Overall cancer death rates continue to fall in the United States, but incidence rates have leveled off among men and increased for women since 2012, according to the Annual Report to the Nation on the Status of Cancer.

During 2013-2017, the overall age-standardized death rate for all cancers was 158.2 per 100,000 population, and the average decline over that period was 1.5% per year. The average annual change was greater for men (–1.8%) than women (–1.4%) for 2013-2017, but the death rate was higher for men (189.3 per 100,000 vs. 135.5 per 100,000) for those years, S. Jane Henley of the Centers for Disease Control and Prevention and associates reported in Cancer.

“The drops in mortality we’re seeing are real, sustained, and a strong indication of what we can do when we work to prevent and treat cancer,” William G. Cance, MD, chief medical and scientific officer of the America Cancer Society, said in a written statement accompanying the report.

Overall cancer incidence for the most recent 5-year period (2012-2016) was 447.9 per 100,000, with rates of 487.9 for men and 421.4 for women, the investigators said.

Incidence dropped by 0.6% per year overall, but that hides a major difference between men, who saw a decrease of 1.0% a year, and women, who experienced an annual increase of 0.2%.

Over those 5 years, cancer incidence also increased by 0.8% annually among children aged 0-14 years and by 0.9% in adolescents and young adults aged 15-39 years, Ms. Henley and associates said in the report, which is a collaborative effort between the CDC, the National Cancer Institute, the American Cancer Society, and the North American Association of Central Cancer Registries.

“[W]e must not be complacent. The cancer incidence data – especially the increase in cancer among women – is a clear reminder that there is more work ahead,” Norman E. Sharpless, MD, director of the National Cancer Institute, said in the accompanying statement.

rfranki@mdedge.com

SOURCE: Henley SJ et al. Cancer. 2020 Mar 12. doi: 10.1002/cncr.32802.

Overall cancer death rates continue to fall in the United States, but incidence rates have leveled off among men and increased for women since 2012, according to the Annual Report to the Nation on the Status of Cancer.

During 2013-2017, the overall age-standardized death rate for all cancers was 158.2 per 100,000 population, and the average decline over that period was 1.5% per year. The average annual change was greater for men (–1.8%) than women (–1.4%) for 2013-2017, but the death rate was higher for men (189.3 per 100,000 vs. 135.5 per 100,000) for those years, S. Jane Henley of the Centers for Disease Control and Prevention and associates reported in Cancer.

“The drops in mortality we’re seeing are real, sustained, and a strong indication of what we can do when we work to prevent and treat cancer,” William G. Cance, MD, chief medical and scientific officer of the America Cancer Society, said in a written statement accompanying the report.

Overall cancer incidence for the most recent 5-year period (2012-2016) was 447.9 per 100,000, with rates of 487.9 for men and 421.4 for women, the investigators said.

Incidence dropped by 0.6% per year overall, but that hides a major difference between men, who saw a decrease of 1.0% a year, and women, who experienced an annual increase of 0.2%.

Over those 5 years, cancer incidence also increased by 0.8% annually among children aged 0-14 years and by 0.9% in adolescents and young adults aged 15-39 years, Ms. Henley and associates said in the report, which is a collaborative effort between the CDC, the National Cancer Institute, the American Cancer Society, and the North American Association of Central Cancer Registries.

“[W]e must not be complacent. The cancer incidence data – especially the increase in cancer among women – is a clear reminder that there is more work ahead,” Norman E. Sharpless, MD, director of the National Cancer Institute, said in the accompanying statement.

rfranki@mdedge.com

SOURCE: Henley SJ et al. Cancer. 2020 Mar 12. doi: 10.1002/cncr.32802.

Overall cancer death rates continue to fall in the United States, but incidence rates have leveled off among men and increased for women since 2012, according to the Annual Report to the Nation on the Status of Cancer.

During 2013-2017, the overall age-standardized death rate for all cancers was 158.2 per 100,000 population, and the average decline over that period was 1.5% per year. The average annual change was greater for men (–1.8%) than women (–1.4%) for 2013-2017, but the death rate was higher for men (189.3 per 100,000 vs. 135.5 per 100,000) for those years, S. Jane Henley of the Centers for Disease Control and Prevention and associates reported in Cancer.

“The drops in mortality we’re seeing are real, sustained, and a strong indication of what we can do when we work to prevent and treat cancer,” William G. Cance, MD, chief medical and scientific officer of the America Cancer Society, said in a written statement accompanying the report.

Overall cancer incidence for the most recent 5-year period (2012-2016) was 447.9 per 100,000, with rates of 487.9 for men and 421.4 for women, the investigators said.

Incidence dropped by 0.6% per year overall, but that hides a major difference between men, who saw a decrease of 1.0% a year, and women, who experienced an annual increase of 0.2%.

Over those 5 years, cancer incidence also increased by 0.8% annually among children aged 0-14 years and by 0.9% in adolescents and young adults aged 15-39 years, Ms. Henley and associates said in the report, which is a collaborative effort between the CDC, the National Cancer Institute, the American Cancer Society, and the North American Association of Central Cancer Registries.

“[W]e must not be complacent. The cancer incidence data – especially the increase in cancer among women – is a clear reminder that there is more work ahead,” Norman E. Sharpless, MD, director of the National Cancer Institute, said in the accompanying statement.

rfranki@mdedge.com

SOURCE: Henley SJ et al. Cancer. 2020 Mar 12. doi: 10.1002/cncr.32802.

The US Food and Drug Administration (FDA) has issued new draft guidance for industry on evaluating the safety of new drugs for type 2 diabetes and removed the “outdated” 12-year-old requirement for standardized cardiovascular outcomes trials (CVOTs).

The new draft guidance, “Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control,” will replace the December 2008 requirement that manufacturers conduct CVOTs to rule out unacceptable cardiovascular safety risk. That move followed concerns raised at the time about the thiazolidinedione class of glucose-lowering drugs.

Since then, “FDA has reviewed the results of several [CVOTs] conducted to meet the December 2008 guidance recommendations. None of the CVOTs to date have identified an increased risk of ischemic cardiovascular events; some of the CVOTs have instead demonstrated a reduced risk for cardiovascular events,” according to the federal register announcement.

In October 2018, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee narrowly voted (10 to 9) to continue requiring CVOTs, but most panel members also recommended some changes to them, including requirements for safety data beyond cardiovascular events.

Based on the CVOT results over the years and the panel’s recommendations, “FDA is revisiting the recommendations of the December 2008 guidance and is now proposing an updated approach to evaluating the safety of new drugs and biologics to improve glycemic control.”

“The new draft guidance does not contain the recommendation that sponsors of all new therapies for type 2 diabetes uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes,” the FDA said.

Instead, the draft calls for at least 4000 patient-years of exposure to the new drug in phase 3 trials and inclusion of study participants with comorbid conditions and/or diabetes complications, including at least 500 with stage 3-4 chronic kidney disease, 600 with established cardiovascular disease, and at least 600 over the age of 65 years.

The FDA is soliciting stakeholder input on these and other issues, including study duration, subject demographics, specific safety concerns, and event adjudication.

In a statement, Lisa Yanoff, MD, acting director of the Division for Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said: “By following previous FDA recommendations, sponsors have shown that new type 2 diabetes drugs do not have excess ischemic cardiovascular risk, which has provided reassuring cardiovascular safety information for millions of diabetes patients. Now, with this proposed approach, we will have broader, valuable safety information for these medications.”

The draft is open for comments for 90 days after March 9, 2020. It is available online, along with a link for submitting comments.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has issued new draft guidance for industry on evaluating the safety of new drugs for type 2 diabetes and removed the “outdated” 12-year-old requirement for standardized cardiovascular outcomes trials (CVOTs).

The new draft guidance, “Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control,” will replace the December 2008 requirement that manufacturers conduct CVOTs to rule out unacceptable cardiovascular safety risk. That move followed concerns raised at the time about the thiazolidinedione class of glucose-lowering drugs.

Since then, “FDA has reviewed the results of several [CVOTs] conducted to meet the December 2008 guidance recommendations. None of the CVOTs to date have identified an increased risk of ischemic cardiovascular events; some of the CVOTs have instead demonstrated a reduced risk for cardiovascular events,” according to the federal register announcement.

In October 2018, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee narrowly voted (10 to 9) to continue requiring CVOTs, but most panel members also recommended some changes to them, including requirements for safety data beyond cardiovascular events.

Based on the CVOT results over the years and the panel’s recommendations, “FDA is revisiting the recommendations of the December 2008 guidance and is now proposing an updated approach to evaluating the safety of new drugs and biologics to improve glycemic control.”

“The new draft guidance does not contain the recommendation that sponsors of all new therapies for type 2 diabetes uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes,” the FDA said.

Instead, the draft calls for at least 4000 patient-years of exposure to the new drug in phase 3 trials and inclusion of study participants with comorbid conditions and/or diabetes complications, including at least 500 with stage 3-4 chronic kidney disease, 600 with established cardiovascular disease, and at least 600 over the age of 65 years.

The FDA is soliciting stakeholder input on these and other issues, including study duration, subject demographics, specific safety concerns, and event adjudication.

In a statement, Lisa Yanoff, MD, acting director of the Division for Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said: “By following previous FDA recommendations, sponsors have shown that new type 2 diabetes drugs do not have excess ischemic cardiovascular risk, which has provided reassuring cardiovascular safety information for millions of diabetes patients. Now, with this proposed approach, we will have broader, valuable safety information for these medications.”

The draft is open for comments for 90 days after March 9, 2020. It is available online, along with a link for submitting comments.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has issued new draft guidance for industry on evaluating the safety of new drugs for type 2 diabetes and removed the “outdated” 12-year-old requirement for standardized cardiovascular outcomes trials (CVOTs).

The new draft guidance, “Type 2 Diabetes Mellitus: Evaluating the Safety of New Drugs for Improving Glycemic Control,” will replace the December 2008 requirement that manufacturers conduct CVOTs to rule out unacceptable cardiovascular safety risk. That move followed concerns raised at the time about the thiazolidinedione class of glucose-lowering drugs.

Since then, “FDA has reviewed the results of several [CVOTs] conducted to meet the December 2008 guidance recommendations. None of the CVOTs to date have identified an increased risk of ischemic cardiovascular events; some of the CVOTs have instead demonstrated a reduced risk for cardiovascular events,” according to the federal register announcement.

In October 2018, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee narrowly voted (10 to 9) to continue requiring CVOTs, but most panel members also recommended some changes to them, including requirements for safety data beyond cardiovascular events.

Based on the CVOT results over the years and the panel’s recommendations, “FDA is revisiting the recommendations of the December 2008 guidance and is now proposing an updated approach to evaluating the safety of new drugs and biologics to improve glycemic control.”

“The new draft guidance does not contain the recommendation that sponsors of all new therapies for type 2 diabetes uniformly rule out a specific degree of risk for ischemic cardiovascular adverse outcomes,” the FDA said.

Instead, the draft calls for at least 4000 patient-years of exposure to the new drug in phase 3 trials and inclusion of study participants with comorbid conditions and/or diabetes complications, including at least 500 with stage 3-4 chronic kidney disease, 600 with established cardiovascular disease, and at least 600 over the age of 65 years.

The FDA is soliciting stakeholder input on these and other issues, including study duration, subject demographics, specific safety concerns, and event adjudication.

In a statement, Lisa Yanoff, MD, acting director of the Division for Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research, said: “By following previous FDA recommendations, sponsors have shown that new type 2 diabetes drugs do not have excess ischemic cardiovascular risk, which has provided reassuring cardiovascular safety information for millions of diabetes patients. Now, with this proposed approach, we will have broader, valuable safety information for these medications.”

The draft is open for comments for 90 days after March 9, 2020. It is available online, along with a link for submitting comments.

This article first appeared on Medscape.com.

