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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.
Corticosteroid bursts may increase risk of sepsis, GI bleeding in children
The adverse events are rare, and the risk attenuates in subsequent months, the analysis shows. Still, the study “provides evidence that corticosteroid bursts are not innocuous but may pose potentially serious health risks,” study author Tsung-Chieh Yao, MD, PhD, and colleagues said. “Clinicians prescribing corticosteroid bursts to children need to weigh the benefits against the risks of severe adverse events.”
The study, which was published online in JAMA Pediatrics, indicates that oral corticosteroids are “not a benign medication, which is something that we should have all along known,” commented Harold J. Farber, MD, MSPH, professor of pediatrics at Baylor College of Medicine and a pediatric pulmonologist at Texas Children’s Hospital, both in Houston.
While oral corticosteroids may be important for the treatment of asthma, inflammatory bowel disease, and rheumatoid arthritis, they often are overprescribed – a phenomenon that Dr. Farber and collaborators saw when they analyzed data from children with public health insurance in Texas.
The medication is “not uncommonly used for minor asthma exacerbations or minor respiratory symptoms, which do not require oral steroids,” said Dr. Farber, who was not involved with the study. “What this study tells us is to save it for when they are really needed,” such as to treat a severe asthma exacerbation.
Despite the risk of adverse events, oral corticosteroids remain an important medication, and clinicians should aim to strike “the right balance,” Dr. Farber said.
Prior research has shown that the long-term use of oral corticosteroids is associated with adverse events such as infections, glaucoma, hyperglycemia, cardiovascular diseases, and osteoporosis. In addition, data indicate that corticosteroid bursts are associated with GI bleeding and sepsis in adults. But few studies have looked at the risk of corticosteroid bursts in children, the researchers said.
To evaluate associations of corticosteroid bursts – defined as the use of oral corticosteroids for 14 days or less – with GI bleeding, sepsis, pneumonia, and glaucoma in children, Dr. Yao and colleagues analyzed data from the National Health Insurance Research Database in Taiwan between 2013 and 2017. Dr. Yao is affiliated with the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan City, Taiwan.
Of more than 4.5 million children in the database, 42% received at least one corticosteroid burst, typically for acute respiratory tract infections and allergic diseases. The researchers focused on 1,064,587 children who received a single corticosteroid burst, and compared the incidence of adverse events before and after treatment using a self-controlled case series design. “Corticosteroid bursts were significantly associated with a 1.4- to 2.2-fold increase of GI bleeding, sepsis, and pneumonia, but not glaucoma, within the first month after initiation of corticosteroid therapy,” the investigators reported.
Incidence rate ratios in the 5-30 days after starting corticosteroid bursts were 1.41 for GI bleeding, 2.02 for sepsis, 2.19 for pneumonia, and 0.98 for glaucoma, compared with a pretreatment reference period.
The incidence rate per 1,000 person-years for GI bleeding was 2.48 with corticosteroid bursts, compared with 1.88 without corticosteroids. For sepsis, the rates with and without corticosteroids were 0.37 and 0.34, respectively. And for pneumonia, the rates were 25.74 versus 16.39.
Further research is needed to assess the validity of these findings, the authors noted. Because many children receive corticosteroid bursts worldwide, however, the “findings call for a careful reevaluation regarding the prudent use” of this treatment.
The study was supported by grants from the National Health Research Institutes; Ministry of Science and Technology of Taiwan; National Cheng Kung University, Tainan, Taiwan; Chang Gung Medical Foundation; and the National Institutes of Health. A coauthor disclosed grants from GlaxoSmithKline outside of the study.
The adverse events are rare, and the risk attenuates in subsequent months, the analysis shows. Still, the study “provides evidence that corticosteroid bursts are not innocuous but may pose potentially serious health risks,” study author Tsung-Chieh Yao, MD, PhD, and colleagues said. “Clinicians prescribing corticosteroid bursts to children need to weigh the benefits against the risks of severe adverse events.”
The study, which was published online in JAMA Pediatrics, indicates that oral corticosteroids are “not a benign medication, which is something that we should have all along known,” commented Harold J. Farber, MD, MSPH, professor of pediatrics at Baylor College of Medicine and a pediatric pulmonologist at Texas Children’s Hospital, both in Houston.
