ILLUSTRATIVE CASE

A 40-year-old woman presents to your office to establish care. During your interview you realize that she has never been screened for cervical cancer. In fact, she has not had a pelvic exam because she is fearful of the procedure. She would like to know if alternatives exist for cervical cancer screening. What can you suggest?

Although deaths from cervical cancer decreased in the United States from 1975 to 2017, demographic and social disparities in the burden of the disease remain.^2,3 Data from 2016 reveal that cervical cancer incidence per 100,000 women is lowest among white (7.5), Asian-Pacific Islander (5.8), and American Indian/Alaska native (5.6) women, and highest among Hispanic (9.8) and black (8.7) women, which could be explained by lower screening rates in these populations.^4,5 The National Cancer Institute’s publication on reducing cancer health disparities states that the most effective way to reduce cervical cancer incidence and mortality is by increasing screening rates among women who have not been screened or who have not been screened regularly.⁶

The US Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) screening test in 2003.⁷ Evidence now suggests that high-risk HPV screening provides greater protection against cervical cancer than screening with cytology alone.⁸ The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) have changed their recommendations to include primary HPV testing as an alternative method to Pap smears for cervical cancer screening.⁹

An advantage of primary HPV screening is that it can be performed on a specimen collected by the patient, which could potentially increase rates of screening and help to decrease demographic and social disparities. A randomized trial of almost 2000 women ages 21 to 65 years that evaluated the acceptability of this method to patients revealed that more than half of women prefer the idea of a self-collected specimen to one that is collected by a clinician because it is more convenient and obviates the need for a pelvic exam.¹⁰

A meta-analysis of 36 studies and more than 150,000 women concluded that when self-collected samples were used with signal-based assays, the tests were not as sensitive or specific as when clinician-collected samples were used.¹¹ However, the meta-analysis also found that some polymerase chain reaction (PCR)-based HPV tests were similarly sensitive for both self- and clinician-collected samples.

STUDY SUMMARY

PCR vs signal amplification HPV tests with collection by patients vs clinicians

This meta-analysis compared the accuracy of high-risk HPV self-screening with clinician collection of samples (56 diagnostic accuracy trials; total N not provided) in identifying cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) with signal amplification and PCR tests evaluated separately.¹ In addition, this review evaluated strategies to screen women who are underscreened or not screened, which was defined as women who were irregularly or never screened, or did not respond to reminder letters about cervical cancer screening (25 randomized controlled trials [RCTs]; total N not provided).

In the diagnostic accuracy studies, patients collected a vaginal sample themselves and then had a sample taken by a clinician. CIN 2+ or 3+ was confirmed by either colposcopy and biopsy performed on all patients or by a positive high-risk HPV test result. Studies were further divided into those using assays based on signal amplification or PCR.

Continue to: In signal amplification assays...

In signal amplification assays, the pooled sensitivity for CIN 2+ was lower in the group with the self-collected samples than in the clinician-collected sample group (77%; 95% confidence interval [CI], 69%-82% vs 93%; 95% CI, 89%-96%). The pooled specificity to exclude CIN 2+ was also lower in the group with the self-collected samples (84%; 95% CI, 77%-88% vs 86%; 95% CI, 81%-90%). In high-risk HPV assays based on PCR, there was no difference in sensitivity (96%) or specificity (79%) between the specimen groups.

This study offers robust evidence that high-risk HPV PCR-based assays using patient-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

With regard to the pooled relative sensitivity and specificity of signal amplification assays, those using self-swab samples were less sensitive and less specific for CIN 2+ (sensitivity ratio = 0.85; 95% CI, 0.80-0.89; specificity ratio = 0.96; 95% CI, 0.93-0.98) and CIN 3+ (sensitivity ratio = 0.86; 95% CI, 0.76-0.98; specificity ratio = 0.97; 95% CI, 0.95-0.99). Using PCR assays, there was no difference between groups in relative sensitivity for the diagnosis of CIN 2+ (sensitivity ratio = 0.99; 95% CI, 0.97-1.02) and CIN 3+ (sensitivity ratio = 0.99; 95% CI, 0.96-1.02). Relative specificity was slightly lower in the self-swab group for CIN 2+ (specificity ratio = 0.98; 95% CI, 0.97-0.99) and CIN 3+ (specificity ratio = 0.98; 95% CI, 0.97-0.99).

The second analysis to evaluate which outreach strategies are effective methods for screening underscreened/unscreened women found that delivering self-sample kits to patients was more effective than the control method, which was sending reminders to women to undergo conventional screening (95% vs 53%; mean difference [MD], 41%; 95% CI, 3%-78%). Similarly, mailing kits to patients compared favorably to the control method (25% vs 12%; MD, 13%; 95% CI, 10%-15%).

WHAT’S NEW

Self-collected specimens can beas reliable as clinician-collected ones

This is the first study to provide robust evidence that high-risk HPV PCR-based assays using patient self-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

CAVEATS

Balancing lower specificity with reaching underscreened populations

Patients with a positive HPV test result require additional testing. The success rates for this follow-up are not known and could be a barrier to accurate diagnoses because of accessibility and patient willingness to follow up with a pelvic exam. In addition, self-collection may be less specific than cytology and could increase colposcopy referrals that lead to negative findings and overtreatment.¹² However, the increased acceptance of this screening method could make it an effective strategy to reach underscreened or reluctant patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Availability of PCR-based HPV assays may be an issue

HPV PCR assays may not be available at all laboratories, but signal amplification HPV tests have been shown to be inferior to PCR assays. Physicians will have to confirm with their laboratories whether PCR-based HPV assays are available.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 40-year-old woman presents to your office to establish care. During your interview you realize that she has never been screened for cervical cancer. In fact, she has not had a pelvic exam because she is fearful of the procedure. She would like to know if alternatives exist for cervical cancer screening. What can you suggest?

Although deaths from cervical cancer decreased in the United States from 1975 to 2017, demographic and social disparities in the burden of the disease remain.^2,3 Data from 2016 reveal that cervical cancer incidence per 100,000 women is lowest among white (7.5), Asian-Pacific Islander (5.8), and American Indian/Alaska native (5.6) women, and highest among Hispanic (9.8) and black (8.7) women, which could be explained by lower screening rates in these populations.^4,5 The National Cancer Institute’s publication on reducing cancer health disparities states that the most effective way to reduce cervical cancer incidence and mortality is by increasing screening rates among women who have not been screened or who have not been screened regularly.⁶

The US Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) screening test in 2003.⁷ Evidence now suggests that high-risk HPV screening provides greater protection against cervical cancer than screening with cytology alone.⁸ The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) have changed their recommendations to include primary HPV testing as an alternative method to Pap smears for cervical cancer screening.⁹

An advantage of primary HPV screening is that it can be performed on a specimen collected by the patient, which could potentially increase rates of screening and help to decrease demographic and social disparities. A randomized trial of almost 2000 women ages 21 to 65 years that evaluated the acceptability of this method to patients revealed that more than half of women prefer the idea of a self-collected specimen to one that is collected by a clinician because it is more convenient and obviates the need for a pelvic exam.¹⁰

A meta-analysis of 36 studies and more than 150,000 women concluded that when self-collected samples were used with signal-based assays, the tests were not as sensitive or specific as when clinician-collected samples were used.¹¹ However, the meta-analysis also found that some polymerase chain reaction (PCR)-based HPV tests were similarly sensitive for both self- and clinician-collected samples.

STUDY SUMMARY

PCR vs signal amplification HPV tests with collection by patients vs clinicians

This meta-analysis compared the accuracy of high-risk HPV self-screening with clinician collection of samples (56 diagnostic accuracy trials; total N not provided) in identifying cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) with signal amplification and PCR tests evaluated separately.¹ In addition, this review evaluated strategies to screen women who are underscreened or not screened, which was defined as women who were irregularly or never screened, or did not respond to reminder letters about cervical cancer screening (25 randomized controlled trials [RCTs]; total N not provided).

In the diagnostic accuracy studies, patients collected a vaginal sample themselves and then had a sample taken by a clinician. CIN 2+ or 3+ was confirmed by either colposcopy and biopsy performed on all patients or by a positive high-risk HPV test result. Studies were further divided into those using assays based on signal amplification or PCR.

Continue to: In signal amplification assays...

In signal amplification assays, the pooled sensitivity for CIN 2+ was lower in the group with the self-collected samples than in the clinician-collected sample group (77%; 95% confidence interval [CI], 69%-82% vs 93%; 95% CI, 89%-96%). The pooled specificity to exclude CIN 2+ was also lower in the group with the self-collected samples (84%; 95% CI, 77%-88% vs 86%; 95% CI, 81%-90%). In high-risk HPV assays based on PCR, there was no difference in sensitivity (96%) or specificity (79%) between the specimen groups.

This study offers robust evidence that high-risk HPV PCR-based assays using patient-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

With regard to the pooled relative sensitivity and specificity of signal amplification assays, those using self-swab samples were less sensitive and less specific for CIN 2+ (sensitivity ratio = 0.85; 95% CI, 0.80-0.89; specificity ratio = 0.96; 95% CI, 0.93-0.98) and CIN 3+ (sensitivity ratio = 0.86; 95% CI, 0.76-0.98; specificity ratio = 0.97; 95% CI, 0.95-0.99). Using PCR assays, there was no difference between groups in relative sensitivity for the diagnosis of CIN 2+ (sensitivity ratio = 0.99; 95% CI, 0.97-1.02) and CIN 3+ (sensitivity ratio = 0.99; 95% CI, 0.96-1.02). Relative specificity was slightly lower in the self-swab group for CIN 2+ (specificity ratio = 0.98; 95% CI, 0.97-0.99) and CIN 3+ (specificity ratio = 0.98; 95% CI, 0.97-0.99).

The second analysis to evaluate which outreach strategies are effective methods for screening underscreened/unscreened women found that delivering self-sample kits to patients was more effective than the control method, which was sending reminders to women to undergo conventional screening (95% vs 53%; mean difference [MD], 41%; 95% CI, 3%-78%). Similarly, mailing kits to patients compared favorably to the control method (25% vs 12%; MD, 13%; 95% CI, 10%-15%).

WHAT’S NEW

Self-collected specimens can beas reliable as clinician-collected ones

This is the first study to provide robust evidence that high-risk HPV PCR-based assays using patient self-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

CAVEATS

Balancing lower specificity with reaching underscreened populations

Patients with a positive HPV test result require additional testing. The success rates for this follow-up are not known and could be a barrier to accurate diagnoses because of accessibility and patient willingness to follow up with a pelvic exam. In addition, self-collection may be less specific than cytology and could increase colposcopy referrals that lead to negative findings and overtreatment.¹² However, the increased acceptance of this screening method could make it an effective strategy to reach underscreened or reluctant patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Availability of PCR-based HPV assays may be an issue

HPV PCR assays may not be available at all laboratories, but signal amplification HPV tests have been shown to be inferior to PCR assays. Physicians will have to confirm with their laboratories whether PCR-based HPV assays are available.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 40-year-old woman presents to your office to establish care. During your interview you realize that she has never been screened for cervical cancer. In fact, she has not had a pelvic exam because she is fearful of the procedure. She would like to know if alternatives exist for cervical cancer screening. What can you suggest?

Although deaths from cervical cancer decreased in the United States from 1975 to 2017, demographic and social disparities in the burden of the disease remain.^2,3 Data from 2016 reveal that cervical cancer incidence per 100,000 women is lowest among white (7.5), Asian-Pacific Islander (5.8), and American Indian/Alaska native (5.6) women, and highest among Hispanic (9.8) and black (8.7) women, which could be explained by lower screening rates in these populations.^4,5 The National Cancer Institute’s publication on reducing cancer health disparities states that the most effective way to reduce cervical cancer incidence and mortality is by increasing screening rates among women who have not been screened or who have not been screened regularly.⁶

The US Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) screening test in 2003.⁷ Evidence now suggests that high-risk HPV screening provides greater protection against cervical cancer than screening with cytology alone.⁸ The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) have changed their recommendations to include primary HPV testing as an alternative method to Pap smears for cervical cancer screening.⁹

An advantage of primary HPV screening is that it can be performed on a specimen collected by the patient, which could potentially increase rates of screening and help to decrease demographic and social disparities. A randomized trial of almost 2000 women ages 21 to 65 years that evaluated the acceptability of this method to patients revealed that more than half of women prefer the idea of a self-collected specimen to one that is collected by a clinician because it is more convenient and obviates the need for a pelvic exam.¹⁰

A meta-analysis of 36 studies and more than 150,000 women concluded that when self-collected samples were used with signal-based assays, the tests were not as sensitive or specific as when clinician-collected samples were used.¹¹ However, the meta-analysis also found that some polymerase chain reaction (PCR)-based HPV tests were similarly sensitive for both self- and clinician-collected samples.

STUDY SUMMARY

PCR vs signal amplification HPV tests with collection by patients vs clinicians

This meta-analysis compared the accuracy of high-risk HPV self-screening with clinician collection of samples (56 diagnostic accuracy trials; total N not provided) in identifying cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) with signal amplification and PCR tests evaluated separately.¹ In addition, this review evaluated strategies to screen women who are underscreened or not screened, which was defined as women who were irregularly or never screened, or did not respond to reminder letters about cervical cancer screening (25 randomized controlled trials [RCTs]; total N not provided).

In the diagnostic accuracy studies, patients collected a vaginal sample themselves and then had a sample taken by a clinician. CIN 2+ or 3+ was confirmed by either colposcopy and biopsy performed on all patients or by a positive high-risk HPV test result. Studies were further divided into those using assays based on signal amplification or PCR.

Continue to: In signal amplification assays...

In signal amplification assays, the pooled sensitivity for CIN 2+ was lower in the group with the self-collected samples than in the clinician-collected sample group (77%; 95% confidence interval [CI], 69%-82% vs 93%; 95% CI, 89%-96%). The pooled specificity to exclude CIN 2+ was also lower in the group with the self-collected samples (84%; 95% CI, 77%-88% vs 86%; 95% CI, 81%-90%). In high-risk HPV assays based on PCR, there was no difference in sensitivity (96%) or specificity (79%) between the specimen groups.

