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Success in LGBTQ+ medicine requires awareness of risk
Patients who are transgender, for instance, are nine times more likely to commit suicide than the general population (2015 U.S. Transgender Survey (USTS). Inter-university Consortium for Political and Social Research. 2019 May 22. doi: 10.3886/ICPSR37229.v1), and those who are also Black have an estimated HIV prevalence of 62%, demonstrating the cumulative, negative health effects of intersectionality (www.cdc.gov/hiv/group/gender/transgender/hiv-prevalence.html).
“Experiences with marginalization and stigma directly relate to some of the poor physical and mental health outcomes that these patients experience,” Megan McNamara, MD, said during a presentation at the American College of Physicians annual Internal Medicine meeting.
Dr. McNamara, who is director of the Gender Identity Veteran’s Experience (GIVE) Clinic, Veterans Affairs Northeast Ohio Healthcare System, Cleveland, offered a brief guide to managing LGBTQ+ patients. She emphasized increased rates of psychological distress and substance abuse, and encouraged familiarity with specific risks associated with three subgroups: men who have sex with men (MSM), women who have sex with women (WSW), and those who are transgender.
Men who have sex with men
According to Dr. McNamara, preexposure prophylaxis (PrEP) should be offered based on Centers for Disease Control and Prevention eligibility criteria, which require that the patient is HIV negative, has had a male sex partner in the past 6 months, is not in a monogamous relationship, and has had anal sex or a bacterial sexually transmitted infection in the past 6 months. The two PrEP options, emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide, are equally effective and have similar safety profiles, Dr. McNamara said, but patients with impaired renal function should receive the alafenamide formulation.
Dr. McNamara also advised screening gay men for extragenital STIs, noting a 13.3% increased risk. When asked about anal Pap testing for HPV, Dr. McNamara called the subject “very controversial,” and ultimately recommended against it, citing a lack of data linking anal HPV infection and dysplasia with later development of rectal carcinoma, as well as the nonactionable impact of a positive result.
“For me, the issue is ... if [a positive anal Pap test] is not going to change my management, if I don’t know that the anal HPV that I diagnose will result in cancer, should I continue to monitor it?” Dr. McNamara said.
Women who have sex with women
Beyond higher rates of psychological distress and substance abuse among lesbian and bisexual women, Dr. McNamara described increased risks of overweight and obesity, higher rates of smoking, and lower rates of Pap testing, all of which should prompt clinicians to advise accordingly, with cervical cancer screening in alignment with guidelines. Clinicians should also discuss HPV vaccination with patients, taking care to weigh benefits and risks, as “catch-up” HPV vaccination is not unilaterally recommended for adults older than 26 years.
Transgender patients
Discussing transgender patients, Dr. McNamara focused on cross-sex hormone therapy (CSHT), first noting the significant psychological benefits, including improvements in depression, somatization, interpersonal sensitivity, hostility, anxiety, phobic anxiety/agoraphobia, and quality of life.
According to Dr. McNamara, CSHT is relatively simple and may be safely administered by primary care providers. For transmasculine patients, testosterone supplementation is all that is needed, whereas transfeminine patients will require spironolactone or GnRH agonists to reduce testosterone and estradiol to increase feminizing hormones to pubertal levels.
CSHT is not without risks, Dr. McNamara said, including “very high” risks of erythrocytosis among transmasculine patients and venous thromboembolic disease among transfeminine patients; but these risks need to be considered in the context of an approximate 40% suicide rate among transgender individuals.
“I can tell you in my own practice that these [suicide] data ring true,” Dr. McNamara said. “Many, many of my patients have attempted suicide, so [CSHT] is something that you really want to think about right away.”
Even when additional risk factors are present, such as preexisting cardiovascular disease, Dr. McNamara suggested that “there are very few absolute contraindications to CSHT,” and described it as a “life-sustaining treatment” that should be viewed analogously with any other long-term management strategy, such as therapy for diabetes or hypertension.
Fostering a transgender-friendly practice
In an interview, Nicole Nisly, MD, codirector of the LGBTQ+ Clinic at the University of Iowa Hospitals and Clinics, Iowa City, reflected upon Dr. McNamara’s presentation, noting that primary care providers – with a little education – are the best candidates to care for transgender patients.
“I think [primary care providers] do a better job [caring for transgender patients] than endocrinologists, honestly, because they can provide care for the whole person,” Dr. Nisly said. “They can do a Pap, they can do STI screening, they can assess mood, they can [evaluate] safety, and the whole person, as opposed to endocrinologists, who do hormone therapy, but somebody else does everything else.”
Dr. Nisly emphasized the importance of personalizing care for transgender individuals, which depends upon a welcoming practice environment, with careful attention to language.
Foremost, Dr. Nisly recommended asking patients for their preferred name, sexual orientation, and gender identity.
“One of the most difficult things [for transgender patients] is to see notes with the wrong name – the name that makes them feel uncomfortable – or the wrong pronoun,” Dr. Nisly said. “That’s very important to the community.”
Dr. Nisly also recommended an alternative term for cross-sex hormone therapy.
“I hate cross-sex hormone therapy terminology, honestly,” Dr. Nisly said. “I just think it’s so unwelcoming, and I think most of our patients don’t like the terminology, so we use ‘gender-affirming hormone therapy.’”
Dr. Nisly explained that the term “cross-sex” assumes a conventional definition of sex, which is inherently flawed.
When discussing certain medical risk factors, such as pregnancy or HIV, it is helpful to know “sex assigned at birth” for both patients and their sexual partners, Dr. Nisly said. It’s best to ask in this way, instead of using terms like “boyfriend” or “girlfriend,” as “sex assigned at birth” is “terminology the community recognizes, affirms, and feels comfortable with.”
Concerning management of medical risk factors, Dr. Nisly offered some additional perspectives.
For one, she recommended giving PrEP to any patient who has a desire to be on PrEP, noting that this desire can indicate a change in future sexual practices, which the CDC criteria do not anticipate. She also advised in-hospital self-swabbing for extragenital STIs, as this can increase patient comfort and adherence. And, in contrast with Dr. McNamara, Dr. Nisly recommended anal Pap screening for any man that has sex with men and anyone with HIV of any gender. She noted that rates of anal dysplasia are “pretty high” among men who have sex with men, and that detection may reduce cancer risk.
For clinicians who would like to learn more about caring for transgender patients, Dr. Nisly recommended that they start by reading the World Professional Association for Transgender Health guidelines.
“It’s about 300 pages,” Dr. Nisly said, “but it is great.”
Dr. McNamara and Dr. Nisly reported no conflicts of interest.
Patients who are transgender, for instance, are nine times more likely to commit suicide than the general population (2015 U.S. Transgender Survey (USTS). Inter-university Consortium for Political and Social Research. 2019 May 22. doi: 10.3886/ICPSR37229.v1), and those who are also Black have an estimated HIV prevalence of 62%, demonstrating the cumulative, negative health effects of intersectionality (www.cdc.gov/hiv/group/gender/transgender/hiv-prevalence.html).
“Experiences with marginalization and stigma directly relate to some of the poor physical and mental health outcomes that these patients experience,” Megan McNamara, MD, said during a presentation at the American College of Physicians annual Internal Medicine meeting.
Dr. McNamara, who is director of the Gender Identity Veteran’s Experience (GIVE) Clinic, Veterans Affairs Northeast Ohio Healthcare System, Cleveland, offered a brief guide to managing LGBTQ+ patients. She emphasized increased rates of psychological distress and substance abuse, and encouraged familiarity with specific risks associated with three subgroups: men who have sex with men (MSM), women who have sex with women (WSW), and those who are transgender.
Men who have sex with men
According to Dr. McNamara, preexposure prophylaxis (PrEP) should be offered based on Centers for Disease Control and Prevention eligibility criteria, which require that the patient is HIV negative, has had a male sex partner in the past 6 months, is not in a monogamous relationship, and has had anal sex or a bacterial sexually transmitted infection in the past 6 months. The two PrEP options, emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide, are equally effective and have similar safety profiles, Dr. McNamara said, but patients with impaired renal function should receive the alafenamide formulation.
Dr. McNamara also advised screening gay men for extragenital STIs, noting a 13.3% increased risk. When asked about anal Pap testing for HPV, Dr. McNamara called the subject “very controversial,” and ultimately recommended against it, citing a lack of data linking anal HPV infection and dysplasia with later development of rectal carcinoma, as well as the nonactionable impact of a positive result.
“For me, the issue is ... if [a positive anal Pap test] is not going to change my management, if I don’t know that the anal HPV that I diagnose will result in cancer, should I continue to monitor it?” Dr. McNamara said.
Women who have sex with women
Beyond higher rates of psychological distress and substance abuse among lesbian and bisexual women, Dr. McNamara described increased risks of overweight and obesity, higher rates of smoking, and lower rates of Pap testing, all of which should prompt clinicians to advise accordingly, with cervical cancer screening in alignment with guidelines. Clinicians should also discuss HPV vaccination with patients, taking care to weigh benefits and risks, as “catch-up” HPV vaccination is not unilaterally recommended for adults older than 26 years.
Transgender patients
Discussing transgender patients, Dr. McNamara focused on cross-sex hormone therapy (CSHT), first noting the significant psychological benefits, including improvements in depression, somatization, interpersonal sensitivity, hostility, anxiety, phobic anxiety/agoraphobia, and quality of life.
According to Dr. McNamara, CSHT is relatively simple and may be safely administered by primary care providers. For transmasculine patients, testosterone supplementation is all that is needed, whereas transfeminine patients will require spironolactone or GnRH agonists to reduce testosterone and estradiol to increase feminizing hormones to pubertal levels.
CSHT is not without risks, Dr. McNamara said, including “very high” risks of erythrocytosis among transmasculine patients and venous thromboembolic disease among transfeminine patients; but these risks need to be considered in the context of an approximate 40% suicide rate among transgender individuals.
“I can tell you in my own practice that these [suicide] data ring true,” Dr. McNamara said. “Many, many of my patients have attempted suicide, so [CSHT] is something that you really want to think about right away.”
Even when additional risk factors are present, such as preexisting cardiovascular disease, Dr. McNamara suggested that “there are very few absolute contraindications to CSHT,” and described it as a “life-sustaining treatment” that should be viewed analogously with any other long-term management strategy, such as therapy for diabetes or hypertension.
Fostering a transgender-friendly practice
In an interview, Nicole Nisly, MD, codirector of the LGBTQ+ Clinic at the University of Iowa Hospitals and Clinics, Iowa City, reflected upon Dr. McNamara’s presentation, noting that primary care providers – with a little education – are the best candidates to care for transgender patients.
“I think [primary care providers] do a better job [caring for transgender patients] than endocrinologists, honestly, because they can provide care for the whole person,” Dr. Nisly said. “They can do a Pap, they can do STI screening, they can assess mood, they can [evaluate] safety, and the whole person, as opposed to endocrinologists, who do hormone therapy, but somebody else does everything else.”
Dr. Nisly emphasized the importance of personalizing care for transgender individuals, which depends upon a welcoming practice environment, with careful attention to language.
Foremost, Dr. Nisly recommended asking patients for their preferred name, sexual orientation, and gender identity.
“One of the most difficult things [for transgender patients] is to see notes with the wrong name – the name that makes them feel uncomfortable – or the wrong pronoun,” Dr. Nisly said. “That’s very important to the community.”
Dr. Nisly also recommended an alternative term for cross-sex hormone therapy.
“I hate cross-sex hormone therapy terminology, honestly,” Dr. Nisly said. “I just think it’s so unwelcoming, and I think most of our patients don’t like the terminology, so we use ‘gender-affirming hormone therapy.’”
Dr. Nisly explained that the term “cross-sex” assumes a conventional definition of sex, which is inherently flawed.
When discussing certain medical risk factors, such as pregnancy or HIV, it is helpful to know “sex assigned at birth” for both patients and their sexual partners, Dr. Nisly said. It’s best to ask in this way, instead of using terms like “boyfriend” or “girlfriend,” as “sex assigned at birth” is “terminology the community recognizes, affirms, and feels comfortable with.”
Concerning management of medical risk factors, Dr. Nisly offered some additional perspectives.
For one, she recommended giving PrEP to any patient who has a desire to be on PrEP, noting that this desire can indicate a change in future sexual practices, which the CDC criteria do not anticipate. She also advised in-hospital self-swabbing for extragenital STIs, as this can increase patient comfort and adherence. And, in contrast with Dr. McNamara, Dr. Nisly recommended anal Pap screening for any man that has sex with men and anyone with HIV of any gender. She noted that rates of anal dysplasia are “pretty high” among men who have sex with men, and that detection may reduce cancer risk.
For clinicians who would like to learn more about caring for transgender patients, Dr. Nisly recommended that they start by reading the World Professional Association for Transgender Health guidelines.
“It’s about 300 pages,” Dr. Nisly said, “but it is great.”
Dr. McNamara and Dr. Nisly reported no conflicts of interest.
Patients who are transgender, for instance, are nine times more likely to commit suicide than the general population (2015 U.S. Transgender Survey (USTS). Inter-university Consortium for Political and Social Research. 2019 May 22. doi: 10.3886/ICPSR37229.v1), and those who are also Black have an estimated HIV prevalence of 62%, demonstrating the cumulative, negative health effects of intersectionality (www.cdc.gov/hiv/group/gender/transgender/hiv-prevalence.html).
“Experiences with marginalization and stigma directly relate to some of the poor physical and mental health outcomes that these patients experience,” Megan McNamara, MD, said during a presentation at the American College of Physicians annual Internal Medicine meeting.
