Federal Practitioner

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

Nearly one-third of adults over age 65 developed one or more new medical conditions in the weeks following a COVID-19 infection, according to new research.

The findings of the observational study, which were published in the BMJ, show the risk of a new condition being triggered by COVID is more than twice as high in seniors, compared with younger patients. Plus, the researchers observed an even higher risk among those who were hospitalized, with nearly half (46%) of patients having developed new conditions after the acute COVID-19 infection period.

Respiratory failure with shortness of breath was the most common postacute sequela, but a wide range of heart, kidney, lung, liver, cognitive, mental health, and other conditions were diagnosed at least 3 weeks after initial infection and persisted beyond 30 days.

This is one of the first studies to specifically describe the incidence and severity of new conditions triggered by COVID-19 infection in a general sample of older adults, said study author Ken Cohen MD, FACP, executive director of translational research at Optum Labs and national senior medical director at Optum Care.

“Much of what has been published on the postacute sequelae of COVID-19 has been predominantly from a younger population, and many of the patients had been hospitalized,” Dr. Cohen noted. “This was the first study to focus on a large population of seniors, most of whom did not require hospitalization.”

Dr. Cohen and colleagues reviewed the health insurance records of more than 133,000 Medicare beneficiaries aged 65 or older who were diagnosed with COVID-19 before April 2020. They also matched individuals by age, race, sex, hospitalization status, and other factors to comparison groups without COVID-19 (one from 2020 and one from 2019), and to a group diagnosed with other lower respiratory tract viral infections before the pandemic.
 

Risk of developing new conditions was higher in hospitalized

After acute COVID-19 infection, 32% of seniors sought medical care for at least one new medical condition in 2020, compared with 21% of uninfected people in the same year.

The most commonly observed conditions included:

• Respiratory failure (7.55% higher risk).
• Fatigue (5.66% higher risk).
• High blood pressure (4.43% higher risk).
• Memory problems (2.63% higher risk).
• Kidney injury (2.59% higher risk).
• Mental health diagnoses (2.5% higher risk).
• Blood-clotting disorders (1.47 % higher risk).
• Heart rhythm disorders (2.9% higher risk).

The risk of developing new conditions was even higher among those 23,486 who were hospitalized in 2020. Those individuals showed a 23.6% higher risk for developing at least one new condition, compared with uninfected seniors in the same year. Also, patients older than 75 had a higher risk for neurological disorders, including dementia, encephalopathy, and memory problems. The researchers also found that respiratory failure and kidney injury were significantly more likely to affect men and Black patients.

When those who had COVID were compared with the group with other lower respiratory viral infections before the pandemic, only the risks of respiratory failure (2.39% higher), dementia (0.71% higher), and fatigue (0.18% higher) were higher.

Primary care providers can learn from these data to better evaluate and manage their geriatric patients with COVID-19 infection, said Amit Shah, MD, a geriatrician with the Mayo Clinic in Phoenix, in an interview.

“We must assess older patients who have had COVID-19 for more than just improvement from the respiratory symptoms of COVID-19 in post-COVID follow-up visits,” he said. “Older individuals with frailty have vulnerability to subsequent complications from severe illnesses and it is common to see post-illness diagnoses, such as new diagnosis of delirium; dementia; or renal, respiratory, or cardiac issues that is precipitated by the original illness. This study confirms that this is likely the case with COVID-19 as well.

“Primary care physicians should be vigilant for these complications, including attention to the rehabilitation needs of older patients with longer-term postviral fatigue from COVID-19,” Dr. Shah added.
 

Data predates ‘Omicron wave’

It remains uncertain whether sequelae will differ with the Omicron variant, but the findings remain applicable, Dr. Cohen said.

“We know that illness from the Omicron variant is on average less severe in those that have been vaccinated. However, throughout the Omicron wave, individuals who have not been vaccinated continue to have significant rates of serious illness and hospitalization,” he said.

“Our findings showed that serious illness with hospitalization was associated with a higher rate of sequelae. It can therefore be inferred that the rates of sequelae seen in our study would continue to occur in unvaccinated individuals who contract Omicron, but might occur less frequently in vaccinated individuals who contract Omicron and have less severe illness.”

Dr. Cohen serves as a consultant for Pfizer. Dr. Shah has disclosed no relevant financial relationships.

MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.

The findings were published online in PeerJ.

The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.

The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.

“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”

Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.

“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”

Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.

Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”

If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.

The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.

“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”

Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
 

Differentiating HCC from cirrhosis

Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.

Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.

The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).

“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.

Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).

The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.

Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
 

Catching cancer early

Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.

“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.

“You don’t want to identify cancer when it’s bad, and you don’t have any options.

This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”

Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.

Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.

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

MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.

The findings were published online in PeerJ.

The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.

The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.

“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”

Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.

“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”

Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.

Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”

If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.

The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.

“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”

Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
 

Differentiating HCC from cirrhosis

Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.

Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.

The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).

“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.

Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).

The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.

Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
 

Catching cancer early

Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.

“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.

“You don’t want to identify cancer when it’s bad, and you don’t have any options.

This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”

Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.

Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.

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

MicroRNAs (miRNAs) that signal hepatocellular carcinoma (HCC), the most common type of liver cancer, have been detected in saliva for the first time, according to results from a pilot study.

The findings were published online in PeerJ.

The small, noncoding RNAs regulate many cellular functions and affect cancer development and progression.

The discovery has the potential to offer a noninvasive alternative or complement to available detection tools – ultrasound and the blood biomarker alpha fetoprotein (AFP) – which lack sensitivity, said Daniel Rotroff, PhD, MSPH, senior author of the study and a researcher in the Department of Quantitative Health Sciences at the Cleveland Clinic.

“Right now, the current clinical tools are not adequate,” he told this news organization. “They miss approximately 40% to 50% of the patients who have HCC.”

Scientists are interested in finding better ways to detect liver cancer, the rates of which are growing rapidly. HCC represents 80% of all liver cancers.

“HCC and liver cancer are the fastest growing cancers in the United States,” Dr. Rotroff said. “They are the fifth and seventh leading cause of cancer death in men and women, respectively.”

Driving the growth are increases in hepatitis C, obesity, fatty liver disease, and alcoholism.

Nancy Reau, MD, the Richard B. Capps Chair of Hepatology and section chief, Hepatology, at Rush Medical College, Chicago, who was not part of the study, told this news organization that despite the study’s being relatively small in scale, the preliminary information it provides is nonetheless “really attractive.”

If larger studies confirm the results, the discovery could open up the possibility of patients mailing in saliva samples from their homes to screen for liver cancer.

The pandemic, she noted, highlighted the shortcomings of ultrasound in screening for liver cancer, as it required patients to come into a facility.

“You’d love to have a biomarker that was more accessible and accurate,” she said. “It would have lots of applicability where cancer surveillance is less available.”

Dr. Rotroff added that “we do know saliva samples can be stable at room temperature. It opens up possibilities to expand the net of being able to screen a wider number of patients.”
 

Differentiating HCC from cirrhosis

Investigators at the Cleveland Clinic performed small RNA sequencing in 20 patients with HCC and compared the findings to sequencing of 19 patients with cirrhosis.