This study offers robust evidence that high-risk HPV PCR-based assays using patient-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

With regard to the pooled relative sensitivity and specificity of signal amplification assays, those using self-swab samples were less sensitive and less specific for CIN 2+ (sensitivity ratio = 0.85; 95% CI, 0.80-0.89; specificity ratio = 0.96; 95% CI, 0.93-0.98) and CIN 3+ (sensitivity ratio = 0.86; 95% CI, 0.76-0.98; specificity ratio = 0.97; 95% CI, 0.95-0.99). Using PCR assays, there was no difference between groups in relative sensitivity for the diagnosis of CIN 2+ (sensitivity ratio = 0.99; 95% CI, 0.97-1.02) and CIN 3+ (sensitivity ratio = 0.99; 95% CI, 0.96-1.02). Relative specificity was slightly lower in the self-swab group for CIN 2+ (specificity ratio = 0.98; 95% CI, 0.97-0.99) and CIN 3+ (specificity ratio = 0.98; 95% CI, 0.97-0.99).

The second analysis to evaluate which outreach strategies are effective methods for screening underscreened/unscreened women found that delivering self-sample kits to patients was more effective than the control method, which was sending reminders to women to undergo conventional screening (95% vs 53%; mean difference [MD], 41%; 95% CI, 3%-78%). Similarly, mailing kits to patients compared favorably to the control method (25% vs 12%; MD, 13%; 95% CI, 10%-15%).

WHAT’S NEW

Self-collected specimens can beas reliable as clinician-collected ones

This is the first study to provide robust evidence that high-risk HPV PCR-based assays using patient self-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

CAVEATS

Balancing lower specificity with reaching underscreened populations

Patients with a positive HPV test result require additional testing. The success rates for this follow-up are not known and could be a barrier to accurate diagnoses because of accessibility and patient willingness to follow up with a pelvic exam. In addition, self-collection may be less specific than cytology and could increase colposcopy referrals that lead to negative findings and overtreatment.¹² However, the increased acceptance of this screening method could make it an effective strategy to reach underscreened or reluctant patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Availability of PCR-based HPV assays may be an issue

HPV PCR assays may not be available at all laboratories, but signal amplification HPV tests have been shown to be inferior to PCR assays. Physicians will have to confirm with their laboratories whether PCR-based HPV assays are available.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

THE CASE

A 67-year-old woman with type 2 diabetes mellitus and hypertension presented to our family medicine office for evaluation of excessive flatulence, belching, and bloating that had worsened over the previous 6 months. The patient said the symptoms occurred throughout the day but were most noticeable after eating meals. She had a 5-year history of heartburn and chronic cough. We initially suspected gastroesophageal reflux disease (GERD). However, trials with several different proton pump inhibitors (PPIs) over a 3-year period did not provide any relief. Lifestyle modifications such as losing weight; remaining upright for at least 3 hours after eating; and eliminating gluten, dairy, soy, and alcohol from her diet did not alleviate her symptoms.

At the current presentation, the physical examination was normal, and an upper endoscopy was unremarkable except for some mild gastric irritation. A urea breath test was negative for Helicobacter pylori, and a chest radiograph to investigate the cause of the chronic cough was normal. The patient’s increased symptoms after eating indicated that a sensitivity to food antibodies might be at work. The absence of urticaria and anaphylaxis correlated with an IgG-mediated rather than an IgE-mediated reaction.

Due to the high cost of IgG testing, we recommended that the patient start a 6-week elimination diet that excluded the most common culprits for food allergies: dairy, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soy.¹ We also recommended that she eliminate alcohol (because of its role in exacerbating GERD); however, excluding these foods from her diet did not provide sufficient relief of her symptoms. We subsequently recommended a serum IgG food antibody test.

THE DIAGNOSIS

The results of the test were positive for IgG-mediated allergy to vegetables in the onion family, as indicated by a high (3+) antibody presence. The patient told us she consumed onions up to 3 times daily in her meals. We recommended that she eliminate onions from her diet. At a follow-up appointment 3 months later, the patient reported that the flatulence, belching, and bloating after eating had resolved and her heartburn had decreased. When we asked about her chronic cough, the patient mentioned she had not experienced it for a few months and had forgotten about it.

DISCUSSION

The most common food sensitivity test is the scratch test, which only measures IgE antibodies. However, past studies have suggested that IgE is not the only mediator in certain symptoms related to food allergy. It is thought that these symptoms may instead be IgG mediated.² Normally, IgG antibodies do not form in the digestive tract because the epithelium creates a barrier that is impermeable to antigens. However, antigens can bypass the epithelium and reach immune cells in states of inflammation where the epithelium is damaged. This contact with immune cells provides an opportunity for development of IgG antibodies.³ Successive interactions with these antigens leads to defensive and inflammatory processes that manifest as food allergies.

Rather than the typical IgE-mediated presentations (eg, urticaria, anaphylaxis), patients with IgG-mediated allergies experience more subtle symptoms, such as bloating, heartburn, and cough.

Rather than the typical IgE-mediated presentations (eg, urticaria, anaphylaxis), patients with IgG-mediated allergies experience more subtle symptoms, such as nausea, abdominal pain, diarrhea, flatulence, cramping, bloating, heartburn, cough, bronchoconstriction, eczema, stiff joints, headache, and/or increased risk of infection.⁴ One study showed that eliminating IgG-sensitive foods (eg, dairy, eggs) improved symptoms in migraine patients.⁵ Likewise, a separate study showed that patients with irritable bowel syndrome experienced improved symptoms after eliminating foods for which they had high IgG sensitivity.⁶

Casting a wider net. Whereas scratch testing only looks at IgE-mediated allergies, serum IgG food antibody testing looks for both IgE- and IgG-mediated reactions. IgE-mediated food allergies are monitored via the scratch test as a visual expression of a histamine reaction on the skin. However, serum IgG food antibody testing identifies culprit foods via enzyme-linked immunosorbent assay.

Continue to: Furthermore, the serum antibody test...

Furthermore, the serum antibody test also identifies allergenic foods whose symptoms have a delayed onset of 4 to 72 hours.⁷ Without this test, those symptoms may be wrongfully attributed to other conditions, and prescribed treatments will not treat the root cause of the reaction.⁸ The information provided in the serum antibody test allows the patient to develop a tailored elimination diet and eliminate causative food(s) faster. Without this test, we may not have identified onions as the allergenic food in our patient.

THE TAKEAWAY

Recent guidelines emphasize that IgG testing plays no role in the diagnosis of food allergies or intolerance.¹ This may indeed be true for the general population, but other studies have shown IgG testing to be of value for specific diagnoses such as migraines or irritable bowel syndrome.^5,6 Given our patient’s unique presentation and lack of response to traditional treatments, IgG testing was warranted. This case demonstrates the importance of IgG food antibody testing as part of a second-tier diagnostic workup when a patient’s gastrointestinal symptoms are not alleviated by traditional interventions.

CORRESPONDENCE
Elizabeth A. Khan, MD, Personalized Longevity Medical Center, 1146 South Cedar Crest Boulevard, Allentown, PA 18103; info@plmc.life.

THE CASE

A 67-year-old woman with type 2 diabetes mellitus and hypertension presented to our family medicine office for evaluation of excessive flatulence, belching, and bloating that had worsened over the previous 6 months. The patient said the symptoms occurred throughout the day but were most noticeable after eating meals. She had a 5-year history of heartburn and chronic cough. We initially suspected gastroesophageal reflux disease (GERD). However, trials with several different proton pump inhibitors (PPIs) over a 3-year period did not provide any relief. Lifestyle modifications such as losing weight; remaining upright for at least 3 hours after eating; and eliminating gluten, dairy, soy, and alcohol from her diet did not alleviate her symptoms.

At the current presentation, the physical examination was normal, and an upper endoscopy was unremarkable except for some mild gastric irritation. A urea breath test was negative for Helicobacter pylori, and a chest radiograph to investigate the cause of the chronic cough was normal. The patient’s increased symptoms after eating indicated that a sensitivity to food antibodies might be at work. The absence of urticaria and anaphylaxis correlated with an IgG-mediated rather than an IgE-mediated reaction.

Due to the high cost of IgG testing, we recommended that the patient start a 6-week elimination diet that excluded the most common culprits for food allergies: dairy, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soy.¹ We also recommended that she eliminate alcohol (because of its role in exacerbating GERD); however, excluding these foods from her diet did not provide sufficient relief of her symptoms. We subsequently recommended a serum IgG food antibody test.

THE DIAGNOSIS

The results of the test were positive for IgG-mediated allergy to vegetables in the onion family, as indicated by a high (3+) antibody presence. The patient told us she consumed onions up to 3 times daily in her meals. We recommended that she eliminate onions from her diet. At a follow-up appointment 3 months later, the patient reported that the flatulence, belching, and bloating after eating had resolved and her heartburn had decreased. When we asked about her chronic cough, the patient mentioned she had not experienced it for a few months and had forgotten about it.

DISCUSSION

The most common food sensitivity test is the scratch test, which only measures IgE antibodies. However, past studies have suggested that IgE is not the only mediator in certain symptoms related to food allergy. It is thought that these symptoms may instead be IgG mediated.² Normally, IgG antibodies do not form in the digestive tract because the epithelium creates a barrier that is impermeable to antigens. However, antigens can bypass the epithelium and reach immune cells in states of inflammation where the epithelium is damaged. This contact with immune cells provides an opportunity for development of IgG antibodies.³ Successive interactions with these antigens leads to defensive and inflammatory processes that manifest as food allergies.

Rather than the typical IgE-mediated presentations (eg, urticaria, anaphylaxis), patients with IgG-mediated allergies experience more subtle symptoms, such as bloating, heartburn, and cough.

Rather than the typical IgE-mediated presentations (eg, urticaria, anaphylaxis), patients with IgG-mediated allergies experience more subtle symptoms, such as nausea, abdominal pain, diarrhea, flatulence, cramping, bloating, heartburn, cough, bronchoconstriction, eczema, stiff joints, headache, and/or increased risk of infection.⁴ One study showed that eliminating IgG-sensitive foods (eg, dairy, eggs) improved symptoms in migraine patients.⁵ Likewise, a separate study showed that patients with irritable bowel syndrome experienced improved symptoms after eliminating foods for which they had high IgG sensitivity.⁶

Casting a wider net. Whereas scratch testing only looks at IgE-mediated allergies, serum IgG food antibody testing looks for both IgE- and IgG-mediated reactions. IgE-mediated food allergies are monitored via the scratch test as a visual expression of a histamine reaction on the skin. However, serum IgG food antibody testing identifies culprit foods via enzyme-linked immunosorbent assay.

Continue to: Furthermore, the serum antibody test...

Furthermore, the serum antibody test also identifies allergenic foods whose symptoms have a delayed onset of 4 to 72 hours.⁷ Without this test, those symptoms may be wrongfully attributed to other conditions, and prescribed treatments will not treat the root cause of the reaction.⁸ The information provided in the serum antibody test allows the patient to develop a tailored elimination diet and eliminate causative food(s) faster. Without this test, we may not have identified onions as the allergenic food in our patient.

THE TAKEAWAY

Recent guidelines emphasize that IgG testing plays no role in the diagnosis of food allergies or intolerance.¹ This may indeed be true for the general population, but other studies have shown IgG testing to be of value for specific diagnoses such as migraines or irritable bowel syndrome.^5,6 Given our patient’s unique presentation and lack of response to traditional treatments, IgG testing was warranted. This case demonstrates the importance of IgG food antibody testing as part of a second-tier diagnostic workup when a patient’s gastrointestinal symptoms are not alleviated by traditional interventions.

CORRESPONDENCE
Elizabeth A. Khan, MD, Personalized Longevity Medical Center, 1146 South Cedar Crest Boulevard, Allentown, PA 18103; info@plmc.life.

THE CASE

A 67-year-old woman with type 2 diabetes mellitus and hypertension presented to our family medicine office for evaluation of excessive flatulence, belching, and bloating that had worsened over the previous 6 months. The patient said the symptoms occurred throughout the day but were most noticeable after eating meals. She had a 5-year history of heartburn and chronic cough. We initially suspected gastroesophageal reflux disease (GERD). However, trials with several different proton pump inhibitors (PPIs) over a 3-year period did not provide any relief. Lifestyle modifications such as losing weight; remaining upright for at least 3 hours after eating; and eliminating gluten, dairy, soy, and alcohol from her diet did not alleviate her symptoms.

At the current presentation, the physical examination was normal, and an upper endoscopy was unremarkable except for some mild gastric irritation. A urea breath test was negative for Helicobacter pylori, and a chest radiograph to investigate the cause of the chronic cough was normal. The patient’s increased symptoms after eating indicated that a sensitivity to food antibodies might be at work. The absence of urticaria and anaphylaxis correlated with an IgG-mediated rather than an IgE-mediated reaction.

Due to the high cost of IgG testing, we recommended that the patient start a 6-week elimination diet that excluded the most common culprits for food allergies: dairy, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat, and soy.¹ We also recommended that she eliminate alcohol (because of its role in exacerbating GERD); however, excluding these foods from her diet did not provide sufficient relief of her symptoms. We subsequently recommended a serum IgG food antibody test.

THE DIAGNOSIS

The results of the test were positive for IgG-mediated allergy to vegetables in the onion family, as indicated by a high (3+) antibody presence. The patient told us she consumed onions up to 3 times daily in her meals. We recommended that she eliminate onions from her diet. At a follow-up appointment 3 months later, the patient reported that the flatulence, belching, and bloating after eating had resolved and her heartburn had decreased. When we asked about her chronic cough, the patient mentioned she had not experienced it for a few months and had forgotten about it.

DISCUSSION

The most common food sensitivity test is the scratch test, which only measures IgE antibodies. However, past studies have suggested that IgE is not the only mediator in certain symptoms related to food allergy. It is thought that these symptoms may instead be IgG mediated.² Normally, IgG antibodies do not form in the digestive tract because the epithelium creates a barrier that is impermeable to antigens. However, antigens can bypass the epithelium and reach immune cells in states of inflammation where the epithelium is damaged. This contact with immune cells provides an opportunity for development of IgG antibodies.³ Successive interactions with these antigens leads to defensive and inflammatory processes that manifest as food allergies.

Rather than the typical IgE-mediated presentations (eg, urticaria, anaphylaxis), patients with IgG-mediated allergies experience more subtle symptoms, such as bloating, heartburn, and cough.