While oral corticosteroids may be important for the treatment of asthma, inflammatory bowel disease, and rheumatoid arthritis, they often are overprescribed – a phenomenon that Dr. Farber and collaborators saw when they analyzed data from children with public health insurance in Texas.
The medication is “not uncommonly used for minor asthma exacerbations or minor respiratory symptoms, which do not require oral steroids,” said Dr. Farber, who was not involved with the study. “What this study tells us is to save it for when they are really needed,” such as to treat a severe asthma exacerbation.
Despite the risk of adverse events, oral corticosteroids remain an important medication, and clinicians should aim to strike “the right balance,” Dr. Farber said.
Prior research has shown that the long-term use of oral corticosteroids is associated with adverse events such as infections, glaucoma, hyperglycemia, cardiovascular diseases, and osteoporosis. In addition, data indicate that corticosteroid bursts are associated with GI bleeding and sepsis in adults. But few studies have looked at the risk of corticosteroid bursts in children, the researchers said.
To evaluate associations of corticosteroid bursts – defined as the use of oral corticosteroids for 14 days or less – with GI bleeding, sepsis, pneumonia, and glaucoma in children, Dr. Yao and colleagues analyzed data from the National Health Insurance Research Database in Taiwan between 2013 and 2017. Dr. Yao is affiliated with the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan City, Taiwan.
Of more than 4.5 million children in the database, 42% received at least one corticosteroid burst, typically for acute respiratory tract infections and allergic diseases. The researchers focused on 1,064,587 children who received a single corticosteroid burst, and compared the incidence of adverse events before and after treatment using a self-controlled case series design. “Corticosteroid bursts were significantly associated with a 1.4- to 2.2-fold increase of GI bleeding, sepsis, and pneumonia, but not glaucoma, within the first month after initiation of corticosteroid therapy,” the investigators reported.
Incidence rate ratios in the 5-30 days after starting corticosteroid bursts were 1.41 for GI bleeding, 2.02 for sepsis, 2.19 for pneumonia, and 0.98 for glaucoma, compared with a pretreatment reference period.
The incidence rate per 1,000 person-years for GI bleeding was 2.48 with corticosteroid bursts, compared with 1.88 without corticosteroids. For sepsis, the rates with and without corticosteroids were 0.37 and 0.34, respectively. And for pneumonia, the rates were 25.74 versus 16.39.
Further research is needed to assess the validity of these findings, the authors noted. Because many children receive corticosteroid bursts worldwide, however, the “findings call for a careful reevaluation regarding the prudent use” of this treatment.
The study was supported by grants from the National Health Research Institutes; Ministry of Science and Technology of Taiwan; National Cheng Kung University, Tainan, Taiwan; Chang Gung Medical Foundation; and the National Institutes of Health. A coauthor disclosed grants from GlaxoSmithKline outside of the study.
The adverse events are rare, and the risk attenuates in subsequent months, the analysis shows. Still, the study “provides evidence that corticosteroid bursts are not innocuous but may pose potentially serious health risks,” study author Tsung-Chieh Yao, MD, PhD, and colleagues said. “Clinicians prescribing corticosteroid bursts to children need to weigh the benefits against the risks of severe adverse events.”
The study, which was published online in JAMA Pediatrics, indicates that oral corticosteroids are “not a benign medication, which is something that we should have all along known,” commented Harold J. Farber, MD, MSPH, professor of pediatrics at Baylor College of Medicine and a pediatric pulmonologist at Texas Children’s Hospital, both in Houston.
While oral corticosteroids may be important for the treatment of asthma, inflammatory bowel disease, and rheumatoid arthritis, they often are overprescribed – a phenomenon that Dr. Farber and collaborators saw when they analyzed data from children with public health insurance in Texas.
The medication is “not uncommonly used for minor asthma exacerbations or minor respiratory symptoms, which do not require oral steroids,” said Dr. Farber, who was not involved with the study. “What this study tells us is to save it for when they are really needed,” such as to treat a severe asthma exacerbation.