Liver cirrhosis is the primary risk factor for developing HCC, so distinguishing patients with HCC from this cohort of high-risk patients serves as a proof of principle.

The sequencing showed that 4,565 precursor and mature miRNAs were detected in saliva and that 365 were significantly different between those with HCC compared to cirrhosis (false discovery rate, P < .05).

“Interestingly, 283 of these miRNAs were significantly downregulated in patients with HCC,” the authors write.

Machine learning found a combination of 10 miRNAs and covariates that accurately classified patients with HCC (area under the curve = 0.87).

The researchers note that miRNAs have been found in saliva and have shown potential as noninvasive biomarkers for a number of other cancers, including breast, oral, and lung cancers.

Additionally, Dr. Rotroff said, microRNAs have been shown to be altered in the tumor tissue of HCC, compared with the surrounding tissue.
 

Catching cancer early

Dr. Reau noted that a strength of the study is that it validated the biomarker in a diverse group of patients already diagnosed with liver cancer, including people with early-stage cancer, those who underwent transplantation, and those with recurrent cancer.

“Everyone searching for biomarkers is looking to make sure that the surveillance tool identifies the patient when it can pay off with early treatment,” Dr. Reau said.

“You don’t want to identify cancer when it’s bad, and you don’t have any options.

This is a little bit where AFP sometimes fails. Even if ultrasound isn’t that accurate, it still generally identifies people when they fit within curative guidelines.”

Dr. Rotroff also stressed the importance of detecting the cancers early, noting that the prognosis for patients with HCC before it has metastasized is greater than 4 years, but the prognosis drops to less than 1 year if it has metastasized.

Dr. Rotroff has an equity stake in Clarified Precision Medicine. He holds intellectual property related to the detection of HCC. Dr. Reau reports no relevant financial relationships.

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

Women who used marijuana (cannabis) at least four times in the previous month (heavy users) were less likely to have type 2 diabetes than women who were light users or nonusers, in a nationally representative U.S. observational study.

In contrast, there were no differences in the prevalence of type 2 diabetes in men who were light or heavy cannabis users versus nonusers.
 

Kerkez/Getty Images

These findings are based on data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), whereby participants self-reported their cannabis use.

The study by Ayobami S. Ogunsola, MD, MPH, a graduate student at Texas A&M University, College Station, and colleagues was recently published in Cannabis and Cannabinoid Research. 
 

What do the findings mean?

Although overall findings linking cannabis use and diabetes have been inconsistent, the gender differences in the current study are consistent with animal studies and some clinical studies, senior author Ibraheem M. Karaye, MD, MPH, said in an interview.

However, these gender differences need to be confirmed, and “we strongly recommend that more biological or biochemical studies be conducted that could actually tell us the mechanisms,” said Dr. Karaye, an assistant professor in the department of population health, Hofstra University, Hempstead, N.Y.

“It’s indisputable that medical marijuana has some medical benefits,” he added. “Women [who use cannabis] have been shown to lose more weight than men, for example.”

“If women [cannabis users] are less likely to develop diabetes or more likely to express improvement of symptoms of diabetes,” he noted, “this means that hyperglycemic medications that are being prescribed should be watched scrupulously. Otherwise, there is a risk that [women] may overrespond.”

That is, Dr. Karaye continued, women “may be at risk of developing hypoglycemia because the cannabis is acting synergistically with the regular drug that is being used to treat the diabetes.” 

U.S. clinicians, especially in states with legalized medical marijuana, need to be aware of the potential synergy.

“One would have to consider the patient as a whole,” he stressed. “For example, a woman that uses medical marijuana may actually respond differently to hyperglycemic medication.”
 

Conflicting reports explained by sex differences?

Evidence on whether cannabis use is linked with type 2 diabetes is limited and conflicting, the researchers wrote. They hypothesized that these conflicting findings might be explained by sex differences.

To “help inform current diabetes prevention and mitigation efforts,” they investigated sex differences in cannabis use and prevalence of type 2 diabetes in 15,602 men and women in the 2013-2014, 2015-2016, and 2017-2018 NHANES surveys.

Participants were classified as having type 2 diabetes if they had a physician’s diagnosis; a 2-hour plasma glucose of at least 200 mg/dL (in a glucose tolerance test); fasting blood glucose of at least 126 mg/dL; or A1c of at least 6.5%.

About half of respondents were women (52%) and close to half (44%) were age 18-39.

More than a third (38%) had a body mass index (BMI) of at least 30 kg/m2, indicating obesity.

Roughly 1 in 10 had a diagnosis of type 2 diabetes (13.5%) or A1c of at least 6.5% (9.8%).

Close to a fifth smoked cigarettes (16%). Similarly, 14.5% used cannabis at least four times a week, 3.3% used it less often, and the rest did not use it. Half of participants were not physically active (49%).

Just over half had at least a college education (55%).

Heavy cannabis users were more likely to be younger than age 40 (57% of men, 57% of women), college graduates (54% of men, 63% of women), cigarette smokers (79% of men, 83% of women), and physically inactive (39% of men, 49% of women).

Among women, heavy cannabis users were 49% less likely to have type 2 diabetes than nonusers, after adjusting for age, sex, race/ethnicity, educational level, physical activity, tobacco use, alcohol use, marital status, difficulty walking, employment status, income, and BMI (adjusted odds ratio, 0.51; 95% confidence interval, 0.31-0.84).

There were no significant differences between light cannabis users versus nonusers and diabetes prevalence in women, or between light or heavy cannabis users versus nonusers and diabetes prevalence in men.
 

Limitations, yet biologically plausible

The researchers acknowledged several study limitations.

They do not know how long participants had used marijuana. The men and women may have underreported their cannabis use, especially in states where medical marijuana was not legal, and the NHANES data did not specify whether the cannabis was recreational or medicinal.

The study may have been underpowered to detect a smaller difference in men who used versus did not use marijuana.

And importantly, this was an observational study (a snapshot at one point in time), so it cannot say whether the heavy cannabis use in women caused a decreased likelihood of diabetes.

Nevertheless, the inverse association between cannabis use and presence of type 2 diabetes is biologically plausible, Dr. Ogunsola and colleagues wrote.

The two major cannabis compounds, cannabidiol and delta-9-tetrahydrocannabinol, stimulate CBD1 and CBD2 receptors in the central and peripheral nervous systems, respectively. And “activation of the CBD1 receptor increases insulin secretion, glucagon, and somatostatin, and activates metabolic processes in fat and skeletal muscles – mechanisms that improve glucose disposal,” they explained.

The researchers speculated that the sex differences they found for this association may be caused by differences in sex hormones, or the endocannabinoid system, or fat deposits.

Therefore, “additional studies are needed to investigate the sex-based heterogeneity reported in this study and to elucidate potential mechanisms for the observation,” they concluded.

The study did not receive any funding and the researchers have no relevant financial disclosures.

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

Women who used marijuana (cannabis) at least four times in the previous month (heavy users) were less likely to have type 2 diabetes than women who were light users or nonusers, in a nationally representative U.S. observational study.

