Federal Practitioner

First responders to the World Trade Center (WTC) attacks on Sept. 11, 2001, who have cognitive impairment show cortical thinning across multiple brain regions, including those commonly affected by Alzheimer’s disease, suggest results from the first structural neuroimaging study conducted in this population. The study clarifies that a neurodegenerative condition is present in first responders who experience cognitive impairment in midlife, which “is incredibly important to know,” said lead author Sean Clouston, PhD, of Stony Brook (N.Y.) University.

The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were published online in Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.
 

Brain atrophy in midlife

During the 9/11 attack and in its aftermath, WTC responders were exposed to a range of inhaled neurotoxicants, as well as extreme psychosocial stressors. A growing number of WTC responders who are now in their 50s and early 60s are experiencing early cognitive impairment.

Using MRI, the investigators examined cortical thickness (CTX), a surrogate marker for neurodegeneration, in 99 mostly male WTC responders; 48 had cognitive impairment, and 51 did not. The age range of the participants was 45 to 65 years, a range during which cortical atrophy is uncommon in the general population, the researchers noted.

Compared with cognitively normal responders, those with cognitive impairment were found to have reductions in CTX across the whole brain and across 21 of 34 cortical regions, including frontal, temporal, and occipital lobes.

In both cognitively impaired and cognitively unimpaired WTC responders, CTX was reduced in the entorhinal and temporal cortices compared with normative data, but reductions were greater with cognitive impairment. Posttraumatic distress disorder (PTSD) status was not predictive of a reduction in CTX across groups.

Dr. Clouston said the level of reduction in CTX in many responders is similar to that commonly found in patients with dementia and may reflect early-stage dementia occurring in midlife.

Limitations of the study include the small sample size, the cross-sectional design, the unique nature of the exposure, and a lack of a non-WTC external control group.
 

‘Illuminating’ study

Keith N. Fargo, PhD, director of scientific engagement for the Alzheimer’s Association, called the findings “interesting and illuminating” but cautioned that it is not possible to show cause and effect with this type of study.

“We also don’t know when cortical thinning might have started or how quickly it might be progressing,” Dr. Fargo said in an interview.

He noted that the pattern of cortical thinning is “somewhat consistent with what we see among people who live with high levels of air pollution, which is an emerging risk factor for Alzheimer’s disease and other dementias.”

The Lancet Commission on Dementia Prevention, Intervention, and Care added air pollution to its list of modifiable risk factors for dementia, which was recently updated.

Clinicians “need to be aware that their middle-aged 9/11 first responders are at a higher risk level for cognitive impairment, as well as PTSD and depression,” Dr. Fargo said.

The study was funded by the Centers for Disease Control and Prevention and the National Institute on Aging. Dr. Clouston and Dr. Fargo have reported no relevant financial relationships.
 

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

First responders to the World Trade Center (WTC) attacks on Sept. 11, 2001, who have cognitive impairment show cortical thinning across multiple brain regions, including those commonly affected by Alzheimer’s disease, suggest results from the first structural neuroimaging study conducted in this population. The study clarifies that a neurodegenerative condition is present in first responders who experience cognitive impairment in midlife, which “is incredibly important to know,” said lead author Sean Clouston, PhD, of Stony Brook (N.Y.) University.

The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were published online in Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.
 

Brain atrophy in midlife

During the 9/11 attack and in its aftermath, WTC responders were exposed to a range of inhaled neurotoxicants, as well as extreme psychosocial stressors. A growing number of WTC responders who are now in their 50s and early 60s are experiencing early cognitive impairment.

Using MRI, the investigators examined cortical thickness (CTX), a surrogate marker for neurodegeneration, in 99 mostly male WTC responders; 48 had cognitive impairment, and 51 did not. The age range of the participants was 45 to 65 years, a range during which cortical atrophy is uncommon in the general population, the researchers noted.

Compared with cognitively normal responders, those with cognitive impairment were found to have reductions in CTX across the whole brain and across 21 of 34 cortical regions, including frontal, temporal, and occipital lobes.

In both cognitively impaired and cognitively unimpaired WTC responders, CTX was reduced in the entorhinal and temporal cortices compared with normative data, but reductions were greater with cognitive impairment. Posttraumatic distress disorder (PTSD) status was not predictive of a reduction in CTX across groups.

Dr. Clouston said the level of reduction in CTX in many responders is similar to that commonly found in patients with dementia and may reflect early-stage dementia occurring in midlife.

Limitations of the study include the small sample size, the cross-sectional design, the unique nature of the exposure, and a lack of a non-WTC external control group.
 

‘Illuminating’ study

Keith N. Fargo, PhD, director of scientific engagement for the Alzheimer’s Association, called the findings “interesting and illuminating” but cautioned that it is not possible to show cause and effect with this type of study.

“We also don’t know when cortical thinning might have started or how quickly it might be progressing,” Dr. Fargo said in an interview.

He noted that the pattern of cortical thinning is “somewhat consistent with what we see among people who live with high levels of air pollution, which is an emerging risk factor for Alzheimer’s disease and other dementias.”

The Lancet Commission on Dementia Prevention, Intervention, and Care added air pollution to its list of modifiable risk factors for dementia, which was recently updated.

Clinicians “need to be aware that their middle-aged 9/11 first responders are at a higher risk level for cognitive impairment, as well as PTSD and depression,” Dr. Fargo said.

The study was funded by the Centers for Disease Control and Prevention and the National Institute on Aging. Dr. Clouston and Dr. Fargo have reported no relevant financial relationships.
 

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

First responders to the World Trade Center (WTC) attacks on Sept. 11, 2001, who have cognitive impairment show cortical thinning across multiple brain regions, including those commonly affected by Alzheimer’s disease, suggest results from the first structural neuroimaging study conducted in this population. The study clarifies that a neurodegenerative condition is present in first responders who experience cognitive impairment in midlife, which “is incredibly important to know,” said lead author Sean Clouston, PhD, of Stony Brook (N.Y.) University.

The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and were published online in Alzheimer’s and Dementia: Diagnosis, Assessment and Disease Monitoring.
 

Brain atrophy in midlife

During the 9/11 attack and in its aftermath, WTC responders were exposed to a range of inhaled neurotoxicants, as well as extreme psychosocial stressors. A growing number of WTC responders who are now in their 50s and early 60s are experiencing early cognitive impairment.

Using MRI, the investigators examined cortical thickness (CTX), a surrogate marker for neurodegeneration, in 99 mostly male WTC responders; 48 had cognitive impairment, and 51 did not. The age range of the participants was 45 to 65 years, a range during which cortical atrophy is uncommon in the general population, the researchers noted.

Compared with cognitively normal responders, those with cognitive impairment were found to have reductions in CTX across the whole brain and across 21 of 34 cortical regions, including frontal, temporal, and occipital lobes.

In both cognitively impaired and cognitively unimpaired WTC responders, CTX was reduced in the entorhinal and temporal cortices compared with normative data, but reductions were greater with cognitive impairment. Posttraumatic distress disorder (PTSD) status was not predictive of a reduction in CTX across groups.

Dr. Clouston said the level of reduction in CTX in many responders is similar to that commonly found in patients with dementia and may reflect early-stage dementia occurring in midlife.

Limitations of the study include the small sample size, the cross-sectional design, the unique nature of the exposure, and a lack of a non-WTC external control group.
 

‘Illuminating’ study

Keith N. Fargo, PhD, director of scientific engagement for the Alzheimer’s Association, called the findings “interesting and illuminating” but cautioned that it is not possible to show cause and effect with this type of study.

“We also don’t know when cortical thinning might have started or how quickly it might be progressing,” Dr. Fargo said in an interview.

He noted that the pattern of cortical thinning is “somewhat consistent with what we see among people who live with high levels of air pollution, which is an emerging risk factor for Alzheimer’s disease and other dementias.”

The Lancet Commission on Dementia Prevention, Intervention, and Care added air pollution to its list of modifiable risk factors for dementia, which was recently updated.

Clinicians “need to be aware that their middle-aged 9/11 first responders are at a higher risk level for cognitive impairment, as well as PTSD and depression,” Dr. Fargo said.

The study was funded by the Centers for Disease Control and Prevention and the National Institute on Aging. Dr. Clouston and Dr. Fargo have reported no relevant financial relationships.
 

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

Over the last several decades science has fallen off this country’s radar screen. Yes, STEM (science, technology, engineering, and mathematics) has recently had a brief moment in the spotlight as a buzzword de jour. But the critical importance of careful and systematic investigation into the world around us using observation and trial and error is a tough sell to a large segment of our population.

SDI Productions/iStock/Getty Images

The COVID-19 pandemic is providing an excellent opportunity for science and medicine to showcase their star qualities. Of course some people in leadership positions persist in disregarding the value of scientific investigation. But I get the feeling that the fear generated by the pandemic is creating some converts among many previous science skeptics. This gathering enthusiasm among the general population is a predictably slow process because that’s the way science works. It often doesn’t provide quick answers. And it is difficult for the nonscientist to see the beauty in the reality that the things we thought were true 2 months ago are likely to be proven wrong today as more observations accumulate.

Unfortunately, even in this time of renewal, science and medicine continue to generate a bumper crop of bad apples. A recent New York Times article examines the career of one such unscrupulous physician/scientist whose recent exploits threaten to undo much of the positive image the pandemic has cast on science (“The Doctor Behind the Disputed Covid Data,” by Ellen Gabler and Roni Caryn Rabin, The New York Times, July 27, 2020). The subject of the article is the physician who was responsible for providing some of the large data sets on which several papers were published about the apparent ineffectiveness and danger of using hydroxychloroquine in COVID-19 patients. The authenticity of the data sets recently has been seriously questioned, and the articles have been retracted by the journals in which they had appeared.

Based on numerous interviews with coworkers, the Times reporters present a strong case that this individual’s long history of unreliability make his association with allegedly fraudulent data set not surprising but maybe even predictable. At one point in his training, there appears to have been serious questions about advancing the physician to the next level. Despite these concerns, he was allowed to continue and complete his specialty training. It is of note that in his last year of clinical practice, the physician became the subject of three serious malpractice claims that question his competence.

I suspect that some of you have crossed paths with physicians whose competence and/or moral character you found concerning. Were they peers? Were you the individual’s supervisor or was he or she your mentor? How did you respond? Did anyone respond at all?

There has been a lot written and said in recent months about how and when to respond to respond to sexual harassment in the workplace. But I don’t recall reading any articles that discuss how one should respond to incompetence. Of course competency can be a relative term, but in most cases significant incompetence is hard to miss because it tends to be repeated.