Despite the risk of adverse events, oral corticosteroids remain an important medication, and clinicians should aim to strike “the right balance,” Dr. Farber said.
Prior research has shown that the long-term use of oral corticosteroids is associated with adverse events such as infections, glaucoma, hyperglycemia, cardiovascular diseases, and osteoporosis. In addition, data indicate that corticosteroid bursts are associated with GI bleeding and sepsis in adults. But few studies have looked at the risk of corticosteroid bursts in children, the researchers said.
To evaluate associations of corticosteroid bursts – defined as the use of oral corticosteroids for 14 days or less – with GI bleeding, sepsis, pneumonia, and glaucoma in children, Dr. Yao and colleagues analyzed data from the National Health Insurance Research Database in Taiwan between 2013 and 2017. Dr. Yao is affiliated with the division of allergy, asthma, and rheumatology in the department of pediatrics at Chang Gung Memorial Hospital in Taoyuan City, Taiwan.
Of more than 4.5 million children in the database, 42% received at least one corticosteroid burst, typically for acute respiratory tract infections and allergic diseases. The researchers focused on 1,064,587 children who received a single corticosteroid burst, and compared the incidence of adverse events before and after treatment using a self-controlled case series design. “Corticosteroid bursts were significantly associated with a 1.4- to 2.2-fold increase of GI bleeding, sepsis, and pneumonia, but not glaucoma, within the first month after initiation of corticosteroid therapy,” the investigators reported.
Incidence rate ratios in the 5-30 days after starting corticosteroid bursts were 1.41 for GI bleeding, 2.02 for sepsis, 2.19 for pneumonia, and 0.98 for glaucoma, compared with a pretreatment reference period.
The incidence rate per 1,000 person-years for GI bleeding was 2.48 with corticosteroid bursts, compared with 1.88 without corticosteroids. For sepsis, the rates with and without corticosteroids were 0.37 and 0.34, respectively. And for pneumonia, the rates were 25.74 versus 16.39.
Further research is needed to assess the validity of these findings, the authors noted. Because many children receive corticosteroid bursts worldwide, however, the “findings call for a careful reevaluation regarding the prudent use” of this treatment.
The study was supported by grants from the National Health Research Institutes; Ministry of Science and Technology of Taiwan; National Cheng Kung University, Tainan, Taiwan; Chang Gung Medical Foundation; and the National Institutes of Health. A coauthor disclosed grants from GlaxoSmithKline outside of the study.
FROM JAMA PEDIATRICS
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.
A Pivotal Moment in Cancer Surgery, Captured on Film
Few ever see this side of cancer care. Our cameras go behind the scenes as a surgical oncologist faces a crucial moment in the OR in this first episode of a new video series, The Oncologists.
Medscape Oncology © 2021 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.
Few ever see this side of cancer care. Our cameras go behind the scenes as a surgical oncologist faces a crucial moment in the OR in this first episode of a new video series, The Oncologists.
Medscape Oncology © 2021 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.
Few ever see this side of cancer care. Our cameras go behind the scenes as a surgical oncologist faces a crucial moment in the OR in this first episode of a new video series, The Oncologists.
Medscape Oncology © 2021 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: A Pivotal Moment in Cancer Surgery, Captured on Film - Medscape - Feb 18, 2021.
Hyperprogression on immunotherapy: When outcomes are much worse
Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.
A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.
This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.
There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.
HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”
“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.
But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.
“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.
He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
Existing data on HPD
HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.
In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.
The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.
That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).
Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.
In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.
However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.
“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.
Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.
Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.
Both groups of authors emphasize the urgent need for prospective studies.
It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.
The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.
The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.
Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.
“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
Steps for solving the HPD mystery
“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”
Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.
“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”
Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.
Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.
The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.
“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.
“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.
Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.
He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.
“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
Current treatment decision-making
Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.
For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.
“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.
Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.
Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).
“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”
A version of this article first appeared on Medscape.com.
Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.
A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.
This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.
There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.
HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”
“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.
But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.
“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.
He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
Existing data on HPD
HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.
In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.
The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.
That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).
Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.
In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.
However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.
“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.
Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.
Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.