In his book, “Scam Me If You Can,” fraud expert Frank Abagnale relates the case of a 5-year-old boy whose pediatrician’s computer was hacked, compromising his name, birth date, Social Security number, insurance information, and medical records. The result was a bureaucratic nightmare that may well continue for the rest of that unfortunate young patient’s life. One can only speculate on the difficulties he might have as adult in obtaining a line of credit, or in proving his medical identity to physicians and hospitals.

tomprout/E+

Medical identity theft is increasingly popular with scam artists, because it is so lucrative. Everything a crook needs to commit ordinary identity theft – your Social Security number, bank account numbers, etc. – sells for about $25 on the black market; add health insurance and medical records, and the price can jump to $1,000 or more. That’s because there is a far greater potential yield from medical identity theft – and once your personal information and medical records are breached, they are in the Cloud for the rest of your life, available to anyone who wants to buy them. Older patients are particularly vulnerable: Medicare billing scams cost taxpayers more than $60 billion a year.

If your office’s computer system does not have effective fraud protection, you could be held liable for any fraud committed with information stolen from it – and if the information is resold years later and reused to commit more fraud, you’ll be liable for that, too. That’s why I strongly recommend that you invest in high-quality security technology and software, so that in the event of a breach, the security company will at least share in the fault and the liability. (As always, I have no financial interest in any product or industry mentioned in this column.)

Even with adequate protection, breaches can still occur, so all medical offices should have a breach response plan in place, covering how to halt security breaches, and how to handle any lost or stolen data. Your computer and security vendors can help with formulating such a plan. Patients affected by a breach need to be contacted as well, so they may put a freeze on accounts or send out fraud alerts.

Patients also need to be aware of the risks. If your EHR includes an online portal to communicate protected information to patients, it may be secure on your end, but patients are unlikely to have similar protection on their home computers. If you offer online patient portal services, you should make your patients aware of measures they can take to protect their data once it arrives on their computers or phones.

Patients should also be warned of the risks that come with sharing medical information with others. If they are asked to reveal medical data via phone or email, they need to ask who is requesting it, and why. Any unsolicited calls inquiring about their medical information, from someone who can’t or won’t confirm their identity, should be considered extremely suspicious.

We tell our patients to protect their insurance numbers as carefully as they guard their Social Security number and other valuable data, and to shred any medical paperwork they no longer need, including labels on prescription bottles. And if they see something on an Explanation of Benefits that doesn’t look right, they should question it immediately. We encourage them to take advantage of the free services at MyMedicare.gov, including Medicare Summary Notices provided every 3 months (if any services or medical supplies are received during that period), to make sure they’re being billed only for services they have received.

Your staff should be made aware of the potential for “friendly fraud,” which is defined as theft of identity and medical information by patients’ friends or family members. (According to some studies, as much as 50% of all medical identity theft may be committed this way.) Staffers should never divulge insurance numbers, diagnoses, lab reports, or any other privileged information to family or friends, whether by phone, fax, mail, or in person, without written permission from the patient. And when callers claiming to be patients request information about themselves, your employees should be alert for “red flags.” For example, legitimate patients won’t stumble over simple questions (such as “What is your birth date?”) or request test results or diagnoses that they should already know about.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

In his book, “Scam Me If You Can,” fraud expert Frank Abagnale relates the case of a 5-year-old boy whose pediatrician’s computer was hacked, compromising his name, birth date, Social Security number, insurance information, and medical records. The result was a bureaucratic nightmare that may well continue for the rest of that unfortunate young patient’s life. One can only speculate on the difficulties he might have as adult in obtaining a line of credit, or in proving his medical identity to physicians and hospitals.

tomprout/E+

Medical identity theft is increasingly popular with scam artists, because it is so lucrative. Everything a crook needs to commit ordinary identity theft – your Social Security number, bank account numbers, etc. – sells for about $25 on the black market; add health insurance and medical records, and the price can jump to $1,000 or more. That’s because there is a far greater potential yield from medical identity theft – and once your personal information and medical records are breached, they are in the Cloud for the rest of your life, available to anyone who wants to buy them. Older patients are particularly vulnerable: Medicare billing scams cost taxpayers more than $60 billion a year.

If your office’s computer system does not have effective fraud protection, you could be held liable for any fraud committed with information stolen from it – and if the information is resold years later and reused to commit more fraud, you’ll be liable for that, too. That’s why I strongly recommend that you invest in high-quality security technology and software, so that in the event of a breach, the security company will at least share in the fault and the liability. (As always, I have no financial interest in any product or industry mentioned in this column.)

Even with adequate protection, breaches can still occur, so all medical offices should have a breach response plan in place, covering how to halt security breaches, and how to handle any lost or stolen data. Your computer and security vendors can help with formulating such a plan. Patients affected by a breach need to be contacted as well, so they may put a freeze on accounts or send out fraud alerts.

Patients also need to be aware of the risks. If your EHR includes an online portal to communicate protected information to patients, it may be secure on your end, but patients are unlikely to have similar protection on their home computers. If you offer online patient portal services, you should make your patients aware of measures they can take to protect their data once it arrives on their computers or phones.

Patients should also be warned of the risks that come with sharing medical information with others. If they are asked to reveal medical data via phone or email, they need to ask who is requesting it, and why. Any unsolicited calls inquiring about their medical information, from someone who can’t or won’t confirm their identity, should be considered extremely suspicious.

We tell our patients to protect their insurance numbers as carefully as they guard their Social Security number and other valuable data, and to shred any medical paperwork they no longer need, including labels on prescription bottles. And if they see something on an Explanation of Benefits that doesn’t look right, they should question it immediately. We encourage them to take advantage of the free services at MyMedicare.gov, including Medicare Summary Notices provided every 3 months (if any services or medical supplies are received during that period), to make sure they’re being billed only for services they have received.

Your staff should be made aware of the potential for “friendly fraud,” which is defined as theft of identity and medical information by patients’ friends or family members. (According to some studies, as much as 50% of all medical identity theft may be committed this way.) Staffers should never divulge insurance numbers, diagnoses, lab reports, or any other privileged information to family or friends, whether by phone, fax, mail, or in person, without written permission from the patient. And when callers claiming to be patients request information about themselves, your employees should be alert for “red flags.” For example, legitimate patients won’t stumble over simple questions (such as “What is your birth date?”) or request test results or diagnoses that they should already know about.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

In his book, “Scam Me If You Can,” fraud expert Frank Abagnale relates the case of a 5-year-old boy whose pediatrician’s computer was hacked, compromising his name, birth date, Social Security number, insurance information, and medical records. The result was a bureaucratic nightmare that may well continue for the rest of that unfortunate young patient’s life. One can only speculate on the difficulties he might have as adult in obtaining a line of credit, or in proving his medical identity to physicians and hospitals.

tomprout/E+

Medical identity theft is increasingly popular with scam artists, because it is so lucrative. Everything a crook needs to commit ordinary identity theft – your Social Security number, bank account numbers, etc. – sells for about $25 on the black market; add health insurance and medical records, and the price can jump to $1,000 or more. That’s because there is a far greater potential yield from medical identity theft – and once your personal information and medical records are breached, they are in the Cloud for the rest of your life, available to anyone who wants to buy them. Older patients are particularly vulnerable: Medicare billing scams cost taxpayers more than $60 billion a year.

If your office’s computer system does not have effective fraud protection, you could be held liable for any fraud committed with information stolen from it – and if the information is resold years later and reused to commit more fraud, you’ll be liable for that, too. That’s why I strongly recommend that you invest in high-quality security technology and software, so that in the event of a breach, the security company will at least share in the fault and the liability. (As always, I have no financial interest in any product or industry mentioned in this column.)

Even with adequate protection, breaches can still occur, so all medical offices should have a breach response plan in place, covering how to halt security breaches, and how to handle any lost or stolen data. Your computer and security vendors can help with formulating such a plan. Patients affected by a breach need to be contacted as well, so they may put a freeze on accounts or send out fraud alerts.

Patients also need to be aware of the risks. If your EHR includes an online portal to communicate protected information to patients, it may be secure on your end, but patients are unlikely to have similar protection on their home computers. If you offer online patient portal services, you should make your patients aware of measures they can take to protect their data once it arrives on their computers or phones.

Patients should also be warned of the risks that come with sharing medical information with others. If they are asked to reveal medical data via phone or email, they need to ask who is requesting it, and why. Any unsolicited calls inquiring about their medical information, from someone who can’t or won’t confirm their identity, should be considered extremely suspicious.

We tell our patients to protect their insurance numbers as carefully as they guard their Social Security number and other valuable data, and to shred any medical paperwork they no longer need, including labels on prescription bottles. And if they see something on an Explanation of Benefits that doesn’t look right, they should question it immediately. We encourage them to take advantage of the free services at MyMedicare.gov, including Medicare Summary Notices provided every 3 months (if any services or medical supplies are received during that period), to make sure they’re being billed only for services they have received.

Your staff should be made aware of the potential for “friendly fraud,” which is defined as theft of identity and medical information by patients’ friends or family members. (According to some studies, as much as 50% of all medical identity theft may be committed this way.) Staffers should never divulge insurance numbers, diagnoses, lab reports, or any other privileged information to family or friends, whether by phone, fax, mail, or in person, without written permission from the patient. And when callers claiming to be patients request information about themselves, your employees should be alert for “red flags.” For example, legitimate patients won’t stumble over simple questions (such as “What is your birth date?”) or request test results or diagnoses that they should already know about.
 

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

PHOENIX – Statin use for the secondary prevention of cardiovascular disease increased modestly between 2008 and 2017 in the United States, but more than 40% of patients with established atherosclerotic cardiovascular disease are still not on a statin.

Doug Brunk/MDedge News

In addition, even after release of the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014;129:S1-45) that markedly increased the pool of eligible patients, disparities exist in the proportion of women versus men, and blacks and Hispanics versus whites with atherosclerotic cardiovascular disease (ASCVD) who are currently receiving a statin.

“Despite repeated calls for the use of statins for secondary prevention of CVD in multiple guidelines, gender and racial inequalities in the use of statins persist,” Joseph A. Salami, MD, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the American Heart Association. “Cardiovascular disease remains the leading cause of death in the U.S. In 2017, it was responsible for 647,457 deaths. We have an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps. Action is needed.”

Dr. Salami, a biostatistician with the Baptist Health South Florida Center for Advanced Analytics in Coral Gables, based his remarks on an analysis of data contained in the 2008-2017 Medical Expenditure Panel Survey (MEPS), a national representative survey sponsored by the Agency for Healthcare Research and Quality. “Between 2013 and 2018 there were six different guidelines released encouraging statin use among ASCVD patients,” he said. “Besides the good number needed to treat, statin use on secondary prevention of CVD is cost effective.”

Given the proven efficacy of statin use in the prevention of CVD, he and his associates set out to examine trends in the proportion of adults with ASCVD using statins and to assess for gender and racial differences in their use. The researchers used ICD-9 and ICD-10 codes to define ASCVD among the MEPS study population, as well as self-reported history of coronary artery disease, peripheral artery disease, and stroke. After excluding adults aged younger than 40 years and those without ASCVD, this left a population of 15,911 patients. Of these, 44% were female, their mean age was 62 years, and 72% were Caucasian.

Overall, statin use increased from 50% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 (P = .01). However, the annual percentage change in statin use was 0.25% among men versus 0.14% among women (P = .022). “Each year during the study period, more than 3 million women with ASCVD were not prescribed a statin, which translated into about 36 million adult-years,” Dr. Salami said. “In 2017, 16% of these women were African Americans and 15% were Hispanic.”

Logistic regression analysis revealed that in 2017, females with ASCVD were less likely to be prescribed a statin, compared with males (odds ratio, 0.52; P less than .001). In addition, compared with whites, blacks were less likely to be prescribed a statin (OR, 0.69; P = .012), as were Hispanics (OR, 0.62; P = .003). “In a multivariate logistic regression controlling for age, health insurance status, and comorbidities, the gender disparity remained statistically significant, but the racial disparity did not,” Dr. Salami said.

