Journal of Clinical Outcomes Management

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

BOSTON – Following infection with SARS-CoV-2 infection, patients between the ages of 18 and 65 were at a significantly increased for developing certain cutaneous autoimmune and vascular diseases. This predominately favored systemic disease states with cutaneous involvement, rather than skin-limited processes.

The findings come from a large multicenter analysis that Zachary Holcomb, MD, presented during a late-breaking abstract session at the annual meeting of the American Academy of Dermatology.

Doug Brunk, MDedge News

“Viral triggers have been implicated in the pathogenesis of rheumatologic disease, but information regarding development of autoimmune disease following SARS-CoV-2 infection is limited,” said Dr. Holcomb, chief resident in the Harvard Combined Internal Medicine–Dermatology Residency, Boston. “Given its proposed thromboinflammatory pathobiology, we hypothesized that SARS-CoV-2 infection increases the risk of development of autoimmune disease with cutaneous manifestations and sought to define incidence rates of newly-diagnosed autoimmune diseases following SARS-CoV-2 infection.”

The researchers drew from the TriNetX Dataworks platform, an online cloud-based system that contains aggregated and deidentified patient information from about 75 million patients across 48 health care organizations. The infected cohort was defined as having a positive lab test for severe SARS-CoV-2 within the study window using Logical Observation Identifiers Names and Codes (LOINCs). Healthy controls consisted of a documented health care contact (inpatient or outpatient visit) during the study window without a positive SARS-CoV-2 lab test. Each cohort included patients aged 18-65 at the time of the study, and patients with previously diagnosed cutaneous autoimmune or vascular diseases were excluded from the analysis.

After propensity matching, the COVID-19 infected cohort and the healthy cohort included 1,904,864 patients each, with no baseline differences in age at index event, ethnicity, race, or sex. The study window was between April 1, 2020, and Oct. 1, 2020. The index event was a COVID-19 infection for the infected group and first documented health care contact in the healthy control group. The researchers looked at a window of 60 days following this index event for new incidence of cutaneous or vascular disease.

In the realm of connective tissue and related diseases, they found the incidence was increased among the COVID-19 infected group compared with controls for dermatomyositis (risk ratio, 2.273; P = .0196), scleroderma (RR, 1.959; P = .0001), and systemic lupus erythematosus (RR, 1.401; P < .0001). They also noted a significant decrease in the new incidence of alopecia areata in the COVID-19 infected group compared with controls (RR, 0.527; P < .0001).

No significant differences in the incidence of bullous and papulosquamous diseases were observed between the two groups. However, sarcoidosis was significantly more common in the COVID-19–infected group compared with controls (RR, 2.086; P < .001). “When taking all of these autoinflammatory diseases as a whole, there was an increased incidence in the COVID-19 infected group overall with a RR of 1.168 (P < .0001),” Dr. Holcomb said.

In the realm of vascular skin diseases, there was an increased incidence in the COVID-19 infected group in acrocyanosis (RR, 2.825; P < .001), Raynaud’s phenomenon (RR, 1.462; P < .0001), cutaneous small vessel vasculitis (RR, 1.714; P < .0001), granulomatosis with polyangiitis (RR, 2.667; P = .0002), and temporal arteritis (RR, 1.900; P = .0038).

“Interestingly, despite the academic and lay press reports of COVID toes, we did not see that in our data related to the COVID-infected group,” he said.

Dr. Holcomb acknowledged certain limitations of the study, including a narrow study window with a relatively short follow-up. “We were able to propensity match based on baseline demographics but not necessarily so based on health status and prior autoimmune disease,” he said. In addition, since the study was limited to those aged 18-65, the results may not be generalizable to pediatric and elderly patients, he said.

He described the study findings as “somewhat hypothesis-generating.” For instance, “why would we have more of a systemic process [at play?]. Our theory is that the severe inflammatory nature of COVID-19 leads to a lot of internal organ damage and exposure of autoantigens in that process, with relative skin sparing.”

One of the session moderators, Robert Paul Dellavalle, MD, PhD, professor of dermatology at the University of Colorado, Aurora, characterized the findings as “intriguing” but preliminary. “It would be interesting to look at more recent cohorts and see how vaccination for COVID-19 would impact the incidence rates of some of these diseases,” he said.

When asked for comment, Jeffrey A. Sparks, MD, MMSc, a rheumatologist at Brigham and Women's Hospital and assistant professor of medicine at Harvard Medical School, both in Boston, said, "This is an interesting study that should be followed up. Viral triggers have been known to precede autoimmune diseases so it will be very important to understand whether COVID-19 also impacts systemic autoimmune rheumatic diseases. I would be interested in differences in surveillance between the infection and control groups early in the pandemic. Many patients were avoiding interaction with the health care system at that point." 

Dr. Holcomb reported having no financial disclosures. Dr. Dellavalle disclosed that he is a consultant for Altus Labs and ParaPRO LLC. He has received grants and research funding from Pfizer.

* This story was updated on 3/29/22.

Cancer survivors who spend more than 8 hours of the day sitting are five times more likely to die over the ensuing years than their peers who spend less time sitting. Being physically active, on the other hand, lowers the risk of early death, new research shows.

What’s “alarming” is that so many cancer survivors have a sedentary lifestyle, Chao Cao and Lin Yang, PhD, with Alberta Health Services in Calgary, who worked on the study, said in an interview.

The American Cancer Society recommends that cancer survivors follow the same physical activity guidance as the general population. The target is 150-300 minutes of moderate activity or 75-150 minutes of vigorous activity each week (or a combination of these).

“Getting to or exceeding the upper limit of 300 minutes is ideal,” Mr. Cao and Dr. Yang say.

Yet in their study of more than 1,500 cancer survivors, more than half (57%) were inactive, reporting no weekly leisure-time physical activity in the past week.

About 16% were “insufficiently” active, or getting less than 150 minutes per week. Meanwhile, 28% were active, achieving more than 150 minutes of weekly physical activity.

Digging deeper, the researchers found that more than one-third of cancer survivors reported sitting for 6-8 hours each day, and one-quarter reported sitting for more than 8 hours per day.

Over the course of up to 9 years, 293 of the cancer survivors died – 114 from cancer, 41 from heart diseases, and 138 from other causes.