It is easy for the airports and subway systems to post signs that say “If you see something say something.” It’s a different story for hospitals and medical schools that may have systems in place for reporting and following up on poor practice. But my sense is that there are too many cases that slip through the cracks.

This is another example of a problem for which I don’t have a solution. However, if this column prompts just one of you who sees something to say something then I have had a good day.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Over the last several decades science has fallen off this country’s radar screen. Yes, STEM (science, technology, engineering, and mathematics) has recently had a brief moment in the spotlight as a buzzword de jour. But the critical importance of careful and systematic investigation into the world around us using observation and trial and error is a tough sell to a large segment of our population.

SDI Productions/iStock/Getty Images

The COVID-19 pandemic is providing an excellent opportunity for science and medicine to showcase their star qualities. Of course some people in leadership positions persist in disregarding the value of scientific investigation. But I get the feeling that the fear generated by the pandemic is creating some converts among many previous science skeptics. This gathering enthusiasm among the general population is a predictably slow process because that’s the way science works. It often doesn’t provide quick answers. And it is difficult for the nonscientist to see the beauty in the reality that the things we thought were true 2 months ago are likely to be proven wrong today as more observations accumulate.

Unfortunately, even in this time of renewal, science and medicine continue to generate a bumper crop of bad apples. A recent New York Times article examines the career of one such unscrupulous physician/scientist whose recent exploits threaten to undo much of the positive image the pandemic has cast on science (“The Doctor Behind the Disputed Covid Data,” by Ellen Gabler and Roni Caryn Rabin, The New York Times, July 27, 2020). The subject of the article is the physician who was responsible for providing some of the large data sets on which several papers were published about the apparent ineffectiveness and danger of using hydroxychloroquine in COVID-19 patients. The authenticity of the data sets recently has been seriously questioned, and the articles have been retracted by the journals in which they had appeared.

Based on numerous interviews with coworkers, the Times reporters present a strong case that this individual’s long history of unreliability make his association with allegedly fraudulent data set not surprising but maybe even predictable. At one point in his training, there appears to have been serious questions about advancing the physician to the next level. Despite these concerns, he was allowed to continue and complete his specialty training. It is of note that in his last year of clinical practice, the physician became the subject of three serious malpractice claims that question his competence.

I suspect that some of you have crossed paths with physicians whose competence and/or moral character you found concerning. Were they peers? Were you the individual’s supervisor or was he or she your mentor? How did you respond? Did anyone respond at all?

There has been a lot written and said in recent months about how and when to respond to respond to sexual harassment in the workplace. But I don’t recall reading any articles that discuss how one should respond to incompetence. Of course competency can be a relative term, but in most cases significant incompetence is hard to miss because it tends to be repeated.

It is easy for the airports and subway systems to post signs that say “If you see something say something.” It’s a different story for hospitals and medical schools that may have systems in place for reporting and following up on poor practice. But my sense is that there are too many cases that slip through the cracks.

This is another example of a problem for which I don’t have a solution. However, if this column prompts just one of you who sees something to say something then I have had a good day.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

Over the last several decades science has fallen off this country’s radar screen. Yes, STEM (science, technology, engineering, and mathematics) has recently had a brief moment in the spotlight as a buzzword de jour. But the critical importance of careful and systematic investigation into the world around us using observation and trial and error is a tough sell to a large segment of our population.

SDI Productions/iStock/Getty Images

The COVID-19 pandemic is providing an excellent opportunity for science and medicine to showcase their star qualities. Of course some people in leadership positions persist in disregarding the value of scientific investigation. But I get the feeling that the fear generated by the pandemic is creating some converts among many previous science skeptics. This gathering enthusiasm among the general population is a predictably slow process because that’s the way science works. It often doesn’t provide quick answers. And it is difficult for the nonscientist to see the beauty in the reality that the things we thought were true 2 months ago are likely to be proven wrong today as more observations accumulate.

Unfortunately, even in this time of renewal, science and medicine continue to generate a bumper crop of bad apples. A recent New York Times article examines the career of one such unscrupulous physician/scientist whose recent exploits threaten to undo much of the positive image the pandemic has cast on science (“The Doctor Behind the Disputed Covid Data,” by Ellen Gabler and Roni Caryn Rabin, The New York Times, July 27, 2020). The subject of the article is the physician who was responsible for providing some of the large data sets on which several papers were published about the apparent ineffectiveness and danger of using hydroxychloroquine in COVID-19 patients. The authenticity of the data sets recently has been seriously questioned, and the articles have been retracted by the journals in which they had appeared.

Based on numerous interviews with coworkers, the Times reporters present a strong case that this individual’s long history of unreliability make his association with allegedly fraudulent data set not surprising but maybe even predictable. At one point in his training, there appears to have been serious questions about advancing the physician to the next level. Despite these concerns, he was allowed to continue and complete his specialty training. It is of note that in his last year of clinical practice, the physician became the subject of three serious malpractice claims that question his competence.

I suspect that some of you have crossed paths with physicians whose competence and/or moral character you found concerning. Were they peers? Were you the individual’s supervisor or was he or she your mentor? How did you respond? Did anyone respond at all?

There has been a lot written and said in recent months about how and when to respond to respond to sexual harassment in the workplace. But I don’t recall reading any articles that discuss how one should respond to incompetence. Of course competency can be a relative term, but in most cases significant incompetence is hard to miss because it tends to be repeated.

It is easy for the airports and subway systems to post signs that say “If you see something say something.” It’s a different story for hospitals and medical schools that may have systems in place for reporting and following up on poor practice. But my sense is that there are too many cases that slip through the cracks.

This is another example of a problem for which I don’t have a solution. However, if this column prompts just one of you who sees something to say something then I have had a good day.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

All patients with cancer who are candidates for systemic anticancer therapy should be screened for hepatitis B virus (HBV) infection prior to or at the start of therapy, according to an updated provisional clinical opinion (PCO) from the American Society of Clinical Oncology.

“This is a new approach [that] will actively take system changes ... but it will ultimately be safer for patients – and that is crucial,” commented Jessica P. Hwang, MD, MPH, cochair of the American Society of Clinical Oncology HBV Screening Expert Panel and the first author of the PCO.

Uptake of this universal screening approach would streamline testing protocols and identify more patients at risk for HBV reactivation who should receive prophylactic antiviral therapy, Dr. Hwang said in an interview.

The PCO calls for antiviral prophylaxis during and for at least 12 months after therapy for those with chronic HBV infection who are receiving any systemic anticancer treatment and for those with have had HBV in the past and are receiving any therapies that pose a risk for HBV reactivation.

“Hepatitis B reactivation can cause really terrible outcomes, like organ failure and even death,” Dr. Hwang, who is also a professor at the University of Texas MD Anderson Cancer Center, Houston, commented in an interview.

“This whole [issue of] reactivation and adverse outcomes with anticancer therapies is completely preventable with good planning, good communication, comanagement with specialists, and antiviral therapy and monitoring,” she added.

The updated opinion was published online July 27 in the Journal of Clinical Oncology.

It was developed in response to new data that call into question the previously recommended risk-adaptive approach to HBV screening of cancer patients, say the authors.

ASCO PCOs are developed “to provide timely clinical guidance” on the basis of emerging practice-changing information. This is the second update to follow the initial HBV screening PCO, published in 2010. In the absence of clear consensus because of limited data, the original PCO called for a risk-based approach to screening. A 2015 update extended the recommendation for screening to patients starting anti-CD20 therapy or who are to undergo stem cell transplant and to those with risk factors for HBV exposure.

The current update provides “a clinically pragmatic approach to HBV screening and management” that is based on the latest findings, say the authors. These include findings from a multicenter prospective cohort study of more than 3000 patients. In that study, 21% of patients with chronic HBV had no known risk factors for the infection. In another large prospective observational cohort study, led by Dr. Hwang, which included more than 2100 patients with cancer, 90% had one or more significant risk factors for HBV infection, making selective screening “inefficient and impractical,” she said.

“The results of these two studies suggest that a universal screening approach, its potential harms (e.g., patient and clinician anxiety about management, financial burden associated with antiviral therapy) notwithstanding, is the most efficient, clinically pragmatic approach to HBV screening in persons anticipating systemic anticancer treatment,” the authors comment.

The screening recommended in the PCO requires three tests: hepatitis B surface antigen (HBsAg), core antibody total immunoglobulin or IgG, and antibody to HBsAg tests.

Anticancer therapy should not be delayed pending the results, they write.

Planning for monitoring and long-term prophylaxis for chronic HBV infection should involve a clinician experienced in HBV management, the authors write. Management of those with past infection should be individualized. Alternatively, patients with past infection can be carefully monitored rather than given prophylactic treatment, as long as frequent and consistent follow-up is possible to allow for rapid initiation of antiviral therapy in the event of reactivation, they say.

Hormonal therapy without systemic anticancer therapy is not likely to lead to HBV reactivation in patients with chronic or past infection; antiviral therapy and management of these patients should follow relevant national HBV guidelines, they note.

Challenges in implementing universal HBV screening

The expert panel acknowledges the challenges associated with implementation of universal HBV screening as recommended in their report and notes that electronic health record–based approaches that use alerts to prompt screening have demonstrated success. In one study of high-risk primary care patients, an EHR alert system significantly increased testing rates (odds ratio, 2.64 in comparison with a control group without alerts), and another study that used a simple “sticky-note” alert system to promote referral of HBsAg patients to hepatologists increased referrals from 28% to 73%.

In a cancer population, a “comprehensive set of multimodal interventions,” including pharmacy staff checks for screening prior to anti-CD20 therapy administration and electronic medication order reviews to assess for appropriate testing and treatment before anti-CD20 therapy, increased testing rates to greater than 90% and antiviral prophylaxis rates to more than 80%.

A study of 965 patients in Taiwan showed that a computer-assisted reminder system that prompted for testing prior to ordering anticancer therapy increased screening from 8% to 86% but was less effective for improving the rates of antiviral prophylaxis for those who tested positive for HBV, particularly among physicians treating patients with nonhematologic malignancies.

“Future studies will be needed to make universal HBV screening and linkage to care efficient and systematic, likely based in EHR systems,” the panel says. The authors note that “[o]ngoing studies of HBV tests such as ultrasensitive HBsAg, HBV RNA, and hepatitis B core antigen are being studied and may be useful in predicting risk of HBV reactivation.”