In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, characterized the study’s findings as sobering. “This should be an eye-opener for all of us in medicine, whether we are physicians, pharmacists, nurses, or researchers,” said Dr. Brown, who is a cardiologist and physician scientist at the Mayo Clinic in Rochester, Minn. “We’re all in this together, and we all have a role to play in addressing social determinants of health. I think we need to recognize the fact that we’re not treating blacks, Hispanics, and women to the degree that we should be, compared to whites and men. I think we need to do better, and we need to figure out how to reach that population, and how to improve.”

Dr. Salami acknowledged certain limitations of the study, including the fact that MEPS was carried out in a noninstitutionalized adult population and that the definition of ASCVD was based partly on self-report. “Therefore, an underestimation of number adults with ASCVD is likely,” he said. “We also couldn’t determine adherence to medication nor long-term use of statins among adults with ASCVD.”

He concluded his presentation by noting that, over the 10-year study period, there were about 71.2 million ASCVD adult-years without a statin prescription. “That is a staggering number,” Dr. Salami said.

He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Salami A et al. Epi/Lifestyle 2020, Abstract 4.

PHOENIX – Statin use for the secondary prevention of cardiovascular disease increased modestly between 2008 and 2017 in the United States, but more than 40% of patients with established atherosclerotic cardiovascular disease are still not on a statin.

Doug Brunk/MDedge News

In addition, even after release of the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014;129:S1-45) that markedly increased the pool of eligible patients, disparities exist in the proportion of women versus men, and blacks and Hispanics versus whites with atherosclerotic cardiovascular disease (ASCVD) who are currently receiving a statin.

“Despite repeated calls for the use of statins for secondary prevention of CVD in multiple guidelines, gender and racial inequalities in the use of statins persist,” Joseph A. Salami, MD, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the American Heart Association. “Cardiovascular disease remains the leading cause of death in the U.S. In 2017, it was responsible for 647,457 deaths. We have an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps. Action is needed.”

Dr. Salami, a biostatistician with the Baptist Health South Florida Center for Advanced Analytics in Coral Gables, based his remarks on an analysis of data contained in the 2008-2017 Medical Expenditure Panel Survey (MEPS), a national representative survey sponsored by the Agency for Healthcare Research and Quality. “Between 2013 and 2018 there were six different guidelines released encouraging statin use among ASCVD patients,” he said. “Besides the good number needed to treat, statin use on secondary prevention of CVD is cost effective.”

Given the proven efficacy of statin use in the prevention of CVD, he and his associates set out to examine trends in the proportion of adults with ASCVD using statins and to assess for gender and racial differences in their use. The researchers used ICD-9 and ICD-10 codes to define ASCVD among the MEPS study population, as well as self-reported history of coronary artery disease, peripheral artery disease, and stroke. After excluding adults aged younger than 40 years and those without ASCVD, this left a population of 15,911 patients. Of these, 44% were female, their mean age was 62 years, and 72% were Caucasian.

Overall, statin use increased from 50% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 (P = .01). However, the annual percentage change in statin use was 0.25% among men versus 0.14% among women (P = .022). “Each year during the study period, more than 3 million women with ASCVD were not prescribed a statin, which translated into about 36 million adult-years,” Dr. Salami said. “In 2017, 16% of these women were African Americans and 15% were Hispanic.”

Logistic regression analysis revealed that in 2017, females with ASCVD were less likely to be prescribed a statin, compared with males (odds ratio, 0.52; P less than .001). In addition, compared with whites, blacks were less likely to be prescribed a statin (OR, 0.69; P = .012), as were Hispanics (OR, 0.62; P = .003). “In a multivariate logistic regression controlling for age, health insurance status, and comorbidities, the gender disparity remained statistically significant, but the racial disparity did not,” Dr. Salami said.

In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, characterized the study’s findings as sobering. “This should be an eye-opener for all of us in medicine, whether we are physicians, pharmacists, nurses, or researchers,” said Dr. Brown, who is a cardiologist and physician scientist at the Mayo Clinic in Rochester, Minn. “We’re all in this together, and we all have a role to play in addressing social determinants of health. I think we need to recognize the fact that we’re not treating blacks, Hispanics, and women to the degree that we should be, compared to whites and men. I think we need to do better, and we need to figure out how to reach that population, and how to improve.”

Dr. Salami acknowledged certain limitations of the study, including the fact that MEPS was carried out in a noninstitutionalized adult population and that the definition of ASCVD was based partly on self-report. “Therefore, an underestimation of number adults with ASCVD is likely,” he said. “We also couldn’t determine adherence to medication nor long-term use of statins among adults with ASCVD.”

He concluded his presentation by noting that, over the 10-year study period, there were about 71.2 million ASCVD adult-years without a statin prescription. “That is a staggering number,” Dr. Salami said.

He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Salami A et al. Epi/Lifestyle 2020, Abstract 4.

PHOENIX – Statin use for the secondary prevention of cardiovascular disease increased modestly between 2008 and 2017 in the United States, but more than 40% of patients with established atherosclerotic cardiovascular disease are still not on a statin.

Doug Brunk/MDedge News

In addition, even after release of the 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (Circulation. 2014;129:S1-45) that markedly increased the pool of eligible patients, disparities exist in the proportion of women versus men, and blacks and Hispanics versus whites with atherosclerotic cardiovascular disease (ASCVD) who are currently receiving a statin.

“Despite repeated calls for the use of statins for secondary prevention of CVD in multiple guidelines, gender and racial inequalities in the use of statins persist,” Joseph A. Salami, MD, MPH, said at the Epidemiology and Prevention/Lifestyle and Cardiometabolic Health meeting, sponsored by the American Heart Association. “Cardiovascular disease remains the leading cause of death in the U.S. In 2017, it was responsible for 647,457 deaths. We have an opportunity to improve CVD-related outcomes and cost by intensifying efforts to use statins for the secondary prevention of CVD and closing gender and racial gaps. Action is needed.”

Dr. Salami, a biostatistician with the Baptist Health South Florida Center for Advanced Analytics in Coral Gables, based his remarks on an analysis of data contained in the 2008-2017 Medical Expenditure Panel Survey (MEPS), a national representative survey sponsored by the Agency for Healthcare Research and Quality. “Between 2013 and 2018 there were six different guidelines released encouraging statin use among ASCVD patients,” he said. “Besides the good number needed to treat, statin use on secondary prevention of CVD is cost effective.”

Given the proven efficacy of statin use in the prevention of CVD, he and his associates set out to examine trends in the proportion of adults with ASCVD using statins and to assess for gender and racial differences in their use. The researchers used ICD-9 and ICD-10 codes to define ASCVD among the MEPS study population, as well as self-reported history of coronary artery disease, peripheral artery disease, and stroke. After excluding adults aged younger than 40 years and those without ASCVD, this left a population of 15,911 patients. Of these, 44% were female, their mean age was 62 years, and 72% were Caucasian.

Overall, statin use increased from 50% in 2008 to 58.7% in 2017, with an average annual percentage change of 0.95% between 2010 and 2017 (P = .01). However, the annual percentage change in statin use was 0.25% among men versus 0.14% among women (P = .022). “Each year during the study period, more than 3 million women with ASCVD were not prescribed a statin, which translated into about 36 million adult-years,” Dr. Salami said. “In 2017, 16% of these women were African Americans and 15% were Hispanic.”

Logistic regression analysis revealed that in 2017, females with ASCVD were less likely to be prescribed a statin, compared with males (odds ratio, 0.52; P less than .001). In addition, compared with whites, blacks were less likely to be prescribed a statin (OR, 0.69; P = .012), as were Hispanics (OR, 0.62; P = .003). “In a multivariate logistic regression controlling for age, health insurance status, and comorbidities, the gender disparity remained statistically significant, but the racial disparity did not,” Dr. Salami said.

In an interview, one of the meeting session’s moderators, Sherry-Ann Brown, MD, PhD, characterized the study’s findings as sobering. “This should be an eye-opener for all of us in medicine, whether we are physicians, pharmacists, nurses, or researchers,” said Dr. Brown, who is a cardiologist and physician scientist at the Mayo Clinic in Rochester, Minn. “We’re all in this together, and we all have a role to play in addressing social determinants of health. I think we need to recognize the fact that we’re not treating blacks, Hispanics, and women to the degree that we should be, compared to whites and men. I think we need to do better, and we need to figure out how to reach that population, and how to improve.”

Dr. Salami acknowledged certain limitations of the study, including the fact that MEPS was carried out in a noninstitutionalized adult population and that the definition of ASCVD was based partly on self-report. “Therefore, an underestimation of number adults with ASCVD is likely,” he said. “We also couldn’t determine adherence to medication nor long-term use of statins among adults with ASCVD.”

He concluded his presentation by noting that, over the 10-year study period, there were about 71.2 million ASCVD adult-years without a statin prescription. “That is a staggering number,” Dr. Salami said.

He reported having no financial disclosures.

dbrunk@mdedge.com

SOURCE: Salami A et al. Epi/Lifestyle 2020, Abstract 4.

ORLANDO – Response to checkpoint inhibitors was associated with pretreatment absolute lymphocyte count (pALC) and neutrophil-lymphocyte ratio (pNLR) in patients with kidney or bladder cancer treated in a real-world setting.

Sharon Worcester/MDedge News

In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.

Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.

Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).

Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.

“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.

Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.

Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.

“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.

She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.

sworcester@mdedge.com

SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.

ORLANDO – Response to checkpoint inhibitors was associated with pretreatment absolute lymphocyte count (pALC) and neutrophil-lymphocyte ratio (pNLR) in patients with kidney or bladder cancer treated in a real-world setting.

Sharon Worcester/MDedge News

In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.

Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.

Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).

Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.

“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.

Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.

Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.

“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.

She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.

sworcester@mdedge.com

SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.

ORLANDO – Response to checkpoint inhibitors was associated with pretreatment absolute lymphocyte count (pALC) and neutrophil-lymphocyte ratio (pNLR) in patients with kidney or bladder cancer treated in a real-world setting.

Sharon Worcester/MDedge News

In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.

Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.

Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.

Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).

Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.

“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.

Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.

Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.

“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.

She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.

sworcester@mdedge.com

SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.

The monoamine oxidase inhibitor phenelzine (Nardil) appeared safe and active in a phase 2 trial of patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer.

“We sought to investigate if phenelzine would exert an anticancer effect demonstrated by decreasing PSA [prostate-specific antigen] values in biochemically recurrent prostate cancer patients,” study author Mitchell E. Gross, MD, PhD, of the University of Southern California, Los Angeles, and colleagues wrote. Their findings were published in Prostate Cancer and Prostatic Diseases.

The single-arm study included 20 patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer who received primary treatment with either radical prostatectomy (n = 18) or radiotherapy (n = 2). Study subjects had normal levels of free testosterone (50 ng/dL or above) and showed no evidence of metastatic disease on bone and CT imaging.

With respect to dosing, 18 patients were successfully titrated to the target dose of 30 mg of oral phenelzine twice daily. Five of these patients subsequently had their dose increased to 45 mg twice daily. Each dosing cycle was 28 days, with escalations occurring during the first 2 weeks of therapy.

Therapy was continued until disease progression, patient preference, therapy interruption of more than 2 weeks from study-related toxicity, or physician decision.

The primary outcome measured was PSA reduction of at least 50% from baseline. Psychiatric outcomes were also evaluated using the Hospital Anxiety and Depression Scale.

The median treatment duration was 326 days (range, 40-954 days). Among 20 evaluable patients, 5 patients (25%) achieved a PSA reduction of at least 30% from baseline, and 2 patients (10%) achieved a reduction of at least 50% from baseline.

At 12 weeks, 17 patients were still on treatment. Four patients (24%) had PSA reductions of at least 30%, and one patient (6%) had a PSA reduction of at least 50%.