After accounting for things that might influence the results, the risk of dying from any cause or cancer was about 65% lower in cancer survivors who were physically active, relative to their inactive peers.

Sitting for long periods was especially risky, according to the study in JAMA Oncology.

Compared with cancer survivors who sat for less than 4 hours each day, cancer survivors who reported sitting for more than 8 hours a day had nearly twice the risk of dying from any cause and more than twice the risk of dying from cancer.

Cancer survivors who sat for more than 8 hours a day, and were inactive or not active enough, had as much as five times the risk of death from any cause or cancer.

“Be active and sit less, move more, and move frequently,” advise Mr. Cao and Dr. Yang. “Avoiding prolonged sitting is essential for most cancer survivors to reduce excess mortality risks.”

A version of this article first appeared on WebMD.com.

Cancer survivors who spend more than 8 hours of the day sitting are five times more likely to die over the ensuing years than their peers who spend less time sitting. Being physically active, on the other hand, lowers the risk of early death, new research shows.

What’s “alarming” is that so many cancer survivors have a sedentary lifestyle, Chao Cao and Lin Yang, PhD, with Alberta Health Services in Calgary, who worked on the study, said in an interview.

The American Cancer Society recommends that cancer survivors follow the same physical activity guidance as the general population. The target is 150-300 minutes of moderate activity or 75-150 minutes of vigorous activity each week (or a combination of these).

“Getting to or exceeding the upper limit of 300 minutes is ideal,” Mr. Cao and Dr. Yang say.

Yet in their study of more than 1,500 cancer survivors, more than half (57%) were inactive, reporting no weekly leisure-time physical activity in the past week.

About 16% were “insufficiently” active, or getting less than 150 minutes per week. Meanwhile, 28% were active, achieving more than 150 minutes of weekly physical activity.

Digging deeper, the researchers found that more than one-third of cancer survivors reported sitting for 6-8 hours each day, and one-quarter reported sitting for more than 8 hours per day.

Over the course of up to 9 years, 293 of the cancer survivors died – 114 from cancer, 41 from heart diseases, and 138 from other causes.

After accounting for things that might influence the results, the risk of dying from any cause or cancer was about 65% lower in cancer survivors who were physically active, relative to their inactive peers.

Sitting for long periods was especially risky, according to the study in JAMA Oncology.

Compared with cancer survivors who sat for less than 4 hours each day, cancer survivors who reported sitting for more than 8 hours a day had nearly twice the risk of dying from any cause and more than twice the risk of dying from cancer.

Cancer survivors who sat for more than 8 hours a day, and were inactive or not active enough, had as much as five times the risk of death from any cause or cancer.

“Be active and sit less, move more, and move frequently,” advise Mr. Cao and Dr. Yang. “Avoiding prolonged sitting is essential for most cancer survivors to reduce excess mortality risks.”

A version of this article first appeared on WebMD.com.

Cancer survivors who spend more than 8 hours of the day sitting are five times more likely to die over the ensuing years than their peers who spend less time sitting. Being physically active, on the other hand, lowers the risk of early death, new research shows.

What’s “alarming” is that so many cancer survivors have a sedentary lifestyle, Chao Cao and Lin Yang, PhD, with Alberta Health Services in Calgary, who worked on the study, said in an interview.

The American Cancer Society recommends that cancer survivors follow the same physical activity guidance as the general population. The target is 150-300 minutes of moderate activity or 75-150 minutes of vigorous activity each week (or a combination of these).

“Getting to or exceeding the upper limit of 300 minutes is ideal,” Mr. Cao and Dr. Yang say.

Yet in their study of more than 1,500 cancer survivors, more than half (57%) were inactive, reporting no weekly leisure-time physical activity in the past week.

About 16% were “insufficiently” active, or getting less than 150 minutes per week. Meanwhile, 28% were active, achieving more than 150 minutes of weekly physical activity.

Digging deeper, the researchers found that more than one-third of cancer survivors reported sitting for 6-8 hours each day, and one-quarter reported sitting for more than 8 hours per day.

Over the course of up to 9 years, 293 of the cancer survivors died – 114 from cancer, 41 from heart diseases, and 138 from other causes.

After accounting for things that might influence the results, the risk of dying from any cause or cancer was about 65% lower in cancer survivors who were physically active, relative to their inactive peers.

Sitting for long periods was especially risky, according to the study in JAMA Oncology.

Compared with cancer survivors who sat for less than 4 hours each day, cancer survivors who reported sitting for more than 8 hours a day had nearly twice the risk of dying from any cause and more than twice the risk of dying from cancer.

Cancer survivors who sat for more than 8 hours a day, and were inactive or not active enough, had as much as five times the risk of death from any cause or cancer.

“Be active and sit less, move more, and move frequently,” advise Mr. Cao and Dr. Yang. “Avoiding prolonged sitting is essential for most cancer survivors to reduce excess mortality risks.”

A version of this article first appeared on WebMD.com.

Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.

The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.

The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.

”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.

Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”

The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.

They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.

Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
 

The study

The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).

Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).

There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.

Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).

Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.

“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”

They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
 

Commentary

An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.

“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.

They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.

Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.

Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”

Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.

Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”

Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”

The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.

This article was updated 3/25/22.

Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.

The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.

The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.

”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.

Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”

The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.

They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.

Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
 

The study

The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).

Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).

There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.

Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).

Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.

“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”

They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
 

Commentary

An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.

“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.

They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.

Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.

Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”

Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.

Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”

Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”

The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.

This article was updated 3/25/22.

Pediatric care centers are a significant point of access for intimate partner violence referrals, according to data from an IPV prevention program embedded in Boston Children’s Hospital.

The pediatric hospital’s embedded Advocacy for Women and Kids in Emergencies (AWAKE) program found an increase in IPV consults and referrals during the COVID-19 pandemic, particularly for emotional abuse. Despite the shift away from in-office consultations, care was effectively delivered remotely by telehealth.

The findings highlight the importance of pediatric primary care as a point of access for IPV survivor support, the authors concluded.

”Programming for survivors (including patients, family members, and staff) of intimate partner violence is critical in the pediatric hospital setting, especially during the COVID-19 pandemic,” Rehana Rahman, MSW, and colleagues wrote in Pediatrics.