Rather than the typical IgE-mediated presentations (eg, urticaria, anaphylaxis), patients with IgG-mediated allergies experience more subtle symptoms, such as nausea, abdominal pain, diarrhea, flatulence, cramping, bloating, heartburn, cough, bronchoconstriction, eczema, stiff joints, headache, and/or increased risk of infection.⁴ One study showed that eliminating IgG-sensitive foods (eg, dairy, eggs) improved symptoms in migraine patients.⁵ Likewise, a separate study showed that patients with irritable bowel syndrome experienced improved symptoms after eliminating foods for which they had high IgG sensitivity.⁶

Casting a wider net. Whereas scratch testing only looks at IgE-mediated allergies, serum IgG food antibody testing looks for both IgE- and IgG-mediated reactions. IgE-mediated food allergies are monitored via the scratch test as a visual expression of a histamine reaction on the skin. However, serum IgG food antibody testing identifies culprit foods via enzyme-linked immunosorbent assay.

Continue to: Furthermore, the serum antibody test...

Furthermore, the serum antibody test also identifies allergenic foods whose symptoms have a delayed onset of 4 to 72 hours.⁷ Without this test, those symptoms may be wrongfully attributed to other conditions, and prescribed treatments will not treat the root cause of the reaction.⁸ The information provided in the serum antibody test allows the patient to develop a tailored elimination diet and eliminate causative food(s) faster. Without this test, we may not have identified onions as the allergenic food in our patient.

THE TAKEAWAY

Recent guidelines emphasize that IgG testing plays no role in the diagnosis of food allergies or intolerance.¹ This may indeed be true for the general population, but other studies have shown IgG testing to be of value for specific diagnoses such as migraines or irritable bowel syndrome.^5,6 Given our patient’s unique presentation and lack of response to traditional treatments, IgG testing was warranted. This case demonstrates the importance of IgG food antibody testing as part of a second-tier diagnostic workup when a patient’s gastrointestinal symptoms are not alleviated by traditional interventions.

CORRESPONDENCE
Elizabeth A. Khan, MD, Personalized Longevity Medical Center, 1146 South Cedar Crest Boulevard, Allentown, PA 18103; info@plmc.life.

Every person who received Moderna’s COVID-19 vaccine, mRNA-1273, developed an immune response to the virus that causes it, the company says in a news release.

Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.

The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.

A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.

The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.

The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.

In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.

Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.

The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older

Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.

This article first appeared on WebMD.com.

Every person who received Moderna’s COVID-19 vaccine, mRNA-1273, developed an immune response to the virus that causes it, the company says in a news release.

Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.

The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.

A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.

The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.

The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.

In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.

Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.

The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older

Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.

This article first appeared on WebMD.com.

Every person who received Moderna’s COVID-19 vaccine, mRNA-1273, developed an immune response to the virus that causes it, the company says in a news release.

Researchers also reported some side effects in the 45 people in the phase I study, but no significant safety issues, the news release says.

The vaccine is among hundreds being tested worldwide in an effort to halt the pandemic that has killed nearly 600,000 worldwide.

A researcher testing the vaccine called the results encouraging but cautioned more study is needed. “Importantly, the vaccine resulted in a robust immune response,” Evan Anderson, MD, principal investigator for the trial at Emory University, says in a news release. Emory and Kaiser Permanente Washington Health Research Institute were the two sites for the study.

The company is already testing the vaccine in a larger group of people, known as a phase II trial. It plans to begin phase III trials in late July. Phase III trials involve testing the vaccine on an even larger group and are the final step before FDA approval.

The study results are published in The New England Journal of Medicine. The study was led by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Moderna’s vaccine uses messenger RNA, also called mRNA. It carries the instruction for making the spike protein, a key protein on the surface of the virus that allows it to enter cells when a person is infected. After it’s injected, it goes to the immune cells and instructs them to make copies of the spike protein, acting as if the cells have been infected with the actual coronavirus. This allows other immune cells to develop immunity.

In the study, participants were divided into three groups of 15 people each. All groups received two vaccinations 28 days apart. Each group received a different strength of the vaccine – either 25, 100, or 250 micrograms.

Every person in the study developed antibodies that can block the infection. Most commonly reported side effects after the second vaccination in the 100-microgram group were fatigue, chills, headache, and muscle pains, ranging from mild to moderately severe.

The phase II study has 300 heathy adults ages 18-55, along with another 300 ages 55 and older

Moderna says it hopes to include about 30,000 participants at the 100-microgram dose level in the U.S. for the phase III trial. The estimated start date is July 27.

This article first appeared on WebMD.com.

A recent report by the Centers for Disease Control and Prevention (CDC) documents the trends in oral and pharyngeal cancers (OPC) in the United States over a 10-year period, 2007-2016.¹ The rate of OPC began to increase in 1999 and has been increasing ever since. The age-adjusted rate in 2007 was 10.89/100,000 compared with 11.7/100,000 in 2016 (TABLE 1¹). This is an annual relative increase of about 6% per year. In absolute numbers, there were 35,076 cases in 2007 and 44,419 in 2016.¹ The trends in ­incidence of OPC vary by anatomical site, with some increasing and others declining.

There are 3 known causal factors related to OPC: tobacco use, alcohol use, and human papillomavirus (HPV) infection. The CDC estimates that, overall, 70% of OPCs are caused by HPV.² However, while cancers at some oropharyngeal sites are likely related to HPV infection, cancers at other sites are not. The rising overall incidence of OPC is being driven by increases in HPV-related cancers at an average rate of 2.1% per year, while the rates at non-HPV-associated sites have been declining by 0.4% per year.¹ It is also important to appreciate that HPV causes cancer at other anatomical sites (TABLE 2²) and is responsible for an estimated 35,000 cancers per year.²

There is some evidence that if clinicians actively engage with parents about their vaccination concerns and address them head on, same-day vaccination rates can improve.

Other trends of note in all OPCs combined are increasing rates among non-­Hispanic whites and Asian-Pacific Islanders; decreasing rates among Hispanics and African Americans; increasing rates among males with no real change in rates among females; increasing rates in those 50 to 79 years of age; decreasing rates among those 40 to 49 years of age; and unchanged rates in other age groups.¹

The role of the family physician

Preventing OPC and all HPV-related cancers begins by encouraging patients to reduce alcohol and tobacco use and by emphasizing the importance of HPV vaccination. Educate teens and parents/guardians about HPV vaccine and its safety. Screen for tobacco and alcohol use, and offer brief clinical interventions as needed to decrease usage.

Recommendations by the US Preventive Services Task Force regarding screening for, and reducing use of, tobacco and alcohol, as well as screening for cervical cancer, are listed in TABLE 3.^3-6 Remember that cervical cancer screening is both a primary and secondary intervention: It can reduce mortality by preventing cervical cancer (via treatment of precancerous lesions) and by detecting cervical cancer early at more treatable stages.

HPV vaccination essentials. CDC recommendations for the use of HPV vaccine and the vaccine dosing schedule appear in TABLE 4.⁷ While it is true that the best evidence for HPV vaccine’s prevention of cancer comes from the study of cervical and anal cancers, it is reasonable to expect that it will also be proven over time to prevent other HPV-caused cancers as the rate of HPV infections declines.

HPV vaccine is underused. In a 2018 survey, only 68.1% of adolescents had received 1 or more doses of HPV vaccine, and only 51.1% were up to date.⁸ In contrast, 86.6% had received 1 or more doses of quadrivalent meningococcal vaccine; 88.9% had received 1 or more doses of tetanus, diphtheria & acellular pertussis vaccine; 91.9% were up to date with 2 or more doses of measles, mumps & rubella vaccine; and 92.1% were up to date with hepatitis B vaccine, with 3 or more doses.⁸

Continue to: Address parental concerns, including these 5 false beliefs

Address parental concerns, including these 5 false beliefs

One study found 5 major false beliefs parents hold about HPV vaccine⁹:

1. Vaccination is not effective at preventing cancer.
2. Pap smears are sufficient to prevent cervical cancer.
3. HPV vaccination is not safe.
4. HPV vaccination is not needed since most infections are naturally cleared by the immune system.
5. Eleven to 12 years of age is too young to vaccinate.

There is some evidence that if clinicians actively engage with parents about these concerns and address them head on, same-day vaccination rates can improve.¹⁰

We can expect to see HPV-associated OPC decline in the coming years due to the delayed effects on cancer incidence by the HPV vaccine. These anticipated declines will be more dramatic if we can increase the uptake of the HPV vaccine.

A recent report by the Centers for Disease Control and Prevention (CDC) documents the trends in oral and pharyngeal cancers (OPC) in the United States over a 10-year period, 2007-2016.¹ The rate of OPC began to increase in 1999 and has been increasing ever since. The age-adjusted rate in 2007 was 10.89/100,000 compared with 11.7/100,000 in 2016 (TABLE 1¹). This is an annual relative increase of about 6% per year. In absolute numbers, there were 35,076 cases in 2007 and 44,419 in 2016.¹ The trends in ­incidence of OPC vary by anatomical site, with some increasing and others declining.

There are 3 known causal factors related to OPC: tobacco use, alcohol use, and human papillomavirus (HPV) infection. The CDC estimates that, overall, 70% of OPCs are caused by HPV.² However, while cancers at some oropharyngeal sites are likely related to HPV infection, cancers at other sites are not. The rising overall incidence of OPC is being driven by increases in HPV-related cancers at an average rate of 2.1% per year, while the rates at non-HPV-associated sites have been declining by 0.4% per year.¹ It is also important to appreciate that HPV causes cancer at other anatomical sites (TABLE 2²) and is responsible for an estimated 35,000 cancers per year.²

There is some evidence that if clinicians actively engage with parents about their vaccination concerns and address them head on, same-day vaccination rates can improve.

Other trends of note in all OPCs combined are increasing rates among non-­Hispanic whites and Asian-Pacific Islanders; decreasing rates among Hispanics and African Americans; increasing rates among males with no real change in rates among females; increasing rates in those 50 to 79 years of age; decreasing rates among those 40 to 49 years of age; and unchanged rates in other age groups.¹

The role of the family physician

Preventing OPC and all HPV-related cancers begins by encouraging patients to reduce alcohol and tobacco use and by emphasizing the importance of HPV vaccination. Educate teens and parents/guardians about HPV vaccine and its safety. Screen for tobacco and alcohol use, and offer brief clinical interventions as needed to decrease usage.

Recommendations by the US Preventive Services Task Force regarding screening for, and reducing use of, tobacco and alcohol, as well as screening for cervical cancer, are listed in TABLE 3.^3-6 Remember that cervical cancer screening is both a primary and secondary intervention: It can reduce mortality by preventing cervical cancer (via treatment of precancerous lesions) and by detecting cervical cancer early at more treatable stages.

HPV vaccination essentials. CDC recommendations for the use of HPV vaccine and the vaccine dosing schedule appear in TABLE 4.⁷ While it is true that the best evidence for HPV vaccine’s prevention of cancer comes from the study of cervical and anal cancers, it is reasonable to expect that it will also be proven over time to prevent other HPV-caused cancers as the rate of HPV infections declines.

HPV vaccine is underused. In a 2018 survey, only 68.1% of adolescents had received 1 or more doses of HPV vaccine, and only 51.1% were up to date.⁸ In contrast, 86.6% had received 1 or more doses of quadrivalent meningococcal vaccine; 88.9% had received 1 or more doses of tetanus, diphtheria & acellular pertussis vaccine; 91.9% were up to date with 2 or more doses of measles, mumps & rubella vaccine; and 92.1% were up to date with hepatitis B vaccine, with 3 or more doses.⁸

Continue to: Address parental concerns, including these 5 false beliefs

Address parental concerns, including these 5 false beliefs

One study found 5 major false beliefs parents hold about HPV vaccine⁹:

1. Vaccination is not effective at preventing cancer.
2. Pap smears are sufficient to prevent cervical cancer.
3. HPV vaccination is not safe.
4. HPV vaccination is not needed since most infections are naturally cleared by the immune system.
5. Eleven to 12 years of age is too young to vaccinate.

There is some evidence that if clinicians actively engage with parents about these concerns and address them head on, same-day vaccination rates can improve.¹⁰

We can expect to see HPV-associated OPC decline in the coming years due to the delayed effects on cancer incidence by the HPV vaccine. These anticipated declines will be more dramatic if we can increase the uptake of the HPV vaccine.

A recent report by the Centers for Disease Control and Prevention (CDC) documents the trends in oral and pharyngeal cancers (OPC) in the United States over a 10-year period, 2007-2016.¹ The rate of OPC began to increase in 1999 and has been increasing ever since. The age-adjusted rate in 2007 was 10.89/100,000 compared with 11.7/100,000 in 2016 (TABLE 1¹). This is an annual relative increase of about 6% per year. In absolute numbers, there were 35,076 cases in 2007 and 44,419 in 2016.¹ The trends in ­incidence of OPC vary by anatomical site, with some increasing and others declining.

There are 3 known causal factors related to OPC: tobacco use, alcohol use, and human papillomavirus (HPV) infection. The CDC estimates that, overall, 70% of OPCs are caused by HPV.² However, while cancers at some oropharyngeal sites are likely related to HPV infection, cancers at other sites are not. The rising overall incidence of OPC is being driven by increases in HPV-related cancers at an average rate of 2.1% per year, while the rates at non-HPV-associated sites have been declining by 0.4% per year.¹ It is also important to appreciate that HPV causes cancer at other anatomical sites (TABLE 2²) and is responsible for an estimated 35,000 cancers per year.²

There is some evidence that if clinicians actively engage with parents about their vaccination concerns and address them head on, same-day vaccination rates can improve.

Other trends of note in all OPCs combined are increasing rates among non-­Hispanic whites and Asian-Pacific Islanders; decreasing rates among Hispanics and African Americans; increasing rates among males with no real change in rates among females; increasing rates in those 50 to 79 years of age; decreasing rates among those 40 to 49 years of age; and unchanged rates in other age groups.¹

The role of the family physician

Preventing OPC and all HPV-related cancers begins by encouraging patients to reduce alcohol and tobacco use and by emphasizing the importance of HPV vaccination. Educate teens and parents/guardians about HPV vaccine and its safety. Screen for tobacco and alcohol use, and offer brief clinical interventions as needed to decrease usage.