The most common grade 2 or higher phenelzine-related adverse effects were dizziness (35%), hypertension (30%), and edema (10%). Serious toxicities included one case of grade 4 hypertension and two cases of grade 3 syncope, which required treatment discontinuation.

With respect to mood outcomes, Hospital Anxiety and Depression Scale scores showed a significant decline in anxiety symptoms but no difference in depressive symptoms.

The researchers acknowledged that two key limitations of this study were the small sample size and the absence of a placebo arm. Hence, the results may not accurately reflect long-term clinically relevant outcomes, such as overall survival or disease progression.

“Further studies would be needed to determine if [monoamine oxidase inhibitors], used alone or in combination with other agents, may delay clinical progression and metastasis,” the researchers concluded.

This study was funded by the USC-Taiwan Center for Translational Research and the National Cancer Institute. Some of the authors disclosed financial affiliations with Amgen, Astellas, AstraZeneca, Bayer, and other companies.

SOURCE: Gross ME et al. Prostate Cancer Prostatic Dis. 2020 Mar 3. doi: 10.1038/s41391-020-0211-9.

The monoamine oxidase inhibitor phenelzine (Nardil) appeared safe and active in a phase 2 trial of patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer.

“We sought to investigate if phenelzine would exert an anticancer effect demonstrated by decreasing PSA [prostate-specific antigen] values in biochemically recurrent prostate cancer patients,” study author Mitchell E. Gross, MD, PhD, of the University of Southern California, Los Angeles, and colleagues wrote. Their findings were published in Prostate Cancer and Prostatic Diseases.

The single-arm study included 20 patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer who received primary treatment with either radical prostatectomy (n = 18) or radiotherapy (n = 2). Study subjects had normal levels of free testosterone (50 ng/dL or above) and showed no evidence of metastatic disease on bone and CT imaging.

With respect to dosing, 18 patients were successfully titrated to the target dose of 30 mg of oral phenelzine twice daily. Five of these patients subsequently had their dose increased to 45 mg twice daily. Each dosing cycle was 28 days, with escalations occurring during the first 2 weeks of therapy.

Therapy was continued until disease progression, patient preference, therapy interruption of more than 2 weeks from study-related toxicity, or physician decision.

The primary outcome measured was PSA reduction of at least 50% from baseline. Psychiatric outcomes were also evaluated using the Hospital Anxiety and Depression Scale.

The median treatment duration was 326 days (range, 40-954 days). Among 20 evaluable patients, 5 patients (25%) achieved a PSA reduction of at least 30% from baseline, and 2 patients (10%) achieved a reduction of at least 50% from baseline.

At 12 weeks, 17 patients were still on treatment. Four patients (24%) had PSA reductions of at least 30%, and one patient (6%) had a PSA reduction of at least 50%.

The most common grade 2 or higher phenelzine-related adverse effects were dizziness (35%), hypertension (30%), and edema (10%). Serious toxicities included one case of grade 4 hypertension and two cases of grade 3 syncope, which required treatment discontinuation.

With respect to mood outcomes, Hospital Anxiety and Depression Scale scores showed a significant decline in anxiety symptoms but no difference in depressive symptoms.

The researchers acknowledged that two key limitations of this study were the small sample size and the absence of a placebo arm. Hence, the results may not accurately reflect long-term clinically relevant outcomes, such as overall survival or disease progression.

“Further studies would be needed to determine if [monoamine oxidase inhibitors], used alone or in combination with other agents, may delay clinical progression and metastasis,” the researchers concluded.

This study was funded by the USC-Taiwan Center for Translational Research and the National Cancer Institute. Some of the authors disclosed financial affiliations with Amgen, Astellas, AstraZeneca, Bayer, and other companies.

SOURCE: Gross ME et al. Prostate Cancer Prostatic Dis. 2020 Mar 3. doi: 10.1038/s41391-020-0211-9.

The monoamine oxidase inhibitor phenelzine (Nardil) appeared safe and active in a phase 2 trial of patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer.

“We sought to investigate if phenelzine would exert an anticancer effect demonstrated by decreasing PSA [prostate-specific antigen] values in biochemically recurrent prostate cancer patients,” study author Mitchell E. Gross, MD, PhD, of the University of Southern California, Los Angeles, and colleagues wrote. Their findings were published in Prostate Cancer and Prostatic Diseases.

The single-arm study included 20 patients with biochemically recurrent, nonmetastatic, castrate-sensitive prostate cancer who received primary treatment with either radical prostatectomy (n = 18) or radiotherapy (n = 2). Study subjects had normal levels of free testosterone (50 ng/dL or above) and showed no evidence of metastatic disease on bone and CT imaging.

With respect to dosing, 18 patients were successfully titrated to the target dose of 30 mg of oral phenelzine twice daily. Five of these patients subsequently had their dose increased to 45 mg twice daily. Each dosing cycle was 28 days, with escalations occurring during the first 2 weeks of therapy.

Therapy was continued until disease progression, patient preference, therapy interruption of more than 2 weeks from study-related toxicity, or physician decision.

The primary outcome measured was PSA reduction of at least 50% from baseline. Psychiatric outcomes were also evaluated using the Hospital Anxiety and Depression Scale.

The median treatment duration was 326 days (range, 40-954 days). Among 20 evaluable patients, 5 patients (25%) achieved a PSA reduction of at least 30% from baseline, and 2 patients (10%) achieved a reduction of at least 50% from baseline.

At 12 weeks, 17 patients were still on treatment. Four patients (24%) had PSA reductions of at least 30%, and one patient (6%) had a PSA reduction of at least 50%.

The most common grade 2 or higher phenelzine-related adverse effects were dizziness (35%), hypertension (30%), and edema (10%). Serious toxicities included one case of grade 4 hypertension and two cases of grade 3 syncope, which required treatment discontinuation.

With respect to mood outcomes, Hospital Anxiety and Depression Scale scores showed a significant decline in anxiety symptoms but no difference in depressive symptoms.

The researchers acknowledged that two key limitations of this study were the small sample size and the absence of a placebo arm. Hence, the results may not accurately reflect long-term clinically relevant outcomes, such as overall survival or disease progression.

“Further studies would be needed to determine if [monoamine oxidase inhibitors], used alone or in combination with other agents, may delay clinical progression and metastasis,” the researchers concluded.

This study was funded by the USC-Taiwan Center for Translational Research and the National Cancer Institute. Some of the authors disclosed financial affiliations with Amgen, Astellas, AstraZeneca, Bayer, and other companies.

SOURCE: Gross ME et al. Prostate Cancer Prostatic Dis. 2020 Mar 3. doi: 10.1038/s41391-020-0211-9.

Martha Clare Morris, ScD, a pioneer in research linking nutrition to brain health and a creator of the breakthrough MIND diet, has died of cancer at the age of 64.

Morris was a professor in the Department of Internal Medicine, assistant provost of community research, and director of the Rush Institute for Healthy Aging at Rush University, in Chicago, Illinois. She was also a director of the internal medicine department’s Section of Community Epidemiology.

Long-time friend and colleague Julie A. Schneider, MD, the Deborah R. and Edgar D. Jannotta Presidential Professor of Pathology and Neurological Sciences, Rush University Medical Center, described Morris as creative, passionate, and adventurous.

Her death was “a shock” to the scientific community, Schneider told Medscape Medical News.

“It’s a tragic loss in so many ways,” said Schneider, who is also associate director of the Rush Alzheimer’s Disease Center. She was a very well-respected nutritional epidemiologist and was passionate about her work; she had just so much unwavering commitment to it.

Diet, said Schneider, is “notoriously a hard thing to study” because “it’s so intertwined with lifestyle” and other factors that create “barriers” to conducting such research.

But Morris had a unique and creative talent for filtering out what might be the individual contribution of a particular modifiable risk factor, said Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, who also knew Morris both personally and professionally.

“Humble” trailblazer

Morris’s pioneering research examined the connection between nutrition and the prevention of cognitive decline. Taking results from this research, she developed the MIND diet – a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension – along with colleagues at both Rush and Harvard Universities.

The MIND diet – an acronym for Mediterranean-DASH Intervention for Neurodegenerative Delay – emphasizes brain-healthy foods, including leafy green vegetables, nuts, berries, chicken, fish, whole grains, beans, olive oil, and moderate amounts of red wine. The diet limits consumption of red meat, butter, margarine, and processed foods.

In 2015, Morris published her initial findings on the MIND diet in Alzheimer’s and Dementia. Reported by Medscape Medical News at that time, the study showed that the diet protected cardiovascular health and slowed cognitive decline in older individuals.

The excitement around the findings inspired Morris to write “Diet for the Mind,” which was published in 2017. The book summarizes the benefits of the MIND diet and includes brain-healthy recipes created by her daughter Laura, who is a chef. Despite many accolades, Morris was “humble” about this project, said Schneider.

“This was not about publicity and trying to get a book out; she wanted to see if this diet really was going to change people’s lives. She wanted to bring it into the community,” she said.

Proud legacy

Since 2017, Morris had led a large clinical trial of the effectiveness of the MIND diet in preventing cognitive decline. The first study of its kind, the trial received a $14.5 million grant from the National Institutes of Health (NIH). Results of this study are expected in 2021.

The MIND diet was ranked among the top 10 diets for five consecutive years in US News and World Report.

Morris’s nutrition-related research went beyond diets and examined the impact of individual nutrients. One of her studies, published in 2018 and reported by Medscape Medical News, suggested that the presence of folate, phylloquinone, and lutein – nutrients found in relatively large amounts in green leafy vegetables – may account for why consuming a daily serving of these vegetables slows cognitive decline.

One of the most recent studies from Morris’ group, published in January 2020 and reported by Medscape Medical News at that time, provided the first evidence that dietary flavonols, which are found in many fruits and vegetables, are associated with a significantly reduced risk for dementia.

What Morris did so well was to “look at the big picture” and “think about commonalities that cross nutritional components” of diets such as MIND, DASH, the Mediterranean diet, and the Nordic diet, which is similar to the Mediterranean diet but highlights local foods such as fish from Nordic regions, Snyder told Medscape Medical News.

Morris was instrumental in getting the Alzheimer’s Association’s US POINTER (US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk) study off the ground. The 2-year clinical trial is testing whether combining a healthy diet with exercise, cognitive and social stimulation, and the management of cardiovascular conditions protects cognitive function in older adults who are at increased risk for cognitive decline.

This study will be part of her legacy, said Snyder.

“She will be remembered for her perseverance to get us to a place where we can be looking at nutrition as a modifiable risk factor and now testing it in trials that she helped to set up,” she said.

Even before her involvement with US POINTER, Morris had long been an active volunteer for the Alzheimer’s Association, said Snyder.

“She contributed significant time and expertise as we looked at the state of the evidence around nutrition and other lifestyle and behavioral interventions.”

We’ll ‘always have Paris’

While Morris was “truly passionate” about diet and health “both professionally and personally,” she also had a fun side, said Schneider. She remembers she and Morris had a chance meeting in Paris, where they spent an entire day going to museums and restaurants and just talking about life and their travels. To the end, they joked they would “always have Paris,” said Schneider.

She was also a loyal friend. Morris threw a baby shower when Schneider was pregnant, organizing every detail, despite her extremely busy schedule.

Family was another of Morris’s passions. Snyder recalls Morris’s face lighting up when she talked about her children and grandchildren. She also remembers her friend’s zest for life. “She had an energy that was contagious.”

Morris also loved the outdoors and was a keen adventurer. She once trained for weeks before a long bike trip with her daughter and would take a helicopter to access remote backcountry on hiking excursions.

“She wanted to try everything,” said Schneider.

An author or contributor to more than 80 articles in peer-reviewed journals, Morris also served two terms (from 2011 to 2013) as chair of the NIH’s Neurological, Aging and Musculoskeletal Epidemiology Study Section.

She left behind multiple grants for various studies. One unique study, said Schneider, investigated the relationship between iron and other metals in the brain and the neuropathology of Alzheimer disease.