Their results align with other research demonstrating an overall increase in violence against women and girls during the pandemic – a phenomenon the World Health Organization has called the “shadow pandemic.”

The challenges of accessing care during the COVID-19 restrictions demonstrate the utility of telehealth as a modality for providing assessment, support, and referrals, the authors stated.

They pointed to certain advantages in supporting IPV survivors virtually, including the ability to speak alone with the survivor, which is often not possible during in-person visits with children in the room.

Other research has documented that health care delivery via telemedicine, especially video teleconferencing, during the pandemic can be as effective as in-office visits. In fact, care providers may be able to pick up on significant visual cues on video that go unnoticed in the immediacy of the office setting.
 

The study

The researchers examined COVID-19–related variations in consultations and referrals in the 11 months before the COVID-19 pandemic (April 1, 2019, to Feb. 29, 2020) and those following its emergence (April 1, 2020, to Feb. 28, 2021).

Face-to-face consults declined from 28% to 2% (P < .001) after COVID-19 emergence, while total consults increased from 240 to 295 (P < .001), primarily for emotional abuse (from 195 to 264, P = .007).

There were no significant changes in the number of consults for other reasons or in the number of reasons recorded for each consult.

Psychoeducation referrals also rose significantly from 199 to 273 (P < .001), while referrals to community resources decreased significantly from 111 to 95 (P < .001).

Primary care was the only practice setting demonstrating significant differences in the overall number of and specific reasons for consultation, as well as associated referral types before and after COVID emergence.

“We hypothesize that this increase may be attributable to the fact that, although many survivors were at home with partners who use abusive behaviors, obligatory pediatric primary care visits may have been a rare opportunity for them to leave their residence and seek support,” the investigators wrote. “Our data support the importance of a domestic violence program in pediatric hospitals and suggest that such support be available as a standard part of care.”

They further suggested that support and assessment may be effective regardless of whether that care is performed face-to-face or via telehealth.
 

Commentary

An accompanying editorial noted that intimate partner violence affects one in five children and has profound health effects on survivors and their children.

“The health, economic, and social ramifications of the COVID-19 pandemic have created unique challenges for families experiencing IPV, by increasing isolation, decreasing available safe and secure services and spaces (e.g., schools), and compounding preexisting inequities, especially for families from marginalized communities,” wrote Maya Ragavan, MD, MS, MPH, and Elizabeth Miller, MD, PhD, of the department of pediatrics at the University of Pittsburgh.

They stressed that pediatric health care providers should be aware of the emotionally coercive control used by abusive partners during the pandemic, including social isolation, manipulating child custody, and taking stimulus money.

Dr. Ragavan and Dr. Miller agreed with the authors that pediatric health care settings can play an important role in supporting families exposed to intimate partner violence, particularly by developing partnerships with IPV aid agencies.

Many pediatric offices may not have access to a comprehensive service like AWAKE, highlighting the importance of developing partnerships with community-based IPV agencies, which have been working innovatively during the pandemic to support families experiencing IPV. “Pediatric health care providers should work to develop formalized partnerships with IPV agencies to assist with staff training, clinical protocols and policies to address IPV, including survivor-centered approaches to care when IPV is disclosed,” they wrote. “Health care settings must recognize that IPV agencies are integral to the pediatric medical home and essential collaborators in the provision of healing-centered care for IPV survivors and their children.”

Among these, Futures Without Violence, a national violence-prevention advocacy and policy organization, offers recommendations on collaboration via the IPV Health Partners website.

Matthew I. Harris, MD, a pediatric emergency physician at Cohen Children’s Medical Center in New York, concurred that the pediatric care setting can be an access point for IPV referrals. “Whether a child comes into our center with an ear infection or an injury, there’s a standard screening process for safety in the home,” he said in an interview. That standard filtering identifies the presence of smoking, alcohol, guns, and potential abusers. “It’s not uncommon that we discover violence or physical, verbal, or sexual abuse not only toward the child but also another family member, including IPV.”

Children’s hospitals are well positioned to identify at-risk families and refer them to appropriate protective services, Dr. Harris said. “Ultimately, we are charged with the responsibility of ensuring children have a safe home environment and that involves minimizing any harmful impact on other family members, including those exposed to IPV.”

The authors received no funding for this study and reported no competing interests. Dr. Ragavan had no relevant conflicts of interest to disclose. Dr. Miller reported royalties for writing content for UpToDate. Dr. Harris disclosed no competing interests.

This article was updated 3/25/22.

The College of American Pathologists (CAP) guidance outperforms the Royal College of Pathologists (RCPath) guidance in predicting recurrence and survival following resection of oral cavity squamous cell carcinoma (OCSCC), according to a retrospective study.

Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.

RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.

In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.

The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.

The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.

Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.

The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.

The College of American Pathologists (CAP) guidance outperforms the Royal College of Pathologists (RCPath) guidance in predicting recurrence and survival following resection of oral cavity squamous cell carcinoma (OCSCC), according to a retrospective study.

Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.

RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.

In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.

The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.

The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.

Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.

The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.

The College of American Pathologists (CAP) guidance outperforms the Royal College of Pathologists (RCPath) guidance in predicting recurrence and survival following resection of oral cavity squamous cell carcinoma (OCSCC), according to a retrospective study.

Treatment of OCSCC involves resection of the primary tumor, followed by neck dissection or postoperative radiotherapy when needed, but choice of treatment requires an accurate assessment of resection margins. Previous studies have failed to consistently show a correlation between margin status and clinical outcomes. Tumor size, depth of invasion, and other factors may explain inconsistent findings, but another possibility is the variability in how margin status is defined.

RCPath and CAP are among the most commonly used definitions. RCPath defines a positive margin as invasive tumor within 1 mm of the surgical margin, while CAP defines a positive margin as the presence of primary tumor or high-grade dysplasia at the margin itself. CAP recommends determination of a “final margin status” that also considers separately submitted extra tumor bed margins. Nevertheless, multiple studies have shown that reliance on the main tumor specimen outperformed the combined approach in predicting recurrence and survival.

In a study published online March 7 in Oral Oncology, researchers examined records from 300 patients (33.7% of whom were female) at South Infirmary Victoria University Hospital in Ireland between 2007 and 2020. The researchers found that 28.7% had margins determined by the RCPath definition and 16.7% according to the CAP definition. Forty-nine percent underwent extra tumor bed resections.