Recommendations by the US Preventive Services Task Force regarding screening for, and reducing use of, tobacco and alcohol, as well as screening for cervical cancer, are listed in TABLE 3.^3-6 Remember that cervical cancer screening is both a primary and secondary intervention: It can reduce mortality by preventing cervical cancer (via treatment of precancerous lesions) and by detecting cervical cancer early at more treatable stages.

HPV vaccination essentials. CDC recommendations for the use of HPV vaccine and the vaccine dosing schedule appear in TABLE 4.⁷ While it is true that the best evidence for HPV vaccine’s prevention of cancer comes from the study of cervical and anal cancers, it is reasonable to expect that it will also be proven over time to prevent other HPV-caused cancers as the rate of HPV infections declines.

HPV vaccine is underused. In a 2018 survey, only 68.1% of adolescents had received 1 or more doses of HPV vaccine, and only 51.1% were up to date.⁸ In contrast, 86.6% had received 1 or more doses of quadrivalent meningococcal vaccine; 88.9% had received 1 or more doses of tetanus, diphtheria & acellular pertussis vaccine; 91.9% were up to date with 2 or more doses of measles, mumps & rubella vaccine; and 92.1% were up to date with hepatitis B vaccine, with 3 or more doses.⁸

Continue to: Address parental concerns, including these 5 false beliefs

Address parental concerns, including these 5 false beliefs

One study found 5 major false beliefs parents hold about HPV vaccine⁹:

1. Vaccination is not effective at preventing cancer.
2. Pap smears are sufficient to prevent cervical cancer.
3. HPV vaccination is not safe.
4. HPV vaccination is not needed since most infections are naturally cleared by the immune system.
5. Eleven to 12 years of age is too young to vaccinate.

There is some evidence that if clinicians actively engage with parents about these concerns and address them head on, same-day vaccination rates can improve.¹⁰

We can expect to see HPV-associated OPC decline in the coming years due to the delayed effects on cancer incidence by the HPV vaccine. These anticipated declines will be more dramatic if we can increase the uptake of the HPV vaccine.

People with a body mass index of 30 kg/m² or above are at significantly increased risk for severe COVID-19, while a BMI of 35 and higher dramatically increases the risk for death, new research suggests.

The data, from nearly 500 patients hospitalized with COVID-19 in March and April 2020, were published in the European Journal of Endocrinology by Matteo Rottoli, MD, of the Alma Mater Studiorum, University of Bologna (Italy), and colleagues.

The data support the recent change by the Centers for Disease Control and Prevention to lower the cutoff for categorizing a person at increased risk from COVID-19 from a BMI of 40 down to 30. However, in the United Kingdom, the National Health Service still lists only a BMI of 40 or above as placing a person at “moderate risk (clinically vulnerable).”

“This finding calls for prevention and treatment strategies to reduce the risk of infection and hospitalization in patients with relevant degrees of obesity, supporting a revision of the BMI cutoff of 40 kg/m², which was proposed as an independent risk factor for an adverse outcome of COVID-19 in the ... guidelines for social distancing in the United Kingdom: It may be appropriate to include patients with BMI >30 among those at higher risk for COVID-19 severe progression,” the authors wrote.

The study included 482 adults admitted with confirmed COVID-19 to a single Italian hospital between March 1 and April 20, 2020. Of those, 41.9% had a BMI of less than 25 (normal weight), 36.5% had a BMI of 25-29.9 (overweight), and 21.6% had BMI of at least 30 (obese). Of the obese group, 20 (4.1%) had BMIs of at least 35, while 18 patients (3.7%) had BMIs of less than 20 (underweight).

Among those with obesity, 51.9% experienced respiratory failure, 36.4% were admitted to the ICU, 25% required mechanical ventilation, and 29.8% died within 30 days of symptom onset.

Patients with BMIs of at least 30 had significantly increased risks for respiratory failure (odds ratio, 2.48; P = .001), ICU admission (OR, 5.28; P < .001), and death (2.35, P = .017), compared with those with lower BMIs. Within the group classified as obese, the risks of respiratory failure and ICU admission were higher, with BMIs of 30-34.9 (OR, 2.32; P = .004 and OR, 4.96; P < .001, respectively) and for BMIs of at least 35 (OR, 3.24; P = .019 and OR, 6.58; P < .001, respectively).

The risk of death was significantly higher among patients with a BMI of at least 35 (OR, 12.1; P < .001).

Every 1-unit increase in BMI was significantly associated with all outcomes, but there was no significant difference in any outcome between the 25-29.9 BMI category and normal weight. In all models, the BMI cutoff for increased risk was 30.

The authors reported no disclosures.

SOURCE: Rottoli M et al. Eur J Endocrinol. 2020 Jul 1. doi: 10.1530/EJE-20-054.

People with a body mass index of 30 kg/m² or above are at significantly increased risk for severe COVID-19, while a BMI of 35 and higher dramatically increases the risk for death, new research suggests.

The data, from nearly 500 patients hospitalized with COVID-19 in March and April 2020, were published in the European Journal of Endocrinology by Matteo Rottoli, MD, of the Alma Mater Studiorum, University of Bologna (Italy), and colleagues.

The data support the recent change by the Centers for Disease Control and Prevention to lower the cutoff for categorizing a person at increased risk from COVID-19 from a BMI of 40 down to 30. However, in the United Kingdom, the National Health Service still lists only a BMI of 40 or above as placing a person at “moderate risk (clinically vulnerable).”

“This finding calls for prevention and treatment strategies to reduce the risk of infection and hospitalization in patients with relevant degrees of obesity, supporting a revision of the BMI cutoff of 40 kg/m², which was proposed as an independent risk factor for an adverse outcome of COVID-19 in the ... guidelines for social distancing in the United Kingdom: It may be appropriate to include patients with BMI >30 among those at higher risk for COVID-19 severe progression,” the authors wrote.

The study included 482 adults admitted with confirmed COVID-19 to a single Italian hospital between March 1 and April 20, 2020. Of those, 41.9% had a BMI of less than 25 (normal weight), 36.5% had a BMI of 25-29.9 (overweight), and 21.6% had BMI of at least 30 (obese). Of the obese group, 20 (4.1%) had BMIs of at least 35, while 18 patients (3.7%) had BMIs of less than 20 (underweight).

Among those with obesity, 51.9% experienced respiratory failure, 36.4% were admitted to the ICU, 25% required mechanical ventilation, and 29.8% died within 30 days of symptom onset.

Patients with BMIs of at least 30 had significantly increased risks for respiratory failure (odds ratio, 2.48; P = .001), ICU admission (OR, 5.28; P < .001), and death (2.35, P = .017), compared with those with lower BMIs. Within the group classified as obese, the risks of respiratory failure and ICU admission were higher, with BMIs of 30-34.9 (OR, 2.32; P = .004 and OR, 4.96; P < .001, respectively) and for BMIs of at least 35 (OR, 3.24; P = .019 and OR, 6.58; P < .001, respectively).

The risk of death was significantly higher among patients with a BMI of at least 35 (OR, 12.1; P < .001).

Every 1-unit increase in BMI was significantly associated with all outcomes, but there was no significant difference in any outcome between the 25-29.9 BMI category and normal weight. In all models, the BMI cutoff for increased risk was 30.

The authors reported no disclosures.

SOURCE: Rottoli M et al. Eur J Endocrinol. 2020 Jul 1. doi: 10.1530/EJE-20-054.

People with a body mass index of 30 kg/m² or above are at significantly increased risk for severe COVID-19, while a BMI of 35 and higher dramatically increases the risk for death, new research suggests.

The data, from nearly 500 patients hospitalized with COVID-19 in March and April 2020, were published in the European Journal of Endocrinology by Matteo Rottoli, MD, of the Alma Mater Studiorum, University of Bologna (Italy), and colleagues.

The data support the recent change by the Centers for Disease Control and Prevention to lower the cutoff for categorizing a person at increased risk from COVID-19 from a BMI of 40 down to 30. However, in the United Kingdom, the National Health Service still lists only a BMI of 40 or above as placing a person at “moderate risk (clinically vulnerable).”

“This finding calls for prevention and treatment strategies to reduce the risk of infection and hospitalization in patients with relevant degrees of obesity, supporting a revision of the BMI cutoff of 40 kg/m², which was proposed as an independent risk factor for an adverse outcome of COVID-19 in the ... guidelines for social distancing in the United Kingdom: It may be appropriate to include patients with BMI >30 among those at higher risk for COVID-19 severe progression,” the authors wrote.

The study included 482 adults admitted with confirmed COVID-19 to a single Italian hospital between March 1 and April 20, 2020. Of those, 41.9% had a BMI of less than 25 (normal weight), 36.5% had a BMI of 25-29.9 (overweight), and 21.6% had BMI of at least 30 (obese). Of the obese group, 20 (4.1%) had BMIs of at least 35, while 18 patients (3.7%) had BMIs of less than 20 (underweight).

Among those with obesity, 51.9% experienced respiratory failure, 36.4% were admitted to the ICU, 25% required mechanical ventilation, and 29.8% died within 30 days of symptom onset.

Patients with BMIs of at least 30 had significantly increased risks for respiratory failure (odds ratio, 2.48; P = .001), ICU admission (OR, 5.28; P < .001), and death (2.35, P = .017), compared with those with lower BMIs. Within the group classified as obese, the risks of respiratory failure and ICU admission were higher, with BMIs of 30-34.9 (OR, 2.32; P = .004 and OR, 4.96; P < .001, respectively) and for BMIs of at least 35 (OR, 3.24; P = .019 and OR, 6.58; P < .001, respectively).

The risk of death was significantly higher among patients with a BMI of at least 35 (OR, 12.1; P < .001).

Every 1-unit increase in BMI was significantly associated with all outcomes, but there was no significant difference in any outcome between the 25-29.9 BMI category and normal weight. In all models, the BMI cutoff for increased risk was 30.

The authors reported no disclosures.

SOURCE: Rottoli M et al. Eur J Endocrinol. 2020 Jul 1. doi: 10.1530/EJE-20-054.

We live in historic times. A worldwide pandemic is surging in the United States, with millions infected and the world’s highest death rate. Many of our hospitals are overwhelmed. Schools have been closed for months. Businesses are struggling, and unemployment is at record levels. The murder of George Floyd unleashed an outpouring of grief and rage over police brutality and structural racism.

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The value of knowing about these risk factors would seem self-evident; it would inform a patient’s health care from screening for cancer or heart disease, referral for mild depressive symptoms, and counseling about alcohol consumption. But this research did not lead to the establishment of routine screening for childhood adversity in primary care practices. There are multiple reasons for this, including growing pressure on physician time and discomfort with starting conversations about potentially traumatic material. But perhaps the greatest obstacle has been uncertainty about what to offer patients who screened in. What is the treatment for a high ACE score?

Even without treatments, we have learned much about childhood adversity since Dr. Anda and Dr. Felitti published their landmark study. Other more chronic adverse childhood experiences also contribute to adult health risk, such as poverty, homelessness, discrimination, community violence, parental chronic illness, or disability or placement in foster care. Having a high ACE score does not only affect health in adulthood. Children with an ACE score of 4 are 2 times as likely to have asthma^2,3 and allergies³, 2 times as likely to be obese⁴, 3 times as likely to have headaches³ and dental problems^5,6, 4 times as likely to have depression^7,8, 5 times as likely to have ADHD^8,9, 7 times as likely to have high rates of school absenteeism³ and aggression¹⁰, and over 30 times as likely to have learning or behavioral problems at school⁴. There is a growing body of knowledge about how chronic, severe stress in childhood affects can lead to pathological alterations in neuroendocrine and immune function. But this has not led to any concrete treatments that may be preventive or reparative.

Movement toward expanding screening nonetheless has accelerated. In California, Nadine Burke-Harris, MD, a pediatrician who studied ACEs and children’s health was named the state’s first Surgeon General in 2019 and spearheaded an effort to make screening for ACEs easier. Starting in 2020, MediCal will pay for annual screenings, and the state is offering training and resources on how to screen and what to do with the information to help patients and families.

The coronavirus pandemic has only highlighted the risks of childhood adversity. The burden of infection and mortality has been borne disproportionately by people of color and those with multiple chronic medical conditions (obesity, cardiovascular disease, diabetes, etc.). While viruses do not discriminate, they are more likely to infect those with higher risk of exposure and to kill those who are physiologically vulnerable.

And the pandemic increases the risk for adversity for today’s children and families. When children cannot attend school, financially vulnerable parents may have to choose between supervising them or feeding them. Families who suddenly are all in a small apartment together without school or other outside supports may be at higher risk for domestic violence and child abuse. Unemployment and financial uncertainty will increase the rates of substance abuse and depression amongst parents. And the serious illness or death of a parent will be a more common event for children in the year ahead. One of these risk factors may increase the likelihood of others.

Beyond the obvious need for substantial policy changes focused on housing, education, and health care, there are immediate and concrete strategies that can build resilience in children and their families. And resilience can build on itself, as children face subsequent challenges with the support of caring connected adults.

The critical first step is asking. Then listen calmly and supportively, normalizing for parents and children how common these experiences are. Explain how they affect health and well-being. Explain that adversity and its consequences are not their fault. Then educate them about what is in their control: the skills they can practice to buffer against the consequences of adversity and build resilience. They sound simple, but still require effort and work. And the pandemic has created some difficulty (social distancing) and opportunity (more family time, fewer school demands).
 

Sleep

Help parents establish and protect consistent, restful sleep for their children. They can set a consistent bedtime and a calm routine, with screens all off at least 30 minutes before sleep and reading before sleep. Restful sleep is physiologically and psychologically protective to everyone in a family.

Movement

Beyond directly improving physical health, establishing habits of exercise – especially outside – every day can effectively manage ongoing stress, build skills of self-regulation, and help with sleep.

Find out what parents and their children like to do together (walking the dog, shooting hoops, even dancing) and help them devise ways to create family routines around exercise.
 

Nutrition

Food should be a source of pleasure, but stress can make food into a source of comfort or escape. Help parents to create realistic ways to consistently offer healthy family meals and discourage unhealthy habits.

