is consistent.

Because AG is commonly underdiagnosed, the authors advise that gastroenterologists and pathologists should improve coordination to maximize diagnosis of the condition, and they call for comparative clinical trials to improve risk stratification algorithms and surveillance strategies.

The authors disclose no relevant conflicts of interest.

A new clinical practice update expert review for the diagnosis and management of atrophic gastritis (AG) from the American Gastroenterological Association focuses on cases linked to Helicobacter pylori infection or autoimmunity.

This update addresses a sparsity of guidelines for AG in the United States and should be seen as complementary to the AGA Clinical Practice Guidelines on Management of Gastric Intestinal Metaplasia, according to the authors led by Shailja C. Shah, MD, MPH, of the gastroenterology section at Veterans Affairs San Diego Healthcare System and the division of gastroenterology at the University of California, San Diego.

The 2020 guidelines didn’t specifically discuss diagnosis and management of AG; however, a diagnosis of intestinal metaplasia based on gastric histopathology indicates the presence AG since metaplasia occurs in atrophic mucosa. Nevertheless, AG often goes unmentioned in histopathology reports. Such omissions are important because AG is an important stage in the potential development of gastric cancer.

AG is believed to result from genetic and environmental factors. The two primary triggers for the condition are H. pylori infection (HpAG) and autoimmunity (AIG). The condition results from chronic inflammation and replacement of normal gastric glandular structures with connective tissue or nonnative epithelium. It can proceed to other precancerous conditions, including gastric intestinal metaplasia and dysplasia. An estimated 15% of the U.S. population has AG, according to the authors, although this prevalence could be higher in populations with higher rates of H. pylori infection. AIG is rare, occurring in 0.5%-2% of the U.S. population.

Among individuals with AG, 0.1%-0.3% per year go on to develop gastric adenocarcinoma, though additional factors could heighten this risk. Furthermore, 0.4%-0.7% per year go on develop type 1 neuroendocrine tumors.

HpAG and AIG have different patterns of mucosal involvement. During diagnosis, the authors advised careful mucosal visualization with air insufflation and mucosal cleansing. High-definition white-light endoscopy is more sensitive than traditional WLE in the identification of premalignant mucosal changes.

AG diagnosis should be confirmed by histopathology. The updated Sydney protocol should be used to obtain biopsies, and serum pepsinogens can be used to identify extensive atrophy, though this testing is not generally available in the United States for clinical use. When histology results are suggestive of AIG, the presence of parietal cell antibodies and intrinsic factor antibodies can contribute to a diagnosis, although the former can be prone to false positives because of H. pylori infection, and the latter has low sensitivity.

Patients identified with AG should be tested for H. pylori and treated for infection, followed by nonserologic testing to confirm treatment success. If H. pylori is present, successful eradication may allow for reversal of AG to normal gastric mucosa; however, patients may have irreversible changes. This could leave them at elevated risk of further progression, though elimination of H. pylori does appear to blunt that risk somewhat.

Neoplastic complications from AG are rare, and the benefits of surveillance among those with AG have not been demonstrated in prospective trials. Observational trials show that severe AG is associated with greater risk of gastric adenocarcinoma, and other factors, such as comorbidities and patient values and priorities, should inform decision-making. When called for, providers should consider surveillance endoscopies every 3 years, though the authors noted that the optimal surveillance interval is unknown. Factors such as the quality of the original endoscopy, family history of gastric cancer, and a history of immigration from regions with high rates of H. pylori infection may impact decisions on surveillance intervals.

AG can lead to iron or vitamin B₁₂ deficiency, so patients with AG, especially those with corpus-predominant AG, should be evaluated for both. AG should also be considered as a differential diagnosis in patients presenting with either deficiency.

A diagnosis of AIG should be accompanied by screening for autoimmune thyroid disease, and type 1 diabetes or Addison’s disease may also be indicated if clinical presentation is consistent.

Because AG is commonly underdiagnosed, the authors advise that gastroenterologists and pathologists should improve coordination to maximize diagnosis of the condition, and they call for comparative clinical trials to improve risk stratification algorithms and surveillance strategies.

The authors disclose no relevant conflicts of interest.

Lupin Pharmaceuticals is recalling all batches of irbesartan tablets USP 75 mg, 150 mg, and 300 mg and irbesartan and hydrochlorothiazide (HCTZ) tablets USP 150 mg/12.5 mg and 300 mg/12.5 mg because of the potential presence of the N-nitrosoirbesartan impurity.

“As part of Lupin’s ongoing assessment, analysis revealed that certain tested active pharmaceutical ingredient (API) batches (but not finished product batches) were above the specification limit for the impurity, N-nitrosoirbesartan,” the company said in a news release posted on the U.S. Food and Drug Administration’s website. It notes that the impurity is a “probable human carcinogen.”

Lupin discontinued the marketing of irbesartan and irbesartan/HCTZ tablets on Jan. 7, 2021. It says it “has received no reports of illness that appear to relate to this issue” and is issuing the recall out of “an abundance of caution.”