The mean follow-up period was 49 months, 64 months for surviving patients. Multivariate analyses accounting for other established prognosticators found that local recurrence was associated with CAP margins (odds ratio [OR], 1.86; 955 confidence interval [CI], 1.02-3.48) and T3/T4 classification (OR, 2.80; 95% CI, 1.53-5.13). CAP margins predicted disease-specific survival (OR, 2.28; 95% CI, 1.53-5.13) and narrowly missed significance in predicting overall survival (OR, 1.65; 95% CI, 0.99-2.75). RCPath margins were not predictive.

The researchers found a significant association between RCPath definition and metastatic nodal disease and extranodal extension, but there was no such relationship between these negative predictors and CAP and final margin status. “This finding may explain the superior independent prognostic ability of CAP margin status over RCPath in our cohort and is consistent with that of previous studies, which concluded that other histological risk factors are more important than margin status in predicting outcome,” the authors wrote.

Studies suggest that margins fewer than 1 mm remain a high-risk group, with worse survival outcomes than those of patients with 1- to 5-mm margins, even if the risk is lower than tumor at margins. “The optimum cut-off between low-risk and high-risk margins in OCSCC remains unresolved,” the authors wrote.

The study was retrospective and relied on data from a single center, and the patients included in the study may not be directly comparable to other OCSCC patients. The study was funded by the Head and Neck Oncology Fund, South Infirmary Victoria University Hospital.

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.

A higher rate of serrated polyp detection was associated with a reduced risk of postcolonoscopy colorectal cancer, based on data from nearly 20,000 patients and 142 endoscopists, according to a study published in Gastrointestinal Endoscopy.

Higher rates of adenoma detection reduce the risk of postcolonoscopy colorectal cancer (PCCRC), but the data on detection rates for clinically significant serrated polyps and traditional serrated adenomas are limited, wrote Joseph C. Anderson, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“A unique challenge for endoscopists is that serrated polyps exhibit characteristics that can make them more difficult to detect than conventional adenomas. Thus, it is not surprising that several studies have demonstrated a wide variation in serrated polyp detection rates.” Even so, improved detection and resection of these polyps would likely improve CRC prevention, they noted.

The researchers reviewed data from the New Hampshire Colonoscopy Registry to explore the association between clinically significantly serrated polyp (CSSP) detection rates and subsequent PCCRC risk.

The study population included 19,532 patients with follow-up events at least 6 months after an index colonoscopy. Of these, 128 cases of CRC were diagnosed at least 6 months after an index exam. CSSP was defined as any sessile serrated polyp, traditional serrated adenoma, or any large hyperplastic polyp (> 1 cm) or proximal hyperplastic polyp > 5 mm. The exams were performed by 142 endoscopists, 92 of whom were gastroenterologists. The 50 nongastroenterologists included general surgeons, colorectal surgeons, and family practitioners.

The primary outcome was PCCRC, defined as any CRC diagnosis 6 months or longer after an index exam. Clinically significant serrated polyp detection rate (CSSDR) was determined by dividing the total number of complete screening exams with adequate prep and at least one CSSP by the total number of complete exams with adequate prep. CSSDR was divided into tertiles of less than 3%, 3% up to 9%, and 9% or higher.

Overall, the risk for PCCRC 6 months or more after an index exam was significantly lower for exams performed by endoscopists with detection rates of 3% up to 9% and for those with detection rates of 9% or higher compared to those with detection rates below 3% (hazard ratios 0.57 and 0.39, respectively).

Significantly more gastroenterologists were in the higher CSSDR categories compared to nongastroenterologists (P = .00005). The percentages of gastroenterologists in the three tertiles from lowest to highest detection were 15.2%, 50.0%, and 34.8%; compared to 46%, 44.0%, and 10.0%, respectively, for nongastroenterologists.

In adjusted analysis, higher detection rates were associated with lower CRC risk across all time periods.

The researchers also found higher CSSDR categories associated with lower PCCRC risk for exams by endoscopists with ADR rates of 25% or higher.

“It may be reasonable to question whether a separate serrated detection rate is needed in addition to ADR,” the researchers wrote in their discussion of the findings. “These data support our suggestion that endoscopists, even those with an ADR of 25% or higher, calculate their SDR at least once, a recommendation supported by a recent review of the American Gastroenterological Association,” they noted.

The study findings were limited by several factors, including the lack of information on specific endoscopic techniques, a lack of data on the molecular characteristics of the cancers, and potential residual confounding variables, the researchers noted.

However, the results were strengthened by the large number of participating endoscopists and by the longitudinal database that included detection rates for screening exams and detailed polyp pathology, they said. The results support the need for a serrated polyp detection rate benchmark to endure complete polyp detection and validate the use of CSSDR as a quality measure that adds to the knowledge of both colonoscopy quality and the role of the serrated pathway in colorectal cancer, they concluded.
 

Serrated pathway serves as predictor

The current study is an important addition to the knowledge of colorectal cancer risk, Atsushi Sakuraba, MD, PhD, associate professor of medicine at the University of Chicago, said in an interview.

“In addition to the conventional adenoma pathway, the serrated pathway has been recognized to account for a significant portion of colorectal cancer, but whether detection of serrated polyps [is] associated with reduction of CRC remains unknown,” he said.

Dr. Sakuraba said he was not surprised by the study findings. Given that the serrated pathway is now considered to account for approximately 10%-20% of all CRC cases, higher detection rates should result in lower risk of CRC, he noted.

The findings support the value of CSSDR in clinical practice, said Dr. Sakuraba. “The study has shown that a clinically significant serrated polyps detection rate of 3% was associated with lower postcolonoscopy CRC, so endoscopists should introduce this to their practice in addition to adenoma detection rates,” he said.

However, Dr. Sakuraba acknowledged the limitations of the current study and emphasized that it needs to be reproduced in other cohorts. Prospective studies might be helpful as well, he said.

The study received no outside funding. The researchers and Dr. Sakuraba had no financial conflicts to disclose.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

Hospitalized COVID-19 survivors showed greater cognitive impairment 6 months later, compared with patients hospitalized for other causes, but the overall disease burden was similar, based on data from 85 adults with COVID-19.