Dr. McNamara, who is director of the Gender Identity Veteran’s Experience (GIVE) Clinic, Veterans Affairs Northeast Ohio Healthcare System, Cleveland, offered a brief guide to managing LGBTQ+ patients. She emphasized increased rates of psychological distress and substance abuse, and encouraged familiarity with specific risks associated with three subgroups: men who have sex with men (MSM), women who have sex with women (WSW), and those who are transgender.
Men who have sex with men
According to Dr. McNamara, preexposure prophylaxis (PrEP) should be offered based on Centers for Disease Control and Prevention eligibility criteria, which require that the patient is HIV negative, has had a male sex partner in the past 6 months, is not in a monogamous relationship, and has had anal sex or a bacterial sexually transmitted infection in the past 6 months. The two PrEP options, emtricitabine/tenofovir disoproxil fumarate and emtricitabine/tenofovir alafenamide, are equally effective and have similar safety profiles, Dr. McNamara said, but patients with impaired renal function should receive the alafenamide formulation.
Dr. McNamara also advised screening gay men for extragenital STIs, noting a 13.3% increased risk. When asked about anal Pap testing for HPV, Dr. McNamara called the subject “very controversial,” and ultimately recommended against it, citing a lack of data linking anal HPV infection and dysplasia with later development of rectal carcinoma, as well as the nonactionable impact of a positive result.
“For me, the issue is ... if [a positive anal Pap test] is not going to change my management, if I don’t know that the anal HPV that I diagnose will result in cancer, should I continue to monitor it?” Dr. McNamara said.
Women who have sex with women
Beyond higher rates of psychological distress and substance abuse among lesbian and bisexual women, Dr. McNamara described increased risks of overweight and obesity, higher rates of smoking, and lower rates of Pap testing, all of which should prompt clinicians to advise accordingly, with cervical cancer screening in alignment with guidelines. Clinicians should also discuss HPV vaccination with patients, taking care to weigh benefits and risks, as “catch-up” HPV vaccination is not unilaterally recommended for adults older than 26 years.
Transgender patients
Discussing transgender patients, Dr. McNamara focused on cross-sex hormone therapy (CSHT), first noting the significant psychological benefits, including improvements in depression, somatization, interpersonal sensitivity, hostility, anxiety, phobic anxiety/agoraphobia, and quality of life.
According to Dr. McNamara, CSHT is relatively simple and may be safely administered by primary care providers. For transmasculine patients, testosterone supplementation is all that is needed, whereas transfeminine patients will require spironolactone or GnRH agonists to reduce testosterone and estradiol to increase feminizing hormones to pubertal levels.
CSHT is not without risks, Dr. McNamara said, including “very high” risks of erythrocytosis among transmasculine patients and venous thromboembolic disease among transfeminine patients; but these risks need to be considered in the context of an approximate 40% suicide rate among transgender individuals.
“I can tell you in my own practice that these [suicide] data ring true,” Dr. McNamara said. “Many, many of my patients have attempted suicide, so [CSHT] is something that you really want to think about right away.”
Even when additional risk factors are present, such as preexisting cardiovascular disease, Dr. McNamara suggested that “there are very few absolute contraindications to CSHT,” and described it as a “life-sustaining treatment” that should be viewed analogously with any other long-term management strategy, such as therapy for diabetes or hypertension.
Fostering a transgender-friendly practice
In an interview, Nicole Nisly, MD, codirector of the LGBTQ+ Clinic at the University of Iowa Hospitals and Clinics, Iowa City, reflected upon Dr. McNamara’s presentation, noting that primary care providers – with a little education – are the best candidates to care for transgender patients.
“I think [primary care providers] do a better job [caring for transgender patients] than endocrinologists, honestly, because they can provide care for the whole person,” Dr. Nisly said. “They can do a Pap, they can do STI screening, they can assess mood, they can [evaluate] safety, and the whole person, as opposed to endocrinologists, who do hormone therapy, but somebody else does everything else.”
Dr. Nisly emphasized the importance of personalizing care for transgender individuals, which depends upon a welcoming practice environment, with careful attention to language.
Foremost, Dr. Nisly recommended asking patients for their preferred name, sexual orientation, and gender identity.
“One of the most difficult things [for transgender patients] is to see notes with the wrong name – the name that makes them feel uncomfortable – or the wrong pronoun,” Dr. Nisly said. “That’s very important to the community.”
Dr. Nisly also recommended an alternative term for cross-sex hormone therapy.
“I hate cross-sex hormone therapy terminology, honestly,” Dr. Nisly said. “I just think it’s so unwelcoming, and I think most of our patients don’t like the terminology, so we use ‘gender-affirming hormone therapy.’”
Dr. Nisly explained that the term “cross-sex” assumes a conventional definition of sex, which is inherently flawed.
When discussing certain medical risk factors, such as pregnancy or HIV, it is helpful to know “sex assigned at birth” for both patients and their sexual partners, Dr. Nisly said. It’s best to ask in this way, instead of using terms like “boyfriend” or “girlfriend,” as “sex assigned at birth” is “terminology the community recognizes, affirms, and feels comfortable with.”
Concerning management of medical risk factors, Dr. Nisly offered some additional perspectives.
For one, she recommended giving PrEP to any patient who has a desire to be on PrEP, noting that this desire can indicate a change in future sexual practices, which the CDC criteria do not anticipate. She also advised in-hospital self-swabbing for extragenital STIs, as this can increase patient comfort and adherence. And, in contrast with Dr. McNamara, Dr. Nisly recommended anal Pap screening for any man that has sex with men and anyone with HIV of any gender. She noted that rates of anal dysplasia are “pretty high” among men who have sex with men, and that detection may reduce cancer risk.
For clinicians who would like to learn more about caring for transgender patients, Dr. Nisly recommended that they start by reading the World Professional Association for Transgender Health guidelines.
“It’s about 300 pages,” Dr. Nisly said, “but it is great.”
Dr. McNamara and Dr. Nisly reported no conflicts of interest.
FROM INTERNAL MEDICINE 2021
Most labeled penicillin-allergic are no longer intolerant
The mislabeling has implications for patient outcomes and efforts to fight antibiotic resistance, said Olajumoke Fadugba, MD, program director for the allergy and immunology fellowship at University of Pennsylvania Health System, Philadelphia.
About 10% of the general population reports a history of penicillin allergy (up to 15% of hospitalized patients), but up to 90% of patients with that label are able to tolerate penicillin, Dr. Fadugba said. The mislabeling comes either because reactions were improperly characterized early on or people have outgrown the allergy.
“There are data that tell us penicillin IgE-mediated wanes over time and that after 10 years of avoidance of a drug, greater than 80% of patients have a resolution of their penicillin IgE.”
Data also show patients outgrow their aminopenicillin reactions (including those from amoxicillin and Ampicillin) faster than parenteral penicillin reactions, she noted.
Josune Iglesias, MD, assistant professor of internal medicine at Rush University Medical Center in Chicago, said in an interview that she often sees patients who said their parents told them when they were kids that they were allergic to penicillin and that information just keeps getting entered into their records.
She said physicians are aware the penicillin-allergic label is not always accurate, but there is hesitancy to challenge those labels.
“We are cautious because of the potential side effects and the harm that we could cause if we unlabel the patient,” she said. “I think having this information will help us unlabel those patients well so we don’t cause harm.”
Also, the threat to antibiotic resistance is real, she said, when penicillin is eliminated as an option unnecessarily.
When a person is labeled allergic to penicillin, the treatment choices often go to broad-spectrum antibiotics that are more costly, have potentially worse side effects, and may contribute to resistance.
“It’s really important, especially with older people, patients sicker with chronic conditions to really make sure we unlabel those patients [who are not truly penicillin allergic],” Dr. Iglesias said.
The label can also cause harm in the hospital setting and worsen outcomes, according to Dr. Fadugba.
She noted that the penicillin allergy label has been linked with longer hospital length of stay, higher rate of readmission, acute kidney injury, multidrug-resistant organisms such as MRSA, and nosocomial infections including Clostridioides difficile.
Getting an effective drug history is an important part of determining who really has a penicillin allergy.
A questionnaire should ask whether the patient was likely to have had an immediate hypersensitivity to penicillin, such as hives or anaphylaxis, which would be more worrisome than a delayed rash.
Knowing the time frame of the reaction helps determine how likely or unlikely people are to still have the allergy, Dr. Fadugba said. “We also want to ask, have they received a penicillin antibiotic since that initial reaction and have they tolerated it?”
She continued: “If a patient received amoxicillin 2 weeks ago, and they tolerated it, you can essentially remove the allergy label and essentially change that patient’s potential hospital course – that immediate course or future outcomes.”
After obtaining the history, there are choices to make.
If a patient is not allergic, she said, the next step is removing the label and documenting why so that in the future another clinician doesn’t see the deleted label and put it back. If a person is deemed allergic by history, clinicians should document the nature of the reaction and if the patient needs a beta-lactam during a hospitalization or in clinic, make a decision based on what kind of beta-lactam they need.
“Generally, for a fourth-generation cephalosporin, for a distant history of penicillin allergy, you can probably give the full dose or – if you’re conservative – give it cautiously, perhaps 10% initially and then monitor because cross-reactivity is known to be low, about 2%,” Dr. Fadugba said.
If the patient needs a penicillin antibiotic specifically, options are guided by the resources.
If a clinician has personnel or an allergy specialist available, skin testing may be an option and “if negative, you can rule out the allergy,” Dr. Fadugba said.
“If that’s not available and the patient really needs a penicillin, you can consider desensitization,” she said.
However, she said, “If the patient is very high risk, then you have no choice but to use an alternative, especially if you can’t desensitize.”
Dr. Fadugba is a consultant for the Health Resources & Services Administration. Dr. Iglesias disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The mislabeling has implications for patient outcomes and efforts to fight antibiotic resistance, said Olajumoke Fadugba, MD, program director for the allergy and immunology fellowship at University of Pennsylvania Health System, Philadelphia.
About 10% of the general population reports a history of penicillin allergy (up to 15% of hospitalized patients), but up to 90% of patients with that label are able to tolerate penicillin, Dr. Fadugba said. The mislabeling comes either because reactions were improperly characterized early on or people have outgrown the allergy.
“There are data that tell us penicillin IgE-mediated wanes over time and that after 10 years of avoidance of a drug, greater than 80% of patients have a resolution of their penicillin IgE.”
Data also show patients outgrow their aminopenicillin reactions (including those from amoxicillin and Ampicillin) faster than parenteral penicillin reactions, she noted.
Josune Iglesias, MD, assistant professor of internal medicine at Rush University Medical Center in Chicago, said in an interview that she often sees patients who said their parents told them when they were kids that they were allergic to penicillin and that information just keeps getting entered into their records.
She said physicians are aware the penicillin-allergic label is not always accurate, but there is hesitancy to challenge those labels.
“We are cautious because of the potential side effects and the harm that we could cause if we unlabel the patient,” she said. “I think having this information will help us unlabel those patients well so we don’t cause harm.”
Also, the threat to antibiotic resistance is real, she said, when penicillin is eliminated as an option unnecessarily.
When a person is labeled allergic to penicillin, the treatment choices often go to broad-spectrum antibiotics that are more costly, have potentially worse side effects, and may contribute to resistance.
“It’s really important, especially with older people, patients sicker with chronic conditions to really make sure we unlabel those patients [who are not truly penicillin allergic],” Dr. Iglesias said.
The label can also cause harm in the hospital setting and worsen outcomes, according to Dr. Fadugba.
She noted that the penicillin allergy label has been linked with longer hospital length of stay, higher rate of readmission, acute kidney injury, multidrug-resistant organisms such as MRSA, and nosocomial infections including Clostridioides difficile.
Getting an effective drug history is an important part of determining who really has a penicillin allergy.
A questionnaire should ask whether the patient was likely to have had an immediate hypersensitivity to penicillin, such as hives or anaphylaxis, which would be more worrisome than a delayed rash.
Knowing the time frame of the reaction helps determine how likely or unlikely people are to still have the allergy, Dr. Fadugba said. “We also want to ask, have they received a penicillin antibiotic since that initial reaction and have they tolerated it?”
She continued: “If a patient received amoxicillin 2 weeks ago, and they tolerated it, you can essentially remove the allergy label and essentially change that patient’s potential hospital course – that immediate course or future outcomes.”
After obtaining the history, there are choices to make.
If a patient is not allergic, she said, the next step is removing the label and documenting why so that in the future another clinician doesn’t see the deleted label and put it back. If a person is deemed allergic by history, clinicians should document the nature of the reaction and if the patient needs a beta-lactam during a hospitalization or in clinic, make a decision based on what kind of beta-lactam they need.
“Generally, for a fourth-generation cephalosporin, for a distant history of penicillin allergy, you can probably give the full dose or – if you’re conservative – give it cautiously, perhaps 10% initially and then monitor because cross-reactivity is known to be low, about 2%,” Dr. Fadugba said.
If the patient needs a penicillin antibiotic specifically, options are guided by the resources.
If a clinician has personnel or an allergy specialist available, skin testing may be an option and “if negative, you can rule out the allergy,” Dr. Fadugba said.
“If that’s not available and the patient really needs a penicillin, you can consider desensitization,” she said.
However, she said, “If the patient is very high risk, then you have no choice but to use an alternative, especially if you can’t desensitize.”
Dr. Fadugba is a consultant for the Health Resources & Services Administration. Dr. Iglesias disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The mislabeling has implications for patient outcomes and efforts to fight antibiotic resistance, said Olajumoke Fadugba, MD, program director for the allergy and immunology fellowship at University of Pennsylvania Health System, Philadelphia.