In contrast, there were no differences in the prevalence of type 2 diabetes in men who were light or heavy cannabis users versus nonusers.
 

Kerkez/Getty Images

These findings are based on data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), whereby participants self-reported their cannabis use.

The study by Ayobami S. Ogunsola, MD, MPH, a graduate student at Texas A&M University, College Station, and colleagues was recently published in Cannabis and Cannabinoid Research. 
 

What do the findings mean?

Although overall findings linking cannabis use and diabetes have been inconsistent, the gender differences in the current study are consistent with animal studies and some clinical studies, senior author Ibraheem M. Karaye, MD, MPH, said in an interview.

However, these gender differences need to be confirmed, and “we strongly recommend that more biological or biochemical studies be conducted that could actually tell us the mechanisms,” said Dr. Karaye, an assistant professor in the department of population health, Hofstra University, Hempstead, N.Y.

“It’s indisputable that medical marijuana has some medical benefits,” he added. “Women [who use cannabis] have been shown to lose more weight than men, for example.”

“If women [cannabis users] are less likely to develop diabetes or more likely to express improvement of symptoms of diabetes,” he noted, “this means that hyperglycemic medications that are being prescribed should be watched scrupulously. Otherwise, there is a risk that [women] may overrespond.”

That is, Dr. Karaye continued, women “may be at risk of developing hypoglycemia because the cannabis is acting synergistically with the regular drug that is being used to treat the diabetes.” 

U.S. clinicians, especially in states with legalized medical marijuana, need to be aware of the potential synergy.

“One would have to consider the patient as a whole,” he stressed. “For example, a woman that uses medical marijuana may actually respond differently to hyperglycemic medication.”
 

Conflicting reports explained by sex differences?

Evidence on whether cannabis use is linked with type 2 diabetes is limited and conflicting, the researchers wrote. They hypothesized that these conflicting findings might be explained by sex differences.

To “help inform current diabetes prevention and mitigation efforts,” they investigated sex differences in cannabis use and prevalence of type 2 diabetes in 15,602 men and women in the 2013-2014, 2015-2016, and 2017-2018 NHANES surveys.

Participants were classified as having type 2 diabetes if they had a physician’s diagnosis; a 2-hour plasma glucose of at least 200 mg/dL (in a glucose tolerance test); fasting blood glucose of at least 126 mg/dL; or A1c of at least 6.5%.

About half of respondents were women (52%) and close to half (44%) were age 18-39.

More than a third (38%) had a body mass index (BMI) of at least 30 kg/m2, indicating obesity.

Roughly 1 in 10 had a diagnosis of type 2 diabetes (13.5%) or A1c of at least 6.5% (9.8%).

Close to a fifth smoked cigarettes (16%). Similarly, 14.5% used cannabis at least four times a week, 3.3% used it less often, and the rest did not use it. Half of participants were not physically active (49%).

Just over half had at least a college education (55%).

Heavy cannabis users were more likely to be younger than age 40 (57% of men, 57% of women), college graduates (54% of men, 63% of women), cigarette smokers (79% of men, 83% of women), and physically inactive (39% of men, 49% of women).

Among women, heavy cannabis users were 49% less likely to have type 2 diabetes than nonusers, after adjusting for age, sex, race/ethnicity, educational level, physical activity, tobacco use, alcohol use, marital status, difficulty walking, employment status, income, and BMI (adjusted odds ratio, 0.51; 95% confidence interval, 0.31-0.84).

There were no significant differences between light cannabis users versus nonusers and diabetes prevalence in women, or between light or heavy cannabis users versus nonusers and diabetes prevalence in men.
 

Limitations, yet biologically plausible

The researchers acknowledged several study limitations.

They do not know how long participants had used marijuana. The men and women may have underreported their cannabis use, especially in states where medical marijuana was not legal, and the NHANES data did not specify whether the cannabis was recreational or medicinal.

The study may have been underpowered to detect a smaller difference in men who used versus did not use marijuana.

And importantly, this was an observational study (a snapshot at one point in time), so it cannot say whether the heavy cannabis use in women caused a decreased likelihood of diabetes.

Nevertheless, the inverse association between cannabis use and presence of type 2 diabetes is biologically plausible, Dr. Ogunsola and colleagues wrote.

The two major cannabis compounds, cannabidiol and delta-9-tetrahydrocannabinol, stimulate CBD1 and CBD2 receptors in the central and peripheral nervous systems, respectively. And “activation of the CBD1 receptor increases insulin secretion, glucagon, and somatostatin, and activates metabolic processes in fat and skeletal muscles – mechanisms that improve glucose disposal,” they explained.

The researchers speculated that the sex differences they found for this association may be caused by differences in sex hormones, or the endocannabinoid system, or fat deposits.

Therefore, “additional studies are needed to investigate the sex-based heterogeneity reported in this study and to elucidate potential mechanisms for the observation,” they concluded.

The study did not receive any funding and the researchers have no relevant financial disclosures.

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

Women who used marijuana (cannabis) at least four times in the previous month (heavy users) were less likely to have type 2 diabetes than women who were light users or nonusers, in a nationally representative U.S. observational study.

In contrast, there were no differences in the prevalence of type 2 diabetes in men who were light or heavy cannabis users versus nonusers.
 

Kerkez/Getty Images

These findings are based on data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), whereby participants self-reported their cannabis use.

The study by Ayobami S. Ogunsola, MD, MPH, a graduate student at Texas A&M University, College Station, and colleagues was recently published in Cannabis and Cannabinoid Research. 
 

What do the findings mean?

Although overall findings linking cannabis use and diabetes have been inconsistent, the gender differences in the current study are consistent with animal studies and some clinical studies, senior author Ibraheem M. Karaye, MD, MPH, said in an interview.

However, these gender differences need to be confirmed, and “we strongly recommend that more biological or biochemical studies be conducted that could actually tell us the mechanisms,” said Dr. Karaye, an assistant professor in the department of population health, Hofstra University, Hempstead, N.Y.

“It’s indisputable that medical marijuana has some medical benefits,” he added. “Women [who use cannabis] have been shown to lose more weight than men, for example.”

“If women [cannabis users] are less likely to develop diabetes or more likely to express improvement of symptoms of diabetes,” he noted, “this means that hyperglycemic medications that are being prescribed should be watched scrupulously. Otherwise, there is a risk that [women] may overrespond.”

That is, Dr. Karaye continued, women “may be at risk of developing hypoglycemia because the cannabis is acting synergistically with the regular drug that is being used to treat the diabetes.” 

U.S. clinicians, especially in states with legalized medical marijuana, need to be aware of the potential synergy.

“One would have to consider the patient as a whole,” he stressed. “For example, a woman that uses medical marijuana may actually respond differently to hyperglycemic medication.”
 

Conflicting reports explained by sex differences?

Evidence on whether cannabis use is linked with type 2 diabetes is limited and conflicting, the researchers wrote. They hypothesized that these conflicting findings might be explained by sex differences.