Previous studies have shown that cognitive and neuropsychiatric symptoms can occur from 2-6 months after COVID-19 recovery, and such symptoms are known to be associated with hospitalization for other severe medical conditions, Vardan Nersesjan, MD, of Copenhagen University Hospital, and colleagues wrote.

However, it remains unknown if COVID-19 is associated with a unique pattern of cognitive and mental impairment compared with other similarly severe medical conditions, they said.

In a study published in JAMA Psychiatry (2022 Mar 23. doi: 10.1001/jamapsychiatry.2022.0284), the researchers identified 85 adult COVID-19 survivors and 61 controls with non-COVID medical conditions who were treated and released between July 2020 and July 2021. The COVID-19 patients and controls were matched for age, sex, and ICU status. Cognitive impairment was assessed using the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semistructured interview to determine subjective symptoms.

The primary outcomes were the total scores on the MoCA and any new-onset psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses such as depression, neurologic examination findings, and self-reported neuropsychiatric and cognitive symptoms. The mean age of the COVID-19 patients was 56.8 years, and 42% were women.

At 6 months’ follow-up, cognitive status was significantly lower in COVID-19 survivors, compared with controls, based on total geometric mean MoCA scores (26.7 vs. 27.5, P = .01). However, cognitive status improved significantly from 19.2 at hospital discharge to 26.1 at 6 months in 15 of the COVID-19 patients (P = .004), the researchers noted.

New-onset psychiatric diagnoses occurred in 16 COVID-19 patients and 12 of the controls (19% vs. 20%); this difference was not significant.

Secondary outcomes were not significantly different at 6 months between the groups, with the exception of anosmia, which was significantly more common in the COVID-19 patients; however, the significance disappeared in adjusted analysis, the researchers said.

The study findings were limited by several factors including the inability to prove causality because of the case-control feature and by the inability to detect small differences in neuropsychiatric outcomes, the researchers noted.

However, the results were strengthened by the use of a prospectively matched control group with similar disease severity admitted to the same hospital in the same time frame. Although the overall burden of neuropsychiatric and neurologic symptoms and diagnoses appeared similar in COVID-19 patients and those with other medical conditions, more research in larger populations is needed to determine smaller differences in neuropsychiatric profiles, the researchers noted.

Study fills research gap

The study is important at this time because, although prolonged neuropsychiatric and cognitive symptoms have been reported after COVID-19, the field lacked prospective case-control studies with well-matched controls to investigate whether these outcomes differed from those seen in other critical illnesses that had also required hospitalization, corresponding author Michael E. Benros, MD, of the Mental Health Center, Copenhagen, said in an interview.

“I was surprised that there was a significant worse cognitive functioning among COVID-19 patients 6 months after symptom onset also when compared to this well-matched control group that had been hospitalized for non–COVID-19 illness, although the absolute difference between the groups in cognition score were small,” said Dr. Benros. “Another notable finding is the large improvement in cognitive functioning from discharge to follow-up,” he added on behalf of himself and fellow corresponding author Daniel Kondziella, MD.

The study results show that cognitive function affected by COVID-19 and critical illness as observed at discharge showed a substantial improvement at 6 months after symptom onset, said Dr. Benros. “However, the cognitive function was significantly worse among severely ill COVID-19 patients 6 months after symptom onset when compared to a matched control group of individuals hospitalized for non–COVID-19 illness, although this difference in cognitive function was rather small in absolute numbers, and smaller than what had been suggested by other studies that lacked control groups. Strikingly, neuropsychiatric disorders were similar across the two groups, which was also the case when looking at neuropsychiatric symptoms.

“Larger prospective case-control studies of neuropsychiatric and cognitive functioning after COVID-19, compared with matched controls are still needed to detect smaller differences, and more detailed cognitive domains, and with longer follow-up time, which we are currently conducting,” Dr. Benros said.  
 

Controlled studies will help planning

“Lingering neuropsychiatric complications are common after COVID-19, but only controlled studies can tell us whether these complications are specific to COVID-19, rather than a general effect of having been medically ill,” Alasdair G. Rooney, MRCPsych MD PhD, of the University of Edinburgh, said in an interview. “The answer matters ultimately because COVID-19 is a new disease; societies and health care services need to be able to plan for its specific consequences.”

The health status of the control group is important as well. “Most previous studies had compared COVID-19 survivors against healthy controls or patients from a historical database. This new study compared COVID-19 survivors against those hospitalized for other medical causes over the same period,” Dr. Rooney said. “This is a more stringent test of whether COVID-19 has specific neurocognitive and neuropsychiatric consequences.

“The study found that new-onset neuropsychiatric diagnoses and symptoms were no more likely to occur after COVID-19 than after similarly severe medical illnesses,” Dr. Rooney said. “This negative finding runs counter to some earlier studies and may surprise some.” The findings need to be replicated in larger samples, but the current study shows the importance of prospectively recruiting active controls.

“In a subgroup analysis, some patients showed good improvement in cognitive scores between discharge and follow-up. While unsurprising, this is encouraging and suggests that the early postdischarge months are an important time for neurocognitive recovery,” Dr. Rooney noted.

“The findings suggest that COVID-19 may impair attention more selectively than other medical causes of hospitalization. COVID-19 survivors may also be at higher risk of significant overall cognitive impairment than survivors of similarly severe medical illnesses, after a similar duration,” said Dr. Rooney. “If the results are replicated by other prospective studies, they would suggest that there is something about COVID-19 that causes clinically significant neurocognitive difficulties in a minority of survivors.

“Larger well-controlled studies are required, with longer follow-up and more detailed neurocognitive testing,” as the duration of impairment and scope for further recovery are not known, Dr. Rooney added. Also unknown is whether COVID-19 affects attention permanently, or whether recovery is simply slower after COVID-19 compared to other medical illnesses.

“Knowing who is at the greatest risk of severe cognitive impairment after COVID-19 is important and likely to allow tailoring of more effective shielding strategies,” said Dr. Rooney. “This study was conducted before the widespread availability of vaccines for COVID-19. Long-term neuropsychiatric outcomes in vaccinated patients remain largely unknown. Arguably, these are now more important to understand, as future COVID-19 waves will occur mainly among vaccinated individuals.”