“She was really in the prime of her career,” noted Schneider. “She had so much left to give and to offer, so this is tremendously sad.”

According to news reports, Morris (nee Chinn) grew up in Homewood, Illinois, and earned bachelor’s and master’s degrees in sociology from the University of Iowa in Iowa City, where she met her husband, James Morris. The two married in 1978 and had three children.

Morris completed a doctorate in epidemiology at the Harvard School of Public Health. James died in 2012, also from cancer. Morris passed away peacefully at her home on February 15.

Martha Clare Morris, ScD, a pioneer in research linking nutrition to brain health and a creator of the breakthrough MIND diet, has died of cancer at the age of 64.

Morris was a professor in the Department of Internal Medicine, assistant provost of community research, and director of the Rush Institute for Healthy Aging at Rush University, in Chicago, Illinois. She was also a director of the internal medicine department’s Section of Community Epidemiology.

Long-time friend and colleague Julie A. Schneider, MD, the Deborah R. and Edgar D. Jannotta Presidential Professor of Pathology and Neurological Sciences, Rush University Medical Center, described Morris as creative, passionate, and adventurous.

Her death was “a shock” to the scientific community, Schneider told Medscape Medical News.

“It’s a tragic loss in so many ways,” said Schneider, who is also associate director of the Rush Alzheimer’s Disease Center. She was a very well-respected nutritional epidemiologist and was passionate about her work; she had just so much unwavering commitment to it.

Diet, said Schneider, is “notoriously a hard thing to study” because “it’s so intertwined with lifestyle” and other factors that create “barriers” to conducting such research.

But Morris had a unique and creative talent for filtering out what might be the individual contribution of a particular modifiable risk factor, said Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, who also knew Morris both personally and professionally.

“Humble” trailblazer

Morris’s pioneering research examined the connection between nutrition and the prevention of cognitive decline. Taking results from this research, she developed the MIND diet – a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension – along with colleagues at both Rush and Harvard Universities.

The MIND diet – an acronym for Mediterranean-DASH Intervention for Neurodegenerative Delay – emphasizes brain-healthy foods, including leafy green vegetables, nuts, berries, chicken, fish, whole grains, beans, olive oil, and moderate amounts of red wine. The diet limits consumption of red meat, butter, margarine, and processed foods.

In 2015, Morris published her initial findings on the MIND diet in Alzheimer’s and Dementia. Reported by Medscape Medical News at that time, the study showed that the diet protected cardiovascular health and slowed cognitive decline in older individuals.

The excitement around the findings inspired Morris to write “Diet for the Mind,” which was published in 2017. The book summarizes the benefits of the MIND diet and includes brain-healthy recipes created by her daughter Laura, who is a chef. Despite many accolades, Morris was “humble” about this project, said Schneider.

“This was not about publicity and trying to get a book out; she wanted to see if this diet really was going to change people’s lives. She wanted to bring it into the community,” she said.

Proud legacy

Since 2017, Morris had led a large clinical trial of the effectiveness of the MIND diet in preventing cognitive decline. The first study of its kind, the trial received a $14.5 million grant from the National Institutes of Health (NIH). Results of this study are expected in 2021.

The MIND diet was ranked among the top 10 diets for five consecutive years in US News and World Report.

Morris’s nutrition-related research went beyond diets and examined the impact of individual nutrients. One of her studies, published in 2018 and reported by Medscape Medical News, suggested that the presence of folate, phylloquinone, and lutein – nutrients found in relatively large amounts in green leafy vegetables – may account for why consuming a daily serving of these vegetables slows cognitive decline.

One of the most recent studies from Morris’ group, published in January 2020 and reported by Medscape Medical News at that time, provided the first evidence that dietary flavonols, which are found in many fruits and vegetables, are associated with a significantly reduced risk for dementia.

What Morris did so well was to “look at the big picture” and “think about commonalities that cross nutritional components” of diets such as MIND, DASH, the Mediterranean diet, and the Nordic diet, which is similar to the Mediterranean diet but highlights local foods such as fish from Nordic regions, Snyder told Medscape Medical News.

Morris was instrumental in getting the Alzheimer’s Association’s US POINTER (US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk) study off the ground. The 2-year clinical trial is testing whether combining a healthy diet with exercise, cognitive and social stimulation, and the management of cardiovascular conditions protects cognitive function in older adults who are at increased risk for cognitive decline.

This study will be part of her legacy, said Snyder.

“She will be remembered for her perseverance to get us to a place where we can be looking at nutrition as a modifiable risk factor and now testing it in trials that she helped to set up,” she said.

Even before her involvement with US POINTER, Morris had long been an active volunteer for the Alzheimer’s Association, said Snyder.

“She contributed significant time and expertise as we looked at the state of the evidence around nutrition and other lifestyle and behavioral interventions.”

We’ll ‘always have Paris’

While Morris was “truly passionate” about diet and health “both professionally and personally,” she also had a fun side, said Schneider. She remembers she and Morris had a chance meeting in Paris, where they spent an entire day going to museums and restaurants and just talking about life and their travels. To the end, they joked they would “always have Paris,” said Schneider.

She was also a loyal friend. Morris threw a baby shower when Schneider was pregnant, organizing every detail, despite her extremely busy schedule.

Family was another of Morris’s passions. Snyder recalls Morris’s face lighting up when she talked about her children and grandchildren. She also remembers her friend’s zest for life. “She had an energy that was contagious.”

Morris also loved the outdoors and was a keen adventurer. She once trained for weeks before a long bike trip with her daughter and would take a helicopter to access remote backcountry on hiking excursions.

“She wanted to try everything,” said Schneider.

An author or contributor to more than 80 articles in peer-reviewed journals, Morris also served two terms (from 2011 to 2013) as chair of the NIH’s Neurological, Aging and Musculoskeletal Epidemiology Study Section.

She left behind multiple grants for various studies. One unique study, said Schneider, investigated the relationship between iron and other metals in the brain and the neuropathology of Alzheimer disease.

“She was really in the prime of her career,” noted Schneider. “She had so much left to give and to offer, so this is tremendously sad.”

According to news reports, Morris (nee Chinn) grew up in Homewood, Illinois, and earned bachelor’s and master’s degrees in sociology from the University of Iowa in Iowa City, where she met her husband, James Morris. The two married in 1978 and had three children.

Morris completed a doctorate in epidemiology at the Harvard School of Public Health. James died in 2012, also from cancer. Morris passed away peacefully at her home on February 15.

Martha Clare Morris, ScD, a pioneer in research linking nutrition to brain health and a creator of the breakthrough MIND diet, has died of cancer at the age of 64.

Morris was a professor in the Department of Internal Medicine, assistant provost of community research, and director of the Rush Institute for Healthy Aging at Rush University, in Chicago, Illinois. She was also a director of the internal medicine department’s Section of Community Epidemiology.

Long-time friend and colleague Julie A. Schneider, MD, the Deborah R. and Edgar D. Jannotta Presidential Professor of Pathology and Neurological Sciences, Rush University Medical Center, described Morris as creative, passionate, and adventurous.

Her death was “a shock” to the scientific community, Schneider told Medscape Medical News.

“It’s a tragic loss in so many ways,” said Schneider, who is also associate director of the Rush Alzheimer’s Disease Center. She was a very well-respected nutritional epidemiologist and was passionate about her work; she had just so much unwavering commitment to it.

Diet, said Schneider, is “notoriously a hard thing to study” because “it’s so intertwined with lifestyle” and other factors that create “barriers” to conducting such research.

But Morris had a unique and creative talent for filtering out what might be the individual contribution of a particular modifiable risk factor, said Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, who also knew Morris both personally and professionally.

“Humble” trailblazer

Morris’s pioneering research examined the connection between nutrition and the prevention of cognitive decline. Taking results from this research, she developed the MIND diet – a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension – along with colleagues at both Rush and Harvard Universities.

The MIND diet – an acronym for Mediterranean-DASH Intervention for Neurodegenerative Delay – emphasizes brain-healthy foods, including leafy green vegetables, nuts, berries, chicken, fish, whole grains, beans, olive oil, and moderate amounts of red wine. The diet limits consumption of red meat, butter, margarine, and processed foods.

In 2015, Morris published her initial findings on the MIND diet in Alzheimer’s and Dementia. Reported by Medscape Medical News at that time, the study showed that the diet protected cardiovascular health and slowed cognitive decline in older individuals.

The excitement around the findings inspired Morris to write “Diet for the Mind,” which was published in 2017. The book summarizes the benefits of the MIND diet and includes brain-healthy recipes created by her daughter Laura, who is a chef. Despite many accolades, Morris was “humble” about this project, said Schneider.

“This was not about publicity and trying to get a book out; she wanted to see if this diet really was going to change people’s lives. She wanted to bring it into the community,” she said.

Proud legacy

Since 2017, Morris had led a large clinical trial of the effectiveness of the MIND diet in preventing cognitive decline. The first study of its kind, the trial received a $14.5 million grant from the National Institutes of Health (NIH). Results of this study are expected in 2021.

The MIND diet was ranked among the top 10 diets for five consecutive years in US News and World Report.

Morris’s nutrition-related research went beyond diets and examined the impact of individual nutrients. One of her studies, published in 2018 and reported by Medscape Medical News, suggested that the presence of folate, phylloquinone, and lutein – nutrients found in relatively large amounts in green leafy vegetables – may account for why consuming a daily serving of these vegetables slows cognitive decline.

One of the most recent studies from Morris’ group, published in January 2020 and reported by Medscape Medical News at that time, provided the first evidence that dietary flavonols, which are found in many fruits and vegetables, are associated with a significantly reduced risk for dementia.

What Morris did so well was to “look at the big picture” and “think about commonalities that cross nutritional components” of diets such as MIND, DASH, the Mediterranean diet, and the Nordic diet, which is similar to the Mediterranean diet but highlights local foods such as fish from Nordic regions, Snyder told Medscape Medical News.

Morris was instrumental in getting the Alzheimer’s Association’s US POINTER (US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk) study off the ground. The 2-year clinical trial is testing whether combining a healthy diet with exercise, cognitive and social stimulation, and the management of cardiovascular conditions protects cognitive function in older adults who are at increased risk for cognitive decline.

This study will be part of her legacy, said Snyder.

“She will be remembered for her perseverance to get us to a place where we can be looking at nutrition as a modifiable risk factor and now testing it in trials that she helped to set up,” she said.

Even before her involvement with US POINTER, Morris had long been an active volunteer for the Alzheimer’s Association, said Snyder.

“She contributed significant time and expertise as we looked at the state of the evidence around nutrition and other lifestyle and behavioral interventions.”

We’ll ‘always have Paris’

While Morris was “truly passionate” about diet and health “both professionally and personally,” she also had a fun side, said Schneider. She remembers she and Morris had a chance meeting in Paris, where they spent an entire day going to museums and restaurants and just talking about life and their travels. To the end, they joked they would “always have Paris,” said Schneider.

She was also a loyal friend. Morris threw a baby shower when Schneider was pregnant, organizing every detail, despite her extremely busy schedule.

Family was another of Morris’s passions. Snyder recalls Morris’s face lighting up when she talked about her children and grandchildren. She also remembers her friend’s zest for life. “She had an energy that was contagious.”

Morris also loved the outdoors and was a keen adventurer. She once trained for weeks before a long bike trip with her daughter and would take a helicopter to access remote backcountry on hiking excursions.

“She wanted to try everything,” said Schneider.

An author or contributor to more than 80 articles in peer-reviewed journals, Morris also served two terms (from 2011 to 2013) as chair of the NIH’s Neurological, Aging and Musculoskeletal Epidemiology Study Section.

She left behind multiple grants for various studies. One unique study, said Schneider, investigated the relationship between iron and other metals in the brain and the neuropathology of Alzheimer disease.

“She was really in the prime of her career,” noted Schneider. “She had so much left to give and to offer, so this is tremendously sad.”