To “help inform current diabetes prevention and mitigation efforts,” they investigated sex differences in cannabis use and prevalence of type 2 diabetes in 15,602 men and women in the 2013-2014, 2015-2016, and 2017-2018 NHANES surveys.

Participants were classified as having type 2 diabetes if they had a physician’s diagnosis; a 2-hour plasma glucose of at least 200 mg/dL (in a glucose tolerance test); fasting blood glucose of at least 126 mg/dL; or A1c of at least 6.5%.

About half of respondents were women (52%) and close to half (44%) were age 18-39.

More than a third (38%) had a body mass index (BMI) of at least 30 kg/m2, indicating obesity.

Roughly 1 in 10 had a diagnosis of type 2 diabetes (13.5%) or A1c of at least 6.5% (9.8%).

Close to a fifth smoked cigarettes (16%). Similarly, 14.5% used cannabis at least four times a week, 3.3% used it less often, and the rest did not use it. Half of participants were not physically active (49%).

Just over half had at least a college education (55%).

Heavy cannabis users were more likely to be younger than age 40 (57% of men, 57% of women), college graduates (54% of men, 63% of women), cigarette smokers (79% of men, 83% of women), and physically inactive (39% of men, 49% of women).

Among women, heavy cannabis users were 49% less likely to have type 2 diabetes than nonusers, after adjusting for age, sex, race/ethnicity, educational level, physical activity, tobacco use, alcohol use, marital status, difficulty walking, employment status, income, and BMI (adjusted odds ratio, 0.51; 95% confidence interval, 0.31-0.84).

There were no significant differences between light cannabis users versus nonusers and diabetes prevalence in women, or between light or heavy cannabis users versus nonusers and diabetes prevalence in men.
 

Limitations, yet biologically plausible

The researchers acknowledged several study limitations.

They do not know how long participants had used marijuana. The men and women may have underreported their cannabis use, especially in states where medical marijuana was not legal, and the NHANES data did not specify whether the cannabis was recreational or medicinal.

The study may have been underpowered to detect a smaller difference in men who used versus did not use marijuana.

And importantly, this was an observational study (a snapshot at one point in time), so it cannot say whether the heavy cannabis use in women caused a decreased likelihood of diabetes.

Nevertheless, the inverse association between cannabis use and presence of type 2 diabetes is biologically plausible, Dr. Ogunsola and colleagues wrote.

The two major cannabis compounds, cannabidiol and delta-9-tetrahydrocannabinol, stimulate CBD1 and CBD2 receptors in the central and peripheral nervous systems, respectively. And “activation of the CBD1 receptor increases insulin secretion, glucagon, and somatostatin, and activates metabolic processes in fat and skeletal muscles – mechanisms that improve glucose disposal,” they explained.

The researchers speculated that the sex differences they found for this association may be caused by differences in sex hormones, or the endocannabinoid system, or fat deposits.

Therefore, “additional studies are needed to investigate the sex-based heterogeneity reported in this study and to elucidate potential mechanisms for the observation,” they concluded.

The study did not receive any funding and the researchers have no relevant financial disclosures.

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

Guselkumab (Tremfya) received Food and Drug Administration approval for the treatment of psoriatic arthritis (PsA) almost 2 years ago on the basis of a phase 3 trial, but a new substudy from that trial has now demonstrated long-term benefit in the subgroup of patients who entered the trial with axial involvement, according to data presented at the annual meeting of the Canadian Rheumatology Association.

“The symptom relief was clinically meaningful and durable through week 100,” reported Dafna D. Gladman, MD, professor of medicine and director of the psoriatic arthritis program at the University of Toronto.

In the previously published double-blind, placebo-controlled DISCOVER-2 trial, two dosing regimens of the interleukin-23 (IL-23) inhibitor guselkumab were compared with placebo in biologic-naive patients. The active regimens were similarly effective relative to placebo for the primary endpoint of 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24.

In this new long-term subgroup analysis, outcomes at 2 years were evaluated in the 246 patients with axial involvement (33.3% of the total number of 739 evaluable patients). Baseline characteristics across treatment groups in this subset of the DISCOVER-2 trial were similar.
 

Guselkumab exhibits nearly twofold advantage

At 24 weeks relative to baseline, the improvement on multiple axial involvement outcome measures was approximately twofold greater with active therapy than with placebo. For example, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score fell 2.6 points in both active treatment arms versus 1.4 on placebo.

The same relative advantage was observed when the BASDAI spinal pain subscore was isolated. There were also comparable responses on a modified BASDAI that excluded the peripheral pain response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

When evaluated at week 52 and again at week 100, all outcomes employed to evaluate change in axial involvement were sustained. Many were further improved. In patients who initiated therapy on placebo, all of whom were switched to guselkumab at the end of the 24-week double-blind period, at least the same degree of axial symptom control relative to baseline was achieved at both time periods.

Incremental improvement observed over time

“For most measures there was further improvement at 2 years, and there was generally consistent response across patient groups stratified by HLA [human leucocyte antigen] status,” Dr. Gladman reported.

Relative to the 2.6-point reduction in the BASDAI score in the two guselkumab arms at week 24, the reductions reached 3.0, 3.1, and 3.3 at 100 weeks in the every-4-week guselkumab group, every-8-week guselkumab group, and the crossed-over placebo group, respectively. For ASDAS, the reductions at week 24 were 1.4, 1.5, and 0.7 points and reached 1.6, 1.7, and 1.6 points at 100 weeks in the every-4-week, every-8-week, and placebo crossover groups, respectively.

The sustained improvement is consistent with a previous post hoc analysis in which data from the phase 3 DISCOVER-1 trial were pooled with those from DISCOVER-2. This analysis focused on the 312 patients in these studies with axial disease documented by imaging. Again, the study showed improvement at week 24 was sustained at week 52 independent of HLA-B27 status.
 

Need for MRI confirmation seen

The potential problem with this new analysis as well as the previous analysis is the absence of MRI to provide objective evidence of axial involvement, according to Walter P. Maksymowych, MD, professor in the division of rheumatology at the University of Alberta, Edmonton.

Noting that previous studies have indicated that axial involvement assessed by investigators is not reliable even when performed with x-rays, Dr. Maksymowych said these data would be much more reassuring with MRI controls.

“We have seen little correlation between clinical symptoms and MRI manifestations of disease,” he said.

Dr. Gladman conceded this point. Baseline MRI was performed in some of the patients in this subgroup analysis, but it was not mandated. As a result, the data support benefit from guselkumab for symptomatic axial involvement, but she indicated that better evidence of a disease-modifying effect is expected from a more rigorous placebo-controlled trial of guselkumab called STAR.

This trial is requiring MRI at baseline and at week 24 and is using the Spondyloarthritis Research Consortium of Canada (SPARCC) score to assess change. Dr. Gladman said the trial is enrolling “as we speak.”

Overall, Dr. Gladman agreed with Dr. Maksymowych that objective biomarkers are important for demonstrating that treatments are improving long-term outcomes, not just relieving symptoms.