Both groups of authors emphasize the urgent need for prospective studies.
It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.
The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.
The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.
Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.
“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
Steps for solving the HPD mystery
“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”
Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.
“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”
Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.
Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.
The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.
“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.
“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.
Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.
He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.
“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
Current treatment decision-making
Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.
For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.
“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.
Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.
Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).
“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”
A version of this article first appeared on Medscape.com.
Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.
A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.
This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.
There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.
HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”
“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.
But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.
“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.
He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
Existing data on HPD
HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.
In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.
The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.
That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).
Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.
In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.
However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.
“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.
Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.
Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.
Both groups of authors emphasize the urgent need for prospective studies.
It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.
The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.
The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.
Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.
“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
Steps for solving the HPD mystery
“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”
Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.
“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”
Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.
Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.
The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.
“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.
“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.
Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.
He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.
“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
Current treatment decision-making
Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.
For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.
“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.
Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.
Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).
“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”
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.
Ruling out PE in patients with low C-PTP and D dimer of less than 1,000 ng/mL
Background: A pulmonary embolism can be considered ruled out if patients have a low C-PTP for PE and a D-dimer level of less than 500 ng/mL. However, this occurs in approximately 30% of outpatients only. By increasing the D-dimer threshold used to define a negative test to 1,000 ng/mL in patients with a low C-PTP, we might be able to rule out a larger segment of patients and avoid chest imaging.
Study design: Prospective study.
Setting: University-based clinical centers in Canada.
Synopsis: This study enrolled 2,017 patients presenting with symptoms of PE. The Wells’ criteria was used to categorize the patient’s C-PTP as low (0-4.0), moderate (4.5-6.0), or high (6.5 or more). Patients with a low or moderate C-PTP had a D dimer drawn. Those with a low C-PTP and D dimer of less than 1,000 ng/mL or moderate C-PTP and a D dimer of less than 500 ng/mL underwent no further testing. Outcomes were assessed at 90 days. Of the 1,325 patients with a low C-PTP or moderate C-PTP and a negative D-dimer test (less than 1,000 or 500 ng/mL, respectively), none had venous thromboembolism during follow-up (95% confidence interval, 0.00-0.29). This strategy resulted in the use of chest imaging in only 34.3% of patients versus 51.9% using the prior criteria of a D-dimer level of less than 500 ng/mL (difference, –17.6 percentage points; 95% CI, −19.2 to −15.9). One limitation of the study is that almost all patients enrolled were outpatients (only one inpatient).
Bottom line: A combination of a low C-PTP and a D-dimer level of less than 1,000 ng/mL identified a group of patients at low risk for pulmonary embolism during follow-up.
Citation: Kearon C et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med 2019 Nov 28;381:2125-34.
Dr. Santa is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.
Background: A pulmonary embolism can be considered ruled out if patients have a low C-PTP for PE and a D-dimer level of less than 500 ng/mL. However, this occurs in approximately 30% of outpatients only. By increasing the D-dimer threshold used to define a negative test to 1,000 ng/mL in patients with a low C-PTP, we might be able to rule out a larger segment of patients and avoid chest imaging.
Study design: Prospective study.
Setting: University-based clinical centers in Canada.
Synopsis: This study enrolled 2,017 patients presenting with symptoms of PE. The Wells’ criteria was used to categorize the patient’s C-PTP as low (0-4.0), moderate (4.5-6.0), or high (6.5 or more). Patients with a low or moderate C-PTP had a D dimer drawn. Those with a low C-PTP and D dimer of less than 1,000 ng/mL or moderate C-PTP and a D dimer of less than 500 ng/mL underwent no further testing. Outcomes were assessed at 90 days. Of the 1,325 patients with a low C-PTP or moderate C-PTP and a negative D-dimer test (less than 1,000 or 500 ng/mL, respectively), none had venous thromboembolism during follow-up (95% confidence interval, 0.00-0.29). This strategy resulted in the use of chest imaging in only 34.3% of patients versus 51.9% using the prior criteria of a D-dimer level of less than 500 ng/mL (difference, –17.6 percentage points; 95% CI, −19.2 to −15.9). One limitation of the study is that almost all patients enrolled were outpatients (only one inpatient).