About 10% of the general population reports a history of penicillin allergy (up to 15% of hospitalized patients), but up to 90% of patients with that label are able to tolerate penicillin, Dr. Fadugba said. The mislabeling comes either because reactions were improperly characterized early on or people have outgrown the allergy.
“There are data that tell us penicillin IgE-mediated wanes over time and that after 10 years of avoidance of a drug, greater than 80% of patients have a resolution of their penicillin IgE.”
Data also show patients outgrow their aminopenicillin reactions (including those from amoxicillin and Ampicillin) faster than parenteral penicillin reactions, she noted.
Josune Iglesias, MD, assistant professor of internal medicine at Rush University Medical Center in Chicago, said in an interview that she often sees patients who said their parents told them when they were kids that they were allergic to penicillin and that information just keeps getting entered into their records.
She said physicians are aware the penicillin-allergic label is not always accurate, but there is hesitancy to challenge those labels.
“We are cautious because of the potential side effects and the harm that we could cause if we unlabel the patient,” she said. “I think having this information will help us unlabel those patients well so we don’t cause harm.”
Also, the threat to antibiotic resistance is real, she said, when penicillin is eliminated as an option unnecessarily.
When a person is labeled allergic to penicillin, the treatment choices often go to broad-spectrum antibiotics that are more costly, have potentially worse side effects, and may contribute to resistance.
“It’s really important, especially with older people, patients sicker with chronic conditions to really make sure we unlabel those patients [who are not truly penicillin allergic],” Dr. Iglesias said.
The label can also cause harm in the hospital setting and worsen outcomes, according to Dr. Fadugba.
She noted that the penicillin allergy label has been linked with longer hospital length of stay, higher rate of readmission, acute kidney injury, multidrug-resistant organisms such as MRSA, and nosocomial infections including Clostridioides difficile.
Getting an effective drug history is an important part of determining who really has a penicillin allergy.
A questionnaire should ask whether the patient was likely to have had an immediate hypersensitivity to penicillin, such as hives or anaphylaxis, which would be more worrisome than a delayed rash.
Knowing the time frame of the reaction helps determine how likely or unlikely people are to still have the allergy, Dr. Fadugba said. “We also want to ask, have they received a penicillin antibiotic since that initial reaction and have they tolerated it?”
She continued: “If a patient received amoxicillin 2 weeks ago, and they tolerated it, you can essentially remove the allergy label and essentially change that patient’s potential hospital course – that immediate course or future outcomes.”
After obtaining the history, there are choices to make.
If a patient is not allergic, she said, the next step is removing the label and documenting why so that in the future another clinician doesn’t see the deleted label and put it back. If a person is deemed allergic by history, clinicians should document the nature of the reaction and if the patient needs a beta-lactam during a hospitalization or in clinic, make a decision based on what kind of beta-lactam they need.
“Generally, for a fourth-generation cephalosporin, for a distant history of penicillin allergy, you can probably give the full dose or – if you’re conservative – give it cautiously, perhaps 10% initially and then monitor because cross-reactivity is known to be low, about 2%,” Dr. Fadugba said.
If the patient needs a penicillin antibiotic specifically, options are guided by the resources.
If a clinician has personnel or an allergy specialist available, skin testing may be an option and “if negative, you can rule out the allergy,” Dr. Fadugba said.
“If that’s not available and the patient really needs a penicillin, you can consider desensitization,” she said.
However, she said, “If the patient is very high risk, then you have no choice but to use an alternative, especially if you can’t desensitize.”
Dr. Fadugba is a consultant for the Health Resources & Services Administration. Dr. Iglesias disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nonpharma approach a potential ‘game changer’ in schizophrenia?
Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.
“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.
“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.
Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”
The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
Resistance continues
Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.
He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.
However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.
The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:
- The presence of an active and trained therapist.
- Repeated practice of cognitive exercises.
- Structured development of cognitive strategies.
- Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.
The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.
Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.
Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.
The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.
The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.
The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).
Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).
Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).
The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).
Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).
The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).
The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
An overlooked treatment option
Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.
“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”
Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”
CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.
“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.
These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.
“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.
Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.
“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.
One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.
“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.
“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.
Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”
The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
Resistance continues
Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.
He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.
However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.
The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:
- The presence of an active and trained therapist.
- Repeated practice of cognitive exercises.
- Structured development of cognitive strategies.
- Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.
The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.
Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.
Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.
The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.
The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.
The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).
Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).
Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).
The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).
Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).
The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).
The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
An overlooked treatment option
Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.
“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”
Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”
CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.
“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.
These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.
“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.
Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.
“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.
One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.
“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.
“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.
Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”
The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
Resistance continues
Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.
He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.
However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.
The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:
- The presence of an active and trained therapist.
- Repeated practice of cognitive exercises.
- Structured development of cognitive strategies.
- Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.
The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.
Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.
Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.
The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.
The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.
The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).
Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).
Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).
The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).
Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).
The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).
The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
An overlooked treatment option
Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.
“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”
Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”
CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.
“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.
These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.
“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.
Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.
“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.
One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID lockdowns linked to PTSD in patients with eating disorders
COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.
Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.
In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.
Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.
In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
Loss of control
Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.
To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.
The second group served as the control group.
Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.
The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).
In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
Clinical implications
A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.
Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.
These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.
These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.
In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.
They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.
Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
Bulimia patients more vulnerable
After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.
All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.
The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).
Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.
In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).
“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”
The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.
In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
Evidence of recovery
Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.
“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.
“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.
“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.
The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”
The study authors and Dr. Spiegel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.
Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.
In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.
Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.
In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
Loss of control
Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.
To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.
The second group served as the control group.
Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.
The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).
In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
Clinical implications
A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.
Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.
These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.
These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.
In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.
They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.
Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
Bulimia patients more vulnerable
After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.
All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.
The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).
Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.
In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).
“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”
The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.
In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
Evidence of recovery
Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.
“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.
“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.
“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.
The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”
The study authors and Dr. Spiegel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 and its resulting lockdowns are linked to posttraumatic stress disorder symptoms and other adverse outcomes among patients with eating disorders (EDs), two new studies show.
Results of the first study show that patients with EDs had more stress, anxiety, depression, and PTSD-related symptoms during the lockdowns than their mentally healthy peers.
In the second study, treatment-related symptom improvement among patients with bulimia nervosa (BN) slowed following lockdown. In addition, patients with BN or anorexia nervosa (AN) experienced significant worsening of disorder-specific behaviors, including binge eating and overexercising.
Because of the strict lockdown measures introduced by the Italian government to contain the COVID-19 pandemic, “everyday life of all citizens was disrupted,” Veronica Nisticò, MS, Università Degli Studi Di Milano, who led the first study, told delegates attending the virtual European Psychiatric Association 2021 Congress.
In addition to difficulties in accessing health care, “it became difficult to go to the supermarket, to the gym, and to have the social support we were all used to,” all of which had a well-documented impact on mental health, added Ms. Nisticò, who is also affiliated with Aldo Ravelli Research Center for Neurotechnology and Experimental Brain Therapeutics.
Loss of control
Previous research suggests that individuals with EDs experience high levels of anxiety and an increase in binge eating, exercise, and purging behaviors, said Ms. Nisticò.
To investigate further, the researchers conducted a longitudinal study of the changes in prevalence of adverse outcomes. In the study, two assessments were conducted.
The second group served as the control group.
Participants completed an online survey that included several standardized depression and anxiety scales, as well as an ad hoc survey adapted from the Eating Disorder Examination Questionnaire. This assessed changes in restrictive dieting, control over food, body image, and psychological well-being in comparison with prepandemic levels.
The results, which were also recently published online in Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, showed that patients with EDs experienced significantly more stress, anxiety, depression, and PTSD-related symptoms in comparison with control persons (P < .05 for all).
In addition, the investigators found that those with EDs were more fearful of losing control over their eating behavior, spent more time thinking about food and their body, and became more uncomfortable seeing their body than before the lockdown in comparison with those without EDs (P < .05).
Clinical implications
A second assessment, which occurred in June 2020, after lockdown restrictions were lifted, included 40 patients with EDs who had taken part in the first assessment. This time, participants were asked to compare their current eating behavior with their eating behavior during the lockdown.
Although the lifting of lockdown restrictions was associated with significant improvement in PTSD-related symptoms, the impact on stress, anxiety, and depression persisted.
These findings, said Ms. Nisticó, support the hypothesis that specific conditions that occurred during the lockdown had a direct effect on specific ED symptoms.
These findings, she added, should be considered when developing interventions for EDs in the context of individual psychotherapy and when designing large, preventive interventions.
In the second study, Eleonora Rossi, MD, psychiatric unit, department of health sciences, University of Florence (Italy), and colleagues examined the longitudinal impact of the pandemic on individuals with EDs.
They examined 74 patients with AN or BN who had undergone baseline assessments and had completed a number of questionnaires in the first months of 2019 in conjunction with being enrolled in another study.
Participants were treated with enhanced cognitive-behavioral therapy and were reevaluated between November 2019 and January 2020. They were then compared with 97 healthy individuals.
Bulimia patients more vulnerable
After the outbreak of the pandemic, most treatment was administered online, so patients were able to continue therapy, Dr. Rossi said during her presentation.
All participants were assessed again in April 2020, 6 weeks after the start of Italy’s lockdown.
The results, which were published in the International Journal of Eating Disorders, show that the patients with EDs “underwent a significant improvement in terms of general and eating disorder specific psychopathology” during the first treatment period, Dr. Rossi reported. In addition, among those with AN, body mass index increased significantly (P < .05 for all).
Patients with AN continued to improve during the lockdown when therapy was administered online. However, improvements that had occurred among those with BN slowed, Dr. Rossi noted.
In addition, both groups of patients with EDs experienced a worsening of their pathological eating behaviors during the lockdown, in particular, objective binge eating and compensatory physical exercise (P < .05).
“Indeed, the positive trajectory of improvement observed before lockdown was clearly interrupted during the pandemic period,” Dr. Rossi said. This could “represent a possible hint of an imminent exacerbation of the disease.”
The results also suggest that the occurrence of arguments within the household and fear regarding the safety of loved ones predicted an increase in symptoms during the lockdown, she added.
In addition, patients with BN reported more severe COVID-related PTSD symptoms than did those with AN and the control group. This increase in severity of symptoms was more prevalent among patients who had a history of childhood trauma and among those with insecure attachment, suggesting that such patients may be more vulnerable.
Evidence of recovery
Commenting on the studies, David Spiegel, MD, associate chair of psychiatry, Stanford (Calif.) University, noted that EDs commonly occur after physical or sexual trauma earlier in life.
“It’s a standard thing with trauma-related disorders that any other, even relatively minor, traumatic experience can exacerbate PTSD symptoms,” said Dr. Spiegel, who was not involved in the studies. In addition, the trauma of the COVID pandemic “was not minor.
“The relative isolation and the lack of outside contact may focus many people with eating disorders even more on their struggles with how they are taking care of their bodies,” said Dr. Spiegel.
“It struck me that the anorexia nervosa group were more impervious than the bulimia nervosa group, but I think that’s the case with the disorder. In some ways it’s more severe, obviously a more life-threatening disorder,” he added.
The “hopeful thing is that there seemed to be some evidence of recovery and improvement, particularly with the posttraumatic stress exacerbation, as time went on,” Dr. Spiegel said, “and that’s a good thing.”
The study authors and Dr. Spiegel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
LGBTQ patients face unique skin risks
Dermatologists cautioned colleagues to in transgender people, who are especially vulnerable to acne because of hormone therapy.
The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.
In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”
Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).
When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).
Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.
For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”
Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.
In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.
Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.
Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.
What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.
Hormone therapy and acne
In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.
“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.
The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.
In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.
Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).
Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.
Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”
Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.
“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”
Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.
Dermatologists cautioned colleagues to in transgender people, who are especially vulnerable to acne because of hormone therapy.
The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.
In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”
Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).
When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).
Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.
For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”
Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.
In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.
Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.
Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.
What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.
Hormone therapy and acne
In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.
“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.
The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.
In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.
Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).
Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.
Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”
Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.
“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”
Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.
Dermatologists cautioned colleagues to in transgender people, who are especially vulnerable to acne because of hormone therapy.
The identities of sexual minorities “have a significant influence on many facets of health,” dermatologist Matthew Mansh, MD, of the University of Minnesota, Minneapolis, said in a presentation at the American Academy of Dermatology Virtual Meeting Experience.
In regard to skin cancer, he said, “there seems to be consistently higher rates of skin cancer and certain preventable risk behaviors like indoor tanning among sexual minority men.”
Dr. Mansh, codirector of the high-risk nonmelanoma skin cancer clinic at the University of Minnesota, highlighted a report, published in JAMA Dermatology in 2020, that used 2014-2018 U.S. survey data of over 870,000 adults to look at the association between sexual orientation and lifetime prevalence of skin cancer. The investigators found that gay and bisexual men had a higher lifetime prevalence of skin cancer compared with heterosexual men (adjusted odds ratio [aOR], 1.25; 95% confidence interval, 1.03-1.50; P = .02; and aOR, 1.46; 95% CI, 1.01-2.10; P = .04; for gay and bisexual men, respectively).
When compared with heterosexual women, risk among bisexual women was lower (aOR, 0.75; 95% CI, 0.60-0.95; P = .02), but not among lesbian women (aOR, 1.01; 95% CI, 0.77-1.33; P = .95, respectively).
Other studies have reached similar conclusions, Dr. Mansh said, although there’s been fairly little research in this area. What could explain these differences? Factors such as smoking, age, and alcohol use affect skin cancer risk, he said, but these studies control for those variables. Instead, he noted, it’s useful to look at studies of ultraviolet exposure.