The panel also identified a research gap related to HBV reactivation risks “for the growing list of agents that deplete or modulate B cells.” It notes a need for additional research on the cost-effectiveness of HBV screening. The results of prior cost analyses have been inconsistent and vary with respect to the population studied. For example, universal screening and antiviral prophylaxis approaches have been shown to be cost-effective for patients with hematologic malignancies and high HBV reactivation risk but are less so for patients with solid tumors and lower reactivation risk, they explain.

Dr. Hwang said that not one of the more than 2100 patients in her HBV screening cohort study encountered problems with receiving insurance payment for their HBV screening.

“That’s a really strong statement that insurance payers are accepting of this kind of preventative service,” she said.

Expert panel cochair Andrew Artz, MD, commented that there is now greater acceptance of the need for HBV screening across medical specialties.

“There’s growing consensus among hepatologists, infectious disease specialists, oncologists, and HBV specialists that we need to do a better job of finding patients with hepatitis B [who are] about to receive immunocompromising treatment,” Dr. Artz said in an interview.

Dr. Artz is director of the Program for Aging and Blood Cancers and deputy director of the Center for Cancer and Aging at City of Hope Comprehensive Cancer Center, Duarte, California.

He suggested that the growing acceptance is due in part to the increasing number of anticancer therapies available and the resulting increase in the likelihood of patients receiving therapies that could cause reactivation.

More therapies – and more lines of therapy – could mean greater risk, he explained. He said that testing is easy and that universal screening is the simplest approach to determining who needs it. “There’s no question we will have to change practice,” Dr. Artz said in an interview. “But this is easier than the previous approach that essentially wasn’t being followed because it was too difficult to follow and patients were being missed.”

Most clinicians will appreciate having an approach that’s easier to follow, Dr. Artz predicted.

If there’s a challenge it will be in developing partnerships with HBV specialists, particularly in rural areas. In areas where there is a paucity of subspecialists, oncologists will have to “take some ownership of the issue,” as they often do in such settings, he said.

However, with support from pharmacists, administrators, and others in embracing this guidance, implementation can take place at a systems level rather than an individual clinician level, he added.

The recommendations in this updated PCO were all rated as “strong,” with the exception of the recommendation on hormonal therapy in the absence of systemic anticancer therapy, which was rated as “moderate.” All were based on “informal consensus,” with the exception of the key recommendation for universal HBV screening – use of three specific tests – which was “evidence based.”

The expert panel agreed that the benefits outweigh the harms for each recommendation in the update.

Dr. Hwang received research funding to her institution from Gilead Sciences and Merck Sharp & Dohme. She also has a relationship with the Asian Health Foundation. Dr. Artz received research funding from Miltenyi Biotec. All expert panel members’ disclosures are available in the PCO update.

This article first appeared on Medscape.com.

A novel probiotic product (Pendulum Glucose Control) containing gut bacteria strains that are deficient in people with type 2 diabetes modestly improves blood glucose levels, new research suggests.

The findings were published in BMJ Open Diabetes Research & Care by Fanny Perraudeau, PhD, and colleagues, all employees of Pendulum Therapeutics.

The product, classified as a medical food, is currently available for purchase on the company’s website without a prescription.

It contains the oligosaccharide-consuming Akkermansia muciniphila and Bifidobacterium infantis, the butyrate producers Anaerobutyricum hallii, Clostridium beijerinckii, and Clostridium butyricum, along with the “prebiotic” dietary fiber inulin.

In the 12-week trial of people with type 2 diabetes who were already taking metformin, with or without a sulfonylurea, 23 were randomized to the product and 26 received placebo capsules.

Participants in the active-treatment arm had significantly reduced glucose levels after a 3-hour standard meal-tolerance test, by 36.1 mg/dL (P = .05), and average A1c reduction of 0.6 percentage points (P = .054), compared with those taking placebo.

There were no major safety or tolerability issues, only transient gastrointestinal symptoms (nausea, diarrhea) lasting 3-5 days. No changes were seen in body weight, insulin sensitivity, or fasting blood glucose.

Asked to comment on the findings, Nanette I. Steinle, MD, an endocrinologist with expertise in nutrition who was not involved in the research, said that “to me it looks like the research was designed well and they didn’t overstate the results. ... I would say, for folks with mild to modest blood glucose elevations, it could be helpful to augment a healthy lifestyle.”

However, the product is not cheap, so cost could be a limiting factor for some patients, said Dr. Steinle, who is associate professor of medicine at the University of Maryland, Baltimore, and chief of the endocrine section, Maryland Veterans Affairs Health Care System.

Lead author Orville Kolterman, MD, chief medical officer at Pendulum, said in an interview that the formulation’s specificity distinguishes it from most commercially available probiotics.

“The ones sold in stores are reconfigurations of food probiotics, which are primarily aerobic organisms, whereas the abnormalities in the microbiome associated with type 2 diabetes reside in anaerobic organisms, which are more difficult to manufacture,” he explained.

The fiber component, inulin, is important as well, he said. “This product may make the dietary management of type 2 diabetes more effective, in that you need both the fiber and the microbes to ferment the fiber and produce short-chain fatty acids that appear to be very important for many reasons.”

The blood glucose-lowering effect is related in part to the three organisms’ production of butyrate, which binds to epithelial cells in the gut to secrete glucagonlike peptide–1, leading to inhibition of glucagon secretion among other actions.

And Akkermansia muciniphila protects the gut epithelium and has shown some evidence of improving insulin sensitivity and other beneficial metabolic effects in humans.

Dr. Kolterman, who was with Amylin Pharmaceuticals prior to moving to Pendulum, commented: “After doing this for 30 years or so, I’ve come to the strong appreciation that whenever you can do something to move back toward what Mother Nature set up, you’re doing a good thing.”

Clinically, Dr. Kolterman said, “I think perhaps the ideal place to try this would be shortly after diagnosis of type 2 diabetes, before patients go on to pharmacologic therapy.”

However, for practical reasons the study was done in patients who were already taking metformin, he said. “The results we have are that it’s beneficial above and beyond metformin, since [these] patients weren’t controlled with metformin.”

He also noted that it might benefit patients who can’t tolerate metformin or who have prediabetes; there’s an ongoing investigator-initiated study of the latter.

Dr. Steinle also endorsed the possibility that the product may benefit people with prediabetes. “I would suspect this could be very helpful to augment attempts to prevent diabetes. ... The group with prediabetes is huge.”

However, she cautioned, “if the blood glucose is over 200 [mg/dL], I wouldn’t think a probiotic would get them where they need to go.”

Overall, she pointed out that targeting the microbiome is a very active and potentially important field of medical research, and that it has received support from the National Institutes of Health. “I think we’re in the early stages of understanding how what grows in us, and on us, impacts our health and how we may be able to use these organisms to our benefit. I would expect we’ll see more of these probiotics being marketed in various forms.”

Dr. Kolterman is an employee of Pendulum. Dr. Steinle has reported receiving funding from the NIH, and she is conducting a study funded by Kowa through the VA.

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

A novel probiotic product (Pendulum Glucose Control) containing gut bacteria strains that are deficient in people with type 2 diabetes modestly improves blood glucose levels, new research suggests.

The findings were published in BMJ Open Diabetes Research & Care by Fanny Perraudeau, PhD, and colleagues, all employees of Pendulum Therapeutics.

The product, classified as a medical food, is currently available for purchase on the company’s website without a prescription.

It contains the oligosaccharide-consuming Akkermansia muciniphila and Bifidobacterium infantis, the butyrate producers Anaerobutyricum hallii, Clostridium beijerinckii, and Clostridium butyricum, along with the “prebiotic” dietary fiber inulin.

In the 12-week trial of people with type 2 diabetes who were already taking metformin, with or without a sulfonylurea, 23 were randomized to the product and 26 received placebo capsules.

Participants in the active-treatment arm had significantly reduced glucose levels after a 3-hour standard meal-tolerance test, by 36.1 mg/dL (P = .05), and average A1c reduction of 0.6 percentage points (P = .054), compared with those taking placebo.

There were no major safety or tolerability issues, only transient gastrointestinal symptoms (nausea, diarrhea) lasting 3-5 days. No changes were seen in body weight, insulin sensitivity, or fasting blood glucose.

Asked to comment on the findings, Nanette I. Steinle, MD, an endocrinologist with expertise in nutrition who was not involved in the research, said that “to me it looks like the research was designed well and they didn’t overstate the results. ... I would say, for folks with mild to modest blood glucose elevations, it could be helpful to augment a healthy lifestyle.”

However, the product is not cheap, so cost could be a limiting factor for some patients, said Dr. Steinle, who is associate professor of medicine at the University of Maryland, Baltimore, and chief of the endocrine section, Maryland Veterans Affairs Health Care System.

Lead author Orville Kolterman, MD, chief medical officer at Pendulum, said in an interview that the formulation’s specificity distinguishes it from most commercially available probiotics.

“The ones sold in stores are reconfigurations of food probiotics, which are primarily aerobic organisms, whereas the abnormalities in the microbiome associated with type 2 diabetes reside in anaerobic organisms, which are more difficult to manufacture,” he explained.

The fiber component, inulin, is important as well, he said. “This product may make the dietary management of type 2 diabetes more effective, in that you need both the fiber and the microbes to ferment the fiber and produce short-chain fatty acids that appear to be very important for many reasons.”

The blood glucose-lowering effect is related in part to the three organisms’ production of butyrate, which binds to epithelial cells in the gut to secrete glucagonlike peptide–1, leading to inhibition of glucagon secretion among other actions.

And Akkermansia muciniphila protects the gut epithelium and has shown some evidence of improving insulin sensitivity and other beneficial metabolic effects in humans.

Dr. Kolterman, who was with Amylin Pharmaceuticals prior to moving to Pendulum, commented: “After doing this for 30 years or so, I’ve come to the strong appreciation that whenever you can do something to move back toward what Mother Nature set up, you’re doing a good thing.”

Clinically, Dr. Kolterman said, “I think perhaps the ideal place to try this would be shortly after diagnosis of type 2 diabetes, before patients go on to pharmacologic therapy.”

However, for practical reasons the study was done in patients who were already taking metformin, he said. “The results we have are that it’s beneficial above and beyond metformin, since [these] patients weren’t controlled with metformin.”

He also noted that it might benefit patients who can’t tolerate metformin or who have prediabetes; there’s an ongoing investigator-initiated study of the latter.

Dr. Steinle also endorsed the possibility that the product may benefit people with prediabetes. “I would suspect this could be very helpful to augment attempts to prevent diabetes. ... The group with prediabetes is huge.”

However, she cautioned, “if the blood glucose is over 200 [mg/dL], I wouldn’t think a probiotic would get them where they need to go.”