Guselkumab manufacturer Janssen supported the post hoc analysis. Dr. Gladman reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Janssen, Novartis, Pfizer, and UCB. Dr. Maksymowych reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Guselkumab (Tremfya) received Food and Drug Administration approval for the treatment of psoriatic arthritis (PsA) almost 2 years ago on the basis of a phase 3 trial, but a new substudy from that trial has now demonstrated long-term benefit in the subgroup of patients who entered the trial with axial involvement, according to data presented at the annual meeting of the Canadian Rheumatology Association.

“The symptom relief was clinically meaningful and durable through week 100,” reported Dafna D. Gladman, MD, professor of medicine and director of the psoriatic arthritis program at the University of Toronto.

In the previously published double-blind, placebo-controlled DISCOVER-2 trial, two dosing regimens of the interleukin-23 (IL-23) inhibitor guselkumab were compared with placebo in biologic-naive patients. The active regimens were similarly effective relative to placebo for the primary endpoint of 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24.

In this new long-term subgroup analysis, outcomes at 2 years were evaluated in the 246 patients with axial involvement (33.3% of the total number of 739 evaluable patients). Baseline characteristics across treatment groups in this subset of the DISCOVER-2 trial were similar.
 

Guselkumab exhibits nearly twofold advantage

At 24 weeks relative to baseline, the improvement on multiple axial involvement outcome measures was approximately twofold greater with active therapy than with placebo. For example, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score fell 2.6 points in both active treatment arms versus 1.4 on placebo.

The same relative advantage was observed when the BASDAI spinal pain subscore was isolated. There were also comparable responses on a modified BASDAI that excluded the peripheral pain response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

When evaluated at week 52 and again at week 100, all outcomes employed to evaluate change in axial involvement were sustained. Many were further improved. In patients who initiated therapy on placebo, all of whom were switched to guselkumab at the end of the 24-week double-blind period, at least the same degree of axial symptom control relative to baseline was achieved at both time periods.

Incremental improvement observed over time

“For most measures there was further improvement at 2 years, and there was generally consistent response across patient groups stratified by HLA [human leucocyte antigen] status,” Dr. Gladman reported.

Relative to the 2.6-point reduction in the BASDAI score in the two guselkumab arms at week 24, the reductions reached 3.0, 3.1, and 3.3 at 100 weeks in the every-4-week guselkumab group, every-8-week guselkumab group, and the crossed-over placebo group, respectively. For ASDAS, the reductions at week 24 were 1.4, 1.5, and 0.7 points and reached 1.6, 1.7, and 1.6 points at 100 weeks in the every-4-week, every-8-week, and placebo crossover groups, respectively.

The sustained improvement is consistent with a previous post hoc analysis in which data from the phase 3 DISCOVER-1 trial were pooled with those from DISCOVER-2. This analysis focused on the 312 patients in these studies with axial disease documented by imaging. Again, the study showed improvement at week 24 was sustained at week 52 independent of HLA-B27 status.
 

Need for MRI confirmation seen

The potential problem with this new analysis as well as the previous analysis is the absence of MRI to provide objective evidence of axial involvement, according to Walter P. Maksymowych, MD, professor in the division of rheumatology at the University of Alberta, Edmonton.

Noting that previous studies have indicated that axial involvement assessed by investigators is not reliable even when performed with x-rays, Dr. Maksymowych said these data would be much more reassuring with MRI controls.

“We have seen little correlation between clinical symptoms and MRI manifestations of disease,” he said.

Dr. Gladman conceded this point. Baseline MRI was performed in some of the patients in this subgroup analysis, but it was not mandated. As a result, the data support benefit from guselkumab for symptomatic axial involvement, but she indicated that better evidence of a disease-modifying effect is expected from a more rigorous placebo-controlled trial of guselkumab called STAR.

This trial is requiring MRI at baseline and at week 24 and is using the Spondyloarthritis Research Consortium of Canada (SPARCC) score to assess change. Dr. Gladman said the trial is enrolling “as we speak.”

Overall, Dr. Gladman agreed with Dr. Maksymowych that objective biomarkers are important for demonstrating that treatments are improving long-term outcomes, not just relieving symptoms.

Guselkumab manufacturer Janssen supported the post hoc analysis. Dr. Gladman reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Janssen, Novartis, Pfizer, and UCB. Dr. Maksymowych reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Guselkumab (Tremfya) received Food and Drug Administration approval for the treatment of psoriatic arthritis (PsA) almost 2 years ago on the basis of a phase 3 trial, but a new substudy from that trial has now demonstrated long-term benefit in the subgroup of patients who entered the trial with axial involvement, according to data presented at the annual meeting of the Canadian Rheumatology Association.

“The symptom relief was clinically meaningful and durable through week 100,” reported Dafna D. Gladman, MD, professor of medicine and director of the psoriatic arthritis program at the University of Toronto.

In the previously published double-blind, placebo-controlled DISCOVER-2 trial, two dosing regimens of the interleukin-23 (IL-23) inhibitor guselkumab were compared with placebo in biologic-naive patients. The active regimens were similarly effective relative to placebo for the primary endpoint of 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24.

In this new long-term subgroup analysis, outcomes at 2 years were evaluated in the 246 patients with axial involvement (33.3% of the total number of 739 evaluable patients). Baseline characteristics across treatment groups in this subset of the DISCOVER-2 trial were similar.
 

Guselkumab exhibits nearly twofold advantage

At 24 weeks relative to baseline, the improvement on multiple axial involvement outcome measures was approximately twofold greater with active therapy than with placebo. For example, the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score fell 2.6 points in both active treatment arms versus 1.4 on placebo.

The same relative advantage was observed when the BASDAI spinal pain subscore was isolated. There were also comparable responses on a modified BASDAI that excluded the peripheral pain response, and the Ankylosing Spondylitis Disease Activity Score (ASDAS).

When evaluated at week 52 and again at week 100, all outcomes employed to evaluate change in axial involvement were sustained. Many were further improved. In patients who initiated therapy on placebo, all of whom were switched to guselkumab at the end of the 24-week double-blind period, at least the same degree of axial symptom control relative to baseline was achieved at both time periods.

Incremental improvement observed over time

“For most measures there was further improvement at 2 years, and there was generally consistent response across patient groups stratified by HLA [human leucocyte antigen] status,” Dr. Gladman reported.

Relative to the 2.6-point reduction in the BASDAI score in the two guselkumab arms at week 24, the reductions reached 3.0, 3.1, and 3.3 at 100 weeks in the every-4-week guselkumab group, every-8-week guselkumab group, and the crossed-over placebo group, respectively. For ASDAS, the reductions at week 24 were 1.4, 1.5, and 0.7 points and reached 1.6, 1.7, and 1.6 points at 100 weeks in the every-4-week, every-8-week, and placebo crossover groups, respectively.

The sustained improvement is consistent with a previous post hoc analysis in which data from the phase 3 DISCOVER-1 trial were pooled with those from DISCOVER-2. This analysis focused on the 312 patients in these studies with axial disease documented by imaging. Again, the study showed improvement at week 24 was sustained at week 52 independent of HLA-B27 status.
 