According to news reports, Morris (nee Chinn) grew up in Homewood, Illinois, and earned bachelor’s and master’s degrees in sociology from the University of Iowa in Iowa City, where she met her husband, James Morris. The two married in 1978 and had three children.

Morris completed a doctorate in epidemiology at the Harvard School of Public Health. James died in 2012, also from cancer. Morris passed away peacefully at her home on February 15.

NATIONAL HARBOR, MD. – Anticoagulation reduces the risk of leaflet thrombosis at 30 days relative to antiplatelet therapy in low-risk patients undergoing transcatheter aortic valve replacement (TAVR), according to a randomized feasibility study presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute..

Ted Bosworth/MDedge News

At 30 days, oral anticoagulation with warfarin did not appear to be associated with any increased risk of adverse outcomes, including bleeding events, relative to aspirin, according to Toby Rogers, MD, PhD, the scientific lead for the Structural Heart Disease Program at MedStar Heart & Vascular Institute, Washington.

The rationale for this feasibility study, called LRT 2.0, was to evaluate whether anticoagulation after low-risk TAVR reduces the risk of early subclinical leaflet thrombosis, a potential threat to long-term valve survival.

“In the first LRT trial, HALT [hypoattenuated leaflet thickening] was observed in 13.5% of patients on antiplatelet therapy but only 4.8% of those on oral anticoagulation,” Dr. Rogers said.

The two strategies have not been adequately compared, particularly in low-risk patients, according to Dr. Rogers. He noted that current guidelines recommend dual-antiplatelet therapy after TAVR but the oral anticoagulant warfarin after surgical valve replacement, a situation he characterized as a “discrepancy.”

In the multicenter, randomized LRT 2.0 trial, 94 patients undergoing TAVR and meeting prespecified low-risk criteria, such as a Society of Thoracic Surgeons score of 3 or lower, were randomized to warfarin or to aspirin. The study called for an enrollment of 200 patients but was closed early when the Food and Drug Administration approved TAVR for low-risk patients in 2019, causing “enrollment to dry up over night.”

However, an additional registry cohort was included in a separate analysis. This registry cohort consisted of 30 patients who were evaluated for trial inclusion but were found to be inappropriate for randomization because they already had an indication for anticoagulation or had an elevated risk of bleeding. These low-risk TAVR patients were assigned to anticoagulation or antiplatelet therapy as appropriate.

When the randomized groups were compared, the incidence of HALT at 30 days on CT scan was 4.7% among those on warfarin and 16.3% (P = .07) among those taking aspirin. Dr. Rogers believes the near miss for statistical significance was a problem of power, a position supported by the pooled analysis of randomized and registry patients. With the added patients, the difference in HALT did reach significance (3.1% vs. 16.4%; P = .01).

The numerical differences in reduced leaflet motion and hypoattenuated motion favoring anticoagulation trended for significance in the randomized cohort (P = .12) but reached the cusp of significance in the pooled cohort (1.5% vs. 9.4%; P = .052) for both reduced leaflet motion and hypoattenuated motion).

There were no deaths recorded in any treatment arm, whether restricted to the randomized trial or within the pooled cohort. For the pooled cohort, there were more strokes in the aspirin arm (5.4% vs. 1.5%) but Dr. Rogers said that no conclusions could be drawn about relative risk because of the study size and small number of events.

For anticoagulation relative to antiplatelet therapy, respectively, the incidence of new-onset atrial fibrillation (1.5% vs. 1.8%), pacemaker implantation (11.8% vs. 7.1%), major bleeding (1.5% vs. 5.4%), and median length of stay (2.2 vs. 2.4 days) were all similar. The improvements in hemodynamics 30 days after TAVR were substantial and similar in the two groups, according to Dr. Rogers.

Emphasizing that this is a feasibility study, Dr. Rogers cautioned that these data do not necessarily demonstrate that anticoagulation is a better strategy than antiplatelet therapy in low-risk patients after TAVR, but they do associate anticoagulation with a reduced risk of early leaflet thrombosis.

“We fear leaflet thrombosis for the potential that it will negatively impact valve durability, which is particularly important in younger lower-risk patients who might outlive their first valve prosthesis,” Dr. Rogers said.

Panelists at the late-breaking clinical trial session expressed interest in this concept but generally agreed that longer follow-up is needed. This additional follow-up is important for monitoring effect on leaflet thrombosis as well as on the overall impact of these strategies on adverse events.

“We need to see CT scans at later time points because we do not know where this complication comes from. The trigger for leaflet thrombosis might still be there after 30 days,” said Andreas Baumbach, MD, professor of interventional cardiology at the University of Bristol (England). However, he agreed that this is an important line of research, because the potential risk of leaflet thrombosis is “a very important question for us.”

Dr. Rogers reported financial relationships with Edwards Lifesciences and Medtronic.

NATIONAL HARBOR, MD. – Anticoagulation reduces the risk of leaflet thrombosis at 30 days relative to antiplatelet therapy in low-risk patients undergoing transcatheter aortic valve replacement (TAVR), according to a randomized feasibility study presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute..

Ted Bosworth/MDedge News

At 30 days, oral anticoagulation with warfarin did not appear to be associated with any increased risk of adverse outcomes, including bleeding events, relative to aspirin, according to Toby Rogers, MD, PhD, the scientific lead for the Structural Heart Disease Program at MedStar Heart & Vascular Institute, Washington.

The rationale for this feasibility study, called LRT 2.0, was to evaluate whether anticoagulation after low-risk TAVR reduces the risk of early subclinical leaflet thrombosis, a potential threat to long-term valve survival.

“In the first LRT trial, HALT [hypoattenuated leaflet thickening] was observed in 13.5% of patients on antiplatelet therapy but only 4.8% of those on oral anticoagulation,” Dr. Rogers said.

The two strategies have not been adequately compared, particularly in low-risk patients, according to Dr. Rogers. He noted that current guidelines recommend dual-antiplatelet therapy after TAVR but the oral anticoagulant warfarin after surgical valve replacement, a situation he characterized as a “discrepancy.”

In the multicenter, randomized LRT 2.0 trial, 94 patients undergoing TAVR and meeting prespecified low-risk criteria, such as a Society of Thoracic Surgeons score of 3 or lower, were randomized to warfarin or to aspirin. The study called for an enrollment of 200 patients but was closed early when the Food and Drug Administration approved TAVR for low-risk patients in 2019, causing “enrollment to dry up over night.”

However, an additional registry cohort was included in a separate analysis. This registry cohort consisted of 30 patients who were evaluated for trial inclusion but were found to be inappropriate for randomization because they already had an indication for anticoagulation or had an elevated risk of bleeding. These low-risk TAVR patients were assigned to anticoagulation or antiplatelet therapy as appropriate.

When the randomized groups were compared, the incidence of HALT at 30 days on CT scan was 4.7% among those on warfarin and 16.3% (P = .07) among those taking aspirin. Dr. Rogers believes the near miss for statistical significance was a problem of power, a position supported by the pooled analysis of randomized and registry patients. With the added patients, the difference in HALT did reach significance (3.1% vs. 16.4%; P = .01).

The numerical differences in reduced leaflet motion and hypoattenuated motion favoring anticoagulation trended for significance in the randomized cohort (P = .12) but reached the cusp of significance in the pooled cohort (1.5% vs. 9.4%; P = .052) for both reduced leaflet motion and hypoattenuated motion).

There were no deaths recorded in any treatment arm, whether restricted to the randomized trial or within the pooled cohort. For the pooled cohort, there were more strokes in the aspirin arm (5.4% vs. 1.5%) but Dr. Rogers said that no conclusions could be drawn about relative risk because of the study size and small number of events.

For anticoagulation relative to antiplatelet therapy, respectively, the incidence of new-onset atrial fibrillation (1.5% vs. 1.8%), pacemaker implantation (11.8% vs. 7.1%), major bleeding (1.5% vs. 5.4%), and median length of stay (2.2 vs. 2.4 days) were all similar. The improvements in hemodynamics 30 days after TAVR were substantial and similar in the two groups, according to Dr. Rogers.

Emphasizing that this is a feasibility study, Dr. Rogers cautioned that these data do not necessarily demonstrate that anticoagulation is a better strategy than antiplatelet therapy in low-risk patients after TAVR, but they do associate anticoagulation with a reduced risk of early leaflet thrombosis.

“We fear leaflet thrombosis for the potential that it will negatively impact valve durability, which is particularly important in younger lower-risk patients who might outlive their first valve prosthesis,” Dr. Rogers said.

Panelists at the late-breaking clinical trial session expressed interest in this concept but generally agreed that longer follow-up is needed. This additional follow-up is important for monitoring effect on leaflet thrombosis as well as on the overall impact of these strategies on adverse events.

“We need to see CT scans at later time points because we do not know where this complication comes from. The trigger for leaflet thrombosis might still be there after 30 days,” said Andreas Baumbach, MD, professor of interventional cardiology at the University of Bristol (England). However, he agreed that this is an important line of research, because the potential risk of leaflet thrombosis is “a very important question for us.”

Dr. Rogers reported financial relationships with Edwards Lifesciences and Medtronic.

NATIONAL HARBOR, MD. – Anticoagulation reduces the risk of leaflet thrombosis at 30 days relative to antiplatelet therapy in low-risk patients undergoing transcatheter aortic valve replacement (TAVR), according to a randomized feasibility study presented at CRT 2020 sponsored by MedStar Heart & Vascular Institute..

Ted Bosworth/MDedge News

At 30 days, oral anticoagulation with warfarin did not appear to be associated with any increased risk of adverse outcomes, including bleeding events, relative to aspirin, according to Toby Rogers, MD, PhD, the scientific lead for the Structural Heart Disease Program at MedStar Heart & Vascular Institute, Washington.

The rationale for this feasibility study, called LRT 2.0, was to evaluate whether anticoagulation after low-risk TAVR reduces the risk of early subclinical leaflet thrombosis, a potential threat to long-term valve survival.

“In the first LRT trial, HALT [hypoattenuated leaflet thickening] was observed in 13.5% of patients on antiplatelet therapy but only 4.8% of those on oral anticoagulation,” Dr. Rogers said.

The two strategies have not been adequately compared, particularly in low-risk patients, according to Dr. Rogers. He noted that current guidelines recommend dual-antiplatelet therapy after TAVR but the oral anticoagulant warfarin after surgical valve replacement, a situation he characterized as a “discrepancy.”

In the multicenter, randomized LRT 2.0 trial, 94 patients undergoing TAVR and meeting prespecified low-risk criteria, such as a Society of Thoracic Surgeons score of 3 or lower, were randomized to warfarin or to aspirin. The study called for an enrollment of 200 patients but was closed early when the Food and Drug Administration approved TAVR for low-risk patients in 2019, causing “enrollment to dry up over night.”

However, an additional registry cohort was included in a separate analysis. This registry cohort consisted of 30 patients who were evaluated for trial inclusion but were found to be inappropriate for randomization because they already had an indication for anticoagulation or had an elevated risk of bleeding. These low-risk TAVR patients were assigned to anticoagulation or antiplatelet therapy as appropriate.

When the randomized groups were compared, the incidence of HALT at 30 days on CT scan was 4.7% among those on warfarin and 16.3% (P = .07) among those taking aspirin. Dr. Rogers believes the near miss for statistical significance was a problem of power, a position supported by the pooled analysis of randomized and registry patients. With the added patients, the difference in HALT did reach significance (3.1% vs. 16.4%; P = .01).

The numerical differences in reduced leaflet motion and hypoattenuated motion favoring anticoagulation trended for significance in the randomized cohort (P = .12) but reached the cusp of significance in the pooled cohort (1.5% vs. 9.4%; P = .052) for both reduced leaflet motion and hypoattenuated motion).

There were no deaths recorded in any treatment arm, whether restricted to the randomized trial or within the pooled cohort. For the pooled cohort, there were more strokes in the aspirin arm (5.4% vs. 1.5%) but Dr. Rogers said that no conclusions could be drawn about relative risk because of the study size and small number of events.