For example, he highlighted a study published in JAMA Dermatology in 2015, which examined 12-month indoor-tanning rates and skin cancer prevalence by sexual orientation, using data from California and national health interview surveys. The study found that compared with heterosexual men, “sexual minority men had higher rates of indoor tanning by roughly three- to sixfold,” said Dr. Mansh, the lead author. “And this was among respondents who were adults over age 18. People between the ages of 18 and 34 years are important from a skin cancer perspective as it’s well established that exposure to tanning beds at a younger age is most associated with an increased risk of skin cancer.”
Sexual minority men were also significantly more likely to report having skin cancer, compared with heterosexual men.
In the study, sexual minority women had about half the odds of engaging in indoor tanning compared with heterosexual women, and were less likely to report having been diagnosed with nonmelanoma skin cancer, he added.
Other studies suggest that gay and bisexual men live in neighborhoods with more indoor tanning salons and that they may spend more time in the sun outside too, he said. Some research suggests motivations for tanning include social pressure and the desire to improve appearance, he added.
Overall, “we may be able to use these data to add more appropriate screening and recommendations for these patients, which are sorely lacking in dermatology,” and to design targeted behavioral interventions, said Dr. Mansh, codirector of the dermatology gender care clinic at the University of Minnesota.
What can dermatologists do now? In an interview, dermatologist Jon Klint Peebles, MD, of the mid-Atlantic Permanente Medical Group, in Largo, Md., suggested that colleagues ask patients questions about indoor tanning frequency, the motivations for tanning, exposure to outdoor ultraviolet radiation, sunscreen use, and use of photoprotective clothing.
Hormone therapy and acne
In a related presentation at the meeting, Howa Yeung, MD, of the department of dermatology, Emory University, Atlanta, said that in transgender people, estrogen therapy can actually reduce sebum production and often improves acne, while testosterone therapy frequently has the opposite effect.
“We’ve seen some pretty tough cases of acne in transmasculine patients in my practice,” said Dr. Yeung, who highlighted a recently published study that tracked 988 transgender patients in Boston who underwent testosterone therapy. Nearly a third were diagnosed with acne, compared with 6% prior to hormone therapy, and those at the highest risk were aged 18-21.
The prevalence of acne was 25% 2 years after initiation of hormone therapy. “Acne remains a very common issue and not just at the beginning of treatment,” he said.
In 2020, Dr. Yeung and colleagues reported the results of a survey of 696 transgender patients in California and Georgia; most were treated with hormone therapy. They found that 14% of transmasculine patients reported currently having moderate to severe acne diagnosed by a physician, compared with 1% of transfeminine patients.
Dr. Yeung noted that another survey of transmasculine persons who had received testosterone found that those who had moderate to severe acne were more likely to suffer from depression and anxiety than were those who had never had acne (aOR, 2.4; 95% CI, 1.1-5.4; P = .001, for depression; and aOR, 2.7; 95% CI, 1.2-6.3; P = .002, for anxiety).
Acne treatments in transmasculine patients are complicated by the fact that hormone treatments for acne can have feminizing effects, Dr. Yeung said, adding that it’s not clear how clascoterone, a new anti-androgen topical therapy for acne, will affect them. For now, many patients will require isotretinoin for treating acne.
Dr. Peebles cautioned that with isotretinoin, “we still do not yet have solid data on the optimal dosing or duration in the context of testosterone-induced acne, as well as what individual factors may be predictive of treatment success or failure. It is also important to be aware of any planned surgical procedures, whether as part of gender-affirming care or otherwise, given that some surgeons may view isotretinoin as a barrier for some procedures, despite limited data to support this.”
Both Dr. Peebles and Dr. Yeung noted that the iPledge risk management program for isotretinoin patients who may become pregnant is problematic. “A trans man who is assigned female at birth and identifies as a man and has a uterus and ovaries must be registered as a female with reproductive potential,” Dr. Yeung said.
“While the program remains inherently discriminatory, it is important to have an honest conversation with patients about these issues in a sensitive way,” Dr. Peebles noted. “Luckily, there is substantial momentum building around modifying iPLEDGE to become more inclusive. While the mechanics are complicated and involve a variety of entities and advocacy initiatives, we are optimistic that major changes are in the pipeline.”
Dr. Mansh, Dr. Yeung, and Dr. Peebles reported no disclosures.
FROM AAD VMX 2021
Higher MI shock survival with NCSI protocol: Final results
What started as an attempt to standardize care for acute myocardial infarction with cardiogenic shock at a handful of Detroit-area hospitals has led to markedly better survival rates than the traditional flip of a coin, in a nationwide analysis.
Final results from the National Cardiogenic Shock Initiative (NCSI) show 71% of patients survived to discharge and 68% were alive at 30 days.
Patients presenting in stage C or D shock, who comprised the bulk of patients in previous trials, had survival rates of 79% and 77%, respectively.
Among stage E patients, who are in extremis and have typical survival rates of less than 20%, survival was 54% at discharge and 49% at 30 days, co–principal investigator Babar Basir, DO, Henry Ford Hospital, Detroit, reported at the Society for Cardiovascular Angiography and Interventions (SCAI) annual scientific sessions, held virtually.
“This is the first push to really be able to consistently get survival rates over 50%, particularly in those patients who presented in stage C and D shock,” he said. “Really, it’s important to emphasize here the hard work it’s taken to get to this point and all the research that’s been done.”
The NCSI protocol emphasizes rapid identification and support of cardiogenic shock (door to support time <90 minutes), early placement of the Impella (Abiomed) ventricular assist device prior to percutaneous coronary intervention (PCI), and right heart monitoring to reduce the use of inotropes and vasopressors.
Co–principal investigator William O’Neill, MD, also from Henry Ford, previously reported results from the pilot study showing 84% of 30 patients survived to discharge.
The present analysis was based on outcomes of 406 consecutive acute MI patients (mean age, 63.7 years; 24% female) who presented with cardiogenic shock at 32 academic and 48 community hospitals in 29 states and the District of Columbia.
Dr. Basir emphasized that this is the largest prospective North American acute MI cardiogenic shock study in 20 years and recruited “one of the sickest cohorts ever studied.” The average blood pressure among the patients was 77/50 mm Hg; 77% had a lactate of at least 2 mmol/L (mean, 4.8 mmol/L), and 25% were in stage E shock.
One-quarter of patients were transferred from other institutions, 82% presented with ST-segment elevation MI, two-thirds had multivessel disease, and 13% had a left main culprit lesion.
Right heart catheterization was used in 90% of patients, an Impella CP device in 92%, an Impella 2.5 device in 5%, femoral access PCI in 78%, and aspiration thrombectomy in a full 27%.
Despite this sick cohort, survival at 30 days was better than in any previous study of cardiogenic shock, Dr. Basir said. In comparison, 30-day survival rates were 53%, 60%, and 49% in the SHOCK, IABP SHOCK, and CULPRIT SHOCK trials, respectively.
That said, survival over the course of the first year fell to 53% in the entire cohort, 62% in patients with stage C or D shock, and 31% in those in stage E shock.
“One-year mortality continues to be a problem for these patients and emphasizes the need for goal-directed medical therapy, early advanced heart failure follow-up, and novel therapies such as what we are planning with the evaluation of [supersaturated oxygen] SSO2 to reduce infarct sizes in the ISO-SHOCK trial,” set to begin later this year, Dr. Basir said.
Given the promising results in the NCSI, the randomized controlled RECOVER IV trial is planned to begin in 2022, he noted. It will assess whether Impella pre-PCI is superior to PCI without Impella in patients with inclusion criteria similar to that of the NCSI. The DanGer Shock randomized trial is ongoing in Denmark and Germany and assessing all-cause mortality at 6 months with the Impella CP device compared with standard of care.
“We hypothesize that greater utilization of this protocol, and refinement of the escalation strategies will consistently lead to a survival rate greater than 80%,” Dr. Basir concluded.
Past SCAI president Kirk Garratt, MD, Christiana Care, Newark, Del., who moderated a press conference where the data were highlighted, noted that late complications led to a roughly 20% absolute mortality increase from discharge to 1 year, and questioned what percentage could be attributed to the mechanical support offered.
Dr. Basir said that information was not specifically tracked but that many patients presented with multiorgan failure and, irrespective of that, the majority died from ongoing heart failure.
During the formal presentation, panelist Ron Waksman, MD, MedStar Heart Institute, Washington, questioned whether results were different between academic and community centers, but also pointed to the lack of a comparator in the single-arm study.
“It’s very hard to do any comparison historically; we do need to have a control group,” he said. “If you would have opened it to any treatment at the time of the initiative, which is great, but not just limit it to use of the Impella devices, we would have better understanding if there is really a differentiation between one device versus the other devices.”
Dr. Basir replied, “I think that is a very reasonable comment and, in regard to your question, it is always difficult to differentiate between academic and community centers, but these were large community programs that have all of the technologies available in an academic center.”
NCIS is funded in part by unrestricted grants from Abiomed and Chiesi. Dr. Basir reported consulting for Abbott Vascular, Abiomed, Cardiovascular Systems, Chiesi, Procyrion, and Zoll.
A version of this article first appeared on Medscape.com.
What started as an attempt to standardize care for acute myocardial infarction with cardiogenic shock at a handful of Detroit-area hospitals has led to markedly better survival rates than the traditional flip of a coin, in a nationwide analysis.
Final results from the National Cardiogenic Shock Initiative (NCSI) show 71% of patients survived to discharge and 68% were alive at 30 days.
Patients presenting in stage C or D shock, who comprised the bulk of patients in previous trials, had survival rates of 79% and 77%, respectively.
Among stage E patients, who are in extremis and have typical survival rates of less than 20%, survival was 54% at discharge and 49% at 30 days, co–principal investigator Babar Basir, DO, Henry Ford Hospital, Detroit, reported at the Society for Cardiovascular Angiography and Interventions (SCAI) annual scientific sessions, held virtually.
“This is the first push to really be able to consistently get survival rates over 50%, particularly in those patients who presented in stage C and D shock,” he said. “Really, it’s important to emphasize here the hard work it’s taken to get to this point and all the research that’s been done.”
The NCSI protocol emphasizes rapid identification and support of cardiogenic shock (door to support time <90 minutes), early placement of the Impella (Abiomed) ventricular assist device prior to percutaneous coronary intervention (PCI), and right heart monitoring to reduce the use of inotropes and vasopressors.
Co–principal investigator William O’Neill, MD, also from Henry Ford, previously reported results from the pilot study showing 84% of 30 patients survived to discharge.
The present analysis was based on outcomes of 406 consecutive acute MI patients (mean age, 63.7 years; 24% female) who presented with cardiogenic shock at 32 academic and 48 community hospitals in 29 states and the District of Columbia.
Dr. Basir emphasized that this is the largest prospective North American acute MI cardiogenic shock study in 20 years and recruited “one of the sickest cohorts ever studied.” The average blood pressure among the patients was 77/50 mm Hg; 77% had a lactate of at least 2 mmol/L (mean, 4.8 mmol/L), and 25% were in stage E shock.
One-quarter of patients were transferred from other institutions, 82% presented with ST-segment elevation MI, two-thirds had multivessel disease, and 13% had a left main culprit lesion.
Right heart catheterization was used in 90% of patients, an Impella CP device in 92%, an Impella 2.5 device in 5%, femoral access PCI in 78%, and aspiration thrombectomy in a full 27%.
Despite this sick cohort, survival at 30 days was better than in any previous study of cardiogenic shock, Dr. Basir said. In comparison, 30-day survival rates were 53%, 60%, and 49% in the SHOCK, IABP SHOCK, and CULPRIT SHOCK trials, respectively.
That said, survival over the course of the first year fell to 53% in the entire cohort, 62% in patients with stage C or D shock, and 31% in those in stage E shock.
“One-year mortality continues to be a problem for these patients and emphasizes the need for goal-directed medical therapy, early advanced heart failure follow-up, and novel therapies such as what we are planning with the evaluation of [supersaturated oxygen] SSO2 to reduce infarct sizes in the ISO-SHOCK trial,” set to begin later this year, Dr. Basir said.
Given the promising results in the NCSI, the randomized controlled RECOVER IV trial is planned to begin in 2022, he noted. It will assess whether Impella pre-PCI is superior to PCI without Impella in patients with inclusion criteria similar to that of the NCSI. The DanGer Shock randomized trial is ongoing in Denmark and Germany and assessing all-cause mortality at 6 months with the Impella CP device compared with standard of care.
“We hypothesize that greater utilization of this protocol, and refinement of the escalation strategies will consistently lead to a survival rate greater than 80%,” Dr. Basir concluded.
Past SCAI president Kirk Garratt, MD, Christiana Care, Newark, Del., who moderated a press conference where the data were highlighted, noted that late complications led to a roughly 20% absolute mortality increase from discharge to 1 year, and questioned what percentage could be attributed to the mechanical support offered.
Dr. Basir said that information was not specifically tracked but that many patients presented with multiorgan failure and, irrespective of that, the majority died from ongoing heart failure.
During the formal presentation, panelist Ron Waksman, MD, MedStar Heart Institute, Washington, questioned whether results were different between academic and community centers, but also pointed to the lack of a comparator in the single-arm study.
“It’s very hard to do any comparison historically; we do need to have a control group,” he said. “If you would have opened it to any treatment at the time of the initiative, which is great, but not just limit it to use of the Impella devices, we would have better understanding if there is really a differentiation between one device versus the other devices.”
Dr. Basir replied, “I think that is a very reasonable comment and, in regard to your question, it is always difficult to differentiate between academic and community centers, but these were large community programs that have all of the technologies available in an academic center.”
NCIS is funded in part by unrestricted grants from Abiomed and Chiesi. Dr. Basir reported consulting for Abbott Vascular, Abiomed, Cardiovascular Systems, Chiesi, Procyrion, and Zoll.
A version of this article first appeared on Medscape.com.