Need for MRI confirmation seen

The potential problem with this new analysis as well as the previous analysis is the absence of MRI to provide objective evidence of axial involvement, according to Walter P. Maksymowych, MD, professor in the division of rheumatology at the University of Alberta, Edmonton.

Noting that previous studies have indicated that axial involvement assessed by investigators is not reliable even when performed with x-rays, Dr. Maksymowych said these data would be much more reassuring with MRI controls.

“We have seen little correlation between clinical symptoms and MRI manifestations of disease,” he said.

Dr. Gladman conceded this point. Baseline MRI was performed in some of the patients in this subgroup analysis, but it was not mandated. As a result, the data support benefit from guselkumab for symptomatic axial involvement, but she indicated that better evidence of a disease-modifying effect is expected from a more rigorous placebo-controlled trial of guselkumab called STAR.

This trial is requiring MRI at baseline and at week 24 and is using the Spondyloarthritis Research Consortium of Canada (SPARCC) score to assess change. Dr. Gladman said the trial is enrolling “as we speak.”

Overall, Dr. Gladman agreed with Dr. Maksymowych that objective biomarkers are important for demonstrating that treatments are improving long-term outcomes, not just relieving symptoms.

Guselkumab manufacturer Janssen supported the post hoc analysis. Dr. Gladman reported financial relationships with AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Janssen, Novartis, Pfizer, and UCB. Dr. Maksymowych reported financial relationships with AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB.

Young adults hospitalized for a stroke are much more likely to be admitted for a recurrent stroke if they have cannabis use disorder, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.

“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”

The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.

Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”

Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.

Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.

Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.

Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.

A higher rate of recurrent stroke

For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.

They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.

The analysis did not include those who were considered in remission from cannabis use disorder.

Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).

After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).

Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.

But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.

“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”

He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”

Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
 

Hypothesis-generating research

The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.

As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.

The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”

A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.

Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.

A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.

He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”

The study received no outside funding. The authors report no relevant disclosures.

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

Young adults hospitalized for a stroke are much more likely to be admitted for a recurrent stroke if they have cannabis use disorder, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.

“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”

The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.

Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”

Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.

Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.

Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.

Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.

A higher rate of recurrent stroke

For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.

They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.

The analysis did not include those who were considered in remission from cannabis use disorder.

Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).

After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).

Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.

But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.

“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”

He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”

Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
 

Hypothesis-generating research

The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.

As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.

The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”

A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.

Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.

A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.

He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”

The study received no outside funding. The authors report no relevant disclosures.

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

Young adults hospitalized for a stroke are much more likely to be admitted for a recurrent stroke if they have cannabis use disorder, new observational research suggests. “Our analysis shows young marijuana users with a history of stroke or transient ischemic attack remain at significantly high risk for future strokes,” said lead study author Akhil Jain, MD, a resident physician at Mercy Fitzgerald Hospital in Darby, Pennsylvania.

“It’s essential to raise awareness among young adults about the impact of chronic habitual use of marijuana, especially if they have established cardiovascular risk factors or previous stroke.”

The study will be presented during the International Stroke Conference, presented by the American Stroke Association, a division of the American Heart Association.

An increasing number of jurisdictions are allowing marijuana use. To date, 18 states and the District of Columbia have legalized recreational cannabis use, the investigators noted.

Research suggests cannabis use disorder – defined as the chronic habitual use of cannabis – is more prevalent in the young adult population. But Dr. Jain said the population of marijuana users is “a changing dynamic.”

Cannabis use has been linked to an increased risk for first-time stroke or transient ischemic attack (TIA). Traditional stroke risk factors include hypertension, diabetes, and diseases related to blood vessels or blood circulation, including atherosclerosis.

Young adults might have additional stroke risk factors, such as behavioral habits like substance abuse, low physical activity, and smoking, oral contraceptives use among females, and brain infections, especially in the immunocompromised, said Dr. Jain.

Research from the American Heart Association shows stroke rates are increasing among adults 18 to 45 years of age. Each year, young adults account for up to 15% of strokes in the United States.

Prevalence and risk for recurrent stroke in patients with previous stroke or TIA in cannabis users have not been clearly established, the researchers pointed out.

A higher rate of recurrent stroke

For this new study, Dr. Jain and colleagues used data from the National Inpatient Sample from October 2015 to December 2017. They identified hospitalizations among young adults 18 to 45 years of age with a previous history of stroke or TIA.

They then grouped these patients into those with cannabis use disorder (4,690) and those without cannabis use disorder (156,700). The median age in both cohorts was 37 years.

The analysis did not include those who were considered in remission from cannabis use disorder.

Results showed that 6.9% of those with cannabis use disorder were hospitalized for a recurrent stroke, compared with 5.4% of those without cannabis use disorder (P < .001).

After adjustment for demographic factors (age, sex, race, household income), and pre-existing conditions, patients with cannabis use disorder were 48% more likely to be hospitalized for recurrent stroke than those without cannabis use disorder (odds ratio, 1.48; 95% confidence interval, 1.28-1.71; P < .001).

Compared with the group without cannabis use disorder, the cannabis use disorder group had more men (55.2% vs. 40.2%), more African American people (44.6% vs. 37.2%), and more use of tobacco (73.9% vs. 39.6%) and alcohol (16.5% vs. 3.6%). They also had a greater percentage of chronic obstructive pulmonary disease, depression, and psychoses.

But a smaller percentage of those with cannabis use disorder had hypertension (51.3% vs. 55.6%; P = .001) and diabetes (16.3% vs. 22.7%; P < .001), which is an “interesting” finding, said Dr. Jain.

“We observed that even with a lower rate of cardiovascular risk factors, after controlling for all the risk factors, we still found the cannabis users had a higher rate of recurrent stroke.”

He noted this was a retrospective study without a control group. “If both groups had comparable hypertension, then this risk might actually be more evident,” said Dr. Jain. “We need a prospective study with comparable groups.”

Living in low-income neighborhoods and in northeast and southern regions of the United States was also more common in the cannabis use disorder group.
 

Hypothesis-generating research

The study did not investigate the possible mechanisms by which marijuana use might increase stroke risk, but Dr. Jain speculated that these could include factors such as impaired blood vessel function, changes in blood supply, an increased tendency of blood clotting, impaired energy production in brain cells, and an imbalance between molecules that harm healthy tissue and the antioxidant defenses that neutralize them.

As cannabis use may pose a different risk for a new stroke, as opposed a previous stroke, Dr. Jain said it would be interesting to study the amount of “residual function deficit” experienced with the first stroke.

The new study represents “foundational research” upon which other research teams can build, said Dr. Jain. “Our study is hypothesis-generating research for a future prospective randomized controlled trial.”

A limitation of the study is that it did not consider the effect of various doses, duration, and forms of cannabis abuse, or use of medicinal cannabis or other drugs.

Robert L. Page II, PharmD, professor, departments of clinical pharmacy and physical medicine/rehabilitation, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, provided a comment on this new research.

A cannabis use disorder diagnosis provides “specific criteria” with regard to chronicity of use and reflects “more of a physical and psychological dependence upon cannabis,” said Dr. Page, who chaired the writing group for the AHA 2020 cannabis and cardiovascular disease scientific statement.