The study was supported by the Lundbeck Foundation and the Novo Nordisk Foundation. Lead author Dr. Nersesjan had no financial conflicts to disclose. Dr. Benros reported grants from Lundbeck Foundation and Novo Nordisk Foundation during the conduct of the study. Dr. Rooney had no financial conflicts to disclose.

This article was updated 3/25/22.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

A version of this article first appeared on WebMD.com.

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

Perioperative immunotherapy appears to be safe in the setting of resectable hepatocellular carcinoma (HCC), according to findings from an open-label phase 2 clinical trial published in The Lancet Gastroenterology and Hepatolgy.

The study compared the anti-PD1 antibody nivolumab (Opdivo, Bristol Myers Squibb) alone and nivolumab plus the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) among patients with resectable disease at a single center in Sweden. The treatments were found to be “safe and feasible in patients with resectable hepatocellular carcinoma,” wrote researchers who were led by Ahmed O. Kaseb, MD, a medical oncologist with MD Anderson Cancer Center, Houston.

The rate of 5-year tumor recurrence following HCC resection can be as high as 70%, and there are no approved neoadjuvant or adjuvant therapies.

Immune checkpoint therapy has not been well studied in early-stage HCC, but it is used in advanced HCC.

The combination of PDL1 blockade with atezolizumab and VEGF blockade with bevacizumab, is currently a first-line treatment for advanced HCC. “Checkpoint inhibitors targeting PD1 and PDL1 and CTLA4 are active, tolerable, and clinically beneficial against advanced HCC,” according to researchers writing in a Nature Reviews article published in April 2021.

There are other promising immunotherapies under study for HCC, such as additional checkpoint inhibitors, adoptive cell transfer, vaccination, and virotherapy.
 

Small study of 27 patients

The Lancet study included 27 patients (64 years mean age, 19 patients were male). Twenty-three percent of patients on nivolumab alone had a partial pathological response at week 6, while none in the combination group had a response. Among 20 patients who underwent surgery, 3 of 9 (33%) and 3 of 11 (27%) in the combination group experienced a major pathological response. Two patients in the nivolumab and three patients in the combination group achieved a complete pathological response.

Disease progression occurred in 7 of 12 patients who were evaluated in the nivolumab group, and 4 of 13 patients in the combination group. Estimated median time to disease progression in the nivolumab group was 9.4 months (95% confidence interval, 1.47 to not estimable) and 19.53 months (95% CI, 2.33 to not estimable) in the combination group. Two-year progression-free survival was estimated to be 42% (95% CI, 21%-81%) in the nivolumab group and 26% (95% CI, 8%-78%, no significant difference) in the combination group.

Among 20 patients who underwent surgery, 6 patients had experienced a major pathological response. None of the 6 patients had a recurrence after a median follow-up of 26.8 months, versus 7 recurrences among 14 patients without a pathological response (log-rank P = .049).

Seventy-seven percent of patients in the nivolumab group experienced at least one adverse event (23% grade 3-4), as did 86% in the combination group (43% grade 3-4, difference nonsignificant). No patients delayed or canceled surgery because of adverse events.

Patients who had a major pathological response on the combination treatment had higher levels of immune infiltration versus baseline values. Those who had complete pathological responses in the nivolumab group had high infiltration at baseline. Those results imply some optimism for further study. “These data suggest that, with the immune-priming ability of anti–CTLA-4 treatment, nivolumab plus ipilimumab was able to generate a major pathological response even in tumours that had low immune infiltration at baseline,” the authors wrote.

The study was limited by its open-label nature and small sample size, and it was conducted at a single center.

The study was funded by Bristol Myers Squibb and the National Institutes of Health. Dr. Kaseb reports consulting, advisory roles or stock ownership, or both with Bristol-Myers Squibb.
 

Perioperative immunotherapy appears to be safe in the setting of resectable hepatocellular carcinoma (HCC), according to findings from an open-label phase 2 clinical trial published in The Lancet Gastroenterology and Hepatolgy.

The study compared the anti-PD1 antibody nivolumab (Opdivo, Bristol Myers Squibb) alone and nivolumab plus the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) among patients with resectable disease at a single center in Sweden. The treatments were found to be “safe and feasible in patients with resectable hepatocellular carcinoma,” wrote researchers who were led by Ahmed O. Kaseb, MD, a medical oncologist with MD Anderson Cancer Center, Houston.

The rate of 5-year tumor recurrence following HCC resection can be as high as 70%, and there are no approved neoadjuvant or adjuvant therapies.

Immune checkpoint therapy has not been well studied in early-stage HCC, but it is used in advanced HCC.

The combination of PDL1 blockade with atezolizumab and VEGF blockade with bevacizumab, is currently a first-line treatment for advanced HCC. “Checkpoint inhibitors targeting PD1 and PDL1 and CTLA4 are active, tolerable, and clinically beneficial against advanced HCC,” according to researchers writing in a Nature Reviews article published in April 2021.

There are other promising immunotherapies under study for HCC, such as additional checkpoint inhibitors, adoptive cell transfer, vaccination, and virotherapy.
 

Small study of 27 patients

The Lancet study included 27 patients (64 years mean age, 19 patients were male). Twenty-three percent of patients on nivolumab alone had a partial pathological response at week 6, while none in the combination group had a response. Among 20 patients who underwent surgery, 3 of 9 (33%) and 3 of 11 (27%) in the combination group experienced a major pathological response. Two patients in the nivolumab and three patients in the combination group achieved a complete pathological response.

Disease progression occurred in 7 of 12 patients who were evaluated in the nivolumab group, and 4 of 13 patients in the combination group. Estimated median time to disease progression in the nivolumab group was 9.4 months (95% confidence interval, 1.47 to not estimable) and 19.53 months (95% CI, 2.33 to not estimable) in the combination group. Two-year progression-free survival was estimated to be 42% (95% CI, 21%-81%) in the nivolumab group and 26% (95% CI, 8%-78%, no significant difference) in the combination group.

Among 20 patients who underwent surgery, 6 patients had experienced a major pathological response. None of the 6 patients had a recurrence after a median follow-up of 26.8 months, versus 7 recurrences among 14 patients without a pathological response (log-rank P = .049).

