As the number of patients struggling with lingering effects of COVID-19 grows, much of the diagnosis and symptom management will fall on primary care, experts say.

“It could be as many as 5% to 10% who are still having symptoms at 12 weeks. Those numbers are higher if you’re talking about patients who had been hospitalized with COVID-19,” Russ Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston, said in an interview.

A recent study from the Centers for Disease Control and Prevention and Kaiser Permanente Georgia found that among 3,171 nonhospitalized adult patients with COVID-19, 69% had one or more outpatient visits 28 to 180 days after the diagnosis. Two-thirds had a visit for a new primary diagnosis, and about one-third had a new specialist visit. Symptom diagnoses included cough, shortness of breath, chest or throat pain, and fatigue.

These visits have come while cases of acute COVID continue to occur, and there has been an increase in patients returning to primary care after avoiding it while the pandemic surged. For these patients, delay in seeking care has often led a worsening of chronic conditions.

Dr. Phillips pointed to a shortcoming in primary care that will need to be addressed with regard to long-COVID: “We don’t have good systems to follow patients and their symptoms over time.”

Long-COVID will require that kind of care, but current payment systems don’t support proactively reaching out to patients to track them over time, he noted.

“We do a good job of identifying these issues for patients who come in, but it’s the patients who don’t that we worry about the most,” he said.

Dr. Phillips provided examples of the kind of management plans needed to improve outcomes for patients with long-COVID. In anticoagulation clinics, patients who receive blood thinners are monitored closely, and in mental health care, patients with depression are linked with social workers and are monitored regularly.

“Around COVID, those management plans are in their infancy,” he said.

John Brooks, MD, chief medical officer for the CDC’s COVID-19 response, testified in a congressional hearing at the end of April that interim guidance concerning protocols for long-COVID in primary care are forthcoming. He also noted that the CDC is working closely with the Centers for Medicare & Medicaid Services to develop medical coding for long-COVID.

In the meantime, Dr. Phillips said, one strategy is to have patients self-monitor their condition and relay results to primary care physicians electronically.

As an example, Dr. Phillips described a patient with long-COVID who was receiving supplemental oxygen and who wanted to resume her exercise regimen.

She checked her own oxygen saturation levels before and during exercise and reported the levels every few days through their patient portal.

“Very slowly we were able to cut down on her oxygen and increase her exercise capacity until she no longer needed oxygen and could go back to her usual activities of daily living,” he said.

Nurse practitioners, social workers, and other nonphysician care team members may be increasingly relied upon to provide care for long-COVID patients as well, he said.

Additionally, telehealth, which is currently reimbursed the same way as in-person visits are, enables easier access for checking in with patients, he said.
 

Empathy and listening needed

Sabrina Assoumou, MD, MPH, assistant professor of medicine at Boston University, told this news organization that it will be crucial to address health care disparities as long-COVID cases mount.

COVID disproportionately affects communities of color, and it stands to reason that this will be the case for long-COVID as well, she said. Diversifying the workforce will be vital, inasmuch as diagnosis may depend on how well a physician listens to patients as they describe their symptoms, continued Dr. Assoumou, whose primary care practice centers on HIV patients.

The symptoms of long-COVID are vague, she explained, and include brain fog, fatigue, and shortness of breath, and it takes longer to diagnose than many conditions.

Dr. Assoumou said some people were never tested for COVID and never received a diagnosis, yet they are now experiencing the extended effects.

“Long-COVID will force us to go back to the basics – like really listening to our patients,” she said. “We’re definitely going to need to be more empathetic.”
 

No large influx yet

Charles Vega, MD, health sciences clinical professor of family medicine at the University of California, Irvine, said he is skeptical that the primary care system will be overwhelmed with long-COVID cases.

Dr. Vega is a family physician working in the largest safety net clinic in Orange County, California. About 90% of his patients are LatinX, a population disproportionately burdened by COVID, yet he hasn’t seen a surge in long-COVID cases.

He said that may be because patients know there isn’t a treatment for long-COVID. They are well connected through online forums such as Body Politic COVID-19 Support Group and may not feel they need to see a doctor.

“It wasn’t scientists finding [long-COVID], it was patients who developed this disease model themselves,” he said. “That’s where most of the data sharing is.”

Yet, for long-COVID patients who do need care, primary care is the best home for them, Dr. Vega said.

He said the most common symptoms he sees are fatigue and poor activity tolerance. “They get winded going to the bathroom,” he said.

The most difficult symptom is dyspnea, he said. Patients describe being breathless, but it’s not bad enough to qualify for supplemental oxygen.

“Being breathless is a pretty desperate thing and hurts quality of life,” he said.

Most patients describe general malaise.

Care for long-COVID will require medical care and mental health care, Dr. Vega notes. Primary care is already set up to screen and to coordinate care with the appropriate provider.

“I think there’s a role for specialists, but primary care has to be involved,” he said.

Dr. Phillips, Dr. Assoumou, and Dr. Vega report no relevant financial relationships.

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

As the number of patients struggling with lingering effects of COVID-19 grows, much of the diagnosis and symptom management will fall on primary care, experts say.

“It could be as many as 5% to 10% who are still having symptoms at 12 weeks. Those numbers are higher if you’re talking about patients who had been hospitalized with COVID-19,” Russ Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston, said in an interview.

A recent study from the Centers for Disease Control and Prevention and Kaiser Permanente Georgia found that among 3,171 nonhospitalized adult patients with COVID-19, 69% had one or more outpatient visits 28 to 180 days after the diagnosis. Two-thirds had a visit for a new primary diagnosis, and about one-third had a new specialist visit. Symptom diagnoses included cough, shortness of breath, chest or throat pain, and fatigue.

These visits have come while cases of acute COVID continue to occur, and there has been an increase in patients returning to primary care after avoiding it while the pandemic surged. For these patients, delay in seeking care has often led a worsening of chronic conditions.

Dr. Phillips pointed to a shortcoming in primary care that will need to be addressed with regard to long-COVID: “We don’t have good systems to follow patients and their symptoms over time.”

Long-COVID will require that kind of care, but current payment systems don’t support proactively reaching out to patients to track them over time, he noted.

“We do a good job of identifying these issues for patients who come in, but it’s the patients who don’t that we worry about the most,” he said.

Dr. Phillips provided examples of the kind of management plans needed to improve outcomes for patients with long-COVID. In anticoagulation clinics, patients who receive blood thinners are monitored closely, and in mental health care, patients with depression are linked with social workers and are monitored regularly.

“Around COVID, those management plans are in their infancy,” he said.

John Brooks, MD, chief medical officer for the CDC’s COVID-19 response, testified in a congressional hearing at the end of April that interim guidance concerning protocols for long-COVID in primary care are forthcoming. He also noted that the CDC is working closely with the Centers for Medicare & Medicaid Services to develop medical coding for long-COVID.

In the meantime, Dr. Phillips said, one strategy is to have patients self-monitor their condition and relay results to primary care physicians electronically.

As an example, Dr. Phillips described a patient with long-COVID who was receiving supplemental oxygen and who wanted to resume her exercise regimen.

She checked her own oxygen saturation levels before and during exercise and reported the levels every few days through their patient portal.

“Very slowly we were able to cut down on her oxygen and increase her exercise capacity until she no longer needed oxygen and could go back to her usual activities of daily living,” he said.

Nurse practitioners, social workers, and other nonphysician care team members may be increasingly relied upon to provide care for long-COVID patients as well, he said.

Additionally, telehealth, which is currently reimbursed the same way as in-person visits are, enables easier access for checking in with patients, he said.
 

Empathy and listening needed

Sabrina Assoumou, MD, MPH, assistant professor of medicine at Boston University, told this news organization that it will be crucial to address health care disparities as long-COVID cases mount.

COVID disproportionately affects communities of color, and it stands to reason that this will be the case for long-COVID as well, she said. Diversifying the workforce will be vital, inasmuch as diagnosis may depend on how well a physician listens to patients as they describe their symptoms, continued Dr. Assoumou, whose primary care practice centers on HIV patients.

The symptoms of long-COVID are vague, she explained, and include brain fog, fatigue, and shortness of breath, and it takes longer to diagnose than many conditions.

Dr. Assoumou said some people were never tested for COVID and never received a diagnosis, yet they are now experiencing the extended effects.

“Long-COVID will force us to go back to the basics – like really listening to our patients,” she said. “We’re definitely going to need to be more empathetic.”
 

No large influx yet

Charles Vega, MD, health sciences clinical professor of family medicine at the University of California, Irvine, said he is skeptical that the primary care system will be overwhelmed with long-COVID cases.

Dr. Vega is a family physician working in the largest safety net clinic in Orange County, California. About 90% of his patients are LatinX, a population disproportionately burdened by COVID, yet he hasn’t seen a surge in long-COVID cases.