Overall, she pointed out that targeting the microbiome is a very active and potentially important field of medical research, and that it has received support from the National Institutes of Health. “I think we’re in the early stages of understanding how what grows in us, and on us, impacts our health and how we may be able to use these organisms to our benefit. I would expect we’ll see more of these probiotics being marketed in various forms.”

Dr. Kolterman is an employee of Pendulum. Dr. Steinle has reported receiving funding from the NIH, and she is conducting a study funded by Kowa through the VA.

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

A novel probiotic product (Pendulum Glucose Control) containing gut bacteria strains that are deficient in people with type 2 diabetes modestly improves blood glucose levels, new research suggests.

The findings were published in BMJ Open Diabetes Research & Care by Fanny Perraudeau, PhD, and colleagues, all employees of Pendulum Therapeutics.

The product, classified as a medical food, is currently available for purchase on the company’s website without a prescription.

It contains the oligosaccharide-consuming Akkermansia muciniphila and Bifidobacterium infantis, the butyrate producers Anaerobutyricum hallii, Clostridium beijerinckii, and Clostridium butyricum, along with the “prebiotic” dietary fiber inulin.

In the 12-week trial of people with type 2 diabetes who were already taking metformin, with or without a sulfonylurea, 23 were randomized to the product and 26 received placebo capsules.

Participants in the active-treatment arm had significantly reduced glucose levels after a 3-hour standard meal-tolerance test, by 36.1 mg/dL (P = .05), and average A1c reduction of 0.6 percentage points (P = .054), compared with those taking placebo.

There were no major safety or tolerability issues, only transient gastrointestinal symptoms (nausea, diarrhea) lasting 3-5 days. No changes were seen in body weight, insulin sensitivity, or fasting blood glucose.

Asked to comment on the findings, Nanette I. Steinle, MD, an endocrinologist with expertise in nutrition who was not involved in the research, said that “to me it looks like the research was designed well and they didn’t overstate the results. ... I would say, for folks with mild to modest blood glucose elevations, it could be helpful to augment a healthy lifestyle.”

However, the product is not cheap, so cost could be a limiting factor for some patients, said Dr. Steinle, who is associate professor of medicine at the University of Maryland, Baltimore, and chief of the endocrine section, Maryland Veterans Affairs Health Care System.

Lead author Orville Kolterman, MD, chief medical officer at Pendulum, said in an interview that the formulation’s specificity distinguishes it from most commercially available probiotics.

“The ones sold in stores are reconfigurations of food probiotics, which are primarily aerobic organisms, whereas the abnormalities in the microbiome associated with type 2 diabetes reside in anaerobic organisms, which are more difficult to manufacture,” he explained.

The fiber component, inulin, is important as well, he said. “This product may make the dietary management of type 2 diabetes more effective, in that you need both the fiber and the microbes to ferment the fiber and produce short-chain fatty acids that appear to be very important for many reasons.”

The blood glucose-lowering effect is related in part to the three organisms’ production of butyrate, which binds to epithelial cells in the gut to secrete glucagonlike peptide–1, leading to inhibition of glucagon secretion among other actions.

And Akkermansia muciniphila protects the gut epithelium and has shown some evidence of improving insulin sensitivity and other beneficial metabolic effects in humans.

Dr. Kolterman, who was with Amylin Pharmaceuticals prior to moving to Pendulum, commented: “After doing this for 30 years or so, I’ve come to the strong appreciation that whenever you can do something to move back toward what Mother Nature set up, you’re doing a good thing.”

Clinically, Dr. Kolterman said, “I think perhaps the ideal place to try this would be shortly after diagnosis of type 2 diabetes, before patients go on to pharmacologic therapy.”

However, for practical reasons the study was done in patients who were already taking metformin, he said. “The results we have are that it’s beneficial above and beyond metformin, since [these] patients weren’t controlled with metformin.”

He also noted that it might benefit patients who can’t tolerate metformin or who have prediabetes; there’s an ongoing investigator-initiated study of the latter.

Dr. Steinle also endorsed the possibility that the product may benefit people with prediabetes. “I would suspect this could be very helpful to augment attempts to prevent diabetes. ... The group with prediabetes is huge.”

However, she cautioned, “if the blood glucose is over 200 [mg/dL], I wouldn’t think a probiotic would get them where they need to go.”

Overall, she pointed out that targeting the microbiome is a very active and potentially important field of medical research, and that it has received support from the National Institutes of Health. “I think we’re in the early stages of understanding how what grows in us, and on us, impacts our health and how we may be able to use these organisms to our benefit. I would expect we’ll see more of these probiotics being marketed in various forms.”

Dr. Kolterman is an employee of Pendulum. Dr. Steinle has reported receiving funding from the NIH, and she is conducting a study funded by Kowa through the VA.

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

Patients on antithrombotics after an acute MI will face a greater risk for bleeding and secondary cardiovascular (CV) events if they start taking any nonaspirin NSAID, confirms a large observational study.

Like other research before it, the new study suggests those risks will be much lower for some nonaspirin NSAIDs than others. But it may also challenge at least some conventional thinking about the safety of these drugs, and is based solely on a large cohort in South Korea, a group for which such NSAID data has been in short supply.

“It was intriguing that our study presented better safety profiles with celecoxib and meloxicam versus other subtypes of NSAIDs,” noted the report, published online July 27 in the Journal of the American College of Cardiology.

Most of the NSAIDs included in the analysis, “including naproxen, conferred a significantly higher risk for cardiovascular and bleeding events, compared with celecoxib and meloxicam,” wrote the authors, led by Dong Oh Kang, MD, Korea University Guro Hospital, Seoul, South Korea.

A main contribution of the study “is the thorough and comprehensive evaluation of the Korean population by use of the nationwide prescription claims database that reflects real-world clinical practice,” senior author Cheol Ung Choi, MD, PhD, of the same institution, said in an interview.

“Because we included the largest number of patients of any comparable clinical studies on NSAID treatment after MI thus far, our study may allow the generalizability of the adverse events of NSAIDs to all patients by constituting global evidence encompassing different population groups,” Dr. Choi said.

The analysis has limitations along with its strengths, the authors acknowledged, including its observational design and potential for confounding not addressed in statistical adjustments.

Observers of the study concurred, but some cited evidence pointing to such confounding that is serious enough to question the entire study’s validity.

Among the cohort of more than 100,000 patients followed for an average of about 2.3 years after their MI, the adjusted risk of thromboembolic CV events went up almost 7 times for those who took any NSAID for at least 4 consecutive weeks, compared with those who didn’t take NSAIDs, based on prescription records.

Their adjusted risk of bleeding events – which included gastrointestinal, intracranial, respiratory, or urinary tract bleeding or posthemorrhagic anemia, the group writes – was increased 300%.

There was wide variance in the adjusted hazard ratios for outcomes by type of NSAID. The risk of CV events climbed from a low of about 3 with meloxicam and almost 5 for celecoxib to more than 10 and 12 for naproxen and dexibuprofen, respectively.

The hazard ratios for bleeding ranged from about 3 for both meloxicam and celecoxib to more than 6 for naproxen.

Of note, celecoxib and meloxicam both preferentially target the cyclooxygenase type 2 (COX-2) pathway, and naproxen among NSAIDs once had a reputation for relative cardiac safety, although subsequent studies have challenged that notion.

“On the basis of the contemporary guidelines, NSAID treatment should be limited as much as possible after MI; however, our data suggest that celecoxib and meloxicam could be considered possible alternative choices in patients with MI when NSAID prescription is unavoidable,” the group wrote.

They acknowledged some limitations of the analysis, including an observational design and the possibility of unidentified confounders; that mortality outcomes were not available from the National Health Insurance Service database used in the study; and that the 2009-2013 span for the data didn’t allow consideration of more contemporary antiplatelet agents and direct oral anticoagulants.

Also, NSAID use was based on prescriptions without regard to over-the-counter usage. Although use of over-the-counter NSAIDs is common in Korea, “most MI patients in Korea are prescribed most medications, including NSAIDs, in the hospital. So I think that usage of over-the-counter NSAIDs did not change the results,” Dr. Choi said.

“This study breaks new ground by demonstrating cardiovascular safety of meloxicam (and not only of celecoxib), probably because of its higher COX-2 selectivity,” wrote the authors of an accompanying editorial, Juan J. Badimon, PhD, and Carlos G. Santos-Gallego, MD, both of the Icahn School of Medicine at Mount Sinai, New York.

Notably, “this paper rejects the cardiovascular safety of naproxen, which had been suggested classically and in the previous Danish data, but that was not evident in this study.” The finding is consistent with the PRECISION trial, in which both bleeding and CV risk were increased with naproxen versus other NSAIDs, observed Dr. Badimon and Dr. Santos-Gallego.

They agreed with the authors in recommending that, “although NSAID treatment should be avoided in patients with MI, if the use of NSAIDs is inevitable due to comorbidities, the prescription of celecoxib and meloxicam could be considered as alternative options.”

But, “as no study is perfect, this article also presents some limitations,” the editorial agreed, citing some of the same issues noted by Dr. Kang and associates, along with potential confounding by indication and the lack of “clinical information to adjust (e.g., angiographic features, left ventricular function).”

“There’s undoubtedly residual confounding,” James M. Brophy, MD, PhD, a pharmacoepidemiologist at McGill University, Montreal, said in an interview.

The 400%-900% relative risks for CV events “are just too far in left field, compared to everything else we know,” he said. “There has never been a class of drugs that have shown this sort of magnitude of effect for adverse events.”

Even in PRECISION with its more than 24,000 high-coronary-risk patients randomized and followed for 5 years, Dr. Brophy observed, relative risks for the different NSAIDs varied by an order of magnitude of only 1-2.

“You should be interpreting things in the context of what is already known,” Dr. Brophy said. “The only conclusion I would draw is the paper is fatally flawed.”

The registry included 108,232 primarily male patients followed from their first diagnosed MI for CV and bleeding events. About 1.9% were prescribed at least one NSAID for 4 or more consecutive weeks during the follow-up period averaging 2.3 years, the group reported.

The most frequently prescribed NSAID was diclofenac, at about 72% of prescribed NSAIDs in the analysis for CV events and about 69% in the bleeding-event analysis.

Adding any NSAID to post-MI antithrombotic therapy led to an adjusted HR of 6.96 (P < .001) for CV events and 4.08 (P < .001) for bleeding events, compared with no NSAID treatment.

The 88% of the cohort who were on dual-antiplatelet therapy with aspirin and clopidogrel showed very nearly the same risk increases for both endpoints.