For anticoagulation relative to antiplatelet therapy, respectively, the incidence of new-onset atrial fibrillation (1.5% vs. 1.8%), pacemaker implantation (11.8% vs. 7.1%), major bleeding (1.5% vs. 5.4%), and median length of stay (2.2 vs. 2.4 days) were all similar. The improvements in hemodynamics 30 days after TAVR were substantial and similar in the two groups, according to Dr. Rogers.

Emphasizing that this is a feasibility study, Dr. Rogers cautioned that these data do not necessarily demonstrate that anticoagulation is a better strategy than antiplatelet therapy in low-risk patients after TAVR, but they do associate anticoagulation with a reduced risk of early leaflet thrombosis.

“We fear leaflet thrombosis for the potential that it will negatively impact valve durability, which is particularly important in younger lower-risk patients who might outlive their first valve prosthesis,” Dr. Rogers said.

Panelists at the late-breaking clinical trial session expressed interest in this concept but generally agreed that longer follow-up is needed. This additional follow-up is important for monitoring effect on leaflet thrombosis as well as on the overall impact of these strategies on adverse events.

“We need to see CT scans at later time points because we do not know where this complication comes from. The trigger for leaflet thrombosis might still be there after 30 days,” said Andreas Baumbach, MD, professor of interventional cardiology at the University of Bristol (England). However, he agreed that this is an important line of research, because the potential risk of leaflet thrombosis is “a very important question for us.”

Dr. Rogers reported financial relationships with Edwards Lifesciences and Medtronic.

The novel coronavirus (2019-nCoV) is presenting a severe challenge to global health care, but its impact isn’t just felt in the emergency department. Specialists, including dermatologists, must also navigate the presence of the virus and its impact on patients and practices.

Courtesy CDC

A new report from dermatologists in China’s Wuhan province, where the 2019-nCoV outbreak began, outlines initial experiences and provides a blueprint for triaging potential cases before they reach the dermatology clinic. Despite its presence in the epicenter of the outbreak, the hospital has not detected any 2019-nCoV-infected patients in any of its departments.

The commentary appeared in the British Journal of Dermatology and was authored by a group led by Juan Tao of Huazhong University of Science and Technology (Br J Dermatol. 2020 Mar 5. doi: 10.1111/bjd.19011).

The hospital triages all patients at the hospital entrance. Those who are suspected of having 2019-nCoV infection are sent to a designated department. Those with a skin condition who are not suspected of being infected are allowed to go to a dermatology triage center, where they are examined again. If the second examination raises suspicion, they are sent to the designated 2019-nCoV department. If no infection is suspected, or a patient from the 2019-nCoV department is cleared, they are allowed access to the dermatology clinic.

The team also suggested that skin lesions associated with dermatological conditions could lead to increased risk of 2019-nCoV infection. Contacted by email, Dr. Tao outlined a theoretical risk that the virus could lead to infection through contact with subcutaneous tissues, mucosal surfaces, or blood vessels. He did not respond to a request for evidence that such a route of transmission had occurred.

However, Adam Friedman, MD, professor of dermatology at George Washington University, Washington, said he doubted any such transmission would occur since the virus does not infect keratinocytes, and expressed concern that the suggestion could add to the stigma experienced by dermatological patients, whose noticeable rashes can sometimes lead to social avoidance. “I don’t want to add to that,” said Dr. Friedman in an interview.

A critical aspect of dermatology is the immunosuppressive agents often used in dermatology patients. Such drugs could make them more susceptible to infections, or to worse outcomes in the event of disease. Dr. Friedman recounted sending a letter to one patient on an immunosuppressive medication, suggesting that she work remotely. “I think that’s something we have to think about in at-risk individuals. I know there’s such a focus on the elderly, but there’s a large population of individuals on medications that lower their immune system who are going to be at risk for more severe infections,” said Dr. Friedman.

To reduce patient exposure, the commentary recommended that dermatologists perform online consultation for mild and nonemergency cases.

The authors also covered hospitalized patients with primary or secondary skin conditions. A dermatologist is on site at the dermatology triage station to conduct in-depth assessments if needed. If a patient has a fever that is believed to be caused by a dermatologic condition, the on-site dermatologist assists in the consult.

Because some patients may only become symptomatic after admission to a ward, the authors recommend hospitals have a COVID-19 trained contingency group on hand to prevent and control outbreaks within the institution. The team should be in communication with respiratory intensive care and radiology departments to exclude 2019-nCoV when cases develop in-hospital, and to ensure proper care infected patients who require it.

When a hospitalized 2019-nCoV-infected patient has a skin condition requiring treatment, the authors recommend that pictures be sent to the dermatologist for evaluation, along with teleconferences to further assess the patient. If necessary, the dermatologist should go to the patient’s bedside, with as much information as possible related in advance in order to minimize bedside exposure.

There was no funding source. Dr. Tao and Dr. Friedman have no relevant financial conflicts.

The novel coronavirus (2019-nCoV) is presenting a severe challenge to global health care, but its impact isn’t just felt in the emergency department. Specialists, including dermatologists, must also navigate the presence of the virus and its impact on patients and practices.

Courtesy CDC

A new report from dermatologists in China’s Wuhan province, where the 2019-nCoV outbreak began, outlines initial experiences and provides a blueprint for triaging potential cases before they reach the dermatology clinic. Despite its presence in the epicenter of the outbreak, the hospital has not detected any 2019-nCoV-infected patients in any of its departments.

The commentary appeared in the British Journal of Dermatology and was authored by a group led by Juan Tao of Huazhong University of Science and Technology (Br J Dermatol. 2020 Mar 5. doi: 10.1111/bjd.19011).

The hospital triages all patients at the hospital entrance. Those who are suspected of having 2019-nCoV infection are sent to a designated department. Those with a skin condition who are not suspected of being infected are allowed to go to a dermatology triage center, where they are examined again. If the second examination raises suspicion, they are sent to the designated 2019-nCoV department. If no infection is suspected, or a patient from the 2019-nCoV department is cleared, they are allowed access to the dermatology clinic.

The team also suggested that skin lesions associated with dermatological conditions could lead to increased risk of 2019-nCoV infection. Contacted by email, Dr. Tao outlined a theoretical risk that the virus could lead to infection through contact with subcutaneous tissues, mucosal surfaces, or blood vessels. He did not respond to a request for evidence that such a route of transmission had occurred.

However, Adam Friedman, MD, professor of dermatology at George Washington University, Washington, said he doubted any such transmission would occur since the virus does not infect keratinocytes, and expressed concern that the suggestion could add to the stigma experienced by dermatological patients, whose noticeable rashes can sometimes lead to social avoidance. “I don’t want to add to that,” said Dr. Friedman in an interview.

A critical aspect of dermatology is the immunosuppressive agents often used in dermatology patients. Such drugs could make them more susceptible to infections, or to worse outcomes in the event of disease. Dr. Friedman recounted sending a letter to one patient on an immunosuppressive medication, suggesting that she work remotely. “I think that’s something we have to think about in at-risk individuals. I know there’s such a focus on the elderly, but there’s a large population of individuals on medications that lower their immune system who are going to be at risk for more severe infections,” said Dr. Friedman.

To reduce patient exposure, the commentary recommended that dermatologists perform online consultation for mild and nonemergency cases.

The authors also covered hospitalized patients with primary or secondary skin conditions. A dermatologist is on site at the dermatology triage station to conduct in-depth assessments if needed. If a patient has a fever that is believed to be caused by a dermatologic condition, the on-site dermatologist assists in the consult.

Because some patients may only become symptomatic after admission to a ward, the authors recommend hospitals have a COVID-19 trained contingency group on hand to prevent and control outbreaks within the institution. The team should be in communication with respiratory intensive care and radiology departments to exclude 2019-nCoV when cases develop in-hospital, and to ensure proper care infected patients who require it.

When a hospitalized 2019-nCoV-infected patient has a skin condition requiring treatment, the authors recommend that pictures be sent to the dermatologist for evaluation, along with teleconferences to further assess the patient. If necessary, the dermatologist should go to the patient’s bedside, with as much information as possible related in advance in order to minimize bedside exposure.

There was no funding source. Dr. Tao and Dr. Friedman have no relevant financial conflicts.

The novel coronavirus (2019-nCoV) is presenting a severe challenge to global health care, but its impact isn’t just felt in the emergency department. Specialists, including dermatologists, must also navigate the presence of the virus and its impact on patients and practices.

Courtesy CDC

A new report from dermatologists in China’s Wuhan province, where the 2019-nCoV outbreak began, outlines initial experiences and provides a blueprint for triaging potential cases before they reach the dermatology clinic. Despite its presence in the epicenter of the outbreak, the hospital has not detected any 2019-nCoV-infected patients in any of its departments.

The commentary appeared in the British Journal of Dermatology and was authored by a group led by Juan Tao of Huazhong University of Science and Technology (Br J Dermatol. 2020 Mar 5. doi: 10.1111/bjd.19011).

The hospital triages all patients at the hospital entrance. Those who are suspected of having 2019-nCoV infection are sent to a designated department. Those with a skin condition who are not suspected of being infected are allowed to go to a dermatology triage center, where they are examined again. If the second examination raises suspicion, they are sent to the designated 2019-nCoV department. If no infection is suspected, or a patient from the 2019-nCoV department is cleared, they are allowed access to the dermatology clinic.

The team also suggested that skin lesions associated with dermatological conditions could lead to increased risk of 2019-nCoV infection. Contacted by email, Dr. Tao outlined a theoretical risk that the virus could lead to infection through contact with subcutaneous tissues, mucosal surfaces, or blood vessels. He did not respond to a request for evidence that such a route of transmission had occurred.

However, Adam Friedman, MD, professor of dermatology at George Washington University, Washington, said he doubted any such transmission would occur since the virus does not infect keratinocytes, and expressed concern that the suggestion could add to the stigma experienced by dermatological patients, whose noticeable rashes can sometimes lead to social avoidance. “I don’t want to add to that,” said Dr. Friedman in an interview.

A critical aspect of dermatology is the immunosuppressive agents often used in dermatology patients. Such drugs could make them more susceptible to infections, or to worse outcomes in the event of disease. Dr. Friedman recounted sending a letter to one patient on an immunosuppressive medication, suggesting that she work remotely. “I think that’s something we have to think about in at-risk individuals. I know there’s such a focus on the elderly, but there’s a large population of individuals on medications that lower their immune system who are going to be at risk for more severe infections,” said Dr. Friedman.

To reduce patient exposure, the commentary recommended that dermatologists perform online consultation for mild and nonemergency cases.

The authors also covered hospitalized patients with primary or secondary skin conditions. A dermatologist is on site at the dermatology triage station to conduct in-depth assessments if needed. If a patient has a fever that is believed to be caused by a dermatologic condition, the on-site dermatologist assists in the consult.

Because some patients may only become symptomatic after admission to a ward, the authors recommend hospitals have a COVID-19 trained contingency group on hand to prevent and control outbreaks within the institution. The team should be in communication with respiratory intensive care and radiology departments to exclude 2019-nCoV when cases develop in-hospital, and to ensure proper care infected patients who require it.

When a hospitalized 2019-nCoV-infected patient has a skin condition requiring treatment, the authors recommend that pictures be sent to the dermatologist for evaluation, along with teleconferences to further assess the patient. If necessary, the dermatologist should go to the patient’s bedside, with as much information as possible related in advance in order to minimize bedside exposure.

There was no funding source. Dr. Tao and Dr. Friedman have no relevant financial conflicts.

Fecal-oral transmission may be part of the COVID-19 clinical picture, according to two reports published in Gastroenterology. The researchers find that RNA and proteins from SARS-CoV-2, the viral cause of COVID-19, are shed in feces early in infection and persist after respiratory symptoms abate.

But the discovery is preliminary. “There is evidence of the virus in stool, but not evidence of infectious virus,” David A. Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine in Norfolk, told Medscape Medical News.