He said that may be because patients know there isn’t a treatment for long-COVID. They are well connected through online forums such as Body Politic COVID-19 Support Group and may not feel they need to see a doctor.

“It wasn’t scientists finding [long-COVID], it was patients who developed this disease model themselves,” he said. “That’s where most of the data sharing is.”

Yet, for long-COVID patients who do need care, primary care is the best home for them, Dr. Vega said.

He said the most common symptoms he sees are fatigue and poor activity tolerance. “They get winded going to the bathroom,” he said.

The most difficult symptom is dyspnea, he said. Patients describe being breathless, but it’s not bad enough to qualify for supplemental oxygen.

“Being breathless is a pretty desperate thing and hurts quality of life,” he said.

Most patients describe general malaise.

Care for long-COVID will require medical care and mental health care, Dr. Vega notes. Primary care is already set up to screen and to coordinate care with the appropriate provider.

“I think there’s a role for specialists, but primary care has to be involved,” he said.

Dr. Phillips, Dr. Assoumou, and Dr. Vega report no relevant financial relationships.

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

As the number of patients struggling with lingering effects of COVID-19 grows, much of the diagnosis and symptom management will fall on primary care, experts say.

“It could be as many as 5% to 10% who are still having symptoms at 12 weeks. Those numbers are higher if you’re talking about patients who had been hospitalized with COVID-19,” Russ Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston, said in an interview.

A recent study from the Centers for Disease Control and Prevention and Kaiser Permanente Georgia found that among 3,171 nonhospitalized adult patients with COVID-19, 69% had one or more outpatient visits 28 to 180 days after the diagnosis. Two-thirds had a visit for a new primary diagnosis, and about one-third had a new specialist visit. Symptom diagnoses included cough, shortness of breath, chest or throat pain, and fatigue.

These visits have come while cases of acute COVID continue to occur, and there has been an increase in patients returning to primary care after avoiding it while the pandemic surged. For these patients, delay in seeking care has often led a worsening of chronic conditions.

Dr. Phillips pointed to a shortcoming in primary care that will need to be addressed with regard to long-COVID: “We don’t have good systems to follow patients and their symptoms over time.”

Long-COVID will require that kind of care, but current payment systems don’t support proactively reaching out to patients to track them over time, he noted.

“We do a good job of identifying these issues for patients who come in, but it’s the patients who don’t that we worry about the most,” he said.

Dr. Phillips provided examples of the kind of management plans needed to improve outcomes for patients with long-COVID. In anticoagulation clinics, patients who receive blood thinners are monitored closely, and in mental health care, patients with depression are linked with social workers and are monitored regularly.

“Around COVID, those management plans are in their infancy,” he said.

John Brooks, MD, chief medical officer for the CDC’s COVID-19 response, testified in a congressional hearing at the end of April that interim guidance concerning protocols for long-COVID in primary care are forthcoming. He also noted that the CDC is working closely with the Centers for Medicare & Medicaid Services to develop medical coding for long-COVID.

In the meantime, Dr. Phillips said, one strategy is to have patients self-monitor their condition and relay results to primary care physicians electronically.

As an example, Dr. Phillips described a patient with long-COVID who was receiving supplemental oxygen and who wanted to resume her exercise regimen.

She checked her own oxygen saturation levels before and during exercise and reported the levels every few days through their patient portal.

“Very slowly we were able to cut down on her oxygen and increase her exercise capacity until she no longer needed oxygen and could go back to her usual activities of daily living,” he said.

Nurse practitioners, social workers, and other nonphysician care team members may be increasingly relied upon to provide care for long-COVID patients as well, he said.

Additionally, telehealth, which is currently reimbursed the same way as in-person visits are, enables easier access for checking in with patients, he said.
 

Empathy and listening needed

Sabrina Assoumou, MD, MPH, assistant professor of medicine at Boston University, told this news organization that it will be crucial to address health care disparities as long-COVID cases mount.

COVID disproportionately affects communities of color, and it stands to reason that this will be the case for long-COVID as well, she said. Diversifying the workforce will be vital, inasmuch as diagnosis may depend on how well a physician listens to patients as they describe their symptoms, continued Dr. Assoumou, whose primary care practice centers on HIV patients.

The symptoms of long-COVID are vague, she explained, and include brain fog, fatigue, and shortness of breath, and it takes longer to diagnose than many conditions.

Dr. Assoumou said some people were never tested for COVID and never received a diagnosis, yet they are now experiencing the extended effects.

“Long-COVID will force us to go back to the basics – like really listening to our patients,” she said. “We’re definitely going to need to be more empathetic.”
 

No large influx yet

Charles Vega, MD, health sciences clinical professor of family medicine at the University of California, Irvine, said he is skeptical that the primary care system will be overwhelmed with long-COVID cases.

Dr. Vega is a family physician working in the largest safety net clinic in Orange County, California. About 90% of his patients are LatinX, a population disproportionately burdened by COVID, yet he hasn’t seen a surge in long-COVID cases.

He said that may be because patients know there isn’t a treatment for long-COVID. They are well connected through online forums such as Body Politic COVID-19 Support Group and may not feel they need to see a doctor.

“It wasn’t scientists finding [long-COVID], it was patients who developed this disease model themselves,” he said. “That’s where most of the data sharing is.”

Yet, for long-COVID patients who do need care, primary care is the best home for them, Dr. Vega said.

He said the most common symptoms he sees are fatigue and poor activity tolerance. “They get winded going to the bathroom,” he said.

The most difficult symptom is dyspnea, he said. Patients describe being breathless, but it’s not bad enough to qualify for supplemental oxygen.

“Being breathless is a pretty desperate thing and hurts quality of life,” he said.

Most patients describe general malaise.

Care for long-COVID will require medical care and mental health care, Dr. Vega notes. Primary care is already set up to screen and to coordinate care with the appropriate provider.

“I think there’s a role for specialists, but primary care has to be involved,” he said.

Dr. Phillips, Dr. Assoumou, and Dr. Vega report no relevant financial relationships.

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

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

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

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

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

Although use of some herbal and dietary supplements show statistically greater weight loss compared with placebo, it is not sufficient to benefit health, according to the joint findings of two systematic reviews, which are the first to comprehensively include all available herbal and dietary supplements for weight loss for over 15 years.

Sally Kubetin/MDedge News

“There is currently insufficient evidence to recommend any of the supplements we included in our reviews for weight loss,” stressed lead author Erica Bessell, a PhD candidate from the University of Sydney.

She added that some products with promising results warrant further investigation in well-conducted randomized controlled trials (RCTs) to determine their efficacy and safety.

But, overall, she would like to see a reduction in the number of products on the market without evidence to support their efficacy, “because, as we found, many of the products currently marketed for weight loss just do not work.

“Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them,” she said in an interview. “We would recommend that people trying to lose weight should save their money and seek out evidence-based care instead,” she emphasized.

The research was presented as two posters at this year’s online European Congress on Obesity (ECO). The meeting was presented by the European Association for the Study of Obesity.
 

Herbal and dietary supplement industry booming

Supplements for weight loss are growing in popularity, sustaining a rapidly expanding business sector globally. In the United States, the herbal and dietary supplements industry was estimated to be worth USD $41 billion in 2020, with 15% of Americans having tried a weight loss supplement in their efforts to shed pounds.

In light of this, Ms. Bessell said it is increasingly important to ensure supplements are efficacious and safe: “The popularity of these products underscores the urgency of conducting larger, more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss.”

Commenting on the study and the wider issues related to the surge in uptake of herbal and dietary supplements, Susan Arentz, PhD, said the evidence is similar to that for other complex interventions that people attempt for weight loss, including for example exercise, in that it is heterogeneous and low quality.

“One outstanding limitation for herbal medicine was the failure of trialists to validate the contents of interventions. Given the chemical variability of plants grown and harvested in different conditions, and the presence of pharmaceuticals and heavy metals found in some supplements ... future investigations of standardized herbal supplements and RCTs of higher methodological quality are needed,” remarked Dr. Arentz, a board member of the Australasian Integrative Medicine Association and researcher at Western Sydney University.

“Also, further RCTs are warranted due to the consumer preferences for natural treatments, especially in health settings with predominant use of traditional medicines and practices,” said Dr. Arentz.   
 

One review for herbal supplements, one for organic compounds

To accommodate the large number of trials investigating supplements for weight loss, the researchers conducted two systematic reviews, together representing 121 randomized placebo-controlled trials. One of the reviews investigated herbal supplements, and the other examined supplements with isolated organic compounds for example, specific fibers or lipids.  

Many of the included trials had been published in the last decade and had not been previously included in an up-to-date systematic review.

Ms. Bessell added that many studies often had a small sample size or were poorly designed, with insufficient information on the composition of supplements, and often featured little data on long-term effectiveness.