Even small changes like water instead of soda can help, and there are nutritional and emotional benefits to eating a healthy breakfast or dinner together as a family.
 

Connections

Nourishing social connections are protective. Help parents think about protecting time to spend with their children for talking, playing games, or even singing.

They should support their children’s connections to other caring adults, through community organizations (church, community centers, or sports), and they should know who their children’s reliable friends are. Parents will benefit from these supports for themselves, which in turn will benefit the full family.
 

Self-awareness

Activities that cultivate mindfulness are protective. Parents can simply ask how their children are feeling, physically or emotionally, and be able to bear it when it is uncomfortable. Work towards nonjudgmental awareness of how they are feeling. Learning what is relaxing or recharging for them (exercise, music, a hot bath, a good book, time with a friend) will protect against defaulting into maladaptive coping such as escape, numbing, or avoidance.

Of course, if you learn about symptoms that suggest PTSD, depression, or addiction, you should help your patient connect with effective treatment. The difficulty of referring to a mental health provider does not mean you should not try and bring as many people onto the team and into the orbit of the child and family at risk. It may be easier to access some therapy given the new availability of telemedicine visits across many more systems of care. Although the heaviest burdens of adversity are not being borne equally, the fact that adversity is currently a shared experience makes this a moment of promise.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Dr. Swick and Dr. Jellinek had no relevant financial disclosures. Email them at pdnews@mdedge.com.

References
1. Am J Prev Med. 1998 May;14(4):245-58.
2. Ann Allergy Asthma Immunol. 2015;114: 379-84.
3. BMC Public Health. 2018. doi: 10.1186/s12889-018-5699-8.
4. Child Abuse Negl. 2011 Jun;35(6):408-13.
5. Community Dent Oral Epidemiol. 2015;43:193-9.
6. Community Dent Oral Epidemiol. 2018 Oct;46(5): 442-8.
7. Pediatrics 2016 Apr. doi: 10.1542/peds.2015-4016.
8. Matern Child Health J. 2016 Apr. doi: 10.1007/s10995-015-1915-7.
9. Acad Pediatr. 2017 May-Jun. doi: 10.1016/j.acap.2016.08.013.
10. Pediatrics. 2010 Apr. doi: 10.1542/peds.2009-0597.
 

This article was updated 7/27/2020.

We live in historic times. A worldwide pandemic is surging in the United States, with millions infected and the world’s highest death rate. Many of our hospitals are overwhelmed. Schools have been closed for months. Businesses are struggling, and unemployment is at record levels. The murder of George Floyd unleashed an outpouring of grief and rage over police brutality and structural racism.

Thinkstock

The value of knowing about these risk factors would seem self-evident; it would inform a patient’s health care from screening for cancer or heart disease, referral for mild depressive symptoms, and counseling about alcohol consumption. But this research did not lead to the establishment of routine screening for childhood adversity in primary care practices. There are multiple reasons for this, including growing pressure on physician time and discomfort with starting conversations about potentially traumatic material. But perhaps the greatest obstacle has been uncertainty about what to offer patients who screened in. What is the treatment for a high ACE score?

Even without treatments, we have learned much about childhood adversity since Dr. Anda and Dr. Felitti published their landmark study. Other more chronic adverse childhood experiences also contribute to adult health risk, such as poverty, homelessness, discrimination, community violence, parental chronic illness, or disability or placement in foster care. Having a high ACE score does not only affect health in adulthood. Children with an ACE score of 4 are 2 times as likely to have asthma^2,3 and allergies³, 2 times as likely to be obese⁴, 3 times as likely to have headaches³ and dental problems^5,6, 4 times as likely to have depression^7,8, 5 times as likely to have ADHD^8,9, 7 times as likely to have high rates of school absenteeism³ and aggression¹⁰, and over 30 times as likely to have learning or behavioral problems at school⁴. There is a growing body of knowledge about how chronic, severe stress in childhood affects can lead to pathological alterations in neuroendocrine and immune function. But this has not led to any concrete treatments that may be preventive or reparative.

Movement toward expanding screening nonetheless has accelerated. In California, Nadine Burke-Harris, MD, a pediatrician who studied ACEs and children’s health was named the state’s first Surgeon General in 2019 and spearheaded an effort to make screening for ACEs easier. Starting in 2020, MediCal will pay for annual screenings, and the state is offering training and resources on how to screen and what to do with the information to help patients and families.

The coronavirus pandemic has only highlighted the risks of childhood adversity. The burden of infection and mortality has been borne disproportionately by people of color and those with multiple chronic medical conditions (obesity, cardiovascular disease, diabetes, etc.). While viruses do not discriminate, they are more likely to infect those with higher risk of exposure and to kill those who are physiologically vulnerable.

And the pandemic increases the risk for adversity for today’s children and families. When children cannot attend school, financially vulnerable parents may have to choose between supervising them or feeding them. Families who suddenly are all in a small apartment together without school or other outside supports may be at higher risk for domestic violence and child abuse. Unemployment and financial uncertainty will increase the rates of substance abuse and depression amongst parents. And the serious illness or death of a parent will be a more common event for children in the year ahead. One of these risk factors may increase the likelihood of others.

Beyond the obvious need for substantial policy changes focused on housing, education, and health care, there are immediate and concrete strategies that can build resilience in children and their families. And resilience can build on itself, as children face subsequent challenges with the support of caring connected adults.

The critical first step is asking. Then listen calmly and supportively, normalizing for parents and children how common these experiences are. Explain how they affect health and well-being. Explain that adversity and its consequences are not their fault. Then educate them about what is in their control: the skills they can practice to buffer against the consequences of adversity and build resilience. They sound simple, but still require effort and work. And the pandemic has created some difficulty (social distancing) and opportunity (more family time, fewer school demands).
 

Sleep

Help parents establish and protect consistent, restful sleep for their children. They can set a consistent bedtime and a calm routine, with screens all off at least 30 minutes before sleep and reading before sleep. Restful sleep is physiologically and psychologically protective to everyone in a family.

Movement

Beyond directly improving physical health, establishing habits of exercise – especially outside – every day can effectively manage ongoing stress, build skills of self-regulation, and help with sleep.

Find out what parents and their children like to do together (walking the dog, shooting hoops, even dancing) and help them devise ways to create family routines around exercise.
 

Nutrition

Food should be a source of pleasure, but stress can make food into a source of comfort or escape. Help parents to create realistic ways to consistently offer healthy family meals and discourage unhealthy habits.

Even small changes like water instead of soda can help, and there are nutritional and emotional benefits to eating a healthy breakfast or dinner together as a family.
 

Connections

Nourishing social connections are protective. Help parents think about protecting time to spend with their children for talking, playing games, or even singing.

They should support their children’s connections to other caring adults, through community organizations (church, community centers, or sports), and they should know who their children’s reliable friends are. Parents will benefit from these supports for themselves, which in turn will benefit the full family.
 

Self-awareness

Activities that cultivate mindfulness are protective. Parents can simply ask how their children are feeling, physically or emotionally, and be able to bear it when it is uncomfortable. Work towards nonjudgmental awareness of how they are feeling. Learning what is relaxing or recharging for them (exercise, music, a hot bath, a good book, time with a friend) will protect against defaulting into maladaptive coping such as escape, numbing, or avoidance.

Of course, if you learn about symptoms that suggest PTSD, depression, or addiction, you should help your patient connect with effective treatment. The difficulty of referring to a mental health provider does not mean you should not try and bring as many people onto the team and into the orbit of the child and family at risk. It may be easier to access some therapy given the new availability of telemedicine visits across many more systems of care. Although the heaviest burdens of adversity are not being borne equally, the fact that adversity is currently a shared experience makes this a moment of promise.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Dr. Swick and Dr. Jellinek had no relevant financial disclosures. Email them at pdnews@mdedge.com.

References
1. Am J Prev Med. 1998 May;14(4):245-58.
2. Ann Allergy Asthma Immunol. 2015;114: 379-84.
3. BMC Public Health. 2018. doi: 10.1186/s12889-018-5699-8.
4. Child Abuse Negl. 2011 Jun;35(6):408-13.
5. Community Dent Oral Epidemiol. 2015;43:193-9.
6. Community Dent Oral Epidemiol. 2018 Oct;46(5): 442-8.
7. Pediatrics 2016 Apr. doi: 10.1542/peds.2015-4016.
8. Matern Child Health J. 2016 Apr. doi: 10.1007/s10995-015-1915-7.
9. Acad Pediatr. 2017 May-Jun. doi: 10.1016/j.acap.2016.08.013.
10. Pediatrics. 2010 Apr. doi: 10.1542/peds.2009-0597.
 

This article was updated 7/27/2020.

We live in historic times. A worldwide pandemic is surging in the United States, with millions infected and the world’s highest death rate. Many of our hospitals are overwhelmed. Schools have been closed for months. Businesses are struggling, and unemployment is at record levels. The murder of George Floyd unleashed an outpouring of grief and rage over police brutality and structural racism.

Thinkstock

The value of knowing about these risk factors would seem self-evident; it would inform a patient’s health care from screening for cancer or heart disease, referral for mild depressive symptoms, and counseling about alcohol consumption. But this research did not lead to the establishment of routine screening for childhood adversity in primary care practices. There are multiple reasons for this, including growing pressure on physician time and discomfort with starting conversations about potentially traumatic material. But perhaps the greatest obstacle has been uncertainty about what to offer patients who screened in. What is the treatment for a high ACE score?

Even without treatments, we have learned much about childhood adversity since Dr. Anda and Dr. Felitti published their landmark study. Other more chronic adverse childhood experiences also contribute to adult health risk, such as poverty, homelessness, discrimination, community violence, parental chronic illness, or disability or placement in foster care. Having a high ACE score does not only affect health in adulthood. Children with an ACE score of 4 are 2 times as likely to have asthma^2,3 and allergies³, 2 times as likely to be obese⁴, 3 times as likely to have headaches³ and dental problems^5,6, 4 times as likely to have depression^7,8, 5 times as likely to have ADHD^8,9, 7 times as likely to have high rates of school absenteeism³ and aggression¹⁰, and over 30 times as likely to have learning or behavioral problems at school⁴. There is a growing body of knowledge about how chronic, severe stress in childhood affects can lead to pathological alterations in neuroendocrine and immune function. But this has not led to any concrete treatments that may be preventive or reparative.

Movement toward expanding screening nonetheless has accelerated. In California, Nadine Burke-Harris, MD, a pediatrician who studied ACEs and children’s health was named the state’s first Surgeon General in 2019 and spearheaded an effort to make screening for ACEs easier. Starting in 2020, MediCal will pay for annual screenings, and the state is offering training and resources on how to screen and what to do with the information to help patients and families.

The coronavirus pandemic has only highlighted the risks of childhood adversity. The burden of infection and mortality has been borne disproportionately by people of color and those with multiple chronic medical conditions (obesity, cardiovascular disease, diabetes, etc.). While viruses do not discriminate, they are more likely to infect those with higher risk of exposure and to kill those who are physiologically vulnerable.

And the pandemic increases the risk for adversity for today’s children and families. When children cannot attend school, financially vulnerable parents may have to choose between supervising them or feeding them. Families who suddenly are all in a small apartment together without school or other outside supports may be at higher risk for domestic violence and child abuse. Unemployment and financial uncertainty will increase the rates of substance abuse and depression amongst parents. And the serious illness or death of a parent will be a more common event for children in the year ahead. One of these risk factors may increase the likelihood of others.

Beyond the obvious need for substantial policy changes focused on housing, education, and health care, there are immediate and concrete strategies that can build resilience in children and their families. And resilience can build on itself, as children face subsequent challenges with the support of caring connected adults.

The critical first step is asking. Then listen calmly and supportively, normalizing for parents and children how common these experiences are. Explain how they affect health and well-being. Explain that adversity and its consequences are not their fault. Then educate them about what is in their control: the skills they can practice to buffer against the consequences of adversity and build resilience. They sound simple, but still require effort and work. And the pandemic has created some difficulty (social distancing) and opportunity (more family time, fewer school demands).
 

Sleep

Help parents establish and protect consistent, restful sleep for their children. They can set a consistent bedtime and a calm routine, with screens all off at least 30 minutes before sleep and reading before sleep. Restful sleep is physiologically and psychologically protective to everyone in a family.

Movement

Beyond directly improving physical health, establishing habits of exercise – especially outside – every day can effectively manage ongoing stress, build skills of self-regulation, and help with sleep.

Find out what parents and their children like to do together (walking the dog, shooting hoops, even dancing) and help them devise ways to create family routines around exercise.
 

Nutrition

Food should be a source of pleasure, but stress can make food into a source of comfort or escape. Help parents to create realistic ways to consistently offer healthy family meals and discourage unhealthy habits.

Even small changes like water instead of soda can help, and there are nutritional and emotional benefits to eating a healthy breakfast or dinner together as a family.
 

Connections

Nourishing social connections are protective. Help parents think about protecting time to spend with their children for talking, playing games, or even singing.

They should support their children’s connections to other caring adults, through community organizations (church, community centers, or sports), and they should know who their children’s reliable friends are. Parents will benefit from these supports for themselves, which in turn will benefit the full family.
 

Self-awareness

Activities that cultivate mindfulness are protective. Parents can simply ask how their children are feeling, physically or emotionally, and be able to bear it when it is uncomfortable. Work towards nonjudgmental awareness of how they are feeling. Learning what is relaxing or recharging for them (exercise, music, a hot bath, a good book, time with a friend) will protect against defaulting into maladaptive coping such as escape, numbing, or avoidance.

Of course, if you learn about symptoms that suggest PTSD, depression, or addiction, you should help your patient connect with effective treatment. The difficulty of referring to a mental health provider does not mean you should not try and bring as many people onto the team and into the orbit of the child and family at risk. It may be easier to access some therapy given the new availability of telemedicine visits across many more systems of care. Although the heaviest burdens of adversity are not being borne equally, the fact that adversity is currently a shared experience makes this a moment of promise.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Dr. Swick and Dr. Jellinek had no relevant financial disclosures. Email them at pdnews@mdedge.com.