Further studies are needed to confirm the results “and ensure their generalizability to other populations,” Dr. Choi said. They should be validated especially using the claims data bases of countries near Korea, “such as Japan and Taiwan, to examine the reproducibility of the results in similar ethnic populations.”

That the study focused on a cohort in Korea is a strength, contended the authors as well as Dr. Badimon and Dr. Santos-Gallego, given “that most data about NSAIDs were extracted from Western populations, but the risk of thrombosis/bleeding post-MI varies according to ethnicity,” according to the editorial

Dr. Brophy agreed, but doubted that ethnic differences are responsible for variation in relative risks between the current results and other studies. “There are pharmacogenomic differences between different ethnicities as to how they activate these drugs. But I suspect that sort of difference is really minor. Maybe it leads to a 2% or a 5% difference in risks.”

Dr. Kang and associates, Dr. Badimon, Dr. Santos-Gallego, and Dr. Brophy disclosed no relevant financial relationships.

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

Patients on antithrombotics after an acute MI will face a greater risk for bleeding and secondary cardiovascular (CV) events if they start taking any nonaspirin NSAID, confirms a large observational study.

Like other research before it, the new study suggests those risks will be much lower for some nonaspirin NSAIDs than others. But it may also challenge at least some conventional thinking about the safety of these drugs, and is based solely on a large cohort in South Korea, a group for which such NSAID data has been in short supply.

“It was intriguing that our study presented better safety profiles with celecoxib and meloxicam versus other subtypes of NSAIDs,” noted the report, published online July 27 in the Journal of the American College of Cardiology.

Most of the NSAIDs included in the analysis, “including naproxen, conferred a significantly higher risk for cardiovascular and bleeding events, compared with celecoxib and meloxicam,” wrote the authors, led by Dong Oh Kang, MD, Korea University Guro Hospital, Seoul, South Korea.

A main contribution of the study “is the thorough and comprehensive evaluation of the Korean population by use of the nationwide prescription claims database that reflects real-world clinical practice,” senior author Cheol Ung Choi, MD, PhD, of the same institution, said in an interview.

“Because we included the largest number of patients of any comparable clinical studies on NSAID treatment after MI thus far, our study may allow the generalizability of the adverse events of NSAIDs to all patients by constituting global evidence encompassing different population groups,” Dr. Choi said.

The analysis has limitations along with its strengths, the authors acknowledged, including its observational design and potential for confounding not addressed in statistical adjustments.

Observers of the study concurred, but some cited evidence pointing to such confounding that is serious enough to question the entire study’s validity.

Among the cohort of more than 100,000 patients followed for an average of about 2.3 years after their MI, the adjusted risk of thromboembolic CV events went up almost 7 times for those who took any NSAID for at least 4 consecutive weeks, compared with those who didn’t take NSAIDs, based on prescription records.

Their adjusted risk of bleeding events – which included gastrointestinal, intracranial, respiratory, or urinary tract bleeding or posthemorrhagic anemia, the group writes – was increased 300%.

There was wide variance in the adjusted hazard ratios for outcomes by type of NSAID. The risk of CV events climbed from a low of about 3 with meloxicam and almost 5 for celecoxib to more than 10 and 12 for naproxen and dexibuprofen, respectively.

The hazard ratios for bleeding ranged from about 3 for both meloxicam and celecoxib to more than 6 for naproxen.

Of note, celecoxib and meloxicam both preferentially target the cyclooxygenase type 2 (COX-2) pathway, and naproxen among NSAIDs once had a reputation for relative cardiac safety, although subsequent studies have challenged that notion.

“On the basis of the contemporary guidelines, NSAID treatment should be limited as much as possible after MI; however, our data suggest that celecoxib and meloxicam could be considered possible alternative choices in patients with MI when NSAID prescription is unavoidable,” the group wrote.

They acknowledged some limitations of the analysis, including an observational design and the possibility of unidentified confounders; that mortality outcomes were not available from the National Health Insurance Service database used in the study; and that the 2009-2013 span for the data didn’t allow consideration of more contemporary antiplatelet agents and direct oral anticoagulants.

Also, NSAID use was based on prescriptions without regard to over-the-counter usage. Although use of over-the-counter NSAIDs is common in Korea, “most MI patients in Korea are prescribed most medications, including NSAIDs, in the hospital. So I think that usage of over-the-counter NSAIDs did not change the results,” Dr. Choi said.

“This study breaks new ground by demonstrating cardiovascular safety of meloxicam (and not only of celecoxib), probably because of its higher COX-2 selectivity,” wrote the authors of an accompanying editorial, Juan J. Badimon, PhD, and Carlos G. Santos-Gallego, MD, both of the Icahn School of Medicine at Mount Sinai, New York.

Notably, “this paper rejects the cardiovascular safety of naproxen, which had been suggested classically and in the previous Danish data, but that was not evident in this study.” The finding is consistent with the PRECISION trial, in which both bleeding and CV risk were increased with naproxen versus other NSAIDs, observed Dr. Badimon and Dr. Santos-Gallego.

They agreed with the authors in recommending that, “although NSAID treatment should be avoided in patients with MI, if the use of NSAIDs is inevitable due to comorbidities, the prescription of celecoxib and meloxicam could be considered as alternative options.”

But, “as no study is perfect, this article also presents some limitations,” the editorial agreed, citing some of the same issues noted by Dr. Kang and associates, along with potential confounding by indication and the lack of “clinical information to adjust (e.g., angiographic features, left ventricular function).”

“There’s undoubtedly residual confounding,” James M. Brophy, MD, PhD, a pharmacoepidemiologist at McGill University, Montreal, said in an interview.

The 400%-900% relative risks for CV events “are just too far in left field, compared to everything else we know,” he said. “There has never been a class of drugs that have shown this sort of magnitude of effect for adverse events.”

Even in PRECISION with its more than 24,000 high-coronary-risk patients randomized and followed for 5 years, Dr. Brophy observed, relative risks for the different NSAIDs varied by an order of magnitude of only 1-2.

“You should be interpreting things in the context of what is already known,” Dr. Brophy said. “The only conclusion I would draw is the paper is fatally flawed.”

The registry included 108,232 primarily male patients followed from their first diagnosed MI for CV and bleeding events. About 1.9% were prescribed at least one NSAID for 4 or more consecutive weeks during the follow-up period averaging 2.3 years, the group reported.

The most frequently prescribed NSAID was diclofenac, at about 72% of prescribed NSAIDs in the analysis for CV events and about 69% in the bleeding-event analysis.

Adding any NSAID to post-MI antithrombotic therapy led to an adjusted HR of 6.96 (P < .001) for CV events and 4.08 (P < .001) for bleeding events, compared with no NSAID treatment.

The 88% of the cohort who were on dual-antiplatelet therapy with aspirin and clopidogrel showed very nearly the same risk increases for both endpoints.

Further studies are needed to confirm the results “and ensure their generalizability to other populations,” Dr. Choi said. They should be validated especially using the claims data bases of countries near Korea, “such as Japan and Taiwan, to examine the reproducibility of the results in similar ethnic populations.”

That the study focused on a cohort in Korea is a strength, contended the authors as well as Dr. Badimon and Dr. Santos-Gallego, given “that most data about NSAIDs were extracted from Western populations, but the risk of thrombosis/bleeding post-MI varies according to ethnicity,” according to the editorial

Dr. Brophy agreed, but doubted that ethnic differences are responsible for variation in relative risks between the current results and other studies. “There are pharmacogenomic differences between different ethnicities as to how they activate these drugs. But I suspect that sort of difference is really minor. Maybe it leads to a 2% or a 5% difference in risks.”

Dr. Kang and associates, Dr. Badimon, Dr. Santos-Gallego, and Dr. Brophy disclosed no relevant financial relationships.

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

Patients on antithrombotics after an acute MI will face a greater risk for bleeding and secondary cardiovascular (CV) events if they start taking any nonaspirin NSAID, confirms a large observational study.

Like other research before it, the new study suggests those risks will be much lower for some nonaspirin NSAIDs than others. But it may also challenge at least some conventional thinking about the safety of these drugs, and is based solely on a large cohort in South Korea, a group for which such NSAID data has been in short supply.

“It was intriguing that our study presented better safety profiles with celecoxib and meloxicam versus other subtypes of NSAIDs,” noted the report, published online July 27 in the Journal of the American College of Cardiology.

Most of the NSAIDs included in the analysis, “including naproxen, conferred a significantly higher risk for cardiovascular and bleeding events, compared with celecoxib and meloxicam,” wrote the authors, led by Dong Oh Kang, MD, Korea University Guro Hospital, Seoul, South Korea.

A main contribution of the study “is the thorough and comprehensive evaluation of the Korean population by use of the nationwide prescription claims database that reflects real-world clinical practice,” senior author Cheol Ung Choi, MD, PhD, of the same institution, said in an interview.

“Because we included the largest number of patients of any comparable clinical studies on NSAID treatment after MI thus far, our study may allow the generalizability of the adverse events of NSAIDs to all patients by constituting global evidence encompassing different population groups,” Dr. Choi said.

The analysis has limitations along with its strengths, the authors acknowledged, including its observational design and potential for confounding not addressed in statistical adjustments.

Observers of the study concurred, but some cited evidence pointing to such confounding that is serious enough to question the entire study’s validity.

Among the cohort of more than 100,000 patients followed for an average of about 2.3 years after their MI, the adjusted risk of thromboembolic CV events went up almost 7 times for those who took any NSAID for at least 4 consecutive weeks, compared with those who didn’t take NSAIDs, based on prescription records.

Their adjusted risk of bleeding events – which included gastrointestinal, intracranial, respiratory, or urinary tract bleeding or posthemorrhagic anemia, the group writes – was increased 300%.

There was wide variance in the adjusted hazard ratios for outcomes by type of NSAID. The risk of CV events climbed from a low of about 3 with meloxicam and almost 5 for celecoxib to more than 10 and 12 for naproxen and dexibuprofen, respectively.

The hazard ratios for bleeding ranged from about 3 for both meloxicam and celecoxib to more than 6 for naproxen.

Of note, celecoxib and meloxicam both preferentially target the cyclooxygenase type 2 (COX-2) pathway, and naproxen among NSAIDs once had a reputation for relative cardiac safety, although subsequent studies have challenged that notion.

“On the basis of the contemporary guidelines, NSAID treatment should be limited as much as possible after MI; however, our data suggest that celecoxib and meloxicam could be considered possible alternative choices in patients with MI when NSAID prescription is unavoidable,” the group wrote.