The two reviews primarily analyzed efficacy, not safety, because many of the studies did not report adverse effects.

The first review, published last year in Diabetes, Obesity and Metabolism, looked at 54 placebo-controlled randomized trials up to August 2018 on the effect of herbal supplements on weight loss . The study included 4,331 individuals aged 16 years or older who were overweight or obese. To be clinically meaningful, a weight loss of at least 2.5 kg was required over a period of, most often, 12 weeks or less.

Herbal supplements included in the analysis included green tea, Garcinia cambogia and mangosteen (tropical fruits), white kidney bean, ephedra (a stimulant that increases metabolism), African mango, yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant), veld grape (commonly used in Indian traditional medicine), licorice root, and East Indian Globe Thistle (used in Ayurvedic medicine).

The second review analyzed 67 randomized trials up to December 2019 that compared the effect of dietary supplements containing naturally occurring isolated organic compounds to placebo for weight loss in 5,194 individuals aged 16 years or older who were overweight or obese.

Meta-analyses were conducted for chitosan, glucomannan, conjugated linoleic acid, and fructans comparing the mean weight difference post intervention between participants receiving the dietary supplement and those on placebo.
 

No clinically significant results

Commenting on the overall results, Ms. Bessell said: “Though most supplements were safe for use in the short term, very few were found to produce clinically meaningful weight loss. Those that were found to result in clinically meaningful weight loss had only been investigated in one or two trials, so we need more research.”

The first review on herbal supplements found that only Phaseolus vulgaris (white kidney bean) resulted in significant weight loss compared with placebo, with an average weight difference of 1.61 kg (3.5 pounds). The result was not clinically meaningful, however.

For isolated organic compounds, significant weight differences compared with placebo were seen for chitosan, with a mean difference of 1.84 kg (4 pounds), glucomannan at 1.27 kg (2.8 pounds), and conjugated linoleic acid at 1.08 kg (2.4 pounds).

Again, none of these findings met the criteria for clinical significance (weight loss of 2.5 kg [5.5 pounds] or more).

In addition, some combination preparations containing African mango, veld grape, East Indian Globe Thistle, and mangosteen showed promising results with a mean weight difference of 1.85 kg (4 pounds), but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpreted with caution, the researchers noted.

Other dietary supplements, including modified cellulose – a plant fiber that expands in the stomach to induce a feeling of fullness – and blood orange juice extract, also showed encouraging results but were investigated in one trial and need more evidence before they can be recommended for weight loss, Ms. Bessell added.

She pointed out that some supplements are banned in some countries, such as ephedra (an extract from the plant Ephedra sinica). “This supplement is already banned in many countries because of the risk of serious adverse effects. The possibility of drug interactions may also be present with some other supplements, so health professionals and consumers should be aware of this.”

The isolated organic compounds supplements review was published in the International Journal of Obesity to coincide with the ECO 2021 conference.

Ms. Bessell has declared no relevant conflicts of interests. Dr. Arentz reviewed the systematic review of RCTs of herbal medicine supplements for weight loss published in Diabetes, Obesity and Metabolism.
 

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

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

Those of us treating nonalcoholic fatty liver disease (NAFLD) often find ourselves having similar conversations with our patients. After diagnosis, our next step is usually describing to them how they can improve their outcomes through a healthy diet and exercise.

Westend61/Getty Images

We can point to the latest data espousing the benefits of moderate weight reduction. The recently released American Gastroenterological Association (AGA) Clinical Practice Update gives us compelling evidence of what can be achieved with specific thresholds of total body weight loss: >5% can decrease hepatic steatosis, >7% potentially leads to resolution of nonalcoholic steatohepatitis, and >10% possibly allows for regression or stability of fibrosis.

More often than not, our patients then ask us, “What diet do you recommend?”

The AGA’s Clinical Practice Update recommends that people with NAFLD follow the Mediterranean diet, minimize saturated fatty acid intake (specifically red and processed meat), and limit or eliminate consumption of commercially produced fructose.

It’s a tried-and-true, evidence-based recommendation. Yet, recent data suggest that modifying the Mediterranean diet so that it’s further enriched with specific green polyphenols may yield even more benefits to at-risk patients.
 

The upside of a greener Mediterranean diet

In a recently published study, investigators behind the DIRECT-PLUS clinical trial randomly assigned 294 participants with abdominal obesity/dyslipidemia into three diet groups (all accompanied by physical activity): standard healthy dietary guidelines (HDG), standard Mediterranean, and the so-called green Mediterranean diet.

Both Mediterranean diet groups were calorie restricted and called for 28 g/day of walnuts (+440 mg/day polyphenols provided). However, the green Mediterranean diet was further supplemented with 3-4 cups/day of green tea and 100 g/day of Mankai (a Wolffia globosa aquatic plant strain) in the form of frozen cubes turned into a green shake that replaced dinner (+1,240 mg/day total polyphenols provided). The percent change in intrahepatic fat content was quantified continuously by proton magnetic resonance spectroscopy. NAFLD was defined as an intrahepatic fat content of >5%.

After 18 months, the prevalence of NAFLD declined to 54.8% in the HDG group, 47.9% in the standard Mediterranean group, and 31.5% in the green Mediterranean group. Both Mediterranean groups achieved similar moderate weight loss and had significantly higher total plasma polyphenol levels versus the HDG group. However, the green Mediterranean group achieved significantly greater proportional intrahepatic fat content loss (-38.9%) than both the standard Mediterranean (-19.6; P = .023) and HDG (-12.2%; P < .001) groups.

In isolating the individual components of the diets, researchers determined that the degree of intrahepatic fat content loss was significantly associated with increased Mankai and walnut intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, and changes in microbiome composition and specific bacteria.

The authors suggest that the mechanisms by which polyphenols reduced steatosis and prevented liver injury may include reduced de novo lipogenesis, increased fatty acid oxidation, and reduced oxidative stress.

In an additional analysis, DIRECT-PLUS investigators also revealed the beneficial effects of the green Mediterranean diet on cardiometabolic health. Although both Mediterranean diets achieved similar weight loss (-6.2 kg for green Mediterranean and -5.4 kg for standard Mediterranean), which was superior to that observed in the HDG group (-1.5 kg; P < .001), the green Mediterranean group had a greater reduction in waist circumference than the standard Mediterranean group (-8.6 vs. -6.8 cm, respectively; P = .033). Within 6 months, the green Mediterranean group also achieved a greater decrease in low-density lipoprotein cholesterol levels, diastolic blood pressure, and insulin resistance.
 

A new dietary tool for combating obesity

The rising global incidence of NAFLD has made it even more urgent to identify new and improved ways of preventing the onset of obesity-related complications. To aid those efforts, we’ve been equipped with useful tools for educating our patients and their families, such as the 2020-2025 Dietary Guidelines for Americans from the U.S. Department of Agriculture (USDA), which makes a clear case for the disease-combating effects of healthy eating patterns.

This message does not appear to be making the impact it should, however, particularly among teens and young adults. It was recently reported that in 2017, only 7% of U.S. high school students consumed recommended amounts of fruits and only 2% consumed enough vegetables to meet USDA recommendations.

Novel approaches, including enhanced school and community programs, will be required to address this issue, but so will presenting patients with satisfactory dietary alternatives. Compellingly, DIRECT-PLUS investigators reported an 89.8% retention rate at 18 months among volunteers, who were able to comply with the dietary regimen with no significant complaints regarding taste. This signals that even though the “green” modification is more stringent than the typical Mediterranean regimen, it is one to which participants can adhere.

Although the real-world applicability of this diet remains to be seen, DIRECT-PLUS gives us encouraging evidence that a Mediterranean diet amplified with green plant-based proteins/polyphenols can lead to twice the intrahepatic fat loss, as compared to other nutritional strategies, and reduce the rate of NAFLD.

And as we know, having another dietary option to offer our patients is always a welcome addition to the menu.

Dr. Balistreri is with the department of hepatology & nutrition at Cincinnati Children’s Hospital Medical Center. He has disclosed no relevant financial relationships.

Iris Shai, PhD, one of the authors of the study, “Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial,” is an adviser to Hinoman, which markets Mankai. Ilan Youngster, MD, another author of that study, is medical adviser for MyBiotics.

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

This article was updated May 21, 2021.

Botulinum toxin’s possible effect on improving depression has been discussed for some time. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.

Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.

A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.

Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.

The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
 

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at [email protected]. They had no relevant disclosures.

Botulinum toxin’s possible effect on improving depression has been discussed for some time. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.

Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.

A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.

Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.

The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
 

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at [email protected]. They had no relevant disclosures.

Botulinum toxin’s possible effect on improving depression has been discussed for some time. But confounding factors, such as medications, injection/acupuncture effect, physician interaction or touch, or other life scenarios, have made it difficult to discern botulinum toxin type A’s true effect on mood or psychiatric diagnosis. Now a systematic review and meta-analysis of randomized controlled trials examining botulinum toxin versus placebo provides evidence that botulinum toxin type A (BTX-A) injections are associated with statistically significant improvement in depressive symptoms.