Bottom line: A combination of a low C-PTP and a D-dimer level of less than 1,000 ng/mL identified a group of patients at low risk for pulmonary embolism during follow-up.
Citation: Kearon C et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med 2019 Nov 28;381:2125-34.
Dr. Santa is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.
Background: A pulmonary embolism can be considered ruled out if patients have a low C-PTP for PE and a D-dimer level of less than 500 ng/mL. However, this occurs in approximately 30% of outpatients only. By increasing the D-dimer threshold used to define a negative test to 1,000 ng/mL in patients with a low C-PTP, we might be able to rule out a larger segment of patients and avoid chest imaging.
Study design: Prospective study.
Setting: University-based clinical centers in Canada.
Synopsis: This study enrolled 2,017 patients presenting with symptoms of PE. The Wells’ criteria was used to categorize the patient’s C-PTP as low (0-4.0), moderate (4.5-6.0), or high (6.5 or more). Patients with a low or moderate C-PTP had a D dimer drawn. Those with a low C-PTP and D dimer of less than 1,000 ng/mL or moderate C-PTP and a D dimer of less than 500 ng/mL underwent no further testing. Outcomes were assessed at 90 days. Of the 1,325 patients with a low C-PTP or moderate C-PTP and a negative D-dimer test (less than 1,000 or 500 ng/mL, respectively), none had venous thromboembolism during follow-up (95% confidence interval, 0.00-0.29). This strategy resulted in the use of chest imaging in only 34.3% of patients versus 51.9% using the prior criteria of a D-dimer level of less than 500 ng/mL (difference, –17.6 percentage points; 95% CI, −19.2 to −15.9). One limitation of the study is that almost all patients enrolled were outpatients (only one inpatient).
Bottom line: A combination of a low C-PTP and a D-dimer level of less than 1,000 ng/mL identified a group of patients at low risk for pulmonary embolism during follow-up.
Citation: Kearon C et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med 2019 Nov 28;381:2125-34.
Dr. Santa is assistant professor in the division of hospital medicine, Loyola University Medical Center, Maywood, Ill.
AHA guidance on blood clots linked to COVID-19 vaccine
A newly released report is offering guidance concerning rare conditions associated with COVID-19 as well as vaccines against the virus.
The report was released April 29, 2021, by the American Heart Association/American Stroke Association Stroke Council Leadership in answer to the decision April 23 by the Centers for Disease Control and Prevention and the Food and Drug Administration to lift an earlier “pause” in administration of the Johnson & Johnson (Janssen) vaccine.
That pause had been put in place after reports were received of a possible association between the J&J vaccine and cerebral venous sinus thrombosis (CVST) and thrombosis-thrombocytopenia syndrome (TTS, blood clots plus low blood platelets). CVST and TTS were also linked to patients in Europe and Canada who received the AstraZeneca COVID-19 vaccine.
However, the new report noted that these conditions are very rare.
“The risk of CVST due to infection with COVID-19 is 8-10 times higher than the risk of CVST after receiving a COVID-19 vaccine,” lead author Karen L. Furie, MD, chair of the department of neurology at Brown University, Providence, R.I., said in a press release.
“The public can be reassured by the CDC’s and FDA’s investigation and these statistics – the likelihood of developing CVST after a COVID-19 vaccine is extremely low,” said Dr. Furie, adding that the authors “urge all adults to receive any of the approved COVID-19 vaccines.”
The new guidance, which was published online April 29, 2021, in Stroke, discusses signs and symptoms of CVST and TTS, as well as vaccine-induced immune thrombotic thrombocytopenia (VITT). It also recommends best options for treating these conditions.
Assessing 81 million patients
In their analysis, the investigators assessed a database of 59 health care organizations and 81 million patients, 98% of whom were in the United States.
Of almost 514,000 patients diagnosed with COVID-19 between January 2020 and March 2021, 20 also received a diagnosis of CVST.
Among about 490,000 adults who received either the Pfizer or Moderna vaccines, there were no diagnosed cases of thrombocytopenia.