References
1. Am J Prev Med. 1998 May;14(4):245-58.
2. Ann Allergy Asthma Immunol. 2015;114: 379-84.
3. BMC Public Health. 2018. doi: 10.1186/s12889-018-5699-8.
4. Child Abuse Negl. 2011 Jun;35(6):408-13.
5. Community Dent Oral Epidemiol. 2015;43:193-9.
6. Community Dent Oral Epidemiol. 2018 Oct;46(5): 442-8.
7. Pediatrics 2016 Apr. doi: 10.1542/peds.2015-4016.
8. Matern Child Health J. 2016 Apr. doi: 10.1007/s10995-015-1915-7.
9. Acad Pediatr. 2017 May-Jun. doi: 10.1016/j.acap.2016.08.013.
10. Pediatrics. 2010 Apr. doi: 10.1542/peds.2009-0597.
 

This article was updated 7/27/2020.

For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.

However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.

Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
 

Limited, old evidence

The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”

They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.

Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.

Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).

Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.

However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
 

Psychotic depression markers?

For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.

Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.

Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.

Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.

“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.

The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.

They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.

“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”

She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
 

Confirmatory data

Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”

However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.

Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.

“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”

As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”

Many things that ECT “corrects” are disturbed in psychotic depression, including cortisol homeostasis, which is thought to be affected via the hypothalamic-pituitary-adrenal axis, Petrides added.

That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.

One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.

He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.

The study authors and Petrides have reported no relevant financial relationships.

This article first appeared on Medscape.com.

For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.

However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.

Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
 

Limited, old evidence

The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”

They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.

Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.

Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).

Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.

However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
 

Psychotic depression markers?

For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.

Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.

Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.

Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.

“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.

The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.

They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.

“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”

She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
 

Confirmatory data

Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”

However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.

Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.

“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”

As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”

Many things that ECT “corrects” are disturbed in psychotic depression, including cortisol homeostasis, which is thought to be affected via the hypothalamic-pituitary-adrenal axis, Petrides added.

That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.

One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.

He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.

The study authors and Petrides have reported no relevant financial relationships.

This article first appeared on Medscape.com.

For patients with psychotic depression, response to treatment, remission rates, and cognitive improvement are better following electroconvulsive therapy (ECT) than for patients with nonpsychotic depression, results from a new study suggest.

However, findings from another study suggest that at least some of these differences may be because psychotic patients are referred for ECT earlier in the disease course.

Both studies were presented at the European Psychiatric Association 2020 Congress, which was held online this year because of the COVID-19 pandemic.
 

Limited, old evidence

The first study was led by Christopher Yi Wen Chan, MD, Institute of Mental Health, Singapore. The investigators stated that they have “often observed” superior remission rates with ECT in psychotic versus nonpsychotic depression. However, the evidence base is “limited and mostly more than 10 years old.”

They conducted a retrospective case-control study that included 160 patients – 50 with psychotic depression, and 110 with nonpsychotic depression. All patients had a primary diagnosis of unipolar major depressive disorder and underwent ECT at a tertiary psychiatric institute between January 2016 and January 2018.

Baseline characteristics of the two groups were similar, although patients with psychosis were more likely to have had an involuntary hospital admission and to have had higher baseline scores on the Montreal Cognitive Assessment (MoCA) and Clinical Global Impression–Severity scale (CGI-S) than nonpsychotic patients.

Response rates to ECT were significantly higher for the patients with psychotic depression than for those with nonpsychotic depression (79% vs. 51%; P = .009), as were remission rates (71% vs. 36%; P = .001).

Both groups showed significant improvement following ECT in Montgomery-Åsberg Depression Rating Scale, CGI, and quality-of-life scores.

However, only the participants with psychotic depression showed a significant improvement in MoCA total score (P = .038), as well as on attention (P = .024), language (P = .008), and orientation (P = .021) subdomains.
 

Psychotic depression markers?

For the second study, a team led by Aida De Arriba Arnau, MD, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain, retrospectively analyzed 66 patients with depression who had received ECT. Of these, 26 had psychotic depression, and 40 had nonpsychotic depression.

Response rates were again higher in patients with psychotic vs nonpsychotic depression (92.3% vs. 85.0%). A similar number of sessions was needed to achieve a response.

Improvements in Hamilton Depression Rating Scale scores were significant between the two groups from the start of treatment, although the difference became nonsignificant at week 6.

Arriba Arnau said that there were some notable differences between patients with psychotic depression and those with nonpsychotic depression. For example, the former had “poor functionality, shorter episode duration, and less pharmacological resistance before receiving ECT,” she said.

“So we hypothesized that they might be referred more promptly to ECT treatment,” she added.

The psychotic depression group was significantly older than the group with nonpsychotic depression, at an average of 67.81 years vs 58.96 years.

They also “showed more illness severity and cognitive disturbances at baseline and ... required less anesthetic doses and higher initial stimulus intensity,» Arriba Arnau noted.

“All these features could be the markers of psychotic depression as an entity,” she said. However, the potential impact of age on these differences should be “further studied.”

She added that other aspects, such as age at onset and number of previous episodes, were similar between the groups.
 

Confirmatory data

Commenting on the findings for Medscape Medical News, Georgios Petrides, MD, associate professor of psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, East Garden City, New York, noted that differences in response to ECT between patients with psychotic depression and those with nonpsychotic depression are “well known.”

However, “it’s actually good to present more data that confirm what people are doing in clinical practice,” said Petrides, who was not involved with the research.

Petrides noted that some guidelines recommend ECT as first-line treatment for psychotic depression.

“For nonpsychotic depression, we’d try medications, psychotherapy, and everything else first,” he said. He noted that the current results are “a good replication of what is known so far.”

As to why ECT should be more effective for patients with psychotic depression, he said, “A lot of people think that the biology of psychotic depression is different from the biology of nonpsychotic depression.”

Many things that ECT “corrects” are disturbed in psychotic depression, including cortisol homeostasis, which is thought to be affected via the hypothalamic-pituitary-adrenal axis, Petrides added.

That ECT is more effective in psychotic depression is an “indirect point of evidence” to support that theory.

One aspect that has traditionally dogged the use of ECT has been the stigma that surrounds the procedure, Petrides noted. That’s “always an issue, but it’s getting less and less over time,” he said.

He added that ECT is extremely safe and that it is associated with the “lowest mortality for any procedure performed under general anesthesia,” which helps to reduce the stigma around it, he noted.

The study authors and Petrides have reported no relevant financial relationships.

This article first appeared on Medscape.com.

Seven percent of pregnant women report using prescription opioids during their pregnancy, and almost a third of those women did not receive counseling from a provider on the effects of opioids on their unborn children, according to analysis from the Centers for Disease Control and Prevention.

Data from the Pregnancy Risk Assessment Monitoring System 2019 survey show that 7% of the nearly 21,000 respondents reported using an opioid pain reliever during pregnancy, considerably lower than the fill rates of 14%-22% seen in studies of pharmacy dispensing, Jean Y. Ko, PhD, and associates at the CDC said in the Morbidity and Mortality Weekly Report.

In the current analysis, opioid use during pregnancy varied by age – the rate was highest, 10%, in those aged 19 years and under and dropped as age increased to 6% among those aged 35 and older – and by race/ethnicity – 9% of black women reported use, compared with 7% of Hispanics, 6% of whites, and 7% of all others, the investigators reported.

Use of prescription opioids was significantly higher for two specific groups. Women who smoked cigarettes during the last 3 months of their pregnancy had a 16% rate of opioid use, and those with depression during pregnancy had a rate of 13%, they said.

Physicians caring for pregnant women should seek to identify and address substance use and misuse, and mental health conditions such as depression, history of trauma, posttraumatic stress disorder, and anxiety, the CDC researchers pointed out.

The CDC and the American College of Obstetricians and Gynecologists both recommend that caregivers and patients also need to “discuss and carefully weigh risks and benefits when considering initiation of opioid therapy for chronic pain during pregnancy,” Dr. Ko and associates wrote.

That sort of counseling, however, was not always offered: 32% of the women with self-reported prescription opioid use during their pregnancy said that they had not been counseled about the drugs’ effect on an infant. Some variation was seen by age or race/ethnicity, but the differences were not significant, the researchers reported.

“Opioid prescribing consistent with clinical practice guidelines can ensure that patients, particularly those who are pregnant, have access to safer, more effective chronic pain treatment and reduce the number of persons at risk for opioid misuse, opioid use disorder, and overdose,” the investigators concluded.

Survey data from 32 jurisdictions (30 states, along with the District of Columbia and Puerto Rico) that participate in the monitoring system were included in the analysis, as were data from California and Ohio, which do not participate. All of the respondents had a live birth in the preceding 2-6 months, the researchers explained.

rfranki@mdedge.com

SOURCE: Ko JY et al. MMWR. 2020 Jul 17;69(28):897-903.

Seven percent of pregnant women report using prescription opioids during their pregnancy, and almost a third of those women did not receive counseling from a provider on the effects of opioids on their unborn children, according to analysis from the Centers for Disease Control and Prevention.

Data from the Pregnancy Risk Assessment Monitoring System 2019 survey show that 7% of the nearly 21,000 respondents reported using an opioid pain reliever during pregnancy, considerably lower than the fill rates of 14%-22% seen in studies of pharmacy dispensing, Jean Y. Ko, PhD, and associates at the CDC said in the Morbidity and Mortality Weekly Report.

In the current analysis, opioid use during pregnancy varied by age – the rate was highest, 10%, in those aged 19 years and under and dropped as age increased to 6% among those aged 35 and older – and by race/ethnicity – 9% of black women reported use, compared with 7% of Hispanics, 6% of whites, and 7% of all others, the investigators reported.

Use of prescription opioids was significantly higher for two specific groups. Women who smoked cigarettes during the last 3 months of their pregnancy had a 16% rate of opioid use, and those with depression during pregnancy had a rate of 13%, they said.

Physicians caring for pregnant women should seek to identify and address substance use and misuse, and mental health conditions such as depression, history of trauma, posttraumatic stress disorder, and anxiety, the CDC researchers pointed out.

The CDC and the American College of Obstetricians and Gynecologists both recommend that caregivers and patients also need to “discuss and carefully weigh risks and benefits when considering initiation of opioid therapy for chronic pain during pregnancy,” Dr. Ko and associates wrote.

That sort of counseling, however, was not always offered: 32% of the women with self-reported prescription opioid use during their pregnancy said that they had not been counseled about the drugs’ effect on an infant. Some variation was seen by age or race/ethnicity, but the differences were not significant, the researchers reported.

“Opioid prescribing consistent with clinical practice guidelines can ensure that patients, particularly those who are pregnant, have access to safer, more effective chronic pain treatment and reduce the number of persons at risk for opioid misuse, opioid use disorder, and overdose,” the investigators concluded.

Survey data from 32 jurisdictions (30 states, along with the District of Columbia and Puerto Rico) that participate in the monitoring system were included in the analysis, as were data from California and Ohio, which do not participate. All of the respondents had a live birth in the preceding 2-6 months, the researchers explained.

rfranki@mdedge.com

SOURCE: Ko JY et al. MMWR. 2020 Jul 17;69(28):897-903.

Seven percent of pregnant women report using prescription opioids during their pregnancy, and almost a third of those women did not receive counseling from a provider on the effects of opioids on their unborn children, according to analysis from the Centers for Disease Control and Prevention.

Data from the Pregnancy Risk Assessment Monitoring System 2019 survey show that 7% of the nearly 21,000 respondents reported using an opioid pain reliever during pregnancy, considerably lower than the fill rates of 14%-22% seen in studies of pharmacy dispensing, Jean Y. Ko, PhD, and associates at the CDC said in the Morbidity and Mortality Weekly Report.

In the current analysis, opioid use during pregnancy varied by age – the rate was highest, 10%, in those aged 19 years and under and dropped as age increased to 6% among those aged 35 and older – and by race/ethnicity – 9% of black women reported use, compared with 7% of Hispanics, 6% of whites, and 7% of all others, the investigators reported.

Use of prescription opioids was significantly higher for two specific groups. Women who smoked cigarettes during the last 3 months of their pregnancy had a 16% rate of opioid use, and those with depression during pregnancy had a rate of 13%, they said.

Physicians caring for pregnant women should seek to identify and address substance use and misuse, and mental health conditions such as depression, history of trauma, posttraumatic stress disorder, and anxiety, the CDC researchers pointed out.

The CDC and the American College of Obstetricians and Gynecologists both recommend that caregivers and patients also need to “discuss and carefully weigh risks and benefits when considering initiation of opioid therapy for chronic pain during pregnancy,” Dr. Ko and associates wrote.

That sort of counseling, however, was not always offered: 32% of the women with self-reported prescription opioid use during their pregnancy said that they had not been counseled about the drugs’ effect on an infant. Some variation was seen by age or race/ethnicity, but the differences were not significant, the researchers reported.

“Opioid prescribing consistent with clinical practice guidelines can ensure that patients, particularly those who are pregnant, have access to safer, more effective chronic pain treatment and reduce the number of persons at risk for opioid misuse, opioid use disorder, and overdose,” the investigators concluded.

Survey data from 32 jurisdictions (30 states, along with the District of Columbia and Puerto Rico) that participate in the monitoring system were included in the analysis, as were data from California and Ohio, which do not participate. All of the respondents had a live birth in the preceding 2-6 months, the researchers explained.

rfranki@mdedge.com

SOURCE: Ko JY et al. MMWR. 2020 Jul 17;69(28):897-903.

The use of compounded bioidentical hormone therapies should be limited to patients who are not able to use a hormone therapy product approved by the Food and Drug Administration for reasons of allergy or dosage, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

yacobchuk/Getty Images

In recent years, compounded bioidentical hormone therapies (cBHTs) have been “marketed as a personalized and natural approach to enhanced wellness using tailored preparations that address a myriad of symptoms, including those associated with menopause and aging,” wrote Donald R. Mattison, MD, of the University of Ottawa, and chair of the committee charged with producing the report, and colleagues.

Although both cBHTs and bioidentical hormone therapies (BHTs) contain hormones that are structurally and chemically identical to those in the human body, cBHTs have not undergone the safety, efficacy, and quality control tests of approved FDA products, according to the report.

In addition, cBHTs have no standardization when it comes to medication doses, and the products often are available in topicals such as creams or ointments, as well as pills or pellets. The lack of standards in dosing or form can contribute to the risk of overdose, the report emphasized.