Seventy-seven percent of patients in the nivolumab group experienced at least one adverse event (23% grade 3-4), as did 86% in the combination group (43% grade 3-4, difference nonsignificant). No patients delayed or canceled surgery because of adverse events.

Patients who had a major pathological response on the combination treatment had higher levels of immune infiltration versus baseline values. Those who had complete pathological responses in the nivolumab group had high infiltration at baseline. Those results imply some optimism for further study. “These data suggest that, with the immune-priming ability of anti–CTLA-4 treatment, nivolumab plus ipilimumab was able to generate a major pathological response even in tumours that had low immune infiltration at baseline,” the authors wrote.

The study was limited by its open-label nature and small sample size, and it was conducted at a single center.

The study was funded by Bristol Myers Squibb and the National Institutes of Health. Dr. Kaseb reports consulting, advisory roles or stock ownership, or both with Bristol-Myers Squibb.
 

Perioperative immunotherapy appears to be safe in the setting of resectable hepatocellular carcinoma (HCC), according to findings from an open-label phase 2 clinical trial published in The Lancet Gastroenterology and Hepatolgy.

The study compared the anti-PD1 antibody nivolumab (Opdivo, Bristol Myers Squibb) alone and nivolumab plus the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) among patients with resectable disease at a single center in Sweden. The treatments were found to be “safe and feasible in patients with resectable hepatocellular carcinoma,” wrote researchers who were led by Ahmed O. Kaseb, MD, a medical oncologist with MD Anderson Cancer Center, Houston.

The rate of 5-year tumor recurrence following HCC resection can be as high as 70%, and there are no approved neoadjuvant or adjuvant therapies.

Immune checkpoint therapy has not been well studied in early-stage HCC, but it is used in advanced HCC.

The combination of PDL1 blockade with atezolizumab and VEGF blockade with bevacizumab, is currently a first-line treatment for advanced HCC. “Checkpoint inhibitors targeting PD1 and PDL1 and CTLA4 are active, tolerable, and clinically beneficial against advanced HCC,” according to researchers writing in a Nature Reviews article published in April 2021.

There are other promising immunotherapies under study for HCC, such as additional checkpoint inhibitors, adoptive cell transfer, vaccination, and virotherapy.
 

Small study of 27 patients

The Lancet study included 27 patients (64 years mean age, 19 patients were male). Twenty-three percent of patients on nivolumab alone had a partial pathological response at week 6, while none in the combination group had a response. Among 20 patients who underwent surgery, 3 of 9 (33%) and 3 of 11 (27%) in the combination group experienced a major pathological response. Two patients in the nivolumab and three patients in the combination group achieved a complete pathological response.

Disease progression occurred in 7 of 12 patients who were evaluated in the nivolumab group, and 4 of 13 patients in the combination group. Estimated median time to disease progression in the nivolumab group was 9.4 months (95% confidence interval, 1.47 to not estimable) and 19.53 months (95% CI, 2.33 to not estimable) in the combination group. Two-year progression-free survival was estimated to be 42% (95% CI, 21%-81%) in the nivolumab group and 26% (95% CI, 8%-78%, no significant difference) in the combination group.

Among 20 patients who underwent surgery, 6 patients had experienced a major pathological response. None of the 6 patients had a recurrence after a median follow-up of 26.8 months, versus 7 recurrences among 14 patients without a pathological response (log-rank P = .049).

Seventy-seven percent of patients in the nivolumab group experienced at least one adverse event (23% grade 3-4), as did 86% in the combination group (43% grade 3-4, difference nonsignificant). No patients delayed or canceled surgery because of adverse events.

Patients who had a major pathological response on the combination treatment had higher levels of immune infiltration versus baseline values. Those who had complete pathological responses in the nivolumab group had high infiltration at baseline. Those results imply some optimism for further study. “These data suggest that, with the immune-priming ability of anti–CTLA-4 treatment, nivolumab plus ipilimumab was able to generate a major pathological response even in tumours that had low immune infiltration at baseline,” the authors wrote.

The study was limited by its open-label nature and small sample size, and it was conducted at a single center.

The study was funded by Bristol Myers Squibb and the National Institutes of Health. Dr. Kaseb reports consulting, advisory roles or stock ownership, or both with Bristol-Myers Squibb.
 

Younger, nonsmoking oral cancer patients have a higher risk of death than that of young smokers, and the outcomes may be related to immune deficiencies. The finding comes from a database of oral cavity squamous cell carcinoma (OSCC) patients treated between 1985 and 2015.

“Recent studies have shown an association between high neutrophil to lymphocyte ratio as a marker for poor outcome in several different cancers. This ratio is a surrogate marker for a patient’s immune function. A high ratio indicates an impaired immune function. This means that the ability for the immune system to identify and eradicate abnormal cells which have the potential to form cancer cells is impaired. We don’t know why this is occurring,” said Ian Ganly, MD, PhD, a head and neck surgeon with Memorial Sloan Kettering Cancer Center in New York.

Dr. Ganly is lead author of the new study, published online March 5 in Oral Oncology.

“Physicians should be aware these patients may have impaired immunity and may have a more aggressive presentation and clinical behavior. Such patients may require more comprehensive staging investigations for cancer and may require more comprehensive treatment. Following treatment these patients should also have a detailed and regular follow-up examination with appropriate imaging to detect early recurrence,” he said in an interview.

The research also suggests that immunotherapy may be effective in this group. “However, our findings are only preliminary and further research into this area is required before such therapy can be justified,” Dr. Ganly said.

The study comprised 2,073 patients overall (median age, 62; 43.5% female) and 100 younger nonsmoking patients (median age, 34; 56.0% female). After multivariate analysis, compared to young smokers, nonsmokers with OSCC had a greater risk of mortality (P = .0229), although they had a lower mortality risk than both smokers and nonsmokers over 40. After adjustments, young nonsmokers had a mortality resembling that of older patients, while mortality among young smokers was distinctly lower than that of older patients.

In a subset of 88 young nonsmoking patients, there was a higher neutrophil-to-lymphocyte ratio (median, 2.456) than that of similarly aged patients with thyroid cancer (median, 2.000; P = .0093) or salivary gland benign pathologies (median, 2.158; P = .0343).