Qian et al. analyzed all randomized controlled trials that investigated the efficacy and safety of facial BTX-A injections on patients with a diagnosis of major depressive disorder in PubMed and Web of Science from inception to June 17, 2020. A meta-analysis of the changes in depressive symptoms 6 weeks after BTX-A injections compared with placebo were the primary outcome of the report, while the safety of injections were also assessed.

A total of 417 patients from five randomized controlled trials (189 patients who received BTX-A injections and 228 in the placebo group) were deemed eligible. There was a statistically significant improvement in depressive symptoms in the BTX-A injections compared with placebo (Hedges’ g, –0.82; 95% confidence interval, –1.38 to 0.27). BTX-A injections were well tolerated with mild and temporary adverse events (headache, eyelid ptosis, and upper respiratory tract infection) reported in three of the five studies.

Limitations to the analysis include publication bias due to the limited number of studies in the analysis, the difficulty of being able to reliably blind participants because of potential noticeable cosmetic effects of BTX-A treatment, and the heterogeneity of symptom severity associated with major depressive disorder.

The authors referred to the Global Burden of Disease Study, which estimated that approximately 216 million people experienced major depressive disorder in 2015, the latest data available. MDD symptoms of sadness, fatigue, and loss of interest or pleasure, “incur a tremendous burden on health and finances,” they wrote. According to the Department of Health and Human Services, it is estimated that about 60% of people who commit suicide have had a mood disorder (major depression, bipolar disorder, dysthymia). The high rate of suicide associated with severe depression is also a serious public health concern. While further analysis is clearly warranted, cosmetic BTX-A injections may provide an alternative option in the treatment of depression.
 

Dr. Wesley and Dr. Lily Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. Write to them at [email protected]. They had no relevant disclosures.

Adults in treatment for opioid dependence report high satisfaction with buprenorphine injections, in new findings that researchers say could help improve treatment and management of patients with opioid dependence.

In the DEBUT trial, patients who received weekly or monthly depot buprenorphine had significantly higher overall treatment satisfaction, reduced treatment burden, and higher quality-of-life ratings than peers who received daily treatment with sublingual buprenorphine.

“The study’s focus on patient-reported outcomes (PROs) can help to better inform patients and clinicians when selecting treatment options than the clinical traditional outcomes of opioid dependence treatment studies,” lead investigator Fredrik Tiberg, PhD, president and CEO of Camurus, a pharmaceutical company in Lund, Sweden, said in an interview.

“The positive patient experiences with the depot buprenorphine injection reported in the DEBUT study indicate that long-acting treatments could contribute to advancing the quality of care and access to treatment for patients with opioid dependence/use disorder,” said Dr. Tiberg.

The study was published online May 10 in JAMA Network Open.
 

Novel study

The study was an open-label, parallel-group randomized controlled trial that included 119 patients from six outpatient clinics in Australia; 60 received weekly or monthly depot buprenorphine and 59 received sublingual buprenorphine for 24 weeks.

The primary outcome was global treatment satisfaction, as measured by the 14-question Treatment Satisfaction Questionnaire for Medication (TSQM) at the end of the study at week 24.

The study met its primary endpoint with a significantly higher TSQM global satisfaction score among adults who received depot injections, compared with those who received sublingual buprenorphine (mean score 82.5 vs. 74.3; difference, 8.2; 95% confidence interval, 1.7-14.6; P = .01).

Improvement was also observed for several secondary outcomes, including decreased treatment burden and higher quality of life.

The safety profile was consistent with the known safety profile of buprenorphine, aside from transient, mild-to-moderate injection site reactions.

“To our knowledge, this is the first randomized study that has used a range of PROs to compare outcomes between a long-acting injection and daily dosing of buprenorphine in the treatment of opioid dependence,” the investigators note.

“The study highlights the application of PROs as alternate endpoints to traditional markers of substance use in addiction treatment outcome studies,” they conclude.
 

Giving patients a voice

In an invited commentary, Nora D. Volkow, MD, director of the National Institute on Drug Abuse, and Wilson M. Compton, MD, deputy director of NIDA, note that the “voice of the patient” has been missing from most of the work in medication development, including for opioid use disorder.

The current study addresses this very issue in a “well designed and executed” fashion and the results “consistently demonstrated” the superiority of injectable buprenorphine across many outcomes.

The study highlights the importance of considering PRO measures in clinical trials, Dr. Volkow and Dr. Compton say.

“Even if efficacy is no different for various formulations, PROs may provide an important reason to select a new formulation. Patient preferences and apparently improved function may prove to be useful secondary outcomes in medication trials, and the measures used in this new study deserve consideration,” they write.

In addition, the greater treatment satisfaction by patients receiving extended-release buprenorphine suggests that these formulations “might help to improve long-term retention and, as such, be a valuable tool to help combat the current opioid epidemic and reduce its associated mortality,” they conclude.

This study was supported by Camurus AB. Dr. Tiberg is president and CEO of Camurus AB. A complete list of author disclosures is with the original article. Dr. Volkow and Dr. Compton have disclosed no relevant financial relationships.

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

Adults in treatment for opioid dependence report high satisfaction with buprenorphine injections, in new findings that researchers say could help improve treatment and management of patients with opioid dependence.

In the DEBUT trial, patients who received weekly or monthly depot buprenorphine had significantly higher overall treatment satisfaction, reduced treatment burden, and higher quality-of-life ratings than peers who received daily treatment with sublingual buprenorphine.

“The study’s focus on patient-reported outcomes (PROs) can help to better inform patients and clinicians when selecting treatment options than the clinical traditional outcomes of opioid dependence treatment studies,” lead investigator Fredrik Tiberg, PhD, president and CEO of Camurus, a pharmaceutical company in Lund, Sweden, said in an interview.

“The positive patient experiences with the depot buprenorphine injection reported in the DEBUT study indicate that long-acting treatments could contribute to advancing the quality of care and access to treatment for patients with opioid dependence/use disorder,” said Dr. Tiberg.

The study was published online May 10 in JAMA Network Open.
 

Novel study

The study was an open-label, parallel-group randomized controlled trial that included 119 patients from six outpatient clinics in Australia; 60 received weekly or monthly depot buprenorphine and 59 received sublingual buprenorphine for 24 weeks.

The primary outcome was global treatment satisfaction, as measured by the 14-question Treatment Satisfaction Questionnaire for Medication (TSQM) at the end of the study at week 24.

The study met its primary endpoint with a significantly higher TSQM global satisfaction score among adults who received depot injections, compared with those who received sublingual buprenorphine (mean score 82.5 vs. 74.3; difference, 8.2; 95% confidence interval, 1.7-14.6; P = .01).

Improvement was also observed for several secondary outcomes, including decreased treatment burden and higher quality of life.

The safety profile was consistent with the known safety profile of buprenorphine, aside from transient, mild-to-moderate injection site reactions.

“To our knowledge, this is the first randomized study that has used a range of PROs to compare outcomes between a long-acting injection and daily dosing of buprenorphine in the treatment of opioid dependence,” the investigators note.

“The study highlights the application of PROs as alternate endpoints to traditional markers of substance use in addiction treatment outcome studies,” they conclude.
 

Giving patients a voice

In an invited commentary, Nora D. Volkow, MD, director of the National Institute on Drug Abuse, and Wilson M. Compton, MD, deputy director of NIDA, note that the “voice of the patient” has been missing from most of the work in medication development, including for opioid use disorder.

The current study addresses this very issue in a “well designed and executed” fashion and the results “consistently demonstrated” the superiority of injectable buprenorphine across many outcomes.

The study highlights the importance of considering PRO measures in clinical trials, Dr. Volkow and Dr. Compton say.

“Even if efficacy is no different for various formulations, PROs may provide an important reason to select a new formulation. Patient preferences and apparently improved function may prove to be useful secondary outcomes in medication trials, and the measures used in this new study deserve consideration,” they write.

In addition, the greater treatment satisfaction by patients receiving extended-release buprenorphine suggests that these formulations “might help to improve long-term retention and, as such, be a valuable tool to help combat the current opioid epidemic and reduce its associated mortality,” they conclude.

This study was supported by Camurus AB. Dr. Tiberg is president and CEO of Camurus AB. A complete list of author disclosures is with the original article. Dr. Volkow and Dr. Compton have disclosed no relevant financial relationships.

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

Adults in treatment for opioid dependence report high satisfaction with buprenorphine injections, in new findings that researchers say could help improve treatment and management of patients with opioid dependence.