Dr. Furie reiterated that CVST blood clots “are very rare adverse events,” but recommended that any patient in the ED with a suspected clot should be screened immediately to determine if they received a COVID vaccine during the previous few weeks.
For those who have recently received the COVID-19 vaccine, a suspected clot should be treated with nonheparin anticoagulants, Dr. Furie said.
“No heparin products in any dose should be given for suspected CVST, TTS, or VITT. With the right treatment, most patients can have a full recovery,” she added. The report includes additional, detailed treatment recommendations if one of these conditions are suspected.
Rare events
The authors noted that cases of TTS/VITT occurred up to 2.5 weeks after receiving the J&J vaccine in the United States and up to 3.5 weeks after receiving the AstraZeneca vaccine in Europe.
An April 23 report from the CDC and FDA noted that, out of almost 7 million adults who received the J&J vaccine, the agencies investigated only 15 reported cases of TTS.
An April 7 report from the European Medicines Agency noted that, out of more than 25 million people who received the AstraZeneca vaccine in the European Union, it found 62 cases of CVST.
A statement put out by the American Heart Association/American Stroke Association urges “everyone to receive a COVID-19 vaccine” as soon as possible.
“We are confident the benefits of vaccination far exceed the very small, rare risks,” the organizations said. “The risks of vaccination are also far smaller than the risk of COVID-19 and its potentially fatal consequences.”
A version of this article first appeared on Medscape.com.
A newly released report is offering guidance concerning rare conditions associated with COVID-19 as well as vaccines against the virus.
The report was released April 29, 2021, by the American Heart Association/American Stroke Association Stroke Council Leadership in answer to the decision April 23 by the Centers for Disease Control and Prevention and the Food and Drug Administration to lift an earlier “pause” in administration of the Johnson & Johnson (Janssen) vaccine.
That pause had been put in place after reports were received of a possible association between the J&J vaccine and cerebral venous sinus thrombosis (CVST) and thrombosis-thrombocytopenia syndrome (TTS, blood clots plus low blood platelets). CVST and TTS were also linked to patients in Europe and Canada who received the AstraZeneca COVID-19 vaccine.
However, the new report noted that these conditions are very rare.
“The risk of CVST due to infection with COVID-19 is 8-10 times higher than the risk of CVST after receiving a COVID-19 vaccine,” lead author Karen L. Furie, MD, chair of the department of neurology at Brown University, Providence, R.I., said in a press release.
“The public can be reassured by the CDC’s and FDA’s investigation and these statistics – the likelihood of developing CVST after a COVID-19 vaccine is extremely low,” said Dr. Furie, adding that the authors “urge all adults to receive any of the approved COVID-19 vaccines.”
The new guidance, which was published online April 29, 2021, in Stroke, discusses signs and symptoms of CVST and TTS, as well as vaccine-induced immune thrombotic thrombocytopenia (VITT). It also recommends best options for treating these conditions.
Assessing 81 million patients
In their analysis, the investigators assessed a database of 59 health care organizations and 81 million patients, 98% of whom were in the United States.
Of almost 514,000 patients diagnosed with COVID-19 between January 2020 and March 2021, 20 also received a diagnosis of CVST.
Among about 490,000 adults who received either the Pfizer or Moderna vaccines, there were no diagnosed cases of thrombocytopenia.
Dr. Furie reiterated that CVST blood clots “are very rare adverse events,” but recommended that any patient in the ED with a suspected clot should be screened immediately to determine if they received a COVID vaccine during the previous few weeks.
For those who have recently received the COVID-19 vaccine, a suspected clot should be treated with nonheparin anticoagulants, Dr. Furie said.
“No heparin products in any dose should be given for suspected CVST, TTS, or VITT. With the right treatment, most patients can have a full recovery,” she added. The report includes additional, detailed treatment recommendations if one of these conditions are suspected.
Rare events
The authors noted that cases of TTS/VITT occurred up to 2.5 weeks after receiving the J&J vaccine in the United States and up to 3.5 weeks after receiving the AstraZeneca vaccine in Europe.
An April 23 report from the CDC and FDA noted that, out of almost 7 million adults who received the J&J vaccine, the agencies investigated only 15 reported cases of TTS.