They acknowledged some limitations of the analysis, including an observational design and the possibility of unidentified confounders; that mortality outcomes were not available from the National Health Insurance Service database used in the study; and that the 2009-2013 span for the data didn’t allow consideration of more contemporary antiplatelet agents and direct oral anticoagulants.

Also, NSAID use was based on prescriptions without regard to over-the-counter usage. Although use of over-the-counter NSAIDs is common in Korea, “most MI patients in Korea are prescribed most medications, including NSAIDs, in the hospital. So I think that usage of over-the-counter NSAIDs did not change the results,” Dr. Choi said.

“This study breaks new ground by demonstrating cardiovascular safety of meloxicam (and not only of celecoxib), probably because of its higher COX-2 selectivity,” wrote the authors of an accompanying editorial, Juan J. Badimon, PhD, and Carlos G. Santos-Gallego, MD, both of the Icahn School of Medicine at Mount Sinai, New York.

Notably, “this paper rejects the cardiovascular safety of naproxen, which had been suggested classically and in the previous Danish data, but that was not evident in this study.” The finding is consistent with the PRECISION trial, in which both bleeding and CV risk were increased with naproxen versus other NSAIDs, observed Dr. Badimon and Dr. Santos-Gallego.

They agreed with the authors in recommending that, “although NSAID treatment should be avoided in patients with MI, if the use of NSAIDs is inevitable due to comorbidities, the prescription of celecoxib and meloxicam could be considered as alternative options.”

But, “as no study is perfect, this article also presents some limitations,” the editorial agreed, citing some of the same issues noted by Dr. Kang and associates, along with potential confounding by indication and the lack of “clinical information to adjust (e.g., angiographic features, left ventricular function).”

“There’s undoubtedly residual confounding,” James M. Brophy, MD, PhD, a pharmacoepidemiologist at McGill University, Montreal, said in an interview.

The 400%-900% relative risks for CV events “are just too far in left field, compared to everything else we know,” he said. “There has never been a class of drugs that have shown this sort of magnitude of effect for adverse events.”

Even in PRECISION with its more than 24,000 high-coronary-risk patients randomized and followed for 5 years, Dr. Brophy observed, relative risks for the different NSAIDs varied by an order of magnitude of only 1-2.

“You should be interpreting things in the context of what is already known,” Dr. Brophy said. “The only conclusion I would draw is the paper is fatally flawed.”

The registry included 108,232 primarily male patients followed from their first diagnosed MI for CV and bleeding events. About 1.9% were prescribed at least one NSAID for 4 or more consecutive weeks during the follow-up period averaging 2.3 years, the group reported.

The most frequently prescribed NSAID was diclofenac, at about 72% of prescribed NSAIDs in the analysis for CV events and about 69% in the bleeding-event analysis.

Adding any NSAID to post-MI antithrombotic therapy led to an adjusted HR of 6.96 (P < .001) for CV events and 4.08 (P < .001) for bleeding events, compared with no NSAID treatment.

The 88% of the cohort who were on dual-antiplatelet therapy with aspirin and clopidogrel showed very nearly the same risk increases for both endpoints.

Further studies are needed to confirm the results “and ensure their generalizability to other populations,” Dr. Choi said. They should be validated especially using the claims data bases of countries near Korea, “such as Japan and Taiwan, to examine the reproducibility of the results in similar ethnic populations.”

That the study focused on a cohort in Korea is a strength, contended the authors as well as Dr. Badimon and Dr. Santos-Gallego, given “that most data about NSAIDs were extracted from Western populations, but the risk of thrombosis/bleeding post-MI varies according to ethnicity,” according to the editorial

Dr. Brophy agreed, but doubted that ethnic differences are responsible for variation in relative risks between the current results and other studies. “There are pharmacogenomic differences between different ethnicities as to how they activate these drugs. But I suspect that sort of difference is really minor. Maybe it leads to a 2% or a 5% difference in risks.”

Dr. Kang and associates, Dr. Badimon, Dr. Santos-Gallego, and Dr. Brophy disclosed no relevant financial relationships.

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

Older Americans – people aged 65 or older – make up 15% of the U.S. population, according to the Census Bureau. By the end of this decade, or the year 2030, this proportion will increase to 21% – and all “baby boomers,” those born between 1946 and 1964, will be older than 65.¹ Those demographic developments are occurring alongside a change in societal, legal, and public attitudes on cannabis.

VladK213/Getty Images

Liberalization of cannabis laws across the United States allows for ever easier access to medicinal and recreational cannabis. Traditionally, cannabis use, its effects, and related considerations in the adolescent and young adult populations have commanded significant research attention. Cannabis use in older adults, however, is not as well studied.² An exploration of trends in cannabis use by older adults and potential impact in terms of health is timely and important.

According to data from the National Survey on Drug Use and Health, cannabis use in adults aged 65 years and older appears to have been increasing steadily over the past 2 decades. Use among this group rose from 0.4% in 2006 and 2007, to 2.9% in 2015 and 2016.² And, most recently, use climbed from 3.7% in 2017 to 4.2% in 2018.²

Cannabis use also has risen among other adults. For those aged 50-64, cannabis use increased from 2.8% in 2006-2007 to 4.8% in 2012-2013.^2,3 Meanwhile, from 2015 to 2016, that number increased to 9.0%.^3,4

Past-year cannabis use in the groups of those aged 50-64 and those aged 65 and older appears to be higher in individuals with mental health problems, alcohol use disorder, and nicotine dependence.^5,6 Being male and being unmarried appear to be correlated with past-year cannabis use. Multimorbidity does not appear to be associated with past-year cannabis use. Those using cannabis tend to be long-term users and have first use at a much younger age, typically before age 21. Most older adults who report cannabis use do not perceive use to be of any risk or deem it only a slight risk.

Older adults use cannabis for both recreational and perceived medical benefits. Arthritis, chronic back pain, anxiety, depression, relaxation, stress reduction, and enhancement in terms of creativity are all purported reasons for use. However, there is limited to no evidence for the efficacy of cannabis in helping with those conditions and purposes. Clinical trials have shown that cannabis can be beneficial in managing pain and nausea, but those trials have not been conducted in older adults.^7,8

There is a real risk of cannabis use having a negative impact on the health of older adults. To begin with, the cannabis consumed today is significantly higher in potency than the cannabis that baby boomers were introduced to in their youth. The higher potency, combined with an age-related decline in function experienced by some older adults, makes them vulnerable to its known side effects, such as anxiety, dry mouth, tachycardia, high blood pressure, palpitations, wheezing, confusion, and dizziness.

Cannabis use is reported to bring a fourfold increase in cardiac events within the first hour of ingestion.⁹ Cognitive decline and memory impairment are well known adverse effects of cannabis use. Research has shown significant self-reported cognitive decline in older adults in relation to cannabis use.Cannabis metabolites are known to have an effect on cytochrome P450 enzymes, affecting the metabolism of medication, and increasing the susceptibility of older adults who use cannabis to adverse effects of polypharmacy. Finally, as research on emergency department visits by older adults shows, cannabis use can increase the risk of injury among this cohort.

As in the United States, cannabis use among older adults in Canada has increased significantly. The percentage of older adults who use cannabis in the Canadian province of Ontario, for example, reportedly doubled from 2005 to 2015. In response to this increase, and in anticipation of a rise in problematic use of cannabis and cannabis use disorder in older adults, the Canadian Coalition for Seniors’ Mental Health (through financial support from Substance Use and Addictions Program of Health Canada) has created guidelines on the prevention, assessment, and management of cannabis use disorder in older adults.

In the absence of a set of guidelines specific to the United States, the recommendations made by the coalition should be helpful in the care of older Americans. Among other recommendations, the guidelines highlight the needs for primary care physicians to build a better knowledge base around the use of cannabis in older adults, to screen older adults for cannabis use, and to educate older adults and their families about the risk of cannabis use.⁹

Cannabis use is increasingly popular among older adults¹⁰ for both medicinal and recreational purposes. Research and data supporting its medical benefits are limited, and the potential of harm from its use among older adults is present and significant. Importantly, many older adults who use marijuana have co-occurring mental health issues and substance use disorder(s).

Often, our older patients learn about benefits and harms of cannabis from friends and the Internet rather than from physicians and other clinicians.⁹ We must do our part to make sure that older patients understand the potential negative health impact that cannabis can have on their health. Physicians should screen older adults for marijuana use. Building a better knowledge base around changing trends and views in/on the use and accessibility of cannabis will help physicians better address cannabis use in older adults.
 

Mr. Kaleka is a medical student in the class of 2021 at Central Michigan University College of Medicine, Mount Pleasant. He has no disclosures. Mr. Kaleka would like to thank his mentor, Furhut Janssen, DO, for her continued guidance and support in research on mental health in vulnerable populations.

References

1. Vespa J et al. Demographic turning points for the United States: Population projections for 2020 to 2060. Current Population Reports. Washington: U.S. Census Bureau. 2020 Feb.

2. Han BH et al. Addiction. 2016 Oct 21. doi: 10.1111/add.13670.

3. Han BH and Palamar JJ. Drug Alcohol Depend. 2018 Oct;191:374-81.

4. Han BH and Palamar JJ. JAMA Intern Med. 2020 Feb 4;180(4):609-11.

5. Choi NG et al. Drug Alcohol Abuse. 2018;44(2):215-23.

6. Reynolds IR et al. J Am Griatr Soc. 2018 Nov;66(11):2167-71.

7. Ahmed AIA et al. J Am Geriatr Soc. 2014 Feb;62(2):410-1.

8. Lum HD et al. Gerontol Geriatr Med. 2019 Jan-Dec;5:2333721419843707.

9. Bertram JR et al. Can Geriatr J. 2020 Mar;23(1):135-42.

10. Baumbusch J and Yip IS. Clin Gerontol. 2020 Mar 29;1-7.

Older Americans – people aged 65 or older – make up 15% of the U.S. population, according to the Census Bureau. By the end of this decade, or the year 2030, this proportion will increase to 21% – and all “baby boomers,” those born between 1946 and 1964, will be older than 65.¹ Those demographic developments are occurring alongside a change in societal, legal, and public attitudes on cannabis.

VladK213/Getty Images

Liberalization of cannabis laws across the United States allows for ever easier access to medicinal and recreational cannabis. Traditionally, cannabis use, its effects, and related considerations in the adolescent and young adult populations have commanded significant research attention. Cannabis use in older adults, however, is not as well studied.² An exploration of trends in cannabis use by older adults and potential impact in terms of health is timely and important.