In the DEBUT trial, patients who received weekly or monthly depot buprenorphine had significantly higher overall treatment satisfaction, reduced treatment burden, and higher quality-of-life ratings than peers who received daily treatment with sublingual buprenorphine.

“The study’s focus on patient-reported outcomes (PROs) can help to better inform patients and clinicians when selecting treatment options than the clinical traditional outcomes of opioid dependence treatment studies,” lead investigator Fredrik Tiberg, PhD, president and CEO of Camurus, a pharmaceutical company in Lund, Sweden, said in an interview.

“The positive patient experiences with the depot buprenorphine injection reported in the DEBUT study indicate that long-acting treatments could contribute to advancing the quality of care and access to treatment for patients with opioid dependence/use disorder,” said Dr. Tiberg.

The study was published online May 10 in JAMA Network Open.
 

Novel study

The study was an open-label, parallel-group randomized controlled trial that included 119 patients from six outpatient clinics in Australia; 60 received weekly or monthly depot buprenorphine and 59 received sublingual buprenorphine for 24 weeks.

The primary outcome was global treatment satisfaction, as measured by the 14-question Treatment Satisfaction Questionnaire for Medication (TSQM) at the end of the study at week 24.

The study met its primary endpoint with a significantly higher TSQM global satisfaction score among adults who received depot injections, compared with those who received sublingual buprenorphine (mean score 82.5 vs. 74.3; difference, 8.2; 95% confidence interval, 1.7-14.6; P = .01).

Improvement was also observed for several secondary outcomes, including decreased treatment burden and higher quality of life.

The safety profile was consistent with the known safety profile of buprenorphine, aside from transient, mild-to-moderate injection site reactions.

“To our knowledge, this is the first randomized study that has used a range of PROs to compare outcomes between a long-acting injection and daily dosing of buprenorphine in the treatment of opioid dependence,” the investigators note.

“The study highlights the application of PROs as alternate endpoints to traditional markers of substance use in addiction treatment outcome studies,” they conclude.
 

Giving patients a voice

In an invited commentary, Nora D. Volkow, MD, director of the National Institute on Drug Abuse, and Wilson M. Compton, MD, deputy director of NIDA, note that the “voice of the patient” has been missing from most of the work in medication development, including for opioid use disorder.

The current study addresses this very issue in a “well designed and executed” fashion and the results “consistently demonstrated” the superiority of injectable buprenorphine across many outcomes.

The study highlights the importance of considering PRO measures in clinical trials, Dr. Volkow and Dr. Compton say.

“Even if efficacy is no different for various formulations, PROs may provide an important reason to select a new formulation. Patient preferences and apparently improved function may prove to be useful secondary outcomes in medication trials, and the measures used in this new study deserve consideration,” they write.

In addition, the greater treatment satisfaction by patients receiving extended-release buprenorphine suggests that these formulations “might help to improve long-term retention and, as such, be a valuable tool to help combat the current opioid epidemic and reduce its associated mortality,” they conclude.

This study was supported by Camurus AB. Dr. Tiberg is president and CEO of Camurus AB. A complete list of author disclosures is with the original article. Dr. Volkow and Dr. Compton have disclosed no relevant financial relationships.

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

Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.

pixologicstudio/Thinkstock

“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.

“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.

The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic.  The meeting was presented by the European Association for the Study of Obesity.
 

Tissue samples

Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.

A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.

Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.

Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.  

“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.

Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.

“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.  

Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.

The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.

Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.

Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.

“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
 

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

Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.

pixologicstudio/Thinkstock

“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.

“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.

The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic.  The meeting was presented by the European Association for the Study of Obesity.
 

Tissue samples

Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.

A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.

Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.

Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.  

“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.

Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.

“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.  

Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.

The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.

Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.

Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.

“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
 

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

Protein complexes referred to as inflammasomes, part of the innate immune system that helps regulate inflammation, appear to be an important contributor to the development of obesity-related colon cancer, if not other cancers, according to new research.

pixologicstudio/Thinkstock

“Population-based studies have shown that individuals who are prone to develop chronic inflammatory diseases are at increased risk of cancer, and inflammasomes play an important role in cancer development showing tumor-promoting or tumor-suppressive actions depending on the type of tumor, the specific inflammasome involved, and downstream effector molecules,” Victoria Catalan, PhD, Navarre Institute of Health Research, Pamplona, Spain, explained in an interview.

“So inflammasomes are not only implicated in obesity-associated colon cancer but their role may be more relevant in patients with obesity,” she added.

The new research was presented during the recent European Congress on Obesity, held virtually because of the pandemic.  The meeting was presented by the European Association for the Study of Obesity.
 

Tissue samples

Tissue samples were obtained from 38 individuals who were lean and 61 individuals who were obese, and further divided into those with or without colon cancer.

A new finding from the study was that both obesity and colon cancer increase gene expression levels of the proteins NLRP3, NLRP6, ASC, and NOD2 in visceral adipose tissue (VAT), “suggesting that obesity-associated visceral adipose tissue inflammation creates a microenvironment favorable for colon cancer development,” Dr. Catalan elaborated.

Investigators also found upregulated levels of IL-1-beta in VAT from individuals who were obese as well as those with colon cancer, an observation that strengthens the hypothesis that inflammasome-dependent production of these cytokines may influence colon tumorigenesis, she added.

Dr. Catalan noted that her team has previously shown that blocking the expression of NLRP3 reduces VAT inflammation and significantly attenuates fibrosis that contributes to the development of obesity-associated comorbidities including type 2 diabetes and nonalcoholic fatty liver disease.  

“Whether obesity has an impact on colon cancer through the enhancement of inflammation or via a direct mechanism is largely unclear, and the role of inflammasomes in cancer development is still controversial,” Dr. Catalan cautioned.

Nevertheless, the study showed that tissue samples from patients with colon cancer were associated with reduced expression of NLRP6 and IL-18. Dr. Catalan explained that NLRP6 is an important factor in the intestinal injury response which regulates aspects of healing inflammation. The same protein is also linked to epithelial integrity and the loss of NLRP6, and IL-18 – its main effector in the intestine – has been associated with increased mortality in colorectal cancer.

“Thus, reduced expression of NLRP6 and IL-18 in the colon from patients with colon cancer suggests an impaired regulation in the inflammatory cascade and a decrease in the integrity of the intestinal barrier,” Dr. Catalan suggested. The same experiment revealed that gene expression levels of adiponectin, an anti-inflammatory protein produced by adipose tissue, were similarly reduced in VAT in individuals who were obese as well as those with colon cancer.  

Low levels of adiponectin have, in turn, been linked to a higher risk of colorectal cancer, Dr. Catalan noted. But it has also been recently shown that normal levels of adiponectin inhibit colorectal cancer cell growth. “It is very important to take into account that inflammasomes have contrasting roles in tumorigenesis, demonstrating both detrimental and beneficial effects,” Dr. Catalan observed.

The researchers speculated that NLRP3 agonists may enhance immune function and help reverse the immunosuppressive microenvironment promoted by VAT inflammation. For instance, activation of IL-18 signaling by inflammasomes regulates intestinal tissue repair following the development of colon cancer by triggering the process of re-epithelialization. Development of NLRP3 antagonists that can block the signaling pathway of IL-1-beta is currently an important area of research.

Similarly, the recombinant IL-1 receptor antagonist anakinra (Kineret, Amgen), the neutralizing IL-1-beta antibody canakinumab (Ilaris, Novartis), and the soluble decoy IL-1-beta receptor rilonacept (Arcalyst, Regeneron) are all being evaluated as a strategy to block IL-1-beta signaling, Dr. Catalan pointed out.

Various NLRP3 inflammasome inhibitors are also being developed. “Pharmacological inhibitors of the NLRP3 pathway could offer a [viable] treatment option in a wide array of chronic and autoinflammatory diseases for which no adequate therapies currently exist,” Dr. Catalan speculated.

“Strategies to restore the functions of immunosurveillance of inflammasome components could represent an interesting target to identify and treat patients with obesity at increased risk for developing colon cancer,” the researchers said.
 

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

Results from a large study make a strong case for offering long-acting injectable antipsychotics (LAIs) to patients newly diagnosed with schizophrenia.

Investigators found that among patients who switched to LAIs, mortality was lower and there were fewer suicide attempts in comparison with patients who continued taking the corresponding oral antipsychotic (OAP).

In addition, switching to an LAI antipsychotic within the first 2 years of OAP cut the risk for suicide death by 47%.

“With newly diagnosed schizophrenia, more active consideration of LAIs in this stage for better long-term outcomes (i.e., mortality and suicide risk) should be encouraged, particularly for those who have already exhibited poor adherence attitudes,” Cheng-yi Huang, MD, Bali Psychiatric Center, Ministry of Health and Welfare, New Taipei City, Taiwan, said in an interview.

The study was published online May 11 in JAMA Network Open.
 