Various cBTH products continue to be marketed to the public for age-related hormone symptoms including hot flashes associated with menopause and decreased muscle mass associated with decreased testosterone. However, cBHTs are not approved by the FDA in part because the individually mixed products are not tested to verify the amount of hormone that may be absorbed.

In response to the increased use of cBHTs, the National Academies convened a Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy and commissioned a report.

The two typical reasons to prescribe cBHT are either to provide a medication in an alternate dose not available in approved products or to omit components of a medication to which a patient is allergic, according to the report.

The report includes an algorithm to help guide clinicians in prescribing FDA-approved products, including off-label use of approved products, before cBHT products. “There is a dearth of high-quality evidence ... available to establish whether cBHT preparations are safe or efficacious for their prescribed uses,” the report states.

Of note, the committee also found no guidelines to recommend the use of cBHT products as a substitute for off-label use of FDA-approved BHT products for patients with female sexual dysfunction or gender dysphoria, two conditions for which no FDA-approved BHT products exist.

“The North American Menopause Society applauds the efforts of the National Academies of Sciences, Engineering, and Medicine (NASEM) and endorses their recommendations on compounded bioidentical hormone therapy,” Stephanie S. Faubion, MD, medical director of The North American Menopause Society, wrote in a statement. “As a society, we remain committed to improving the care of midlife women through the promotion of evidence-based research, education, and clinical care.”

A report on the use of cBHTs was important at this time because of the widespread and largely unregulated use of these products with little data to support their safety and efficacy, Dr. Faubion said in an interview.

“There are no indications for use of custom compounded hormone therapy aside from an allergy to a component in the FDA-approved products or lack of availability of the needed dose, which would be exceedingly rare given the variety of forms and doses available with FDA-approved products,” she said.

Main concerns regarding the use of cBHTs are the lack of safety and efficacy data, Dr. Faubion emphasized. “Women believe these products are safer than FDA-approved products because they do not receive a package insert outlining potential risks as they do with FDA-approved products.” A lack of data and safety monitoring of cBHTs means that adverse effects are not monitored and reported, she said. Also, safety concerns persist regarding some forms of cBHTs such as pellets, which were specifically highlighted in the report.

Dr. Faubion said that she “absolutely” agrees with the report’s limited circumstances in which the used of cBHTs would be appropriate. “There are very few reasons why women would need to use compounded hormones instead of the FDA-approved versions, which are regulated for quality, efficacy and safety, readily available in the local pharmacy, and often covered by insurance.”

In terms of the future, “we need more education for women as consumers and for medical providers on this topic,” Dr. Faubion noted. Also, “clearly, there is a dearth of research on the true efficacy and safety of these compounded hormone therapy products.”

The statement from the National Academies crystallizes what experts have been saying for decades, according to Lubna Pal, MBBS, director of the menopause program at Yale University, New Haven, Conn.

The formal recommendations to limit the use of cBHTs “are not novel, but certainly needed,” and the statement “offers guidance regardless of your specialty,” Dr. Pal said in an interview.

There is often a disconnect between consumers’ understanding of compounding and the reality of safety concerns, she said. “We are in a tabloid era,” and education is key to guiding patients toward the FDA-approved treatments with safety data and demonstrated effectiveness, she said. “Safety should be the driving factor.” In compounded products, “there is no consistency that what you get today is the same as what you get tomorrow,” and the lack of standardization of cBHTs increases the risk for adverse events, she emphasized.

For patients with special needs such as allergies or other specialized dosing requirements, as noted in the National Academies statement, clinicians should discuss the options with patients and monitor them regularly to head off potential adverse events such as the development of uterine cancer, said Dr. Pal, who is a member of the Ob.Gyn. News editorial advisory board.

The research involved in creating the report was supported by the Food and Drug Administration.

Dr. Faubion had no financial conflicts to disclose. Dr. Pal had no relevant financial disclosures.

obnews@mdedge.com

SOURCE: Mattison DR et al.; National Academies of Sciences, Engineering, and Medicine. The clinical utility of compounded bioidentical hormone therapy: A review of safety, effectiveness, and use. (Washington, DC: The National Academies Press. 2020.)

The use of compounded bioidentical hormone therapies should be limited to patients who are not able to use a hormone therapy product approved by the Food and Drug Administration for reasons of allergy or dosage, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

yacobchuk/Getty Images

In recent years, compounded bioidentical hormone therapies (cBHTs) have been “marketed as a personalized and natural approach to enhanced wellness using tailored preparations that address a myriad of symptoms, including those associated with menopause and aging,” wrote Donald R. Mattison, MD, of the University of Ottawa, and chair of the committee charged with producing the report, and colleagues.

Although both cBHTs and bioidentical hormone therapies (BHTs) contain hormones that are structurally and chemically identical to those in the human body, cBHTs have not undergone the safety, efficacy, and quality control tests of approved FDA products, according to the report.

In addition, cBHTs have no standardization when it comes to medication doses, and the products often are available in topicals such as creams or ointments, as well as pills or pellets. The lack of standards in dosing or form can contribute to the risk of overdose, the report emphasized.

Various cBTH products continue to be marketed to the public for age-related hormone symptoms including hot flashes associated with menopause and decreased muscle mass associated with decreased testosterone. However, cBHTs are not approved by the FDA in part because the individually mixed products are not tested to verify the amount of hormone that may be absorbed.

In response to the increased use of cBHTs, the National Academies convened a Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy and commissioned a report.

The two typical reasons to prescribe cBHT are either to provide a medication in an alternate dose not available in approved products or to omit components of a medication to which a patient is allergic, according to the report.

The report includes an algorithm to help guide clinicians in prescribing FDA-approved products, including off-label use of approved products, before cBHT products. “There is a dearth of high-quality evidence ... available to establish whether cBHT preparations are safe or efficacious for their prescribed uses,” the report states.

Of note, the committee also found no guidelines to recommend the use of cBHT products as a substitute for off-label use of FDA-approved BHT products for patients with female sexual dysfunction or gender dysphoria, two conditions for which no FDA-approved BHT products exist.

“The North American Menopause Society applauds the efforts of the National Academies of Sciences, Engineering, and Medicine (NASEM) and endorses their recommendations on compounded bioidentical hormone therapy,” Stephanie S. Faubion, MD, medical director of The North American Menopause Society, wrote in a statement. “As a society, we remain committed to improving the care of midlife women through the promotion of evidence-based research, education, and clinical care.”

A report on the use of cBHTs was important at this time because of the widespread and largely unregulated use of these products with little data to support their safety and efficacy, Dr. Faubion said in an interview.

“There are no indications for use of custom compounded hormone therapy aside from an allergy to a component in the FDA-approved products or lack of availability of the needed dose, which would be exceedingly rare given the variety of forms and doses available with FDA-approved products,” she said.

Main concerns regarding the use of cBHTs are the lack of safety and efficacy data, Dr. Faubion emphasized. “Women believe these products are safer than FDA-approved products because they do not receive a package insert outlining potential risks as they do with FDA-approved products.” A lack of data and safety monitoring of cBHTs means that adverse effects are not monitored and reported, she said. Also, safety concerns persist regarding some forms of cBHTs such as pellets, which were specifically highlighted in the report.

Dr. Faubion said that she “absolutely” agrees with the report’s limited circumstances in which the used of cBHTs would be appropriate. “There are very few reasons why women would need to use compounded hormones instead of the FDA-approved versions, which are regulated for quality, efficacy and safety, readily available in the local pharmacy, and often covered by insurance.”

In terms of the future, “we need more education for women as consumers and for medical providers on this topic,” Dr. Faubion noted. Also, “clearly, there is a dearth of research on the true efficacy and safety of these compounded hormone therapy products.”

The statement from the National Academies crystallizes what experts have been saying for decades, according to Lubna Pal, MBBS, director of the menopause program at Yale University, New Haven, Conn.

The formal recommendations to limit the use of cBHTs “are not novel, but certainly needed,” and the statement “offers guidance regardless of your specialty,” Dr. Pal said in an interview.

There is often a disconnect between consumers’ understanding of compounding and the reality of safety concerns, she said. “We are in a tabloid era,” and education is key to guiding patients toward the FDA-approved treatments with safety data and demonstrated effectiveness, she said. “Safety should be the driving factor.” In compounded products, “there is no consistency that what you get today is the same as what you get tomorrow,” and the lack of standardization of cBHTs increases the risk for adverse events, she emphasized.

For patients with special needs such as allergies or other specialized dosing requirements, as noted in the National Academies statement, clinicians should discuss the options with patients and monitor them regularly to head off potential adverse events such as the development of uterine cancer, said Dr. Pal, who is a member of the Ob.Gyn. News editorial advisory board.

The research involved in creating the report was supported by the Food and Drug Administration.

Dr. Faubion had no financial conflicts to disclose. Dr. Pal had no relevant financial disclosures.

obnews@mdedge.com

SOURCE: Mattison DR et al.; National Academies of Sciences, Engineering, and Medicine. The clinical utility of compounded bioidentical hormone therapy: A review of safety, effectiveness, and use. (Washington, DC: The National Academies Press. 2020.)

The use of compounded bioidentical hormone therapies should be limited to patients who are not able to use a hormone therapy product approved by the Food and Drug Administration for reasons of allergy or dosage, according to a new report from the National Academies of Sciences, Engineering, and Medicine.

yacobchuk/Getty Images

In recent years, compounded bioidentical hormone therapies (cBHTs) have been “marketed as a personalized and natural approach to enhanced wellness using tailored preparations that address a myriad of symptoms, including those associated with menopause and aging,” wrote Donald R. Mattison, MD, of the University of Ottawa, and chair of the committee charged with producing the report, and colleagues.

Although both cBHTs and bioidentical hormone therapies (BHTs) contain hormones that are structurally and chemically identical to those in the human body, cBHTs have not undergone the safety, efficacy, and quality control tests of approved FDA products, according to the report.

In addition, cBHTs have no standardization when it comes to medication doses, and the products often are available in topicals such as creams or ointments, as well as pills or pellets. The lack of standards in dosing or form can contribute to the risk of overdose, the report emphasized.

Various cBTH products continue to be marketed to the public for age-related hormone symptoms including hot flashes associated with menopause and decreased muscle mass associated with decreased testosterone. However, cBHTs are not approved by the FDA in part because the individually mixed products are not tested to verify the amount of hormone that may be absorbed.

In response to the increased use of cBHTs, the National Academies convened a Committee on the Clinical Utility of Treating Patients with Compounded Bioidentical Hormone Replacement Therapy and commissioned a report.

The two typical reasons to prescribe cBHT are either to provide a medication in an alternate dose not available in approved products or to omit components of a medication to which a patient is allergic, according to the report.

The report includes an algorithm to help guide clinicians in prescribing FDA-approved products, including off-label use of approved products, before cBHT products. “There is a dearth of high-quality evidence ... available to establish whether cBHT preparations are safe or efficacious for their prescribed uses,” the report states.

Of note, the committee also found no guidelines to recommend the use of cBHT products as a substitute for off-label use of FDA-approved BHT products for patients with female sexual dysfunction or gender dysphoria, two conditions for which no FDA-approved BHT products exist.

“The North American Menopause Society applauds the efforts of the National Academies of Sciences, Engineering, and Medicine (NASEM) and endorses their recommendations on compounded bioidentical hormone therapy,” Stephanie S. Faubion, MD, medical director of The North American Menopause Society, wrote in a statement. “As a society, we remain committed to improving the care of midlife women through the promotion of evidence-based research, education, and clinical care.”

A report on the use of cBHTs was important at this time because of the widespread and largely unregulated use of these products with little data to support their safety and efficacy, Dr. Faubion said in an interview.

“There are no indications for use of custom compounded hormone therapy aside from an allergy to a component in the FDA-approved products or lack of availability of the needed dose, which would be exceedingly rare given the variety of forms and doses available with FDA-approved products,” she said.

Main concerns regarding the use of cBHTs are the lack of safety and efficacy data, Dr. Faubion emphasized. “Women believe these products are safer than FDA-approved products because they do not receive a package insert outlining potential risks as they do with FDA-approved products.” A lack of data and safety monitoring of cBHTs means that adverse effects are not monitored and reported, she said. Also, safety concerns persist regarding some forms of cBHTs such as pellets, which were specifically highlighted in the report.

Dr. Faubion said that she “absolutely” agrees with the report’s limited circumstances in which the used of cBHTs would be appropriate. “There are very few reasons why women would need to use compounded hormones instead of the FDA-approved versions, which are regulated for quality, efficacy and safety, readily available in the local pharmacy, and often covered by insurance.”

In terms of the future, “we need more education for women as consumers and for medical providers on this topic,” Dr. Faubion noted. Also, “clearly, there is a dearth of research on the true efficacy and safety of these compounded hormone therapy products.”

The statement from the National Academies crystallizes what experts have been saying for decades, according to Lubna Pal, MBBS, director of the menopause program at Yale University, New Haven, Conn.

The formal recommendations to limit the use of cBHTs “are not novel, but certainly needed,” and the statement “offers guidance regardless of your specialty,” Dr. Pal said in an interview.

There is often a disconnect between consumers’ understanding of compounding and the reality of safety concerns, she said. “We are in a tabloid era,” and education is key to guiding patients toward the FDA-approved treatments with safety data and demonstrated effectiveness, she said. “Safety should be the driving factor.” In compounded products, “there is no consistency that what you get today is the same as what you get tomorrow,” and the lack of standardization of cBHTs increases the risk for adverse events, she emphasized.

For patients with special needs such as allergies or other specialized dosing requirements, as noted in the National Academies statement, clinicians should discuss the options with patients and monitor them regularly to head off potential adverse events such as the development of uterine cancer, said Dr. Pal, who is a member of the Ob.Gyn. News editorial advisory board.

The research involved in creating the report was supported by the Food and Drug Administration.

Dr. Faubion had no financial conflicts to disclose. Dr. Pal had no relevant financial disclosures.

obnews@mdedge.com

SOURCE: Mattison DR et al.; National Academies of Sciences, Engineering, and Medicine. The clinical utility of compounded bioidentical hormone therapy: A review of safety, effectiveness, and use. (Washington, DC: The National Academies Press. 2020.)

Prostate-specific membrane antigen (PSMA) PET/CT was 27% more accurate than conventional imaging for detecting metastases and staging men prior to curative-intent therapy for high-risk prostate cancer in the phase 3 ProPSMA study.