What started as an attempt to standardize care for acute myocardial infarction with cardiogenic shock at a handful of Detroit-area hospitals has led to markedly better survival rates than the traditional flip of a coin, in a nationwide analysis.
Final results from the National Cardiogenic Shock Initiative (NCSI) show 71% of patients survived to discharge and 68% were alive at 30 days.
Patients presenting in stage C or D shock, who comprised the bulk of patients in previous trials, had survival rates of 79% and 77%, respectively.
Among stage E patients, who are in extremis and have typical survival rates of less than 20%, survival was 54% at discharge and 49% at 30 days, co–principal investigator Babar Basir, DO, Henry Ford Hospital, Detroit, reported at the Society for Cardiovascular Angiography and Interventions (SCAI) annual scientific sessions, held virtually.
“This is the first push to really be able to consistently get survival rates over 50%, particularly in those patients who presented in stage C and D shock,” he said. “Really, it’s important to emphasize here the hard work it’s taken to get to this point and all the research that’s been done.”
The NCSI protocol emphasizes rapid identification and support of cardiogenic shock (door to support time <90 minutes), early placement of the Impella (Abiomed) ventricular assist device prior to percutaneous coronary intervention (PCI), and right heart monitoring to reduce the use of inotropes and vasopressors.
Co–principal investigator William O’Neill, MD, also from Henry Ford, previously reported results from the pilot study showing 84% of 30 patients survived to discharge.
The present analysis was based on outcomes of 406 consecutive acute MI patients (mean age, 63.7 years; 24% female) who presented with cardiogenic shock at 32 academic and 48 community hospitals in 29 states and the District of Columbia.
Dr. Basir emphasized that this is the largest prospective North American acute MI cardiogenic shock study in 20 years and recruited “one of the sickest cohorts ever studied.” The average blood pressure among the patients was 77/50 mm Hg; 77% had a lactate of at least 2 mmol/L (mean, 4.8 mmol/L), and 25% were in stage E shock.
One-quarter of patients were transferred from other institutions, 82% presented with ST-segment elevation MI, two-thirds had multivessel disease, and 13% had a left main culprit lesion.
Right heart catheterization was used in 90% of patients, an Impella CP device in 92%, an Impella 2.5 device in 5%, femoral access PCI in 78%, and aspiration thrombectomy in a full 27%.
Despite this sick cohort, survival at 30 days was better than in any previous study of cardiogenic shock, Dr. Basir said. In comparison, 30-day survival rates were 53%, 60%, and 49% in the SHOCK, IABP SHOCK, and CULPRIT SHOCK trials, respectively.
That said, survival over the course of the first year fell to 53% in the entire cohort, 62% in patients with stage C or D shock, and 31% in those in stage E shock.
“One-year mortality continues to be a problem for these patients and emphasizes the need for goal-directed medical therapy, early advanced heart failure follow-up, and novel therapies such as what we are planning with the evaluation of [supersaturated oxygen] SSO2 to reduce infarct sizes in the ISO-SHOCK trial,” set to begin later this year, Dr. Basir said.
Given the promising results in the NCSI, the randomized controlled RECOVER IV trial is planned to begin in 2022, he noted. It will assess whether Impella pre-PCI is superior to PCI without Impella in patients with inclusion criteria similar to that of the NCSI. The DanGer Shock randomized trial is ongoing in Denmark and Germany and assessing all-cause mortality at 6 months with the Impella CP device compared with standard of care.
“We hypothesize that greater utilization of this protocol, and refinement of the escalation strategies will consistently lead to a survival rate greater than 80%,” Dr. Basir concluded.
Past SCAI president Kirk Garratt, MD, Christiana Care, Newark, Del., who moderated a press conference where the data were highlighted, noted that late complications led to a roughly 20% absolute mortality increase from discharge to 1 year, and questioned what percentage could be attributed to the mechanical support offered.
Dr. Basir said that information was not specifically tracked but that many patients presented with multiorgan failure and, irrespective of that, the majority died from ongoing heart failure.
During the formal presentation, panelist Ron Waksman, MD, MedStar Heart Institute, Washington, questioned whether results were different between academic and community centers, but also pointed to the lack of a comparator in the single-arm study.
“It’s very hard to do any comparison historically; we do need to have a control group,” he said. “If you would have opened it to any treatment at the time of the initiative, which is great, but not just limit it to use of the Impella devices, we would have better understanding if there is really a differentiation between one device versus the other devices.”
Dr. Basir replied, “I think that is a very reasonable comment and, in regard to your question, it is always difficult to differentiate between academic and community centers, but these were large community programs that have all of the technologies available in an academic center.”
NCIS is funded in part by unrestricted grants from Abiomed and Chiesi. Dr. Basir reported consulting for Abbott Vascular, Abiomed, Cardiovascular Systems, Chiesi, Procyrion, and Zoll.
A version of this article first appeared on Medscape.com.
Challenges persist in adolescents with rheumatic disease transitioning to adult care
The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.
“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.
In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.
The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.
“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
Who more often transitions to adult care?
Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.
“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”
Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.
Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).
The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
How young adults prefer to learn transition skills
The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.
“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.
“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.
“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”
Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.
“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”
For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.
“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”
Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.
Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).
An opportunity for other organizations to support transition
The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.
“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.
“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”
The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.
While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.
Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.
“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”
Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).
“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”
None of the individuals quoted in this story had any disclosures to report.
The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.
“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.
In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.
The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.
“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
Who more often transitions to adult care?
Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.
“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”
Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.
Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).
The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
How young adults prefer to learn transition skills
The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.
“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.
“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.
“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”
Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.
“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”
For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.
“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”
Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.
Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).
An opportunity for other organizations to support transition
The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.
“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.
“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”
The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.
While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.
Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.
“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”
Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).
“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”
None of the individuals quoted in this story had any disclosures to report.
The inadequacies and challenges of transitioning pediatric rheumatology patients to adult care were highlighted in several research studies shared at the annual scientific meeting of the Childhood Arthritis and Rheumatology Research Alliance.
“Not surprisingly, these studies demonstrate that transition challenges remain pervasive,” Rebecca Sadun, MD, PhD, who was not involved in any of the research, said in an interview. Nevertheless, she pointed out that one of the studies showed that eight of nine sites participating in one of the studies had at least developed a formal transition policy, and three were able to fully integrate that policy into their health care system despite the ongoing pandemic.
In that study, Joyce Chang, MD, of the Children’s Hospital of Philadelphia and colleagues used structured interviews and then quantitative research to explore processes for transition polices across nine rheumatology sites. Aside from the three that had already implemented their policies, three others were preparing implementation. The other three withdrew because of COVID-19. None of the sites had reached sustainment phase. Six of the sites had access to a social work network, and two sites had fewer than four providers.
The authors found that a higher level of change efficacy or change commitment using the Organizational Readiness for Implementing Change framework did not correspond with reaching implementation.
“The first sites to reach implementation had access to [information technology] support and involved nursing, though this was not sufficient or necessary,” the authors wrote. They noted the need for strategies to reduce the burden of data collection to improve the resilience of implementation efforts against health care system stress.
Who more often transitions to adult care?
Effective transition policies can help reduce the likelihood of young patients falling through the cracks as they grow from adolescence into young adulthood, especially those at highest risk for losing continuity of care.
“Young adults who are both medically and socially complex are at highest risk,” said Dr. Sadun, an assistant professor of adult and pediatric rheumatology at Duke University, Durham, N.C. “This is especially true for patients with systemic illnesses, patients requiring biologic medications, and patients with custody, transportation, and financial barriers.”
Research led by Emily A. Smitherman, MD, an assistant professor of pediatric rheumatology at Children’s of Alabama in Birmingham, looked more closely at who is and is not transitioning their care. The researchers analyzed retrospective data from the CARRA Registry, including the Long-Term Follow-Up Call Registry, through December 2019. Among 1,311 patients with inactive status, 537 of these patients had juvenile idiopathic arthritis and were aged at least 18 years. Only 186 of those patients, however, had data in the Long-Term Follow-Up Registry. Patients who were Black or had lower income were less likely to have data in the Long-Term Follow-Up Registry.
Just over half the patients in the long-term registry had transferred their care to an adult rheumatologist, and 83% overall were under the care of any physician. Patients who transferred their care were significantly more likely to have private insurance (87% vs. 70%; P = .009) and were more likely to be full-time students (74% vs. 58%; P = .036).
The researchers found no association between patients’ disease status at their last CARRA Registry visit and a successful transition to adult care. However, those who had transferred care to an adult rheumatologist tended to have a higher median level of pain (4 vs. 2 on a scale of 0-10) and more disease activity (3 vs. 1 on 0-10 scale) than did those who had not transferred care (P = .022 and P = .011, respectively). A higher proportion of those who transferred care had also experienced morning stiffness over the past week (49% vs. 30%; P = .015).
How young adults prefer to learn transition skills
The third study aimed to better understand the experience and preferences of young adults themselves as they transitioned from pediatric to adult care. Kristine Carandang, PhD, a postdoctoral scholar at the University of California, San Diego, and colleagues first conducted focus groups with 39 adolescents and young adults, ages 16-28 years, who had rheumatic conditions. Using the qualitative data from the focus groups, they designed a survey to capture quantitative data on young patients’ experiences.
“What we’re always trying to work on is, how do we bring that youth voice more clearly into the research literature?” Courtney K. Wells, PhD, MSW, an assistant professor of social work at the University of Wisconsin–River Falls, said in an interview. She noted that both she and Dr. Carandang were patients with rheumatic diseases, so they had lived and grown up with disease themselves and then become researchers.
“We have the information that’s in the literature, but then we also both work with youth in a couple different ways, and what we hear from youth is what we heard in our paper, but it isn’t all represented in the literature,” Dr. Wells said. That disconnect is why they also included two young adults as coauthors in the study.
“As much as we appreciate the model of the six components [of health care transition], we recognize that the youth voice isn’t represented very well,” Dr. Wells said. “The way it’s written is more for doctors and policy makers and targeted for the health care system rather than the young people themselves.”
Their research bore that out. Among 137 survey respondents, aged 18-28 years, the vast majority (89%) were women and most (75%) were White. Half the patients (50%) had a diagnosis of lupus.
“For 9 out of 11 self-management and self-advocacy skills examined, there was a significant difference between how adolescent and young adult patients experienced learning self- management skills versus how they would have preferred to learn the skills,” the researchers concluded. “Overall, adolescent and young adult patients most frequently learned about transition skills from their parents. Most participants would have preferred to learn these skills from their rheumatology team.”
For example, 46.7% of the respondents learned how to communicate their medical history from their parents, but 48.5% would have preferred to learn that from their rheumatology team. Only a quarter (24.8%) had learned that skill from their health care team.
“For most of these skills, they were getting that information from their parents, which is concerning because their parents don’t necessarily have information that is accurate,” Dr. Wells said. “Their parents managed their health care, and they taught them to do it the way they were doing it.”
Just over one-third of respondents said they learned from their parents how to track their symptoms so they could answer the rheumatologists’ questions. Only one in five respondents (20.4%) had learned this skill from their rheumatology team, but 41.2% would have preferred hearing it from their health care team, compared with 22.1% who preferred learning it from their parents.
Nearly half the respondents reported learning from their parents how to advocate for themselves when dissatisfied with their care or symptoms (49.6%) and how to talk to the office staff to make appointments, fill out paperwork, and access health records (47.4%). Just over half (51.5%) would have preferred to learn about office communication from their health care team. Preferences on self-advocacy were split between learning from parents (36.8%) and learning from their health care team (31.6%).
An opportunity for other organizations to support transition
The researchers noted that education did not necessarily need to come only from rheumatologists. Other health care professionals, including nurses and social workers, could help young patients develop skills as well.
“They said they’re also open to talking to other people, but they want their rheumatologist to lead the whole process,” Dr. Wells said. While reimbursement gaps may have presented a barrier in the past, Dr. Wells said that current billing codes have removed that obstacle, allowing physicians to bill for discussing transition skills and care.
“Largely, it’s a time issue,” Dr. Wells said. “Rheumatologists are going to tell patients first about their disease, ask how their medication is working and how their health is. Then, if we have time, we’ll cover the transition pieces, and what it boils down to is that they just don’t have time.”
The respondents indicated an interest in technology that can help their education and transition, such as patient portals, telehealth, and smartphone apps.
While 66.4% of respondents said they would attend an in-person health care appointment to learn skills for transitioning to adult care, 74.5% would attend a telehealth appointment, and 77.2% would complete a structured program within a patient portal.
Dr. Wells said she doesn’t see many of the health care system pressures easing up to allow rheumatologists more time for transition care, but she sees an opportunity for organizations, such as the Arthritis Foundation or Lupus Foundation of America, to step in and help.
“It is a matter of being creative and that, ultimately, is the barrier: Whose job is it to make it happen?” she said. “That’s where some other groups are going to need to be advocates.”
Another notable set of findings from this research was the need for young patients’ access to mental health and sexual/reproductive health services. Just over two-thirds of respondents preferred to discuss these topics with their rheumatology team, but only 59.1% felt comfortable starting the conversation about mental health, and only 47.4% felt comfortable broaching the topic of reproductive/sexual health. Even more patients preferred discussing use of drugs and alcohol with their health care team (71.5%), but more patients also felt comfortable initiating that discussion (72.2%).
“It may be that somebody who’s trained to address those issues, especially the mental health piece, may be more appropriate to have that role, and that’s part of the transition, too, these other larger life issues,” Dr. Wells said. “One of the benefits of going to an adult rheumatologist is that they are the most knowledgeable and prepared to help you with those topics.”
None of the individuals quoted in this story had any disclosures to report.