An April 7 report from the European Medicines Agency noted that, out of more than 25 million people who received the AstraZeneca vaccine in the European Union, it found 62 cases of CVST.
A statement put out by the American Heart Association/American Stroke Association urges “everyone to receive a COVID-19 vaccine” as soon as possible.
“We are confident the benefits of vaccination far exceed the very small, rare risks,” the organizations said. “The risks of vaccination are also far smaller than the risk of COVID-19 and its potentially fatal consequences.”
A version of this article first appeared on Medscape.com.
A newly released report is offering guidance concerning rare conditions associated with COVID-19 as well as vaccines against the virus.
The report was released April 29, 2021, by the American Heart Association/American Stroke Association Stroke Council Leadership in answer to the decision April 23 by the Centers for Disease Control and Prevention and the Food and Drug Administration to lift an earlier “pause” in administration of the Johnson & Johnson (Janssen) vaccine.
That pause had been put in place after reports were received of a possible association between the J&J vaccine and cerebral venous sinus thrombosis (CVST) and thrombosis-thrombocytopenia syndrome (TTS, blood clots plus low blood platelets). CVST and TTS were also linked to patients in Europe and Canada who received the AstraZeneca COVID-19 vaccine.
However, the new report noted that these conditions are very rare.
“The risk of CVST due to infection with COVID-19 is 8-10 times higher than the risk of CVST after receiving a COVID-19 vaccine,” lead author Karen L. Furie, MD, chair of the department of neurology at Brown University, Providence, R.I., said in a press release.
“The public can be reassured by the CDC’s and FDA’s investigation and these statistics – the likelihood of developing CVST after a COVID-19 vaccine is extremely low,” said Dr. Furie, adding that the authors “urge all adults to receive any of the approved COVID-19 vaccines.”
The new guidance, which was published online April 29, 2021, in Stroke, discusses signs and symptoms of CVST and TTS, as well as vaccine-induced immune thrombotic thrombocytopenia (VITT). It also recommends best options for treating these conditions.
Assessing 81 million patients
In their analysis, the investigators assessed a database of 59 health care organizations and 81 million patients, 98% of whom were in the United States.
Of almost 514,000 patients diagnosed with COVID-19 between January 2020 and March 2021, 20 also received a diagnosis of CVST.
Among about 490,000 adults who received either the Pfizer or Moderna vaccines, there were no diagnosed cases of thrombocytopenia.
Dr. Furie reiterated that CVST blood clots “are very rare adverse events,” but recommended that any patient in the ED with a suspected clot should be screened immediately to determine if they received a COVID vaccine during the previous few weeks.
For those who have recently received the COVID-19 vaccine, a suspected clot should be treated with nonheparin anticoagulants, Dr. Furie said.
“No heparin products in any dose should be given for suspected CVST, TTS, or VITT. With the right treatment, most patients can have a full recovery,” she added. The report includes additional, detailed treatment recommendations if one of these conditions are suspected.
Rare events
The authors noted that cases of TTS/VITT occurred up to 2.5 weeks after receiving the J&J vaccine in the United States and up to 3.5 weeks after receiving the AstraZeneca vaccine in Europe.
An April 23 report from the CDC and FDA noted that, out of almost 7 million adults who received the J&J vaccine, the agencies investigated only 15 reported cases of TTS.
An April 7 report from the European Medicines Agency noted that, out of more than 25 million people who received the AstraZeneca vaccine in the European Union, it found 62 cases of CVST.
A statement put out by the American Heart Association/American Stroke Association urges “everyone to receive a COVID-19 vaccine” as soon as possible.
“We are confident the benefits of vaccination far exceed the very small, rare risks,” the organizations said. “The risks of vaccination are also far smaller than the risk of COVID-19 and its potentially fatal consequences.”
A version of this article first appeared on Medscape.com.
Marijuana vaping more common among Hispanic teens
Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.
Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.
“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.
The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.
“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.
Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.
“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.
Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.
“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”
Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.
Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.
Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.
Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.
In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.
“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”
Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.
However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.
The study author and experts disclosed no relevant financial relationships.
Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.
Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.
“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.
The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.
“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.
Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.
“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.
Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.