Powerful incentive to switch

Using data from the Taiwan National Health Insurance Research Database, the investigators identified patients newly diagnosed with schizophrenia who received OAPs from 2002 to 2017.

Within this cohort, they defined the LAI group as patients who switched to LAIs and were prescribed LAIs at least four times within 1 year. The LAI group was propensity matched to patients who continued receiving OAPs of the same compounds. There were 2,614 patients in each group (median age, 30 years).

During the 16-year follow-up period, compared with patients who continued taking the OAP, those who switched to the LAI had a 34% lower risk for all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% confidence interval, 0.54-0.81), a 37% lower risk for natural-cause mortality (aHR, 0.63; 95% CI, 0.52-0.76), and a 28% lower risk for suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55-0.93).

The risk for suicide mortality was 47% lower for patients who switched to LAIs within the first 2 years of having begun taking the OAP (aHR, 0.53; 95% CI, 0.30-0.92).

A recent study from Canada found that the suicide rate among patients with schizophrenia spectrum disorders was more than 20 times higher than that of the general population.

“Clinically, most psychiatrists use LAIs with a conservative attitude, and the reasons for this attitude are generally not well supported by current scientific evidence,” Dr. Huang and colleagues note in their article.

Dr. Huang said the study provides a powerful incentive to begin treatment with LAIs for patients newly diagnosed with schizophrenia.

“Because this study compared depot versus the same oral compound, as soon as patients show response and tolerability to the OAP, they will benefit much more when switching to LAI of the same compound,” Dr. Huang told this news organization.
 

‘Remarkably underutilized’

Commenting on the study for an interview, William Carpenter Jr., MD, Maryland Psychiatric Research Center, University of Maryland, Baltimore, said this report is “very important and in a high-quality journal.”

“LAIs have been remarkably underutilized in the U.S. and not considered as main line and initial treatment. All of this is unfortunate attitude, not science,” Dr. Carpenter said.

There is now evidence that the field is shifting toward LAIs as frontline treatment, “at least conceptually and by research leaders,” he noted.

“In this report, the health and suicide information is new, extremely important, and robust. This report should alert clinicians to possible advantage of LAI in suicide prevention,” Dr. Carpenter added.

Also commenting for this news organization, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences, Staten Island University Hospital, New York, said the findings provide “another very robust argument for LAIs.”

“The decrease in all-cause mortality is really interesting,” said Dr. Sullivan, “and it would be interesting to find out whether some of this reflects improved metabolic states” with LAIs versus OAPs.

The finding that people who switched to LAIs within 2 years were at much lower risk for suicide and other mortality represents a “powerful argument for switching within 2 years,” Dr. Sullivan said.

However, in current clinical practice, clinicians often don’t suggest LAIs until patients have suffered repeated acute episodes of illness after not taking their oral antipsychotics. Such episodes have an impact on the individual and on their nervous system, Dr. Sullivan explained.

“That’s really undesirable. We know from other data that the more episodes someone has, the harder it is to get the illness symptoms under control,” he noted.

“We really ought to be thinking preventively about approaches that will decrease the risk of recurrence, and the evidence in this study is pretty compelling that the LAI was a significant intervention that decreased the risks. Thinking about LAIs as a preventive measure is a message that hasn’t gotten out to the practice community yet,” Dr. Sullivan added.

The study was supported by the Bali Psychiatric Center, Taiwan, through a grant from the Ministry of Health and Welfare. Dr. Huang, Dr. Carpenter, and Dr. Sullivan have disclosed no relevant financial relationships.

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

Results from a large study make a strong case for offering long-acting injectable antipsychotics (LAIs) to patients newly diagnosed with schizophrenia.

Investigators found that among patients who switched to LAIs, mortality was lower and there were fewer suicide attempts in comparison with patients who continued taking the corresponding oral antipsychotic (OAP).

In addition, switching to an LAI antipsychotic within the first 2 years of OAP cut the risk for suicide death by 47%.

“With newly diagnosed schizophrenia, more active consideration of LAIs in this stage for better long-term outcomes (i.e., mortality and suicide risk) should be encouraged, particularly for those who have already exhibited poor adherence attitudes,” Cheng-yi Huang, MD, Bali Psychiatric Center, Ministry of Health and Welfare, New Taipei City, Taiwan, said in an interview.

The study was published online May 11 in JAMA Network Open.
 

Powerful incentive to switch

Using data from the Taiwan National Health Insurance Research Database, the investigators identified patients newly diagnosed with schizophrenia who received OAPs from 2002 to 2017.

Within this cohort, they defined the LAI group as patients who switched to LAIs and were prescribed LAIs at least four times within 1 year. The LAI group was propensity matched to patients who continued receiving OAPs of the same compounds. There were 2,614 patients in each group (median age, 30 years).

During the 16-year follow-up period, compared with patients who continued taking the OAP, those who switched to the LAI had a 34% lower risk for all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% confidence interval, 0.54-0.81), a 37% lower risk for natural-cause mortality (aHR, 0.63; 95% CI, 0.52-0.76), and a 28% lower risk for suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55-0.93).

The risk for suicide mortality was 47% lower for patients who switched to LAIs within the first 2 years of having begun taking the OAP (aHR, 0.53; 95% CI, 0.30-0.92).

A recent study from Canada found that the suicide rate among patients with schizophrenia spectrum disorders was more than 20 times higher than that of the general population.

“Clinically, most psychiatrists use LAIs with a conservative attitude, and the reasons for this attitude are generally not well supported by current scientific evidence,” Dr. Huang and colleagues note in their article.

Dr. Huang said the study provides a powerful incentive to begin treatment with LAIs for patients newly diagnosed with schizophrenia.

“Because this study compared depot versus the same oral compound, as soon as patients show response and tolerability to the OAP, they will benefit much more when switching to LAI of the same compound,” Dr. Huang told this news organization.
 

‘Remarkably underutilized’

Commenting on the study for an interview, William Carpenter Jr., MD, Maryland Psychiatric Research Center, University of Maryland, Baltimore, said this report is “very important and in a high-quality journal.”

“LAIs have been remarkably underutilized in the U.S. and not considered as main line and initial treatment. All of this is unfortunate attitude, not science,” Dr. Carpenter said.

There is now evidence that the field is shifting toward LAIs as frontline treatment, “at least conceptually and by research leaders,” he noted.

“In this report, the health and suicide information is new, extremely important, and robust. This report should alert clinicians to possible advantage of LAI in suicide prevention,” Dr. Carpenter added.

Also commenting for this news organization, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences, Staten Island University Hospital, New York, said the findings provide “another very robust argument for LAIs.”

“The decrease in all-cause mortality is really interesting,” said Dr. Sullivan, “and it would be interesting to find out whether some of this reflects improved metabolic states” with LAIs versus OAPs.

The finding that people who switched to LAIs within 2 years were at much lower risk for suicide and other mortality represents a “powerful argument for switching within 2 years,” Dr. Sullivan said.

However, in current clinical practice, clinicians often don’t suggest LAIs until patients have suffered repeated acute episodes of illness after not taking their oral antipsychotics. Such episodes have an impact on the individual and on their nervous system, Dr. Sullivan explained.

“That’s really undesirable. We know from other data that the more episodes someone has, the harder it is to get the illness symptoms under control,” he noted.

“We really ought to be thinking preventively about approaches that will decrease the risk of recurrence, and the evidence in this study is pretty compelling that the LAI was a significant intervention that decreased the risks. Thinking about LAIs as a preventive measure is a message that hasn’t gotten out to the practice community yet,” Dr. Sullivan added.

The study was supported by the Bali Psychiatric Center, Taiwan, through a grant from the Ministry of Health and Welfare. Dr. Huang, Dr. Carpenter, and Dr. Sullivan have disclosed no relevant financial relationships.

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

Results from a large study make a strong case for offering long-acting injectable antipsychotics (LAIs) to patients newly diagnosed with schizophrenia.

Investigators found that among patients who switched to LAIs, mortality was lower and there were fewer suicide attempts in comparison with patients who continued taking the corresponding oral antipsychotic (OAP).

In addition, switching to an LAI antipsychotic within the first 2 years of OAP cut the risk for suicide death by 47%.

“With newly diagnosed schizophrenia, more active consideration of LAIs in this stage for better long-term outcomes (i.e., mortality and suicide risk) should be encouraged, particularly for those who have already exhibited poor adherence attitudes,” Cheng-yi Huang, MD, Bali Psychiatric Center, Ministry of Health and Welfare, New Taipei City, Taiwan, said in an interview.

The study was published online May 11 in JAMA Network Open.
 

Powerful incentive to switch

Using data from the Taiwan National Health Insurance Research Database, the investigators identified patients newly diagnosed with schizophrenia who received OAPs from 2002 to 2017.