He explained what sets people with cannabis use disorder apart from “run-of-the-mill” recreational cannabis users is that “these are individuals who use a cannabis product, whether it’s smoking it, vaping it, or consuming it via an edible, and are using it on a regular basis, in a chronic fashion.”

The study received no outside funding. The authors report no relevant disclosures.

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

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

Just a few changes to your diet could add years to your life, but the sooner you start the better.

Maintaining a healthy diet is important, but most people find this difficult to do daily. In a new study, researchers examined the effects of individual healthful and nonhealthful types of foods and estimated the impact by age and sex of swapping some for others.

“Sustained change from a typical to an optimized diet from early age could translate into an increase in life expectancy of more than 10 years,” say the Norwegian scientists who conducted the study, published in PLOS Medicine on Feb. 8.

Lisovskaya/iStock/Getty Images

They developed an online tool that anyone can use to get an idea of how individual food choices can affect life expectancy.

The biggest overall impact comes from eating more plant-based foods (legumes), whole grains and nuts, and less red and processed meat. Fruits and vegetables also have a positive health impact, but on average people who eat a typical Western diet are already consuming those in relatively high amounts. Fish is included on the healthful list, whereas sugar-sweetened beverages (sodas) and foods based on refined [white] grains, such as white bread, are among those to be avoided.

The study found that although it’s never too late to start, young adults can expect to see more years gained by adopting healthful eating than would older adults.

“Our results indicate that for individuals with a typical Western diet, sustained dietary changes at any age may give substantial health benefits, although the gains are the largest if changes start early in life,” said the researchers.

Depending on how many healthy dietary “switches” are made and maintained and the amounts consumed, a 20-year-old man in the United States could extend his life up to 13 years, and a 20-year old woman by 11 years.

That number drops with age but changing from a typical diet to the optimized diet at age 60 years could still increase life expectancy by 8 years for women and 9 years for men, and even an 80-year-old female could gain more than 3 years with healthier food choices.

Until now, research in this area has shown health benefits associated with separate food groups or specific diet patterns, while focusing less on the health impact of other dietary changes. The statistical ‘modeling’ approach used in this study bridges that gap, the researchers said.

“Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains,” they concluded.

A version of this article was first published on WebMD.com.

Just a few changes to your diet could add years to your life, but the sooner you start the better.

Maintaining a healthy diet is important, but most people find this difficult to do daily. In a new study, researchers examined the effects of individual healthful and nonhealthful types of foods and estimated the impact by age and sex of swapping some for others.

“Sustained change from a typical to an optimized diet from early age could translate into an increase in life expectancy of more than 10 years,” say the Norwegian scientists who conducted the study, published in PLOS Medicine on Feb. 8.

Lisovskaya/iStock/Getty Images

They developed an online tool that anyone can use to get an idea of how individual food choices can affect life expectancy.

The biggest overall impact comes from eating more plant-based foods (legumes), whole grains and nuts, and less red and processed meat. Fruits and vegetables also have a positive health impact, but on average people who eat a typical Western diet are already consuming those in relatively high amounts. Fish is included on the healthful list, whereas sugar-sweetened beverages (sodas) and foods based on refined [white] grains, such as white bread, are among those to be avoided.

The study found that although it’s never too late to start, young adults can expect to see more years gained by adopting healthful eating than would older adults.

“Our results indicate that for individuals with a typical Western diet, sustained dietary changes at any age may give substantial health benefits, although the gains are the largest if changes start early in life,” said the researchers.

Depending on how many healthy dietary “switches” are made and maintained and the amounts consumed, a 20-year-old man in the United States could extend his life up to 13 years, and a 20-year old woman by 11 years.

That number drops with age but changing from a typical diet to the optimized diet at age 60 years could still increase life expectancy by 8 years for women and 9 years for men, and even an 80-year-old female could gain more than 3 years with healthier food choices.

Until now, research in this area has shown health benefits associated with separate food groups or specific diet patterns, while focusing less on the health impact of other dietary changes. The statistical ‘modeling’ approach used in this study bridges that gap, the researchers said.

“Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains,” they concluded.

A version of this article was first published on WebMD.com.

Just a few changes to your diet could add years to your life, but the sooner you start the better.

Maintaining a healthy diet is important, but most people find this difficult to do daily. In a new study, researchers examined the effects of individual healthful and nonhealthful types of foods and estimated the impact by age and sex of swapping some for others.

“Sustained change from a typical to an optimized diet from early age could translate into an increase in life expectancy of more than 10 years,” say the Norwegian scientists who conducted the study, published in PLOS Medicine on Feb. 8.

Lisovskaya/iStock/Getty Images

They developed an online tool that anyone can use to get an idea of how individual food choices can affect life expectancy.

The biggest overall impact comes from eating more plant-based foods (legumes), whole grains and nuts, and less red and processed meat. Fruits and vegetables also have a positive health impact, but on average people who eat a typical Western diet are already consuming those in relatively high amounts. Fish is included on the healthful list, whereas sugar-sweetened beverages (sodas) and foods based on refined [white] grains, such as white bread, are among those to be avoided.

The study found that although it’s never too late to start, young adults can expect to see more years gained by adopting healthful eating than would older adults.

“Our results indicate that for individuals with a typical Western diet, sustained dietary changes at any age may give substantial health benefits, although the gains are the largest if changes start early in life,” said the researchers.

Depending on how many healthy dietary “switches” are made and maintained and the amounts consumed, a 20-year-old man in the United States could extend his life up to 13 years, and a 20-year old woman by 11 years.

That number drops with age but changing from a typical diet to the optimized diet at age 60 years could still increase life expectancy by 8 years for women and 9 years for men, and even an 80-year-old female could gain more than 3 years with healthier food choices.

Until now, research in this area has shown health benefits associated with separate food groups or specific diet patterns, while focusing less on the health impact of other dietary changes. The statistical ‘modeling’ approach used in this study bridges that gap, the researchers said.

“Understanding the relative health potential of different food groups could enable people to make feasible and significant health gains,” they concluded.

A version of this article was first published on WebMD.com.

Early, permanent discontinuation of venetoclax in the treatment of relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) is linked to shortened survival outcomes, but temporary interruption shows no impact on survival, underscoring the importance of preventing discontinuation.

“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.

Courtsey Memorial Sloan Kettering Cancer Center

“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.

Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.

Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).

The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).

Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).

Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).

The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.

However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.

“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.

“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.

Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”

The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.

Early, permanent discontinuation of venetoclax in the treatment of relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) is linked to shortened survival outcomes, but temporary interruption shows no impact on survival, underscoring the importance of preventing discontinuation.

“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.

Courtsey Memorial Sloan Kettering Cancer Center

“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.

Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.

Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).

The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).

Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).

Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).

The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.

However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.

“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.

“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.

Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”

The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.

Early, permanent discontinuation of venetoclax in the treatment of relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) is linked to shortened survival outcomes, but temporary interruption shows no impact on survival, underscoring the importance of preventing discontinuation.