The researchers are now studying the genomics of tumors found in smokers and nonsmokers and comparing them to tumors in older smokers and nonsmokers with OSCCs. They are performing a similar comparison of the immune environment of the tumors and patients’ immune system function. “For the genomics aspect I am looking to see if there are any unique alterations in the young nonsmokers that may explain the biology of these cancers. If so, there may be some alterations that can be targeted with new drugs. For the immune aspect, our goal is to see if there are any specific alterations in immune function unique to this population. Then it may be possible to deliver specific types of immunotherapy that focus in on these deficiencies,” said Dr. Ganly.

The study was funded by Fundación Alfonso Martín Escudero and the National Institutes of Health. Dr. Ganly has no relevant financial disclosures.

Younger, nonsmoking oral cancer patients have a higher risk of death than that of young smokers, and the outcomes may be related to immune deficiencies. The finding comes from a database of oral cavity squamous cell carcinoma (OSCC) patients treated between 1985 and 2015.

“Recent studies have shown an association between high neutrophil to lymphocyte ratio as a marker for poor outcome in several different cancers. This ratio is a surrogate marker for a patient’s immune function. A high ratio indicates an impaired immune function. This means that the ability for the immune system to identify and eradicate abnormal cells which have the potential to form cancer cells is impaired. We don’t know why this is occurring,” said Ian Ganly, MD, PhD, a head and neck surgeon with Memorial Sloan Kettering Cancer Center in New York.

Dr. Ganly is lead author of the new study, published online March 5 in Oral Oncology.

“Physicians should be aware these patients may have impaired immunity and may have a more aggressive presentation and clinical behavior. Such patients may require more comprehensive staging investigations for cancer and may require more comprehensive treatment. Following treatment these patients should also have a detailed and regular follow-up examination with appropriate imaging to detect early recurrence,” he said in an interview.

The research also suggests that immunotherapy may be effective in this group. “However, our findings are only preliminary and further research into this area is required before such therapy can be justified,” Dr. Ganly said.

The study comprised 2,073 patients overall (median age, 62; 43.5% female) and 100 younger nonsmoking patients (median age, 34; 56.0% female). After multivariate analysis, compared to young smokers, nonsmokers with OSCC had a greater risk of mortality (P = .0229), although they had a lower mortality risk than both smokers and nonsmokers over 40. After adjustments, young nonsmokers had a mortality resembling that of older patients, while mortality among young smokers was distinctly lower than that of older patients.

In a subset of 88 young nonsmoking patients, there was a higher neutrophil-to-lymphocyte ratio (median, 2.456) than that of similarly aged patients with thyroid cancer (median, 2.000; P = .0093) or salivary gland benign pathologies (median, 2.158; P = .0343).

The researchers are now studying the genomics of tumors found in smokers and nonsmokers and comparing them to tumors in older smokers and nonsmokers with OSCCs. They are performing a similar comparison of the immune environment of the tumors and patients’ immune system function. “For the genomics aspect I am looking to see if there are any unique alterations in the young nonsmokers that may explain the biology of these cancers. If so, there may be some alterations that can be targeted with new drugs. For the immune aspect, our goal is to see if there are any specific alterations in immune function unique to this population. Then it may be possible to deliver specific types of immunotherapy that focus in on these deficiencies,” said Dr. Ganly.

The study was funded by Fundación Alfonso Martín Escudero and the National Institutes of Health. Dr. Ganly has no relevant financial disclosures.

Younger, nonsmoking oral cancer patients have a higher risk of death than that of young smokers, and the outcomes may be related to immune deficiencies. The finding comes from a database of oral cavity squamous cell carcinoma (OSCC) patients treated between 1985 and 2015.

“Recent studies have shown an association between high neutrophil to lymphocyte ratio as a marker for poor outcome in several different cancers. This ratio is a surrogate marker for a patient’s immune function. A high ratio indicates an impaired immune function. This means that the ability for the immune system to identify and eradicate abnormal cells which have the potential to form cancer cells is impaired. We don’t know why this is occurring,” said Ian Ganly, MD, PhD, a head and neck surgeon with Memorial Sloan Kettering Cancer Center in New York.

Dr. Ganly is lead author of the new study, published online March 5 in Oral Oncology.

“Physicians should be aware these patients may have impaired immunity and may have a more aggressive presentation and clinical behavior. Such patients may require more comprehensive staging investigations for cancer and may require more comprehensive treatment. Following treatment these patients should also have a detailed and regular follow-up examination with appropriate imaging to detect early recurrence,” he said in an interview.

The research also suggests that immunotherapy may be effective in this group. “However, our findings are only preliminary and further research into this area is required before such therapy can be justified,” Dr. Ganly said.

The study comprised 2,073 patients overall (median age, 62; 43.5% female) and 100 younger nonsmoking patients (median age, 34; 56.0% female). After multivariate analysis, compared to young smokers, nonsmokers with OSCC had a greater risk of mortality (P = .0229), although they had a lower mortality risk than both smokers and nonsmokers over 40. After adjustments, young nonsmokers had a mortality resembling that of older patients, while mortality among young smokers was distinctly lower than that of older patients.

In a subset of 88 young nonsmoking patients, there was a higher neutrophil-to-lymphocyte ratio (median, 2.456) than that of similarly aged patients with thyroid cancer (median, 2.000; P = .0093) or salivary gland benign pathologies (median, 2.158; P = .0343).

The researchers are now studying the genomics of tumors found in smokers and nonsmokers and comparing them to tumors in older smokers and nonsmokers with OSCCs. They are performing a similar comparison of the immune environment of the tumors and patients’ immune system function. “For the genomics aspect I am looking to see if there are any unique alterations in the young nonsmokers that may explain the biology of these cancers. If so, there may be some alterations that can be targeted with new drugs. For the immune aspect, our goal is to see if there are any specific alterations in immune function unique to this population. Then it may be possible to deliver specific types of immunotherapy that focus in on these deficiencies,” said Dr. Ganly.

The study was funded by Fundación Alfonso Martín Escudero and the National Institutes of Health. Dr. Ganly has no relevant financial disclosures.