The accuracy was 92% for PSMA PET/CT and 65% for CT and bone scintigraphy (P < .001), according to data reported at the virtual annual congress of the European Association of Urology and published in The Lancet.

In addition, PSMA PET/CT had greater effects on treatment. First-line imaging led to treatment changes in 28% of the PSMA PET/CT group and 15% of the CT/bone scan group. Second-line imaging led to treatment changes in 27% and 5% of patients, respectively.

“My strong view is that this is practice-changing data,” said study investigator Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne.

Highly relevant secondary outcomes were included in the study, Dr. Hofman said, and results were all in favor of PSMA PET/CT over conventional imaging.

PSMA PET/CT was associated with a lower rate of equivocal or uncertain findings (7% vs. 23%), and half the radiation dose was needed with PSMA PET/CT (8 mSv vs. 19 mSv). Furthermore, PSMA PET/CT was more accurate when used after CT/bone scan than when CT/bone scan was used after PSMA PET/CT (19% vs. 2%).

“PSMA PET/CT has emerged as a potential new gold standard for imaging prostate cancer,” Dr. Hofman said. The images it can produce were “striking” compared to conventional CT, he added. Pelvic and abdominal metastases that are barely visible on CT were “lighting up very brightly” on PSMA PET/CT, he said.

The study also showed that PSMA PET/CT was superior to CT/bone scans for picking up metastases throughout the body. The detection rate was 91% and 59%, respectively, for pelvic nodal metastases and 95% and 74%, respectively, for distant metastases.
 

Study details

ProPSMA is a multicenter, phase 3 trial directly comparing PSMA PET/CT and the standard of imaging. Of 339 men assessed for inclusion across 10 centers in Australia, 302 were randomized. They had a median age of 69 years. All patients had high-risk prostate cancer, which was defined as a prostate-specific antigen level of 20 ng/mL, Gleason Grade Group 3-5, or clinical stage T3 or higher. They were all about to undergo either surgery or radiotherapy with the intention of curing their prostate cancer.

PSMA PET/CT was performed using the gallium-68-labelled PSMA-11 tracer, but the results would likely be no different if another tracer were used, Dr. Hofman said in the discussion following his talk.

Of the three available tracers, there were minor differences, mostly in how they were excreted. However, “they’re all extremely good. I’m not sure anyone’s ever going to undertake a head-to-head study comparing them,” Dr. Hofman said.

“Whichever one you can access, at the cheapest cost, I think, is going to be the best one in your center,” he added. “That really does vary geographically, but I really don’t think one is better or worse than the other.”
 

Praise and criticism

The latest European guidelines acknowledge that PSMA PET/CT is more sensitive for detecting lymph node and bone metastases than the classical workup of abdominopelvic CT and bone scintigraphy, according to invited discussant Matthias Heck, PD Dr. med, of the Technical University of Munich in Germany.

“Molecular imaging using PSMA PET/CT facilitates the detection of small lymph node metastasis, with the size of a few millimeters,” Dr. Heck said.

Although he commended the ProPSMA investigators, Dr. Heck had one criticism of the study design that may have resulted in over-sensitivity of PSMA PET/CT.

“As a urologist, I want to address as a discussion point the low number of histopathologic validation in the ProPSMA study,” he said. “Pelvic lymph node sampling was performed only in 66% of patients treated with radical prostatectomy for high-risk prostate cancer. Hard criteria to define the presence of metastasis were only used in 23% of patients with metastases. Therefore, it is possible that the sensitivity was overestimated by using mainly soft criteria.”

The sensitivity of PSMA PET/CT was 85%, while that of CT/bone scan was 38%. The respective specificities were 98% and 91%.

“What I like most about this study is that, when we perform a PSMA PET/CT, you see the whole body; you don’t see only pelvic lymph nodes,” Dr. Heck said. Since it was not possible to validate distant metastasis by histopathology, he added, this imaging method could clearly help determine the best treatment.

“If we have distant metastasis in the bones or in the lymph nodes outside of the pelvis, it’s clearly unnecessary to direct this patient to undergo local treatment, and we need to think about other treatments,” Dr. Heck said. “Therefore, I think it’s a very important question that is being raised by this study, and we all need to look at the whole body of the patient and not focus only on the pelvic lymph nodes.”

The study was funded by the Prostate Cancer Foundation of Australia. Dr. Hofman said he has no relevant conflicts of interest. Dr. Heck disclosed relationships with Astellas, Janssen, Ipsen, Amgen, Bayer, Heise, Merck, Sanofi, and Takeda.

SOURCES: Hofman M et al. Lancet. March 22, doi: https://doi.org/10.1016/S0140-6736(20)30314-7.

Prostate-specific membrane antigen (PSMA) PET/CT was 27% more accurate than conventional imaging for detecting metastases and staging men prior to curative-intent therapy for high-risk prostate cancer in the phase 3 ProPSMA study.

The accuracy was 92% for PSMA PET/CT and 65% for CT and bone scintigraphy (P < .001), according to data reported at the virtual annual congress of the European Association of Urology and published in The Lancet.

In addition, PSMA PET/CT had greater effects on treatment. First-line imaging led to treatment changes in 28% of the PSMA PET/CT group and 15% of the CT/bone scan group. Second-line imaging led to treatment changes in 27% and 5% of patients, respectively.

“My strong view is that this is practice-changing data,” said study investigator Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne.

Highly relevant secondary outcomes were included in the study, Dr. Hofman said, and results were all in favor of PSMA PET/CT over conventional imaging.

PSMA PET/CT was associated with a lower rate of equivocal or uncertain findings (7% vs. 23%), and half the radiation dose was needed with PSMA PET/CT (8 mSv vs. 19 mSv). Furthermore, PSMA PET/CT was more accurate when used after CT/bone scan than when CT/bone scan was used after PSMA PET/CT (19% vs. 2%).

“PSMA PET/CT has emerged as a potential new gold standard for imaging prostate cancer,” Dr. Hofman said. The images it can produce were “striking” compared to conventional CT, he added. Pelvic and abdominal metastases that are barely visible on CT were “lighting up very brightly” on PSMA PET/CT, he said.

The study also showed that PSMA PET/CT was superior to CT/bone scans for picking up metastases throughout the body. The detection rate was 91% and 59%, respectively, for pelvic nodal metastases and 95% and 74%, respectively, for distant metastases.
 

Study details

ProPSMA is a multicenter, phase 3 trial directly comparing PSMA PET/CT and the standard of imaging. Of 339 men assessed for inclusion across 10 centers in Australia, 302 were randomized. They had a median age of 69 years. All patients had high-risk prostate cancer, which was defined as a prostate-specific antigen level of 20 ng/mL, Gleason Grade Group 3-5, or clinical stage T3 or higher. They were all about to undergo either surgery or radiotherapy with the intention of curing their prostate cancer.

PSMA PET/CT was performed using the gallium-68-labelled PSMA-11 tracer, but the results would likely be no different if another tracer were used, Dr. Hofman said in the discussion following his talk.

Of the three available tracers, there were minor differences, mostly in how they were excreted. However, “they’re all extremely good. I’m not sure anyone’s ever going to undertake a head-to-head study comparing them,” Dr. Hofman said.

“Whichever one you can access, at the cheapest cost, I think, is going to be the best one in your center,” he added. “That really does vary geographically, but I really don’t think one is better or worse than the other.”
 

Praise and criticism

The latest European guidelines acknowledge that PSMA PET/CT is more sensitive for detecting lymph node and bone metastases than the classical workup of abdominopelvic CT and bone scintigraphy, according to invited discussant Matthias Heck, PD Dr. med, of the Technical University of Munich in Germany.

“Molecular imaging using PSMA PET/CT facilitates the detection of small lymph node metastasis, with the size of a few millimeters,” Dr. Heck said.

Although he commended the ProPSMA investigators, Dr. Heck had one criticism of the study design that may have resulted in over-sensitivity of PSMA PET/CT.

“As a urologist, I want to address as a discussion point the low number of histopathologic validation in the ProPSMA study,” he said. “Pelvic lymph node sampling was performed only in 66% of patients treated with radical prostatectomy for high-risk prostate cancer. Hard criteria to define the presence of metastasis were only used in 23% of patients with metastases. Therefore, it is possible that the sensitivity was overestimated by using mainly soft criteria.”

The sensitivity of PSMA PET/CT was 85%, while that of CT/bone scan was 38%. The respective specificities were 98% and 91%.

“What I like most about this study is that, when we perform a PSMA PET/CT, you see the whole body; you don’t see only pelvic lymph nodes,” Dr. Heck said. Since it was not possible to validate distant metastasis by histopathology, he added, this imaging method could clearly help determine the best treatment.

“If we have distant metastasis in the bones or in the lymph nodes outside of the pelvis, it’s clearly unnecessary to direct this patient to undergo local treatment, and we need to think about other treatments,” Dr. Heck said. “Therefore, I think it’s a very important question that is being raised by this study, and we all need to look at the whole body of the patient and not focus only on the pelvic lymph nodes.”

The study was funded by the Prostate Cancer Foundation of Australia. Dr. Hofman said he has no relevant conflicts of interest. Dr. Heck disclosed relationships with Astellas, Janssen, Ipsen, Amgen, Bayer, Heise, Merck, Sanofi, and Takeda.

SOURCES: Hofman M et al. Lancet. March 22, doi: https://doi.org/10.1016/S0140-6736(20)30314-7.

Prostate-specific membrane antigen (PSMA) PET/CT was 27% more accurate than conventional imaging for detecting metastases and staging men prior to curative-intent therapy for high-risk prostate cancer in the phase 3 ProPSMA study.

The accuracy was 92% for PSMA PET/CT and 65% for CT and bone scintigraphy (P < .001), according to data reported at the virtual annual congress of the European Association of Urology and published in The Lancet.

In addition, PSMA PET/CT had greater effects on treatment. First-line imaging led to treatment changes in 28% of the PSMA PET/CT group and 15% of the CT/bone scan group. Second-line imaging led to treatment changes in 27% and 5% of patients, respectively.

“My strong view is that this is practice-changing data,” said study investigator Michael Hofman, MBBS, of the Peter MacCallum Cancer Centre in Melbourne.

Highly relevant secondary outcomes were included in the study, Dr. Hofman said, and results were all in favor of PSMA PET/CT over conventional imaging.

PSMA PET/CT was associated with a lower rate of equivocal or uncertain findings (7% vs. 23%), and half the radiation dose was needed with PSMA PET/CT (8 mSv vs. 19 mSv). Furthermore, PSMA PET/CT was more accurate when used after CT/bone scan than when CT/bone scan was used after PSMA PET/CT (19% vs. 2%).

“PSMA PET/CT has emerged as a potential new gold standard for imaging prostate cancer,” Dr. Hofman said. The images it can produce were “striking” compared to conventional CT, he added. Pelvic and abdominal metastases that are barely visible on CT were “lighting up very brightly” on PSMA PET/CT, he said.

The study also showed that PSMA PET/CT was superior to CT/bone scans for picking up metastases throughout the body. The detection rate was 91% and 59%, respectively, for pelvic nodal metastases and 95% and 74%, respectively, for distant metastases.
 

Study details

ProPSMA is a multicenter, phase 3 trial directly comparing PSMA PET/CT and the standard of imaging. Of 339 men assessed for inclusion across 10 centers in Australia, 302 were randomized. They had a median age of 69 years. All patients had high-risk prostate cancer, which was defined as a prostate-specific antigen level of 20 ng/mL, Gleason Grade Group 3-5, or clinical stage T3 or higher. They were all about to undergo either surgery or radiotherapy with the intention of curing their prostate cancer.

PSMA PET/CT was performed using the gallium-68-labelled PSMA-11 tracer, but the results would likely be no different if another tracer were used, Dr. Hofman said in the discussion following his talk.

Of the three available tracers, there were minor differences, mostly in how they were excreted. However, “they’re all extremely good. I’m not sure anyone’s ever going to undertake a head-to-head study comparing them,” Dr. Hofman said.

“Whichever one you can access, at the cheapest cost, I think, is going to be the best one in your center,” he added. “That really does vary geographically, but I really don’t think one is better or worse than the other.”
 

Praise and criticism

The latest European guidelines acknowledge that PSMA PET/CT is more sensitive for detecting lymph node and bone metastases than the classical workup of abdominopelvic CT and bone scintigraphy, according to invited discussant Matthias Heck, PD Dr. med, of the Technical University of Munich in Germany.

“Molecular imaging using PSMA PET/CT facilitates the detection of small lymph node metastasis, with the size of a few millimeters,” Dr. Heck said.

Although he commended the ProPSMA investigators, Dr. Heck had one criticism of the study design that may have resulted in over-sensitivity of PSMA PET/CT.

“As a urologist, I want to address as a discussion point the low number of histopathologic validation in the ProPSMA study,” he said. “Pelvic lymph node sampling was performed only in 66% of patients treated with radical prostatectomy for high-risk prostate cancer. Hard criteria to define the presence of metastasis were only used in 23% of patients with metastases. Therefore, it is possible that the sensitivity was overestimated by using mainly soft criteria.”

The sensitivity of PSMA PET/CT was 85%, while that of CT/bone scan was 38%. The respective specificities were 98% and 91%.

“What I like most about this study is that, when we perform a PSMA PET/CT, you see the whole body; you don’t see only pelvic lymph nodes,” Dr. Heck said. Since it was not possible to validate distant metastasis by histopathology, he added, this imaging method could clearly help determine the best treatment.

“If we have distant metastasis in the bones or in the lymph nodes outside of the pelvis, it’s clearly unnecessary to direct this patient to undergo local treatment, and we need to think about other treatments,” Dr. Heck said. “Therefore, I think it’s a very important question that is being raised by this study, and we all need to look at the whole body of the patient and not focus only on the pelvic lymph nodes.”

The study was funded by the Prostate Cancer Foundation of Australia. Dr. Hofman said he has no relevant conflicts of interest. Dr. Heck disclosed relationships with Astellas, Janssen, Ipsen, Amgen, Bayer, Heise, Merck, Sanofi, and Takeda.

SOURCES: Hofman M et al. Lancet. March 22, doi: https://doi.org/10.1016/S0140-6736(20)30314-7.