“There’s not a lot of awareness about the fact that you’re probably better off not permanently discontinuing treatment,” Anthony R. Mato, first author of the research published in Haematologica, said in an interview.

Courtsey Memorial Sloan Kettering Cancer Center

“Instead, attempting dose reductions with later resumption to complete the planned schedule for treatment probably could improve outcomes,” said Dr. Mato, who is director of the CLL Program at Memorial Sloan Kettering Cancer Center in New York.

Venetoclax, a potent B-cell lymphoma-2 (BCL2) inhibitor, provides a novel, chemotherapy-free treatment option for first-line and r/r CLL. While its safety profile is manageable, treatment interruptions are very common, and premature discontinuations are reported in about a third of patients, often because of adverse events.

Lacking data on the effects of those interruptions on survival outcomes, Dr. Mato and colleagues conducted a post hoc analysis of the phase 3 MURANO trial. In this open-label study, treatment with six cycles of venetoclax in combination with rituximab followed by venetoclax once daily for a total of 2 years showed superior progression-free survival, compared with six cycles of bendamustine plus rituximab in patients with r/r CLL (P < .0001).

The current analysis involved 194 intention-to-treat patients from the trial’s venetoclax arm, among whom 140 (72%) completed 2 years of therapy, and 54 (28%) prematurely discontinued treatment. The most common reasons for discontinuation were adverse events (53.7%) and disease progression (22.2%).

Among those with early discontinuation for any reason except disease progression, the rate of progression-free survival was significantly inferior, compared with those who completed the treatment (hazard ratio, 5.98; P < .0001), as was the rate or discontinuation caused specifically by adverse events, which most commonly involved neutropenia or thrombocytopenia (HR, 5.82; P < .0001).

Those who discontinued had a mean duration of venetoclax therapy of 11.3 months, compared with 24.4 months for all patients. For each additional month of venetoclax therapy, there was a significantly lower risk of a progression-free survival event (P = .0263) and of an overall survival event (P < .0001).

The treatment interruption rate was much higher, at 69% (134), involving neutropenia in 43% (84) of instances and requiring dose reductions in 23% (45) of cases.

However, in contrast to permanent discontinuations, the temporary interruptions and dose reductions had no significant effect on progression-free or overall survival, regardless of the duration.

“Improved progression-free and overall survival were associated with greater cumulative venetoclax treatment exposure,” the authors wrote.

“The results of these analyses highlight the importance of appropriately managing treatment modifications to ensure optimal outcomes for patients receiving targeted treatment for CLL,” they said.

Key measures including “better supportive care, use of growth factors, and more aggressive strategies for dose reduction could potentially help to improve or decrease the number of patients discontinuing due to an adverse event,” Dr. Mato added.“We can’t say definitively because this is not a randomized study – it’s a retrospective analysis from a randomized study – but those measures likely could have a positive impact on patient outcomes.”

The study received support from Genentech and AbbVie. Dr. Mato reported consulting or other relationships with AbbVie, AstraZeneca, Celgene, DTRM, Genentech, Janssen, Loxo, PCYC, Sunesis, and TG Therapeutics.

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.
 

Viral persistence possible

If one of the main theories holds, it could be that the coronavirus somehow remains in the body in some form for some people after COVID-19.

Mady Hornig, MD, agreed this is a possibility that needs to be investigated further.

“A weakened immune response to an infection may mean that you have cryptic reservoirs of virus that are continuing to cause symptoms,” she said during the briefing. Dr. Hornig is a doctor-scientist specializing in epidemiology at Columbia University, New York.

“That may explain why some patients with long COVID feel better after vaccination,” because the vaccine creates a strong antibody response to fight COVID-19, Dr. Iwasaki said.

Researchers are unearthing additional potential factors contributing to long COVID.

Viral persistence could also reactivate other dormant viruses in the body, such as Epstein-Barr virus (EBV), said Lawrence Purpura, MD, MPH, an infectious disease specialist at New York Presbyterian/Columbia University. Reactivation of Epstein-Barr is one of four identifying signs of long COVID revealed in a Jan. 25 study published in the journal Cell.
 

Immune overactivation also possible?

For other people with long COVID, it’s not the virus sticking around but the body’s reaction that’s the issue.

Investigators suggest autoimmunity plays a role, and they point to the presence of autoantibodies, for example.

When these autoantibodies persist, they can cause tissue and organ damage over time.

Other investigators are proposing “immune exhaustion” in long COVID because of similarities to chronic fatigue syndrome, Dr. Hornig said.

“It should be ‘all hands on deck’ for research into long COVID,” she said. “The number of disabled individuals who will likely qualify for a diagnosis of [chronic fatigue syndrome] is growing by the second.”
 

Forging ahead on future research

It’s clear there is more work to do. There are investigators working on banking tissue samples from people with long COVID to learn more, for example.

Also, finding a biomarker unique to long COVID could vastly improve the precision of diagnosing long COVID, especially if the dog sniffing option does not pan out.

Of the thousands of biomarker possibilities, Dr. Hornig said, “maybe that’s one or two that ultimately make a real impact on patient care. So it’s going to be critical to find those quickly, translate them, and make them available.”

In the meantime, some answers might come from a large study sponsored by the National Institutes of Health. The NIH is funding the “Researching COVID to Enhance Recovery” project using $470 million from the American Rescue Plan. Investigators at NYU Langone Health are leading the effort and plan to share the wealth by funding more than 100 researchers at more than 30 institutions to create a “metacohort” to study long COVID. More information is available at recovercovid.org.

“Fortunately, through the global research effort, we are now really starting to expand our understanding of how long COVID manifests, how common it is, and what the underlying mechanisms may be,” Dr. Purpura said.

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

It’s a story of promise at a time of urgent need.

Scientists are optimistic about new evidence into what is causing long COVID, a panel of research experts brought together by the New York State Department of Health said.

They proposed many theories on what might be driving long COVID. A role for a virus “cryptic reservoir” that could reactivate at any time, “viral remnants” that trigger chronic inflammation, and action by “autoimmune antibodies” that cause ongoing symptoms are possibilities.

In fact, it’s likely that research will show long COVID is a condition with more than one cause, the experts said during a recent webinar.

People might experience post-infection problems, including organ damage that takes time to heal after initial COVID-19 illness. Or they may be living with post-immune factors, including ongoing immune system responses triggered by autoantibodies.

Determining the cause or causes of long COVID is essential for treatment. For example, if one person’s symptoms persist because of an overactive immune system, “we need to provide immunosuppressant therapies,” Akiko Iwasaki, PhD, said. “But we don’t want to give that to someone who has a persistent virus reservoir,” meaning remnants of the virus remain in their bodies.

Interestingly, a study preprint, which has not been peer reviewed, found dogs were accurate more than half the time in sniffing out long COVID, said Dr. Iwasaki, professor of immunobiology and developmental biology at Yale University, New Haven, Conn.

The dogs were tasked with identifying 45 people with long COVID versus 188 people without it. The findings suggest the presence of a unique chemical in the sweat of people with long COVID that could someday lead to a diagnostic test.