FROM CARRA 2021
Modest clinical gain for AF screening of asymptomatic elderly: STROKESTOP
Some, perhaps many, previously unrecognized cases of atrial fibrillation (AF) will come to light in a screening program aimed at older asymptomatic adults. The key question is whether the challenges of such systematic but age-restricted AF screening in the community, with oral anticoagulation (OAC) offered to those found to have the arrhythmia, is worthwhile in preventing events such as death or stroke.
Now there is evidence supporting such a clinical benefit from a large, prospective, randomized trial. A screening program restricted to people 75 or 76 years of age in two Swedish communities, which called on them to use a handheld single-lead ECG system at home intermittently for 2 weeks, was followed by a slight drop in clinical events over about 7 years.
The 4% decline in risk (P = .045) in the STROKESTOP trial’s “intention-to-treat” (ITT) analysis yielded a number needed to treat of 91; that is, that many people had to be targeted by the screening program to prevent one primary-endpoint clinical event.
Those included ischemic stroke, systemic thromboembolism, hospitalization for severe bleeding, and death from any cause, investigators reported April 23 during the virtual European Heart Rhythm Association (EHRA) 2021 Congress.
If that benefit and its significance seem marginal, some secondary findings might be reassuring. Half the population of the target age in the two communities – 13,979 randomly selected people – were invited to join the trial and follow the screening protocol, comprising the ITT cohort. The other half, numbering 13,996, was not invited and served as control subjects.
However, only 51% of the ITT cohort accepted the invitation and participated in the trial; they represented the “as-treated” cohort, observed Emma Svennberg, MD, PhD, Karolinska Institute, Danderyd Hospital, Stockholm, who presented the analysis at the EHRA sessions.
The screening protocol identified untreated AF, whether previously known or unknown, in about 5% of the 7,165 as-treated screening participants; OAC was initiated in about three-fourths of those cases.
The as-treated group, on their own, benefited with a 24% drop in the prospectively defined secondary endpoint of ischemic stroke, compared with the entire control group.
The clinical benefit in the ITT population was “small but significant,” but over the same period in the as-treated cohort, there was a highly significant drop in risk for ischemic stroke, Dr. Svennberg said in an interview.
The trial’s lead message, she said, is that “screening for atrial fibrillation in an elderly population reduces the risk of death and ischemic stroke without increasing the risk of bleeding.”
Caveats: As-treated vs. ITT
But there are caveats that complicate interpretation of the trial and, Dr. Svennberg proposed, point to the importance of that interpretation of both the ITT and as-treated analyses.
“We detected significantly more atrial fibrillation in the group that was randomized to screening. A major strength of our study was that we referred all of those individuals for a structured follow-up within the study,” she said. “Although the focus of the follow-up was oral anticoagulant therapy, other risk factors were also assessed and managed, such as hypertension and diabetes.”
It’s possible that increased detection of AF followed by such structured management contributed to the observed benefit, Dr. Svennberg proposed.
However, the exclusion of those in the prespecified ITT population who declined to be screened or otherwise didn’t participate left an as-treated cohort that was healthier than the ITT population or the control group.
Indeed, the nonparticipating invitees were sicker, with significantly more diabetes, vascular disease, hypertension, and heart failure, and higher CHA2DS2VASc stroke risk scores than those who agreed to participate.
“We took a more difficult route in setting up this study, in that we identified all individuals aged 75 to 76 residing in our two regions and excluded no one,” Dr. Svennberg said in an interview. “That means even individuals with end-stage disease, severe dementia, bedridden in nursing homes, et cetera, were also randomized but perhaps not likely or eligible to participate.”
Therefore, some invitees were unable to join the study even as others might have declined “out of low interest” or other personal reasons, she said. “We believe that this mimics how a population-based screening program would be performed if done in our country.”
In the ITT analysis, screening successfully identified previously unknown or untreated cases of AF, which led to expanded OAC use and intensified risk-factor management, “which was key to a successful outcome.”
In the as-treated analysis, Dr. Svennberg said, “I think a combination of the intervention and the population being overall more healthy was driving the secondary endpoint.”
Systematic vs. opportunistic screening
Although “opportunistic screening in individuals aged 65 and older” is recommended by current European Society of Cardiology guidelines, systematic screening, such as that used in STROKESTOP, has a much weaker evidence base, observed Renate B. Schnabel, MD, PhD, University Heart & Vascular Center, Hamburg, Germany, as the invited discussant after the STROKESTOP presentation.
STROKESTOP “is one of the first studies, if not the first study,” to show a clinical benefit from screening for AF, Dr. Schnabel said.
Fewer-than-projected primary outcome events were seen during the trial, and event curves for screened and control participants didn’t start to separate until about 4 years into the study, she said. It therefore might take a long time for the screened elderly to realize the clinical benefits of screening.
Studies such as the recent SCREEN-AF and mSTOPS have amply shown that AF screening in the asymptomatic elderly can reveal previously unrecognized AF far more often than would be detected in routine practice, allowing them the opportunity to go on OAC. But the trials weren’t able to show whether the benefits of such management outweigh the risks or costs.
Indeed, on April 20, the U.S. Preventive Services Task Force (USPSTF) released a draft recommendation statement concluding that “the current evidence is insufficient to assess the balance of benefits and harms” associated with AF screening in asymptomatic people at least 50 years of age.
In STROKESTOP, however, benefit for the primary outcome reached significance in the prespecified ITT analysis and “appeared to be driven by the reduction in ischemic stroke incidence,” Dr. Schnabel said.
“The future guidelines have gained strong evidence to judge on systematic atrial fibrillation screening” as it was performed in the trial, she said. “How to implement atrial fibrillation screening, including systematic screening in health care systems across Europe and beyond, remains an open question.”
A randomized population
STROKESTOP considered all 75- and 76-year-olds living in Sweden’s Stockholm County (n = 23,888) and the Halland region (n = 4,880) and randomly assigned them to the ITT group or a control group, with stratification by sex, birth year, and geographic region. In both groups, 54.6% were female and the mean CHA2DS2VASc score was 3.5.
People assigned to the ITT cohort were invited to be screened and followed. Those who agreed to participate underwent a baseline ECG assessment to detect or rule out permanent AF. Guideline-based OAC and follow-up was offered to those found with the arrhythmia. Those in sinus rhythm with no history of AF used a handheld single-lead ECG recorder (Zenicor) for 30 seconds twice daily for 14 days.
Structured management, including OAC, was offered to anyone demonstrating sufficient AF, that is, at least one bout without p waves in one 30-second recording or at least two such episodes lasting 10-29 seconds during the 2-week screening period.
In the ITT analysis, the hazard ratio (HR) for the composite clinical primary endpoint was 0.96 (95% confidence interval, 0.920-0.999; P = .045), but in the as-treated analysis, the HR for ischemic stroke was 0.76 (95% CI, 0.68-0.87; P < .001).
“I believe that this will likely be generalizable to most countries’ elderly residents,” Dr. Svennberg said. “I think if we can find a significant difference in our elderly population in Sweden, most countries will be able to do so, or find even more significant results.”
That’s because “baseline detection of AF in Sweden is high,” she said, “so new detection is likely more difficult.” Also, in Sweden, “care can be sought without monetary concern, and prescriptions are provided at low costs to the patients.” Therefore, patients newly identified with AF, whether in studies or not, “would likely be started on therapy.”
It will be important to know whether the screening strategy is cost-effective, Dr. Schnabel said, because “the overall effect, with a hazard ratio of 0.96, is not too big, and costs incurred by systematic screening are comparatively high.”
STROKESTOP “now provides sound information for cost-effectiveness analyses, which to date have largely relied on assumptions.”
STROKESTOP was partially supported by Carl Bennet AB, Boehringer-Ingelheim, Bayer, Bristol-Meyers Squibb, and Pfizer. Dr. Svennberg disclosed receiving fees for lectures or consulting from Bayer, Bristol-Meyers Squibb, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dohme, and Sanofi; and institutional grants from Roche Diagnostics and Carl Bennett Ltd.
A version of this article first appeared on Medscape.com.
Some, perhaps many, previously unrecognized cases of atrial fibrillation (AF) will come to light in a screening program aimed at older asymptomatic adults. The key question is whether the challenges of such systematic but age-restricted AF screening in the community, with oral anticoagulation (OAC) offered to those found to have the arrhythmia, is worthwhile in preventing events such as death or stroke.
Now there is evidence supporting such a clinical benefit from a large, prospective, randomized trial. A screening program restricted to people 75 or 76 years of age in two Swedish communities, which called on them to use a handheld single-lead ECG system at home intermittently for 2 weeks, was followed by a slight drop in clinical events over about 7 years.
The 4% decline in risk (P = .045) in the STROKESTOP trial’s “intention-to-treat” (ITT) analysis yielded a number needed to treat of 91; that is, that many people had to be targeted by the screening program to prevent one primary-endpoint clinical event.
Those included ischemic stroke, systemic thromboembolism, hospitalization for severe bleeding, and death from any cause, investigators reported April 23 during the virtual European Heart Rhythm Association (EHRA) 2021 Congress.
If that benefit and its significance seem marginal, some secondary findings might be reassuring. Half the population of the target age in the two communities – 13,979 randomly selected people – were invited to join the trial and follow the screening protocol, comprising the ITT cohort. The other half, numbering 13,996, was not invited and served as control subjects.
However, only 51% of the ITT cohort accepted the invitation and participated in the trial; they represented the “as-treated” cohort, observed Emma Svennberg, MD, PhD, Karolinska Institute, Danderyd Hospital, Stockholm, who presented the analysis at the EHRA sessions.
The screening protocol identified untreated AF, whether previously known or unknown, in about 5% of the 7,165 as-treated screening participants; OAC was initiated in about three-fourths of those cases.
The as-treated group, on their own, benefited with a 24% drop in the prospectively defined secondary endpoint of ischemic stroke, compared with the entire control group.
The clinical benefit in the ITT population was “small but significant,” but over the same period in the as-treated cohort, there was a highly significant drop in risk for ischemic stroke, Dr. Svennberg said in an interview.
The trial’s lead message, she said, is that “screening for atrial fibrillation in an elderly population reduces the risk of death and ischemic stroke without increasing the risk of bleeding.”
Caveats: As-treated vs. ITT
But there are caveats that complicate interpretation of the trial and, Dr. Svennberg proposed, point to the importance of that interpretation of both the ITT and as-treated analyses.
“We detected significantly more atrial fibrillation in the group that was randomized to screening. A major strength of our study was that we referred all of those individuals for a structured follow-up within the study,” she said. “Although the focus of the follow-up was oral anticoagulant therapy, other risk factors were also assessed and managed, such as hypertension and diabetes.”
It’s possible that increased detection of AF followed by such structured management contributed to the observed benefit, Dr. Svennberg proposed.
However, the exclusion of those in the prespecified ITT population who declined to be screened or otherwise didn’t participate left an as-treated cohort that was healthier than the ITT population or the control group.
Indeed, the nonparticipating invitees were sicker, with significantly more diabetes, vascular disease, hypertension, and heart failure, and higher CHA2DS2VASc stroke risk scores than those who agreed to participate.
“We took a more difficult route in setting up this study, in that we identified all individuals aged 75 to 76 residing in our two regions and excluded no one,” Dr. Svennberg said in an interview. “That means even individuals with end-stage disease, severe dementia, bedridden in nursing homes, et cetera, were also randomized but perhaps not likely or eligible to participate.”
Therefore, some invitees were unable to join the study even as others might have declined “out of low interest” or other personal reasons, she said. “We believe that this mimics how a population-based screening program would be performed if done in our country.”
In the ITT analysis, screening successfully identified previously unknown or untreated cases of AF, which led to expanded OAC use and intensified risk-factor management, “which was key to a successful outcome.”
In the as-treated analysis, Dr. Svennberg said, “I think a combination of the intervention and the population being overall more healthy was driving the secondary endpoint.”
Systematic vs. opportunistic screening
Although “opportunistic screening in individuals aged 65 and older” is recommended by current European Society of Cardiology guidelines, systematic screening, such as that used in STROKESTOP, has a much weaker evidence base, observed Renate B. Schnabel, MD, PhD, University Heart & Vascular Center, Hamburg, Germany, as the invited discussant after the STROKESTOP presentation.
STROKESTOP “is one of the first studies, if not the first study,” to show a clinical benefit from screening for AF, Dr. Schnabel said.
Fewer-than-projected primary outcome events were seen during the trial, and event curves for screened and control participants didn’t start to separate until about 4 years into the study, she said. It therefore might take a long time for the screened elderly to realize the clinical benefits of screening.
Studies such as the recent SCREEN-AF and mSTOPS have amply shown that AF screening in the asymptomatic elderly can reveal previously unrecognized AF far more often than would be detected in routine practice, allowing them the opportunity to go on OAC. But the trials weren’t able to show whether the benefits of such management outweigh the risks or costs.
Indeed, on April 20, the U.S. Preventive Services Task Force (USPSTF) released a draft recommendation statement concluding that “the current evidence is insufficient to assess the balance of benefits and harms” associated with AF screening in asymptomatic people at least 50 years of age.
In STROKESTOP, however, benefit for the primary outcome reached significance in the prespecified ITT analysis and “appeared to be driven by the reduction in ischemic stroke incidence,” Dr. Schnabel said.
“The future guidelines have gained strong evidence to judge on systematic atrial fibrillation screening” as it was performed in the trial, she said. “How to implement atrial fibrillation screening, including systematic screening in health care systems across Europe and beyond, remains an open question.”
A randomized population
STROKESTOP considered all 75- and 76-year-olds living in Sweden’s Stockholm County (n = 23,888) and the Halland region (n = 4,880) and randomly assigned them to the ITT group or a control group, with stratification by sex, birth year, and geographic region. In both groups, 54.6% were female and the mean CHA2DS2VASc score was 3.5.