Within this cohort, they defined the LAI group as patients who switched to LAIs and were prescribed LAIs at least four times within 1 year. The LAI group was propensity matched to patients who continued receiving OAPs of the same compounds. There were 2,614 patients in each group (median age, 30 years).

During the 16-year follow-up period, compared with patients who continued taking the OAP, those who switched to the LAI had a 34% lower risk for all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% confidence interval, 0.54-0.81), a 37% lower risk for natural-cause mortality (aHR, 0.63; 95% CI, 0.52-0.76), and a 28% lower risk for suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55-0.93).

The risk for suicide mortality was 47% lower for patients who switched to LAIs within the first 2 years of having begun taking the OAP (aHR, 0.53; 95% CI, 0.30-0.92).

A recent study from Canada found that the suicide rate among patients with schizophrenia spectrum disorders was more than 20 times higher than that of the general population.

“Clinically, most psychiatrists use LAIs with a conservative attitude, and the reasons for this attitude are generally not well supported by current scientific evidence,” Dr. Huang and colleagues note in their article.

Dr. Huang said the study provides a powerful incentive to begin treatment with LAIs for patients newly diagnosed with schizophrenia.

“Because this study compared depot versus the same oral compound, as soon as patients show response and tolerability to the OAP, they will benefit much more when switching to LAI of the same compound,” Dr. Huang told this news organization.
 

‘Remarkably underutilized’

Commenting on the study for an interview, William Carpenter Jr., MD, Maryland Psychiatric Research Center, University of Maryland, Baltimore, said this report is “very important and in a high-quality journal.”

“LAIs have been remarkably underutilized in the U.S. and not considered as main line and initial treatment. All of this is unfortunate attitude, not science,” Dr. Carpenter said.

There is now evidence that the field is shifting toward LAIs as frontline treatment, “at least conceptually and by research leaders,” he noted.

“In this report, the health and suicide information is new, extremely important, and robust. This report should alert clinicians to possible advantage of LAI in suicide prevention,” Dr. Carpenter added.

Also commenting for this news organization, Timothy Sullivan, MD, chair of psychiatry and behavioral sciences, Staten Island University Hospital, New York, said the findings provide “another very robust argument for LAIs.”

“The decrease in all-cause mortality is really interesting,” said Dr. Sullivan, “and it would be interesting to find out whether some of this reflects improved metabolic states” with LAIs versus OAPs.

The finding that people who switched to LAIs within 2 years were at much lower risk for suicide and other mortality represents a “powerful argument for switching within 2 years,” Dr. Sullivan said.

However, in current clinical practice, clinicians often don’t suggest LAIs until patients have suffered repeated acute episodes of illness after not taking their oral antipsychotics. Such episodes have an impact on the individual and on their nervous system, Dr. Sullivan explained.

“That’s really undesirable. We know from other data that the more episodes someone has, the harder it is to get the illness symptoms under control,” he noted.

“We really ought to be thinking preventively about approaches that will decrease the risk of recurrence, and the evidence in this study is pretty compelling that the LAI was a significant intervention that decreased the risks. Thinking about LAIs as a preventive measure is a message that hasn’t gotten out to the practice community yet,” Dr. Sullivan added.

The study was supported by the Bali Psychiatric Center, Taiwan, through a grant from the Ministry of Health and Welfare. Dr. Huang, Dr. Carpenter, and Dr. Sullivan have disclosed no relevant financial relationships.

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

A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.

Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.

Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.

A critical care specialist who was not involved in the study said that the results are concerning but not surprising.

“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.

The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
 

Retrospective analysis

Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.

Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).

In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).

Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
 

‘Mechanisms unclear’

“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”

They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”

Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.

No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.

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

A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.

Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.

Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.

A critical care specialist who was not involved in the study said that the results are concerning but not surprising.

“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.

The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
 

Retrospective analysis

Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.

Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).

In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).

Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
 

‘Mechanisms unclear’

“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”

They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”

Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.

No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.

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

A study of COVID-19 outcomes across the United States bolsters reports from China and Europe that indicate that patients with chronic obstructive pulmonary disease (COPD) and SARS-CoV-2 infection have worse outcomes than those of patients with COVID-19 who do not have COPD.

Investigators at the University of Texas Medical Branch at Galveston, Texas, combed through electronic health records from four geographic regions of the United States and identified a cohort of 6,056 patients with COPD among 150,775 patients whose records indicate either a diagnostic code or a positive laboratory test result for COVID-19.

Their findings indicate that patients with both COPD and COVID-19 “have worse outcomes compared to non-COPD COVID-19 patients, including 14-day hospitalization, length of stay, ICU admission, 30-day mortality, and use of mechanical ventilation,” Daniel Puebla Neira, MD, and colleagues from the University of Texas Medical Branch reported in a thematic poster presented during the American Thoracic Society (ATS) 2021 virtual international conference.

A critical care specialist who was not involved in the study said that the results are concerning but not surprising.

“If you already have a lung disease and you develop an additional lung disease on top of that, you don’t have as much reserve and you’re not going to tolerate the acute COVID infection,” said ATS expert Marc Moss, MD, Roger S. Mitchell Professor of Medicine in the division of pulmonary sciences and critical care medicine at the University of Colorado, Aurora.

The evidence shows that “patients with COPD should be even more cautious, because if they get sick and develop, they could do worse,” he said in an interview.
 

Retrospective analysis

Dr. Neira and colleagues assessed the characteristics and outcomes of patients with COPD who were treated for COVID-19 in the United States from March through August 2020.

Baseline demographics of the patients with and those without COPD were similar except that the mean age was higher among patients with COPD (68.62 vs. 47.08 years).

In addition, a significantly higher proportion of patients with COPD had comorbidities compared with those without COPD. Comorbidities included diabetes, hypertension, asthma, chronic kidney disease, end-stage renal disease, stroke, heart failure, cancer, coronary artery disease, and liver disease (P < .0001 for all comparisons).

Among patients with COPD, percentages were higher with respect to the following parameters: 14-day hospitalization for any cause (28.7% vs. 10.4%), COVID-19-related 14-day hospitalization (28.1% vs. 9.9%), ICU use (26.3% vs. 17.9%), mechanical ventilation use (26.3% vs. 16.1%), and 30-day mortality (13.6% vs. 7.2%; P < .0001 for all comparisons).
 

‘Mechanisms unclear’

“It is unclear what mechanisms drive the association between COPD and mortality in hospitalized patients with COVID-19,” the investigators wrote. “Several biological factors have been proposed, including chronic lung inflammation, oxidative stress, protease-antiprotease imbalance, and increased airway mediators.”

They recommend use of multivariable logistic regression to tease out the effects of covariates among patients with COPD and COVID-19 and call for research into long-term outcomes for these patients, “as survivors of critical illness are increasingly recognized to have cognitive, psychological, and physical consequences.”

Dr. Moss said that in general, the management of patients with COPD and COVID-19 is similar to that for patients with COVID-19 who do not have COPD, although there may be “subtle” differences, such as ventilator settings for patients with COPD.

No source of funding for the study has been disclosed. The investigators and Dr. Moss have disclosed no relevant financial relationships.

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

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

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

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

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

It’s more evidence that Americans drank more alcohol during the COVID-19 lockdown. Rates of liver and gastrointestinal diseases associated with drinking alcohol rose after the COVID-19 pandemic started, compared with the same period in 2019.

Interestingly, while the overall number of people seeking GI or liver specialist care dropped by 27%, the proportion of consults for alcohol-related GI and liver diseases jumped by nearly 60%, researchers reported.

“We do believe that the lockdown of the pandemic has a direct effect on patients’ alcohol consumption,” senior study author Waihong Chung, MD, said during Digestive Disease Week® (DDW) 2021 preview media briefing on May 13.

“We urge primary care physicians and GI doctors and hepatologists to double down on questioning patients about alcohol use and to identify people who might need help sooner rather than later,” added Dr. Chung, gastroenterologist at Lifespan/Brown University in Providence, R.I.

“You have to ask. If you don’t ask, you don’t know,” Dr. Chung said in an interview when asked how to broach the subject.

Symptoms of alcohol-related GI and liver diseases, especially acute alcoholic hepatitis, can include fatigue, abdominal pain, loss of appetite, and even jaundice in more severe cases. “I want to stress that some of these symptoms appear much later during the course of the disease,” Dr. Chung said. “At the early phase, people might be asymptomatic. By the time people develop symptoms it might be too late. That’s why it’s important to ask.”

“I really believe that physicians of all specialties should make it routine when you have a patient encounter to include assessment for alcohol use,” he added.

Creating a clinical environment where patients feel safe to disclose their alcohol use is likewise essential.

Suggested questions include: Do you drink alcohol? How much did you drink in the past week?

“A few people will be offended by me asking this way, but it helps people who might think they have an alcohol problem open up [about it],” he said.