According to data from the National Survey on Drug Use and Health, cannabis use in adults aged 65 years and older appears to have been increasing steadily over the past 2 decades. Use among this group rose from 0.4% in 2006 and 2007, to 2.9% in 2015 and 2016.² And, most recently, use climbed from 3.7% in 2017 to 4.2% in 2018.²

Cannabis use also has risen among other adults. For those aged 50-64, cannabis use increased from 2.8% in 2006-2007 to 4.8% in 2012-2013.^2,3 Meanwhile, from 2015 to 2016, that number increased to 9.0%.^3,4

Past-year cannabis use in the groups of those aged 50-64 and those aged 65 and older appears to be higher in individuals with mental health problems, alcohol use disorder, and nicotine dependence.^5,6 Being male and being unmarried appear to be correlated with past-year cannabis use. Multimorbidity does not appear to be associated with past-year cannabis use. Those using cannabis tend to be long-term users and have first use at a much younger age, typically before age 21. Most older adults who report cannabis use do not perceive use to be of any risk or deem it only a slight risk.

Older adults use cannabis for both recreational and perceived medical benefits. Arthritis, chronic back pain, anxiety, depression, relaxation, stress reduction, and enhancement in terms of creativity are all purported reasons for use. However, there is limited to no evidence for the efficacy of cannabis in helping with those conditions and purposes. Clinical trials have shown that cannabis can be beneficial in managing pain and nausea, but those trials have not been conducted in older adults.^7,8

There is a real risk of cannabis use having a negative impact on the health of older adults. To begin with, the cannabis consumed today is significantly higher in potency than the cannabis that baby boomers were introduced to in their youth. The higher potency, combined with an age-related decline in function experienced by some older adults, makes them vulnerable to its known side effects, such as anxiety, dry mouth, tachycardia, high blood pressure, palpitations, wheezing, confusion, and dizziness.

Cannabis use is reported to bring a fourfold increase in cardiac events within the first hour of ingestion.⁹ Cognitive decline and memory impairment are well known adverse effects of cannabis use. Research has shown significant self-reported cognitive decline in older adults in relation to cannabis use.Cannabis metabolites are known to have an effect on cytochrome P450 enzymes, affecting the metabolism of medication, and increasing the susceptibility of older adults who use cannabis to adverse effects of polypharmacy. Finally, as research on emergency department visits by older adults shows, cannabis use can increase the risk of injury among this cohort.

As in the United States, cannabis use among older adults in Canada has increased significantly. The percentage of older adults who use cannabis in the Canadian province of Ontario, for example, reportedly doubled from 2005 to 2015. In response to this increase, and in anticipation of a rise in problematic use of cannabis and cannabis use disorder in older adults, the Canadian Coalition for Seniors’ Mental Health (through financial support from Substance Use and Addictions Program of Health Canada) has created guidelines on the prevention, assessment, and management of cannabis use disorder in older adults.

In the absence of a set of guidelines specific to the United States, the recommendations made by the coalition should be helpful in the care of older Americans. Among other recommendations, the guidelines highlight the needs for primary care physicians to build a better knowledge base around the use of cannabis in older adults, to screen older adults for cannabis use, and to educate older adults and their families about the risk of cannabis use.⁹

Cannabis use is increasingly popular among older adults¹⁰ for both medicinal and recreational purposes. Research and data supporting its medical benefits are limited, and the potential of harm from its use among older adults is present and significant. Importantly, many older adults who use marijuana have co-occurring mental health issues and substance use disorder(s).

Often, our older patients learn about benefits and harms of cannabis from friends and the Internet rather than from physicians and other clinicians.⁹ We must do our part to make sure that older patients understand the potential negative health impact that cannabis can have on their health. Physicians should screen older adults for marijuana use. Building a better knowledge base around changing trends and views in/on the use and accessibility of cannabis will help physicians better address cannabis use in older adults.
 

Mr. Kaleka is a medical student in the class of 2021 at Central Michigan University College of Medicine, Mount Pleasant. He has no disclosures. Mr. Kaleka would like to thank his mentor, Furhut Janssen, DO, for her continued guidance and support in research on mental health in vulnerable populations.

References

1. Vespa J et al. Demographic turning points for the United States: Population projections for 2020 to 2060. Current Population Reports. Washington: U.S. Census Bureau. 2020 Feb.

2. Han BH et al. Addiction. 2016 Oct 21. doi: 10.1111/add.13670.

3. Han BH and Palamar JJ. Drug Alcohol Depend. 2018 Oct;191:374-81.

4. Han BH and Palamar JJ. JAMA Intern Med. 2020 Feb 4;180(4):609-11.

5. Choi NG et al. Drug Alcohol Abuse. 2018;44(2):215-23.

6. Reynolds IR et al. J Am Griatr Soc. 2018 Nov;66(11):2167-71.

7. Ahmed AIA et al. J Am Geriatr Soc. 2014 Feb;62(2):410-1.

8. Lum HD et al. Gerontol Geriatr Med. 2019 Jan-Dec;5:2333721419843707.

9. Bertram JR et al. Can Geriatr J. 2020 Mar;23(1):135-42.

10. Baumbusch J and Yip IS. Clin Gerontol. 2020 Mar 29;1-7.

Older Americans – people aged 65 or older – make up 15% of the U.S. population, according to the Census Bureau. By the end of this decade, or the year 2030, this proportion will increase to 21% – and all “baby boomers,” those born between 1946 and 1964, will be older than 65.¹ Those demographic developments are occurring alongside a change in societal, legal, and public attitudes on cannabis.

VladK213/Getty Images

Liberalization of cannabis laws across the United States allows for ever easier access to medicinal and recreational cannabis. Traditionally, cannabis use, its effects, and related considerations in the adolescent and young adult populations have commanded significant research attention. Cannabis use in older adults, however, is not as well studied.² An exploration of trends in cannabis use by older adults and potential impact in terms of health is timely and important.

According to data from the National Survey on Drug Use and Health, cannabis use in adults aged 65 years and older appears to have been increasing steadily over the past 2 decades. Use among this group rose from 0.4% in 2006 and 2007, to 2.9% in 2015 and 2016.² And, most recently, use climbed from 3.7% in 2017 to 4.2% in 2018.²

Cannabis use also has risen among other adults. For those aged 50-64, cannabis use increased from 2.8% in 2006-2007 to 4.8% in 2012-2013.^2,3 Meanwhile, from 2015 to 2016, that number increased to 9.0%.^3,4

Past-year cannabis use in the groups of those aged 50-64 and those aged 65 and older appears to be higher in individuals with mental health problems, alcohol use disorder, and nicotine dependence.^5,6 Being male and being unmarried appear to be correlated with past-year cannabis use. Multimorbidity does not appear to be associated with past-year cannabis use. Those using cannabis tend to be long-term users and have first use at a much younger age, typically before age 21. Most older adults who report cannabis use do not perceive use to be of any risk or deem it only a slight risk.

Older adults use cannabis for both recreational and perceived medical benefits. Arthritis, chronic back pain, anxiety, depression, relaxation, stress reduction, and enhancement in terms of creativity are all purported reasons for use. However, there is limited to no evidence for the efficacy of cannabis in helping with those conditions and purposes. Clinical trials have shown that cannabis can be beneficial in managing pain and nausea, but those trials have not been conducted in older adults.^7,8

There is a real risk of cannabis use having a negative impact on the health of older adults. To begin with, the cannabis consumed today is significantly higher in potency than the cannabis that baby boomers were introduced to in their youth. The higher potency, combined with an age-related decline in function experienced by some older adults, makes them vulnerable to its known side effects, such as anxiety, dry mouth, tachycardia, high blood pressure, palpitations, wheezing, confusion, and dizziness.

Cannabis use is reported to bring a fourfold increase in cardiac events within the first hour of ingestion.⁹ Cognitive decline and memory impairment are well known adverse effects of cannabis use. Research has shown significant self-reported cognitive decline in older adults in relation to cannabis use.Cannabis metabolites are known to have an effect on cytochrome P450 enzymes, affecting the metabolism of medication, and increasing the susceptibility of older adults who use cannabis to adverse effects of polypharmacy. Finally, as research on emergency department visits by older adults shows, cannabis use can increase the risk of injury among this cohort.

As in the United States, cannabis use among older adults in Canada has increased significantly. The percentage of older adults who use cannabis in the Canadian province of Ontario, for example, reportedly doubled from 2005 to 2015. In response to this increase, and in anticipation of a rise in problematic use of cannabis and cannabis use disorder in older adults, the Canadian Coalition for Seniors’ Mental Health (through financial support from Substance Use and Addictions Program of Health Canada) has created guidelines on the prevention, assessment, and management of cannabis use disorder in older adults.

In the absence of a set of guidelines specific to the United States, the recommendations made by the coalition should be helpful in the care of older Americans. Among other recommendations, the guidelines highlight the needs for primary care physicians to build a better knowledge base around the use of cannabis in older adults, to screen older adults for cannabis use, and to educate older adults and their families about the risk of cannabis use.⁹

Cannabis use is increasingly popular among older adults¹⁰ for both medicinal and recreational purposes. Research and data supporting its medical benefits are limited, and the potential of harm from its use among older adults is present and significant. Importantly, many older adults who use marijuana have co-occurring mental health issues and substance use disorder(s).

Often, our older patients learn about benefits and harms of cannabis from friends and the Internet rather than from physicians and other clinicians.⁹ We must do our part to make sure that older patients understand the potential negative health impact that cannabis can have on their health. Physicians should screen older adults for marijuana use. Building a better knowledge base around changing trends and views in/on the use and accessibility of cannabis will help physicians better address cannabis use in older adults.
 

Mr. Kaleka is a medical student in the class of 2021 at Central Michigan University College of Medicine, Mount Pleasant. He has no disclosures. Mr. Kaleka would like to thank his mentor, Furhut Janssen, DO, for her continued guidance and support in research on mental health in vulnerable populations.

References

1. Vespa J et al. Demographic turning points for the United States: Population projections for 2020 to 2060. Current Population Reports. Washington: U.S. Census Bureau. 2020 Feb.