People assigned to the ITT cohort were invited to be screened and followed. Those who agreed to participate underwent a baseline ECG assessment to detect or rule out permanent AF. Guideline-based OAC and follow-up was offered to those found with the arrhythmia. Those in sinus rhythm with no history of AF used a handheld single-lead ECG recorder (Zenicor) for 30 seconds twice daily for 14 days.
Structured management, including OAC, was offered to anyone demonstrating sufficient AF, that is, at least one bout without p waves in one 30-second recording or at least two such episodes lasting 10-29 seconds during the 2-week screening period.
In the ITT analysis, the hazard ratio (HR) for the composite clinical primary endpoint was 0.96 (95% confidence interval, 0.920-0.999; P = .045), but in the as-treated analysis, the HR for ischemic stroke was 0.76 (95% CI, 0.68-0.87; P < .001).
“I believe that this will likely be generalizable to most countries’ elderly residents,” Dr. Svennberg said. “I think if we can find a significant difference in our elderly population in Sweden, most countries will be able to do so, or find even more significant results.”
That’s because “baseline detection of AF in Sweden is high,” she said, “so new detection is likely more difficult.” Also, in Sweden, “care can be sought without monetary concern, and prescriptions are provided at low costs to the patients.” Therefore, patients newly identified with AF, whether in studies or not, “would likely be started on therapy.”
It will be important to know whether the screening strategy is cost-effective, Dr. Schnabel said, because “the overall effect, with a hazard ratio of 0.96, is not too big, and costs incurred by systematic screening are comparatively high.”
STROKESTOP “now provides sound information for cost-effectiveness analyses, which to date have largely relied on assumptions.”
STROKESTOP was partially supported by Carl Bennet AB, Boehringer-Ingelheim, Bayer, Bristol-Meyers Squibb, and Pfizer. Dr. Svennberg disclosed receiving fees for lectures or consulting from Bayer, Bristol-Meyers Squibb, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dohme, and Sanofi; and institutional grants from Roche Diagnostics and Carl Bennett Ltd.
A version of this article first appeared on Medscape.com.
Some, perhaps many, previously unrecognized cases of atrial fibrillation (AF) will come to light in a screening program aimed at older asymptomatic adults. The key question is whether the challenges of such systematic but age-restricted AF screening in the community, with oral anticoagulation (OAC) offered to those found to have the arrhythmia, is worthwhile in preventing events such as death or stroke.
Now there is evidence supporting such a clinical benefit from a large, prospective, randomized trial. A screening program restricted to people 75 or 76 years of age in two Swedish communities, which called on them to use a handheld single-lead ECG system at home intermittently for 2 weeks, was followed by a slight drop in clinical events over about 7 years.
The 4% decline in risk (P = .045) in the STROKESTOP trial’s “intention-to-treat” (ITT) analysis yielded a number needed to treat of 91; that is, that many people had to be targeted by the screening program to prevent one primary-endpoint clinical event.
Those included ischemic stroke, systemic thromboembolism, hospitalization for severe bleeding, and death from any cause, investigators reported April 23 during the virtual European Heart Rhythm Association (EHRA) 2021 Congress.
If that benefit and its significance seem marginal, some secondary findings might be reassuring. Half the population of the target age in the two communities – 13,979 randomly selected people – were invited to join the trial and follow the screening protocol, comprising the ITT cohort. The other half, numbering 13,996, was not invited and served as control subjects.
However, only 51% of the ITT cohort accepted the invitation and participated in the trial; they represented the “as-treated” cohort, observed Emma Svennberg, MD, PhD, Karolinska Institute, Danderyd Hospital, Stockholm, who presented the analysis at the EHRA sessions.
The screening protocol identified untreated AF, whether previously known or unknown, in about 5% of the 7,165 as-treated screening participants; OAC was initiated in about three-fourths of those cases.
The as-treated group, on their own, benefited with a 24% drop in the prospectively defined secondary endpoint of ischemic stroke, compared with the entire control group.
The clinical benefit in the ITT population was “small but significant,” but over the same period in the as-treated cohort, there was a highly significant drop in risk for ischemic stroke, Dr. Svennberg said in an interview.
The trial’s lead message, she said, is that “screening for atrial fibrillation in an elderly population reduces the risk of death and ischemic stroke without increasing the risk of bleeding.”
Caveats: As-treated vs. ITT
But there are caveats that complicate interpretation of the trial and, Dr. Svennberg proposed, point to the importance of that interpretation of both the ITT and as-treated analyses.
“We detected significantly more atrial fibrillation in the group that was randomized to screening. A major strength of our study was that we referred all of those individuals for a structured follow-up within the study,” she said. “Although the focus of the follow-up was oral anticoagulant therapy, other risk factors were also assessed and managed, such as hypertension and diabetes.”
It’s possible that increased detection of AF followed by such structured management contributed to the observed benefit, Dr. Svennberg proposed.
However, the exclusion of those in the prespecified ITT population who declined to be screened or otherwise didn’t participate left an as-treated cohort that was healthier than the ITT population or the control group.
Indeed, the nonparticipating invitees were sicker, with significantly more diabetes, vascular disease, hypertension, and heart failure, and higher CHA2DS2VASc stroke risk scores than those who agreed to participate.
“We took a more difficult route in setting up this study, in that we identified all individuals aged 75 to 76 residing in our two regions and excluded no one,” Dr. Svennberg said in an interview. “That means even individuals with end-stage disease, severe dementia, bedridden in nursing homes, et cetera, were also randomized but perhaps not likely or eligible to participate.”
Therefore, some invitees were unable to join the study even as others might have declined “out of low interest” or other personal reasons, she said. “We believe that this mimics how a population-based screening program would be performed if done in our country.”
In the ITT analysis, screening successfully identified previously unknown or untreated cases of AF, which led to expanded OAC use and intensified risk-factor management, “which was key to a successful outcome.”
In the as-treated analysis, Dr. Svennberg said, “I think a combination of the intervention and the population being overall more healthy was driving the secondary endpoint.”
Systematic vs. opportunistic screening
Although “opportunistic screening in individuals aged 65 and older” is recommended by current European Society of Cardiology guidelines, systematic screening, such as that used in STROKESTOP, has a much weaker evidence base, observed Renate B. Schnabel, MD, PhD, University Heart & Vascular Center, Hamburg, Germany, as the invited discussant after the STROKESTOP presentation.
STROKESTOP “is one of the first studies, if not the first study,” to show a clinical benefit from screening for AF, Dr. Schnabel said.
Fewer-than-projected primary outcome events were seen during the trial, and event curves for screened and control participants didn’t start to separate until about 4 years into the study, she said. It therefore might take a long time for the screened elderly to realize the clinical benefits of screening.
Studies such as the recent SCREEN-AF and mSTOPS have amply shown that AF screening in the asymptomatic elderly can reveal previously unrecognized AF far more often than would be detected in routine practice, allowing them the opportunity to go on OAC. But the trials weren’t able to show whether the benefits of such management outweigh the risks or costs.
Indeed, on April 20, the U.S. Preventive Services Task Force (USPSTF) released a draft recommendation statement concluding that “the current evidence is insufficient to assess the balance of benefits and harms” associated with AF screening in asymptomatic people at least 50 years of age.
In STROKESTOP, however, benefit for the primary outcome reached significance in the prespecified ITT analysis and “appeared to be driven by the reduction in ischemic stroke incidence,” Dr. Schnabel said.
“The future guidelines have gained strong evidence to judge on systematic atrial fibrillation screening” as it was performed in the trial, she said. “How to implement atrial fibrillation screening, including systematic screening in health care systems across Europe and beyond, remains an open question.”
A randomized population
STROKESTOP considered all 75- and 76-year-olds living in Sweden’s Stockholm County (n = 23,888) and the Halland region (n = 4,880) and randomly assigned them to the ITT group or a control group, with stratification by sex, birth year, and geographic region. In both groups, 54.6% were female and the mean CHA2DS2VASc score was 3.5.
People assigned to the ITT cohort were invited to be screened and followed. Those who agreed to participate underwent a baseline ECG assessment to detect or rule out permanent AF. Guideline-based OAC and follow-up was offered to those found with the arrhythmia. Those in sinus rhythm with no history of AF used a handheld single-lead ECG recorder (Zenicor) for 30 seconds twice daily for 14 days.
Structured management, including OAC, was offered to anyone demonstrating sufficient AF, that is, at least one bout without p waves in one 30-second recording or at least two such episodes lasting 10-29 seconds during the 2-week screening period.
In the ITT analysis, the hazard ratio (HR) for the composite clinical primary endpoint was 0.96 (95% confidence interval, 0.920-0.999; P = .045), but in the as-treated analysis, the HR for ischemic stroke was 0.76 (95% CI, 0.68-0.87; P < .001).
“I believe that this will likely be generalizable to most countries’ elderly residents,” Dr. Svennberg said. “I think if we can find a significant difference in our elderly population in Sweden, most countries will be able to do so, or find even more significant results.”
That’s because “baseline detection of AF in Sweden is high,” she said, “so new detection is likely more difficult.” Also, in Sweden, “care can be sought without monetary concern, and prescriptions are provided at low costs to the patients.” Therefore, patients newly identified with AF, whether in studies or not, “would likely be started on therapy.”
It will be important to know whether the screening strategy is cost-effective, Dr. Schnabel said, because “the overall effect, with a hazard ratio of 0.96, is not too big, and costs incurred by systematic screening are comparatively high.”
STROKESTOP “now provides sound information for cost-effectiveness analyses, which to date have largely relied on assumptions.”
STROKESTOP was partially supported by Carl Bennet AB, Boehringer-Ingelheim, Bayer, Bristol-Meyers Squibb, and Pfizer. Dr. Svennberg disclosed receiving fees for lectures or consulting from Bayer, Bristol-Meyers Squibb, Pfizer, Boehringer-Ingelheim, Merck Sharp & Dohme, and Sanofi; and institutional grants from Roche Diagnostics and Carl Bennett Ltd.
A version of this article first appeared on Medscape.com.
Superior survival with sintilimab in squamous NSCLC
Sintilimab improved both overall survival (OS) and progression-free survival (PFS), according to Yuankai Shi, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing.
Dr. Shi presented these findings, from the ORIENT-3 study, at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT041).
ORIENT-3 enrolled and randomized 290 patients with stage IIIB/IIIC or IV sqNSCLC and disease progression during or after first-line platimum-based chemotherapy. They were randomized 1:1 to receive sintilimab at 200 mg or docetaxel at 75 mg/m2intravenously every 3 weeks until disease progression or intolerable toxicity.
The median age was 60 years in the sintilimab arm and 61 years in the docetaxel arm. A majority of patients were men (94% in the sintilimab arm and 90% in the docetaxel arm), most were current or former smokers (90% and 80%, respectively), and more than three-quarters had an ECOG performance status of 1 (76% and 77%, respectively). More than half of patients had a PD-L1 tumor proportion score (TPS) of 1% or greater (57% and 47%, respectively), and 81% of patients in both arms had stage IV disease.
Results: Survival and safety
Patients in the sintilimab arm received a median of 8.0 cycles of therapy (range, 1-45), and those in the docetaxel arm received a median of 2.0 cycles of therapy (range, 1-15).
At a median follow-up of 23.56 months, the median OS was significantly longer in the sintilimab arm than in the docetaxel arm – 11.79 months and 8.25 months, respectively (hazard ratio, 0.74; P = .02489). OS benefits were generally consistent across subgroups.
The secondary endpoints of PFS and objective response rate also favored sintilimab, Dr. Shi reported.
The median PFS was 4.30 months in the sintilimab arm and 2.79 months in the docetaxel arm (HR, 0.52; P < .00001). Confirmed objective response rates were 25.5% and 2.2%, respectively; the median duration of response was 12.45 months and 4.14 months, respectively; and disease control rates were 65.5% and 37.8%, respectively.
“Sintilimab had a favorable safety profile over docetaxel, with a lower frequency of grade 3 or higher treatment-related adverse events, with no new safety signals observed,” Dr. Shi said.
Treatment-related adverse events (TRAEs) occurred in 84.7% of patients receiving sintilimab and 83.1% of those receiving docetaxel. Hypothyroidism was the most common TRAE in the sintilimab arm (18.1%), and alopecia was the most common TRAE in the docetaxel arm (34.6%).
Grade 3 or higher TRAEs were less frequent in the sintilimab arm than in the docetaxel arm (18.1% vs. 36.2%). Rates of discontinuation because of TRAEs were 12.5% and 5.4% in the sintilimab and docetaxel arms, respectively. TRAEs leading to death occurred in five patients in the sintilimab arm and one in the docetaxel arm.
Use in the real world
Noting sintilimab’s significant OS and PFS benefits as well as superior response rate and duration of response, Dr. Shi concluded, “Sintilimab might provide an alternative second-line treatment option for advanced and metastatic sqNSCLC.”
AACR moderator Marina Garassino, MD, of the University of Chicago, commented on the potential utility of sintilimab and tislelizumab, another checkpoint inhibitor that was evaluated in NSCLC in the RATIONALE 303 trial (AACR 2021, Abstract CT039). Dr. Garassino observed that both drugs have demonstrated superiority to docetaxel as second-line therapy in NSCLC.
Although there have been no head-to-head trials, sintilimab and tislelizumab appear to be very similar to the already approved immune checkpoint inhibitors, which are currently being used as first-line treatment.
“That similarity would make them inappropriate for second-line treatment, except in countries where immune checkpoint inhibitors are not yet approved for first-line therapy,” Dr. Garassino noted.