The findings are not entirely unexpected. Both of the coronaviruses behind SARS and MERS are shed in stool, Jinyang Gu, MD, from Shanghai Jiao Tong University School of Medicine in Shanghai, China, and colleagues, note in one of the newly published articles.

In addition, as COVID-19 spread beyond China, clinicians began noticing initial mild gastrointestinal (GI) symptoms in some patients, including diarrhea, nausea, vomiting, and abdominal pain, preceding the hallmark fever, dry cough, and dyspnea. The first patient diagnosed in the United States with COVID-19 reported having 2 days of nausea and vomiting, with viral RNA detected in fecal and respiratory specimens, according to an earlier report.

Gu and colleagues warn that initial investigations would likely have not considered cases that manifested initially only as mild gastrointestinal symptoms.

Although early reports indicated that only about 10% of people with COVID-19 have GI symptoms, it isn’t known whether some infected individuals have only GI symptoms, Johnson said.

The GI manifestations are consistent with the distribution of ACE2 receptors, which serve as entry points for SARS-CoV-2, as well as SARS-CoV-1, which causes SARS. The receptors are most abundant in the cell membranes of lung AT2 cells, as well as in enterocytes in the ileum and colon.

“Altogether, many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” Gu and colleagues conclude.

But Johnson cautions, “gastroenterologists are not the ones managing diagnosis of COVID-19. It is diagnosed as a respiratory illness, but we are seeing concomitant gastrointestinal shedding in stool and saliva, and GI symptoms.”
 

Samples From 73 Patients Studied

In the second article published, Fei Xiao, MD, of Sun Yat-sen University in Guangdong Province, China, and colleagues report detecting viral RNA in samples from the mouths, noses, throats, urine, and feces of 73 patients hospitalized during the first 2 weeks of February.

Of the 73 hospitalized patients, 39 (53.24%; 25 males and 14 females) had viral RNA in their feces, present from 1 to 12 days. Seventeen (23.29%) of the patients continued to have viral RNA in their stool after respiratory symptoms had improved.

One patient underwent endoscopy. There was no evidence of damage to the GI epithelium, but the clinicians detected slightly elevated levels of lymphocytes and plasma cells.

The researcher used laser scanning confocal microscopy to analyze samples taken during the endoscopy. They found evidence of both ACE2 receptors and viral nucleocapsid proteins in the gastric, duodenal, and rectal glandular epithelial cells.

Finding evidence of SARS-CoV-2 throughout the GI system, if not direct infectivity, suggests a fecal-oral route of transmission, the researchers conclude. “Our immunofluorescent data showed that ACE2 protein, a cell receptor for SARS-CoV-2, is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells.”

Detection of viral RNA at different time points in infection, they write, suggests that the virions are continually secreted and therefore likely infectious, which is under investigation. “Prevention of fecal-oral transmission should be taken into consideration to control the spread of the virus,” they write.

Current recommendations do not require that patients’ fecal samples be tested before being considered noninfectious. However, given their findings and evidence from other studies, Xiao and colleagues recommend that real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing of fecal samples be added to current protocols.

Johnson offers practical suggestions based on the “potty hygiene” suggestions he gives to patients dealing with fecal shedding in Clostridioides difficile infection.

“To combat the microaerosolization of C. diff spores, I have patients do a complete bacteriocidal washing out of the toilet bowl, as well as clean surface areas and especially toothbrushes.” Keeping the bowl closed when not in use is important too in preventing “fecal-oral transmission of remnants” of toilet contents, he adds.

The new papers add to other reports suggesting that virus-bearing droplets may reach people in various ways, Johnson said. “Maybe the virus isn’t only spread by a cough or a sneeze.”

The researchers and commentator have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fecal-oral transmission may be part of the COVID-19 clinical picture, according to two reports published in Gastroenterology. The researchers find that RNA and proteins from SARS-CoV-2, the viral cause of COVID-19, are shed in feces early in infection and persist after respiratory symptoms abate.

But the discovery is preliminary. “There is evidence of the virus in stool, but not evidence of infectious virus,” David A. Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine in Norfolk, told Medscape Medical News.

The findings are not entirely unexpected. Both of the coronaviruses behind SARS and MERS are shed in stool, Jinyang Gu, MD, from Shanghai Jiao Tong University School of Medicine in Shanghai, China, and colleagues, note in one of the newly published articles.

In addition, as COVID-19 spread beyond China, clinicians began noticing initial mild gastrointestinal (GI) symptoms in some patients, including diarrhea, nausea, vomiting, and abdominal pain, preceding the hallmark fever, dry cough, and dyspnea. The first patient diagnosed in the United States with COVID-19 reported having 2 days of nausea and vomiting, with viral RNA detected in fecal and respiratory specimens, according to an earlier report.

Gu and colleagues warn that initial investigations would likely have not considered cases that manifested initially only as mild gastrointestinal symptoms.

Although early reports indicated that only about 10% of people with COVID-19 have GI symptoms, it isn’t known whether some infected individuals have only GI symptoms, Johnson said.

The GI manifestations are consistent with the distribution of ACE2 receptors, which serve as entry points for SARS-CoV-2, as well as SARS-CoV-1, which causes SARS. The receptors are most abundant in the cell membranes of lung AT2 cells, as well as in enterocytes in the ileum and colon.

“Altogether, many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” Gu and colleagues conclude.

But Johnson cautions, “gastroenterologists are not the ones managing diagnosis of COVID-19. It is diagnosed as a respiratory illness, but we are seeing concomitant gastrointestinal shedding in stool and saliva, and GI symptoms.”
 

Samples From 73 Patients Studied

In the second article published, Fei Xiao, MD, of Sun Yat-sen University in Guangdong Province, China, and colleagues report detecting viral RNA in samples from the mouths, noses, throats, urine, and feces of 73 patients hospitalized during the first 2 weeks of February.

Of the 73 hospitalized patients, 39 (53.24%; 25 males and 14 females) had viral RNA in their feces, present from 1 to 12 days. Seventeen (23.29%) of the patients continued to have viral RNA in their stool after respiratory symptoms had improved.

One patient underwent endoscopy. There was no evidence of damage to the GI epithelium, but the clinicians detected slightly elevated levels of lymphocytes and plasma cells.

The researcher used laser scanning confocal microscopy to analyze samples taken during the endoscopy. They found evidence of both ACE2 receptors and viral nucleocapsid proteins in the gastric, duodenal, and rectal glandular epithelial cells.

Finding evidence of SARS-CoV-2 throughout the GI system, if not direct infectivity, suggests a fecal-oral route of transmission, the researchers conclude. “Our immunofluorescent data showed that ACE2 protein, a cell receptor for SARS-CoV-2, is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells.”

Detection of viral RNA at different time points in infection, they write, suggests that the virions are continually secreted and therefore likely infectious, which is under investigation. “Prevention of fecal-oral transmission should be taken into consideration to control the spread of the virus,” they write.

Current recommendations do not require that patients’ fecal samples be tested before being considered noninfectious. However, given their findings and evidence from other studies, Xiao and colleagues recommend that real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing of fecal samples be added to current protocols.

Johnson offers practical suggestions based on the “potty hygiene” suggestions he gives to patients dealing with fecal shedding in Clostridioides difficile infection.

“To combat the microaerosolization of C. diff spores, I have patients do a complete bacteriocidal washing out of the toilet bowl, as well as clean surface areas and especially toothbrushes.” Keeping the bowl closed when not in use is important too in preventing “fecal-oral transmission of remnants” of toilet contents, he adds.

The new papers add to other reports suggesting that virus-bearing droplets may reach people in various ways, Johnson said. “Maybe the virus isn’t only spread by a cough or a sneeze.”

The researchers and commentator have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fecal-oral transmission may be part of the COVID-19 clinical picture, according to two reports published in Gastroenterology. The researchers find that RNA and proteins from SARS-CoV-2, the viral cause of COVID-19, are shed in feces early in infection and persist after respiratory symptoms abate.

But the discovery is preliminary. “There is evidence of the virus in stool, but not evidence of infectious virus,” David A. Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine in Norfolk, told Medscape Medical News.

The findings are not entirely unexpected. Both of the coronaviruses behind SARS and MERS are shed in stool, Jinyang Gu, MD, from Shanghai Jiao Tong University School of Medicine in Shanghai, China, and colleagues, note in one of the newly published articles.

In addition, as COVID-19 spread beyond China, clinicians began noticing initial mild gastrointestinal (GI) symptoms in some patients, including diarrhea, nausea, vomiting, and abdominal pain, preceding the hallmark fever, dry cough, and dyspnea. The first patient diagnosed in the United States with COVID-19 reported having 2 days of nausea and vomiting, with viral RNA detected in fecal and respiratory specimens, according to an earlier report.

Gu and colleagues warn that initial investigations would likely have not considered cases that manifested initially only as mild gastrointestinal symptoms.

Although early reports indicated that only about 10% of people with COVID-19 have GI symptoms, it isn’t known whether some infected individuals have only GI symptoms, Johnson said.

The GI manifestations are consistent with the distribution of ACE2 receptors, which serve as entry points for SARS-CoV-2, as well as SARS-CoV-1, which causes SARS. The receptors are most abundant in the cell membranes of lung AT2 cells, as well as in enterocytes in the ileum and colon.

“Altogether, many efforts should be made to be alert on the initial digestive symptoms of COVID-19 for early detection, early diagnosis, early isolation and early intervention,” Gu and colleagues conclude.

But Johnson cautions, “gastroenterologists are not the ones managing diagnosis of COVID-19. It is diagnosed as a respiratory illness, but we are seeing concomitant gastrointestinal shedding in stool and saliva, and GI symptoms.”
 

Samples From 73 Patients Studied

In the second article published, Fei Xiao, MD, of Sun Yat-sen University in Guangdong Province, China, and colleagues report detecting viral RNA in samples from the mouths, noses, throats, urine, and feces of 73 patients hospitalized during the first 2 weeks of February.

Of the 73 hospitalized patients, 39 (53.24%; 25 males and 14 females) had viral RNA in their feces, present from 1 to 12 days. Seventeen (23.29%) of the patients continued to have viral RNA in their stool after respiratory symptoms had improved.

One patient underwent endoscopy. There was no evidence of damage to the GI epithelium, but the clinicians detected slightly elevated levels of lymphocytes and plasma cells.

The researcher used laser scanning confocal microscopy to analyze samples taken during the endoscopy. They found evidence of both ACE2 receptors and viral nucleocapsid proteins in the gastric, duodenal, and rectal glandular epithelial cells.

Finding evidence of SARS-CoV-2 throughout the GI system, if not direct infectivity, suggests a fecal-oral route of transmission, the researchers conclude. “Our immunofluorescent data showed that ACE2 protein, a cell receptor for SARS-CoV-2, is abundantly expressed in the glandular cells of gastric, duodenal and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells.”

Detection of viral RNA at different time points in infection, they write, suggests that the virions are continually secreted and therefore likely infectious, which is under investigation. “Prevention of fecal-oral transmission should be taken into consideration to control the spread of the virus,” they write.

Current recommendations do not require that patients’ fecal samples be tested before being considered noninfectious. However, given their findings and evidence from other studies, Xiao and colleagues recommend that real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing of fecal samples be added to current protocols.

Johnson offers practical suggestions based on the “potty hygiene” suggestions he gives to patients dealing with fecal shedding in Clostridioides difficile infection.

“To combat the microaerosolization of C. diff spores, I have patients do a complete bacteriocidal washing out of the toilet bowl, as well as clean surface areas and especially toothbrushes.” Keeping the bowl closed when not in use is important too in preventing “fecal-oral transmission of remnants” of toilet contents, he adds.

The new papers add to other reports suggesting that virus-bearing droplets may reach people in various ways, Johnson said. “Maybe the virus isn’t only spread by a cough or a sneeze.”

The researchers and commentator have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.