2. Han BH et al. Addiction. 2016 Oct 21. doi: 10.1111/add.13670.

3. Han BH and Palamar JJ. Drug Alcohol Depend. 2018 Oct;191:374-81.

4. Han BH and Palamar JJ. JAMA Intern Med. 2020 Feb 4;180(4):609-11.

5. Choi NG et al. Drug Alcohol Abuse. 2018;44(2):215-23.

6. Reynolds IR et al. J Am Griatr Soc. 2018 Nov;66(11):2167-71.

7. Ahmed AIA et al. J Am Geriatr Soc. 2014 Feb;62(2):410-1.

8. Lum HD et al. Gerontol Geriatr Med. 2019 Jan-Dec;5:2333721419843707.

9. Bertram JR et al. Can Geriatr J. 2020 Mar;23(1):135-42.

10. Baumbusch J and Yip IS. Clin Gerontol. 2020 Mar 29;1-7.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adam B. Hill, MD, is home on a “staycation” this week. Today, he took a 3-hour nap. I know this because I follow Dr. Hill on Twitter, where he has an active feed, a lot of posts, retweets, and more than 20,000 followers.

I also know from Twitter that he is married and has three young children, that he was once suicidal, and has been treated for major depression and alcoholism. As a palliative care doctor, Dr. Hill was required by his state medical board to blow into a breathalyzer several times a day for 5 years – something he felt quite shamed by – and while I’ve never met him, I felt just a little bit proud of this stranger when he was released from the medical board’s oversight.

Dr. Hill’s memoir, “Long Walk Out of the Woods: A Physician’s Story of Addiction, Depression, Hope, and Recovery” (Central Recovery Press, 2019) is the culmination of his efforts to use his difficulties as a way of offering hope and connection to anyone who struggled as he has, or to anyone who has struggled at all. Like his Twitter feed, it is a display of vulnerability and gratitude by someone who has been through dark times then returned to conquer his monsters.

Courtesy Central Recovery Press

He begins by setting the stage for us. “My name is Adam,” he announces in the preface. He tells us his various titles: human being, husband, father, physician, recovering alcoholic, and psychiatric patient. “In the midst of these struggles, working in modern medicine fractured my identity, stole my authenticity, and left me a shell of the person I wanted to be.”

We learn that he tried to buy a gun, but there was a waiting period and he could not purchase the firearm. Instead, he walked into the woods to drink himself to death, with sleeping pills as an add-on – obviously, he didn’t die, and his journey back from his failed suicidal mission is the meat of the book.

Dr. Hill was a quiet and timid child, and he was bullied at school in a way that has lingered on. He struggles with perfectionism and with a sense of never quite belonging. He was a good student, and later a competitive tennis player who was destined for a regional competition until he broke his ankle after drinking just days before the competition. He did well in college, felt more accepted, and went on to medical school after getting in from the wait list. He went on to do a pediatrics residency, and he and his wife moved from Indiana to North Carolina so he could do a hematology oncology fellowship. It was toward the end of his 2-year fellowship when he tried to purchase a gun, then walked into those woods.

His wife called, asked him to come to dinner, and he left the woods before he’d overdosed. After a meeting with his wife, parents, and sister, he returned to psychiatric care, restarted antidepressants, went to Alcoholics Anonymous, and told his employer that he had a problem. This admission started a distressing series of events, including years of being monitored by state medical boards and being labeled an “impaired physician.”

This is the only thing I didn’t like about Dr. Hill’s memoir: As open as he is about his emotional life, there were pieces missing with respect to what actually happened. At this point, I was befuddled as to why he self-reported his difficulties, and it wasn’t until he talked about starting a second fellowship in palliative care in his home state of Indiana that I could fill in some missing pieces. Dr. Hill and his wife purchased a house, and in November, he started his fellowship. The timing was off from the usual start in July, and I realized that perhaps he had gone to an inpatient setting for a number of months – his disclosure to his employer was voluntary, but his treatment likely interfered with his training and couldn’t be hidden. What else transpired he hints at: bottles hidden, driving while intoxicated, a nurse who gave him IV hydration when he came to work with a hangover.

From here, Dr. Hill’s story becomes every doctor’s nightmare. Settled into his new house and weeks into his fellowship, he is called in and fired: His application for a medical license in Indiana has been denied because of his addiction history. He met with a friend of his father’s who worked in a large pediatrics practice. The meeting went well, but the group felt he was too much of a malpractice risk.

He now needs to pay his mortgage and student loans, so he takes a position in Oklahoma with the Indian Health Service. He’s 700 miles from home, living alone in a hotel room, feeling like the work is beneath him, and the chapter is titled “Exile.” His new boss greets him with, “Listen, we all had our own stories that led us here.” Surprisingly, he likes the work and feels supported. If only it weren’t for all that loneliness, and not surprisingly, he relapses despite the mandated breathalyzer. Six beers later, and Dr. Hill is off to Chicago for a rehab program, then back to Oklahoma to finish off his stint.

What happens next is the second time I wondered about the plot of his life: Through “connections and concession,” he returns to Indiana for the palliative care fellowship, and goes on to work at Riley Children’s Hospital.

When a colleague unexpectedly dies from suicide, Dr. Hill tells others that he, too, once entertained suicidal thoughts. The story from here gets better and better: He uses his history of addiction and depression to help others – patients, their parents, and other medical professionals – to conquer their shame, to share their stories, to feel less alone. He and his wife become parents, he remains sober and healthy, and therapy leads him to a place of self-discovery and success.

Intertwined with telling his story, Dr. Hill takes on some of the institutional issues surrounding addiction and mental illness. He feels shamed and punished by the state medical board that mandates the terms of his medical license. Any physician who reads this book will think twice about revealing a diagnosis of depression or substance use disorder. It’s not a new idea that to protect the public, medical boards should ask about current impairments, not a past history or conditions that have been successfully treated. They should encourage treatment, not punish those who seek care.

Dr. Hill writes about how helpful it has been to allow himself to be vulnerable in the aftermath:


In my experience, the more vulnerability I show, the more opportunities I have to connect to other people. I learned the hard way that when I hide my true self from others, I spiral toward shame. Conversely, when I bury my shame, I begin to accept myself as a beautifully flawed human being, and my perspective on the world reflects that. A turn of the vulnerability dial has opened up connections to other people, while turning away pity, judgment, fear, and shame. Meanwhile, when I am to create spaces for vulnerability, permission is granted to have open and honest conversations about mental health conditions on a larger scale. But I would never have learned these lessons without having been humbled by this disease.


Perhaps the thing I liked best about Dr. Hill’s memoir is that he proposes some solutions. He talks about the importance of fighting stigma, how he finds it everywhere, and how the medical field equates mental illnesses with weakness, thereby perpetuating a self-deprecating cycle in those who have them.

Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatry Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore. Dr. Miller has no disclosures.

Adam B. Hill, MD, is home on a “staycation” this week. Today, he took a 3-hour nap. I know this because I follow Dr. Hill on Twitter, where he has an active feed, a lot of posts, retweets, and more than 20,000 followers.

I also know from Twitter that he is married and has three young children, that he was once suicidal, and has been treated for major depression and alcoholism. As a palliative care doctor, Dr. Hill was required by his state medical board to blow into a breathalyzer several times a day for 5 years – something he felt quite shamed by – and while I’ve never met him, I felt just a little bit proud of this stranger when he was released from the medical board’s oversight.

Dr. Hill’s memoir, “Long Walk Out of the Woods: A Physician’s Story of Addiction, Depression, Hope, and Recovery” (Central Recovery Press, 2019) is the culmination of his efforts to use his difficulties as a way of offering hope and connection to anyone who struggled as he has, or to anyone who has struggled at all. Like his Twitter feed, it is a display of vulnerability and gratitude by someone who has been through dark times then returned to conquer his monsters.

Courtesy Central Recovery Press

He begins by setting the stage for us. “My name is Adam,” he announces in the preface. He tells us his various titles: human being, husband, father, physician, recovering alcoholic, and psychiatric patient. “In the midst of these struggles, working in modern medicine fractured my identity, stole my authenticity, and left me a shell of the person I wanted to be.”

We learn that he tried to buy a gun, but there was a waiting period and he could not purchase the firearm. Instead, he walked into the woods to drink himself to death, with sleeping pills as an add-on – obviously, he didn’t die, and his journey back from his failed suicidal mission is the meat of the book.

Dr. Hill was a quiet and timid child, and he was bullied at school in a way that has lingered on. He struggles with perfectionism and with a sense of never quite belonging. He was a good student, and later a competitive tennis player who was destined for a regional competition until he broke his ankle after drinking just days before the competition. He did well in college, felt more accepted, and went on to medical school after getting in from the wait list. He went on to do a pediatrics residency, and he and his wife moved from Indiana to North Carolina so he could do a hematology oncology fellowship. It was toward the end of his 2-year fellowship when he tried to purchase a gun, then walked into those woods.

His wife called, asked him to come to dinner, and he left the woods before he’d overdosed. After a meeting with his wife, parents, and sister, he returned to psychiatric care, restarted antidepressants, went to Alcoholics Anonymous, and told his employer that he had a problem. This admission started a distressing series of events, including years of being monitored by state medical boards and being labeled an “impaired physician.”

This is the only thing I didn’t like about Dr. Hill’s memoir: As open as he is about his emotional life, there were pieces missing with respect to what actually happened. At this point, I was befuddled as to why he self-reported his difficulties, and it wasn’t until he talked about starting a second fellowship in palliative care in his home state of Indiana that I could fill in some missing pieces. Dr. Hill and his wife purchased a house, and in November, he started his fellowship. The timing was off from the usual start in July, and I realized that perhaps he had gone to an inpatient setting for a number of months – his disclosure to his employer was voluntary, but his treatment likely interfered with his training and couldn’t be hidden. What else transpired he hints at: bottles hidden, driving while intoxicated, a nurse who gave him IV hydration when he came to work with a hangover.

From here, Dr. Hill’s story becomes every doctor’s nightmare. Settled into his new house and weeks into his fellowship, he is called in and fired: His application for a medical license in Indiana has been denied because of his addiction history. He met with a friend of his father’s who worked in a large pediatrics practice. The meeting went well, but the group felt he was too much of a malpractice risk.

He now needs to pay his mortgage and student loans, so he takes a position in Oklahoma with the Indian Health Service. He’s 700 miles from home, living alone in a hotel room, feeling like the work is beneath him, and the chapter is titled “Exile.” His new boss greets him with, “Listen, we all had our own stories that led us here.” Surprisingly, he likes the work and feels supported. If only it weren’t for all that loneliness, and not surprisingly, he relapses despite the mandated breathalyzer. Six beers later, and Dr. Hill is off to Chicago for a rehab program, then back to Oklahoma to finish off his stint.

What happens next is the second time I wondered about the plot of his life: Through “connections and concession,” he returns to Indiana for the palliative care fellowship, and goes on to work at Riley Children’s Hospital.