“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”
Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.
Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.
Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.
Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.
In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.
“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”
Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.
However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.
The study author and experts disclosed no relevant financial relationships.
Hispanic adolescents were more likely to use e-cigarettes to vape marijuana than were their Black and White counterparts in 2020, according to a recent study conducted by the Centers for Disease Control and Prevention and published in JAMA Pediatrics.
Researchers found that 25.6% of Hispanic students reported vaping marijuana, compared to 19.4% of Black students and 18.2% of White students. The study, which is an analysis of 2017, 2018, and 2020 results from the National Youth Tobacco Survey, also revealed that increases in this recreational practice occurred among all racial and ethnic groups within those 3 years, with Hispanic students having the largest percent increase, 11.6%, followed by Black students at 8.8% and White students at 7.4%.
“The initial motivation [to do this study] was to gain a better understanding of the prevalence of use of marijuana in e-cigarettes among youth, particularly given the context of the 2019 outbreak of e-cigarette, or vaping, product use–associated lung injury (EVALI),” study author Christina Vaughan Watson, DrPH, health scientist at the CDC’s National Center for Chronic Disease Prevention and Health Promotion, said in an interview.
The findings could help clinicians and physicians understand demographic variations among marijuana vapers and help inform targeted interventions for specific populations.
“Understanding demographic variations among those who are using marijuana in e-cigarettes can help inform evidenced-based interventions that may resonate with specific populations,” Dr. Watson explained.
Margaret Thew, DNP, medical director of adolescent medicine at Children’s Wisconsin in Milwaukee, who was not involved in the study, said in an interview that the findings were “eye opening” and revealed a pattern she hasn’t seen before in her adolescent clinic.
“I would have thought African-American or non-Hispanic Blacks would’ve been a higher group of use, because when we screen kids that’s what we tend to get from the population we see here,” Ms. Thew said.
Ms. Thew said the findings also had made her reconsider her clinic’s approach to screening adolescents for marijuana use as well as address possible language barriers.
“We are probably missing access to some of the kids that we may need to seek out,” she explained. “I also thought it sends a good message that we need to direct some of our education probably a little differently, especially if it’s a Hispanic population and English may not be the primary language.”
Dr. Watson said more research is needed to assess why differences in marijuana use in e-cigarettes exist among youth.
Marijuana use in e-cigarettes has become increasingly popular among U.S. teens, with one in five students in grades 10 and 12 reporting vaping marijuana within the past year in a 2019 study conducted by the National Institute on Drug Abuse.
Dr. Watson and colleagues also found statistically significant increases in vaping marijuana, with 19.5% of students reporting smoking marijuana via e-cigarettes in 2020, compared to 11.1% of them vaping the drug in 2017. They believe the rise in marijuana vaping among youth may be attributed to states increasingly legalizing adult marijuana sales, which could impact ease of access and social acceptance.
Ms. Thew believes the rise in marijuana vaping among youth can be attributed to the legalization of marijuana, which may send “a message to adolescents that it must be safe for them to use,” as well as the increasing popularity of e-cigarettes.
In fact, as of April 2021, marijuana is legal for adults in 16 states and the District of Columbia. Meanwhile, medical marijuana is legal in 36 states, according to the National Conference of State Legislatures.
“I mean, there’s just definitely been a lot more use of [e-cigarettes]. Vaping and things like that definitely took off between 2019 and 2020,” Ms. Thew explained. “And I think marijuana use in itself is going up tremendously, I think more kids who would have used alcohol in the past use weed.”
Although public attitudes toward marijuana have relaxed, previous studies have linked it to memory dysfunction, as well as long-term cognitive effects that can interfere with perception of time and motor function. However, studies also have shown that cannabis use can combat age-related cognitive decline and help with pain reduction.
However, when it comes to adolescents, Dr. Watson and colleagues said e-cigarette use among youth and young adults is unsafe, regardless of the substances used in these products, including marijuana. Furthermore, they said marijuana use can lead to higher risks of more problematic use later in life, adding that evidence-based strategies to reduce marijuana use in e-cigarettes are important for protecting young people.
The study author and experts disclosed no relevant financial relationships.