When asked to comment on the higher treatment-related death rate observed with sintilimab, Dr. Garassino said, “We need to remember that these drugs were developed in China with a population that may have a side effect profile differing from that of a Western population. Also, we are very familiar with this class of drugs and know how to treat their side effects. Similar drugs but different populations and different trials, so it’s very hard to judge.”
Dr. Garassino speculated that with the “super expensive” price tags on the new checkpoint inhibitors, having additional agents that could provide choice and drive prices down would be welcome.
ORIENT-3 was funded by Innovent Biologics and Eli Lilly. Dr. Shi disclosed consultancy for Innovent Biologics. Dr. Garassino disclosed relationships with Eli Lilly, AstraZeneca, Novartis, and several other companies, not including Innovent Biologics.
Sintilimab improved both overall survival (OS) and progression-free survival (PFS), according to Yuankai Shi, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing.
Dr. Shi presented these findings, from the ORIENT-3 study, at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT041).
ORIENT-3 enrolled and randomized 290 patients with stage IIIB/IIIC or IV sqNSCLC and disease progression during or after first-line platimum-based chemotherapy. They were randomized 1:1 to receive sintilimab at 200 mg or docetaxel at 75 mg/m2intravenously every 3 weeks until disease progression or intolerable toxicity.
The median age was 60 years in the sintilimab arm and 61 years in the docetaxel arm. A majority of patients were men (94% in the sintilimab arm and 90% in the docetaxel arm), most were current or former smokers (90% and 80%, respectively), and more than three-quarters had an ECOG performance status of 1 (76% and 77%, respectively). More than half of patients had a PD-L1 tumor proportion score (TPS) of 1% or greater (57% and 47%, respectively), and 81% of patients in both arms had stage IV disease.
Results: Survival and safety
Patients in the sintilimab arm received a median of 8.0 cycles of therapy (range, 1-45), and those in the docetaxel arm received a median of 2.0 cycles of therapy (range, 1-15).
At a median follow-up of 23.56 months, the median OS was significantly longer in the sintilimab arm than in the docetaxel arm – 11.79 months and 8.25 months, respectively (hazard ratio, 0.74; P = .02489). OS benefits were generally consistent across subgroups.
The secondary endpoints of PFS and objective response rate also favored sintilimab, Dr. Shi reported.
The median PFS was 4.30 months in the sintilimab arm and 2.79 months in the docetaxel arm (HR, 0.52; P < .00001). Confirmed objective response rates were 25.5% and 2.2%, respectively; the median duration of response was 12.45 months and 4.14 months, respectively; and disease control rates were 65.5% and 37.8%, respectively.
“Sintilimab had a favorable safety profile over docetaxel, with a lower frequency of grade 3 or higher treatment-related adverse events, with no new safety signals observed,” Dr. Shi said.
Treatment-related adverse events (TRAEs) occurred in 84.7% of patients receiving sintilimab and 83.1% of those receiving docetaxel. Hypothyroidism was the most common TRAE in the sintilimab arm (18.1%), and alopecia was the most common TRAE in the docetaxel arm (34.6%).
Grade 3 or higher TRAEs were less frequent in the sintilimab arm than in the docetaxel arm (18.1% vs. 36.2%). Rates of discontinuation because of TRAEs were 12.5% and 5.4% in the sintilimab and docetaxel arms, respectively. TRAEs leading to death occurred in five patients in the sintilimab arm and one in the docetaxel arm.
Use in the real world
Noting sintilimab’s significant OS and PFS benefits as well as superior response rate and duration of response, Dr. Shi concluded, “Sintilimab might provide an alternative second-line treatment option for advanced and metastatic sqNSCLC.”
AACR moderator Marina Garassino, MD, of the University of Chicago, commented on the potential utility of sintilimab and tislelizumab, another checkpoint inhibitor that was evaluated in NSCLC in the RATIONALE 303 trial (AACR 2021, Abstract CT039). Dr. Garassino observed that both drugs have demonstrated superiority to docetaxel as second-line therapy in NSCLC.
Although there have been no head-to-head trials, sintilimab and tislelizumab appear to be very similar to the already approved immune checkpoint inhibitors, which are currently being used as first-line treatment.
“That similarity would make them inappropriate for second-line treatment, except in countries where immune checkpoint inhibitors are not yet approved for first-line therapy,” Dr. Garassino noted.
When asked to comment on the higher treatment-related death rate observed with sintilimab, Dr. Garassino said, “We need to remember that these drugs were developed in China with a population that may have a side effect profile differing from that of a Western population. Also, we are very familiar with this class of drugs and know how to treat their side effects. Similar drugs but different populations and different trials, so it’s very hard to judge.”
Dr. Garassino speculated that with the “super expensive” price tags on the new checkpoint inhibitors, having additional agents that could provide choice and drive prices down would be welcome.
ORIENT-3 was funded by Innovent Biologics and Eli Lilly. Dr. Shi disclosed consultancy for Innovent Biologics. Dr. Garassino disclosed relationships with Eli Lilly, AstraZeneca, Novartis, and several other companies, not including Innovent Biologics.
Sintilimab improved both overall survival (OS) and progression-free survival (PFS), according to Yuankai Shi, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing.
Dr. Shi presented these findings, from the ORIENT-3 study, at the American Association for Cancer Research Annual Meeting 2021: Week 1 (Abstract CT041).
ORIENT-3 enrolled and randomized 290 patients with stage IIIB/IIIC or IV sqNSCLC and disease progression during or after first-line platimum-based chemotherapy. They were randomized 1:1 to receive sintilimab at 200 mg or docetaxel at 75 mg/m2intravenously every 3 weeks until disease progression or intolerable toxicity.
The median age was 60 years in the sintilimab arm and 61 years in the docetaxel arm. A majority of patients were men (94% in the sintilimab arm and 90% in the docetaxel arm), most were current or former smokers (90% and 80%, respectively), and more than three-quarters had an ECOG performance status of 1 (76% and 77%, respectively). More than half of patients had a PD-L1 tumor proportion score (TPS) of 1% or greater (57% and 47%, respectively), and 81% of patients in both arms had stage IV disease.
Results: Survival and safety
Patients in the sintilimab arm received a median of 8.0 cycles of therapy (range, 1-45), and those in the docetaxel arm received a median of 2.0 cycles of therapy (range, 1-15).
At a median follow-up of 23.56 months, the median OS was significantly longer in the sintilimab arm than in the docetaxel arm – 11.79 months and 8.25 months, respectively (hazard ratio, 0.74; P = .02489). OS benefits were generally consistent across subgroups.
The secondary endpoints of PFS and objective response rate also favored sintilimab, Dr. Shi reported.
The median PFS was 4.30 months in the sintilimab arm and 2.79 months in the docetaxel arm (HR, 0.52; P < .00001). Confirmed objective response rates were 25.5% and 2.2%, respectively; the median duration of response was 12.45 months and 4.14 months, respectively; and disease control rates were 65.5% and 37.8%, respectively.
“Sintilimab had a favorable safety profile over docetaxel, with a lower frequency of grade 3 or higher treatment-related adverse events, with no new safety signals observed,” Dr. Shi said.
Treatment-related adverse events (TRAEs) occurred in 84.7% of patients receiving sintilimab and 83.1% of those receiving docetaxel. Hypothyroidism was the most common TRAE in the sintilimab arm (18.1%), and alopecia was the most common TRAE in the docetaxel arm (34.6%).
Grade 3 or higher TRAEs were less frequent in the sintilimab arm than in the docetaxel arm (18.1% vs. 36.2%). Rates of discontinuation because of TRAEs were 12.5% and 5.4% in the sintilimab and docetaxel arms, respectively. TRAEs leading to death occurred in five patients in the sintilimab arm and one in the docetaxel arm.
Use in the real world
Noting sintilimab’s significant OS and PFS benefits as well as superior response rate and duration of response, Dr. Shi concluded, “Sintilimab might provide an alternative second-line treatment option for advanced and metastatic sqNSCLC.”
AACR moderator Marina Garassino, MD, of the University of Chicago, commented on the potential utility of sintilimab and tislelizumab, another checkpoint inhibitor that was evaluated in NSCLC in the RATIONALE 303 trial (AACR 2021, Abstract CT039). Dr. Garassino observed that both drugs have demonstrated superiority to docetaxel as second-line therapy in NSCLC.
Although there have been no head-to-head trials, sintilimab and tislelizumab appear to be very similar to the already approved immune checkpoint inhibitors, which are currently being used as first-line treatment.
“That similarity would make them inappropriate for second-line treatment, except in countries where immune checkpoint inhibitors are not yet approved for first-line therapy,” Dr. Garassino noted.
When asked to comment on the higher treatment-related death rate observed with sintilimab, Dr. Garassino said, “We need to remember that these drugs were developed in China with a population that may have a side effect profile differing from that of a Western population. Also, we are very familiar with this class of drugs and know how to treat their side effects. Similar drugs but different populations and different trials, so it’s very hard to judge.”
Dr. Garassino speculated that with the “super expensive” price tags on the new checkpoint inhibitors, having additional agents that could provide choice and drive prices down would be welcome.
ORIENT-3 was funded by Innovent Biologics and Eli Lilly. Dr. Shi disclosed consultancy for Innovent Biologics. Dr. Garassino disclosed relationships with Eli Lilly, AstraZeneca, Novartis, and several other companies, not including Innovent Biologics.
FROM AACR 2021
NfL beats T-tau as a prognostic marker of cognitive decline
, new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.
“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.
The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
New tool for dementia diagnosis?
In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.
The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.
To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.
In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.
Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.
However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.
The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.
These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.
Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.
“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
An ‘exciting’ prospect
Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.
The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.
The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.
“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.
The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
New tool for dementia diagnosis?
In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.
The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.
To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.
In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.
Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.
However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.
The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.
These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.
Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.
“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
An ‘exciting’ prospect
Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.
The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.
The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. In certain contexts, T-tau improves cross-sectional analyses of these outcomes, but adding T-tau measurements to NfL measurements does not improve the predictive power of NfL, results of a longitudinal analysis show.
“The major distinction, for cognition at least, was that NfL cross-sectionally was associated with most cognitive outcomes, and longitudinally, higher NfL at baseline was associated with cognitive decline in every domain,” said study investigator Jordan Marks, an MD/PhD student at the Mayo Medical School, Rochester, Minn.
The findings were presented at the American Academy of Neurology’s 2021 annual meeting.
New tool for dementia diagnosis?
In recent years, researchers have studied NfL and T-tau as potential blood-based biomarkers of neurodegeneration. In cross-sectional and longitudinal studies, NfL and T-tau have been associated with worse cognition and with neuroimaging measures of cortical thickness, cortical atrophy, white-matter hyperintensity, and white-matter integrity. However, no previous research has directly compared the prognostic ability of these two biomarkers.
The study included 995 participants without dementia in the Mayo Clinic Study on Aging. All participants underwent measurement of NfL and T-tau and assessment of cognitive status, as well as neuroimaging. The investigators measured NfL and T-tau on the Simoa HD-1 platform. They reexamined patients approximately every 15 months. The median follow-up time was 6.2 years.
To examine associations between baseline plasma NfL or T-tau and cognitive or neuroimaging outcomes, the researchers conducted data analyses using linear mixed effects models and adjusted the data for age, sex, and education. They replicated these analyses using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). For these analyses, they selected 387 participants without dementia who had been followed for a median of 3.0 years.
In all analyses, baseline plasma NfL was more strongly associated with cognitive and neuroimaging outcomes than T-tau. “Baseline plasma NfL was associated with cognitive decline in all domains measured, while T-tau was not associated with cognitive decline,” said Mr. Marks.
Plasma NfL was more strongly associated with decreases in cortical thickness over time than T-tau was. NfL was also more strongly associated with declining hippocampal volume and white-matter changes.
However, in cross-sectional analysis, the combination of elevated NfL levels and elevated T-tau levels at baseline was more strongly associated with decreased global cognition and memory, compared with elevated NfL levels alone. The combination also was more strongly associated with neuroimaging measures, such as temporal cortex thickness and increased number of infarcts. However, in longitudinal analyses, T-tau did not add to the predictive value of NfL.
The analyses using ADNI data yielded similar results. Overall, the results suggest that NfL is a better prognostic marker of neurodegeneration in general, said Mr. Marks.
These findings, he said, may have implications for screening and diagnosis. “I’m definitely hopeful that NfL will be useful in a clinical setting to screen for those at risk of dementia and will be helpful, along with other modalities, like cognitive testing, for dementia diagnosis,” said Mr. Marks.
Future research should examine how changes in these biomarkers are associated with cognitive and neuroimaging outcomes over time.
“We used plasma levels at one point in time in this study, but we need a better sense of how to interpret, for example, what a rise in plasma NfL over a certain time period means for someone’s risk of developing neurodegenerative disease,” Mr. Marks added.
An ‘exciting’ prospect
Commenting on the study, Glen R. Finney, MD, director of the Memory and Cognition Program for Geisinger Health in Wilkes-Barre, Pa., said the findings add to neurologists’ ability to screen for brain diseases. “Evidence of neurodegeneration is part of the modern diagnosis of several disorders. While brain imaging can also provide that and may be needed for other reasons, this could provide an easy, potentially inexpensive way to screen for damage to the brain, giving us an added tool,” said Dr. Finney.
The prospect of using blood plasma markers to explore disease of the brain is exciting, Dr. Finney added. “I would like to see ongoing refinement of this approach and would like to see if there’s other markers in blood that could be used to find what specifically may be causing the damage,” he said.
The study was funded by the National Institutes of Health, the National Institute on Aging, and the GHR Foundation. Mr. Marks and Dr. Finney have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From AAN 2021