The company, however, goes on to note that from Oct. 8, 2018 (the earliest date of shipment from the manufacturing site of any of the affected batches) to September 30 of this year, Lupin received four reports of illness from irbesartan and 0 reports from irbesartan/HCTZ.

Irbesartan is an angiotensin II receptor blocker indicated for treatment of hypertension in patients with type 2 diabetes, elevated serum creatinine, and proteinuria.

Irbesartan/HCTZ tablets include irbesartan and hydrochlorothiazide, a thiazide diuretic, indicated for hypertension in patients not adequately controlled with monotherapy or as an initial therapy in patients likely to need multiple drugs to achieve blood pressure goals.

Lupin is notifying wholesalers, distributors, and retail outlets to immediately discontinue sales of the affected product lots and return them to the company. Specific lot numbers can be found here.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or health care professional for advice regarding an alternative treatment.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the U.S. Food and Drug Administration’s Safety Information and Adverse Event Reporting program.

A version of this article first appeared on Medscape.com.

Lupin Pharmaceuticals is recalling all batches of irbesartan tablets USP 75 mg, 150 mg, and 300 mg and irbesartan and hydrochlorothiazide (HCTZ) tablets USP 150 mg/12.5 mg and 300 mg/12.5 mg because of the potential presence of the N-nitrosoirbesartan impurity.

“As part of Lupin’s ongoing assessment, analysis revealed that certain tested active pharmaceutical ingredient (API) batches (but not finished product batches) were above the specification limit for the impurity, N-nitrosoirbesartan,” the company said in a news release posted on the U.S. Food and Drug Administration’s website. It notes that the impurity is a “probable human carcinogen.”

Lupin discontinued the marketing of irbesartan and irbesartan/HCTZ tablets on Jan. 7, 2021. It says it “has received no reports of illness that appear to relate to this issue” and is issuing the recall out of “an abundance of caution.”

The company, however, goes on to note that from Oct. 8, 2018 (the earliest date of shipment from the manufacturing site of any of the affected batches) to September 30 of this year, Lupin received four reports of illness from irbesartan and 0 reports from irbesartan/HCTZ.

Irbesartan is an angiotensin II receptor blocker indicated for treatment of hypertension in patients with type 2 diabetes, elevated serum creatinine, and proteinuria.

Irbesartan/HCTZ tablets include irbesartan and hydrochlorothiazide, a thiazide diuretic, indicated for hypertension in patients not adequately controlled with monotherapy or as an initial therapy in patients likely to need multiple drugs to achieve blood pressure goals.

Lupin is notifying wholesalers, distributors, and retail outlets to immediately discontinue sales of the affected product lots and return them to the company. Specific lot numbers can be found here.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or health care professional for advice regarding an alternative treatment.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the U.S. Food and Drug Administration’s Safety Information and Adverse Event Reporting program.

A version of this article first appeared on Medscape.com.

Lupin Pharmaceuticals is recalling all batches of irbesartan tablets USP 75 mg, 150 mg, and 300 mg and irbesartan and hydrochlorothiazide (HCTZ) tablets USP 150 mg/12.5 mg and 300 mg/12.5 mg because of the potential presence of the N-nitrosoirbesartan impurity.

“As part of Lupin’s ongoing assessment, analysis revealed that certain tested active pharmaceutical ingredient (API) batches (but not finished product batches) were above the specification limit for the impurity, N-nitrosoirbesartan,” the company said in a news release posted on the U.S. Food and Drug Administration’s website. It notes that the impurity is a “probable human carcinogen.”

Lupin discontinued the marketing of irbesartan and irbesartan/HCTZ tablets on Jan. 7, 2021. It says it “has received no reports of illness that appear to relate to this issue” and is issuing the recall out of “an abundance of caution.”

The company, however, goes on to note that from Oct. 8, 2018 (the earliest date of shipment from the manufacturing site of any of the affected batches) to September 30 of this year, Lupin received four reports of illness from irbesartan and 0 reports from irbesartan/HCTZ.

Irbesartan is an angiotensin II receptor blocker indicated for treatment of hypertension in patients with type 2 diabetes, elevated serum creatinine, and proteinuria.

Irbesartan/HCTZ tablets include irbesartan and hydrochlorothiazide, a thiazide diuretic, indicated for hypertension in patients not adequately controlled with monotherapy or as an initial therapy in patients likely to need multiple drugs to achieve blood pressure goals.

Lupin is notifying wholesalers, distributors, and retail outlets to immediately discontinue sales of the affected product lots and return them to the company. Specific lot numbers can be found here.

The company is advising patients to continue taking their medication and to contact their pharmacist, physician, or health care professional for advice regarding an alternative treatment.

Patients and physicians are also advised to report any adverse events or side effects related to the affected products to MedWatch, the U.S. Food and Drug Administration’s Safety Information and Adverse Event Reporting program.

A version of this article first appeared on Medscape.com.