After Dr. Chung and colleagues noticed an increase in patients with alcohol-related GI and liver diseases, they conducted a hospital system–wide audit. They evaluated 558 inpatient GI consults during a lockdown phase from March 23 to May 10, 2020, and another 713 consults during a reopening phase from June 1 to July 19, 2020. They also compared results with consults from similar periods in 2019.

At the same time, consults for non–alcohol-related liver diseases, such as biliary obstruction/injury, inflammatory bowel disease, and gastrointestinal bleeding, did not change significantly. Also, during reopening the total volume of consults rebounded to 101% of the volume during the same period in 2019.

However, reopening also saw the proportion of these alcohol-related conditions remain elevated by 79%. Patients diagnosed with alcoholic hepatitis increased by 127%, for example. At the same time, patients in this population requiring inpatient endoscopy nearly tripled from 14% to 35%.

Alcohol-related GI and liver diseases included acute alcoholic hepatitis, alcoholic cirrhosis, alcoholic gastritis, alcoholic esophagitis, and pancreatitis. Most patients (70%) were men. Median ages were 56 years during the lockdown phase and 51 years during the reopening phase.

“I think it’s interesting. It fits into what people have anecdotally been suggesting,” said Loren Laine, MD, chief of the section of digestive diseases at Yale University in New Haven, Conn., and moderator of the media briefing.

“It is [also] interesting to see how COVID has changed so many different things over the past year,” he added when asked his opinion of the findings.

Dr. Chung added that not all patients with alcohol use disorders are admitted to a hospital, “so we believe that the health problems related to increased alcohol use may be even higher in the community.”

Although the study was conducted in one health system in one state, Dr. Chung said, “we do believe that the result of our study is an accurate reflection of what’s happening in many other urban and suburban cities in the United States.”

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

The PD-L1 inhibitor atezolizumab (Tecentriq) combined with carboplatin has shown signs of clinical activity in women with metastatic invasive lobular breast cancer (ILC) according to the first results to come from the ongoing GELATO trial.

The 6-month objective response rate was 19%, based on 4 of 21 patients who could be evaluated exhibiting a partial response to the chemoimmunotherapy. A further two (10%) patients had stable disease, meaning that clinical benefit rate was 29%.

GELATO (AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular Breast Cancer) is a phase 2 trial being conducted at four Dutch centers. The primary premise of the study is that “there’s an immune-related subtype of ILC,” researcher Leonie Voorwerk, BSc, reported at the European Society for Medical Oncology: Breast Cancer virtual meeting (Abstract LBA3).

This ILC subtype is “characterized by high expression of immune-related genes and high levels of TILs [tumor-infiltrating lymphocytes] and PDL-1,” said Ms. Voorwerk, a PhD student working with medical oncologist Marleen Kok, MD, PhD, at the Netherlands Cancer Institute in Amsterdam.

Furthermore, she added, in vitro data suggest sensitivity of immune-related-ILCs to platinum and there is preclinical work showing that there is synergy between platinum-based chemotherapy and checkpoint blockade.
 

First chemoimmunotherapy trial in lobular cancer setting

GELATO is a significant trial as it is “the first chemoimmunotherapy trial in metastatic lobular breast cancer,” said Sylvia Adams, MD, professor of medicine and director of the Breast Cancer Center at NYU Langone Health in New York City.

“Of note, the further research should include the immune-related genes and TMB [tumor mutational burden],” proposed Dr. Adams, who was not involved in the trial.

“We should look to tumor mutational burden because while it is not typically high in early disease, metastatic lesions can have higher TMB,” she explained. “Also, metastatic ILC is known to have higher tumor mutational burden compared to IDC [invasive ductal carcinoma], so this is an important thing along with the clinical factors as described in looking at outcomes.”
 

Trial design and patient characteristics

GELATO is a single-arm, nonrandomized trial in which 37 patients with metastatic ILC were screened for inclusion between November 2017 and January 2021. A total of 26 of these patients were registered for the trial, and 23 have so far received at least one cycle of atezolizumab.

Prerequisites for entry into the trial were that patients had to have negative or aberrant E-cadherin, a characteristic feature of ILC. Patients with estrogen receptor (ER)-positive (ER+) disease could be included, but they had to be proven to be resistant to endocrine therapies. No more than two prior lines of palliative chemotherapy were allowed, and all participants had to have lactose dehydrogenase levels of less than 2 times the upper limit of normal.

Patients were then treated with up to 12 cycles of weekly carboplatin (AUC = 1.5 mg/mL/min), with atezolizumab (1,200 mg) added in from cycle 3 onward. Treatment was continued until disease progression or unacceptable toxicity occurred.

“Baseline characteristics were mainly as expected for this patient population,” Ms. Voorwerk stated. Patients were aged 45-89 years, with a median of 60 years. Around half each had a WHO performance status of 0 or 1, and around half each had one to two or three or more metastatic sites; 78% had liver metastases.

“But I want to highlight that we included five patients with the triple-negative ILC,” said Ms. Voorwerk, also highlighting that approximately 50% of patients had received prior palliative chemotherapy. Later in her presentation she noted that four out of the six patients that showed any clinical benefit had triple negative disease.
 

Key findings and next steps

The primary endpoint was progression-free survival (PFS) at 6 months, with secondary endpoints of the best overall response rate, PFS at 1 year, overall survival, and safety.

While details of the latter three endpoints are yet to be reported, Ms. Voorwerk noted that there was a median duration of response of 12 weeks and the median PFS was 15 weeks. The primary endpoint of PFS was met as four patients were free of progression at 6 months and the statistical method used called for patients to be progression free at this time point.

“We observed that stromal TILs and CD8+ cells were not associated with clinical benefits,” said Ms. Voorwerk. There was, however, “a slight trend” toward higher PD-L1 expression in responding patients.

“Further translational research is needed to provide the rationale for new strategies to improve checkpoint blockade in patients with lobular breast cancer,” she concluded.

Dr. Adams concurred, adding that a future research question was whether either atezolizumab or carboplatin was contributing to the response. This is “difficult to tell as the study was a single arm trial.”

Another question, said Dr. Adams, is are “anti-CDK 4/6 inhibitors helpful in improving response rates and durability?” In the trial, 70% of patients had prior exposure to CDK 4/6 inhibitors.

The GELATO trial was sponsored by the Netherlands Cancer Institute with funding from Roche Pharma AG. Ms. Voorwerk had nothing to disclose. Dr. Adams disclosed uncompensated consulting or advisory roles with Bristol-Myers Squibb, Genentech, and Merck from whom she has received research funding. Dr. Adams also disclosed research funding from Amgen, Celgene, and Novartis.

The PD-L1 inhibitor atezolizumab (Tecentriq) combined with carboplatin has shown signs of clinical activity in women with metastatic invasive lobular breast cancer (ILC) according to the first results to come from the ongoing GELATO trial.

The 6-month objective response rate was 19%, based on 4 of 21 patients who could be evaluated exhibiting a partial response to the chemoimmunotherapy. A further two (10%) patients had stable disease, meaning that clinical benefit rate was 29%.

GELATO (AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular Breast Cancer) is a phase 2 trial being conducted at four Dutch centers. The primary premise of the study is that “there’s an immune-related subtype of ILC,” researcher Leonie Voorwerk, BSc, reported at the European Society for Medical Oncology: Breast Cancer virtual meeting (Abstract LBA3).

This ILC subtype is “characterized by high expression of immune-related genes and high levels of TILs [tumor-infiltrating lymphocytes] and PDL-1,” said Ms. Voorwerk, a PhD student working with medical oncologist Marleen Kok, MD, PhD, at the Netherlands Cancer Institute in Amsterdam.

Furthermore, she added, in vitro data suggest sensitivity of immune-related-ILCs to platinum and there is preclinical work showing that there is synergy between platinum-based chemotherapy and checkpoint blockade.
 

First chemoimmunotherapy trial in lobular cancer setting

GELATO is a significant trial as it is “the first chemoimmunotherapy trial in metastatic lobular breast cancer,” said Sylvia Adams, MD, professor of medicine and director of the Breast Cancer Center at NYU Langone Health in New York City.

“Of note, the further research should include the immune-related genes and TMB [tumor mutational burden],” proposed Dr. Adams, who was not involved in the trial.

“We should look to tumor mutational burden because while it is not typically high in early disease, metastatic lesions can have higher TMB,” she explained. “Also, metastatic ILC is known to have higher tumor mutational burden compared to IDC [invasive ductal carcinoma], so this is an important thing along with the clinical factors as described in looking at outcomes.”
 

Trial design and patient characteristics

GELATO is a single-arm, nonrandomized trial in which 37 patients with metastatic ILC were screened for inclusion between November 2017 and January 2021. A total of 26 of these patients were registered for the trial, and 23 have so far received at least one cycle of atezolizumab.

Prerequisites for entry into the trial were that patients had to have negative or aberrant E-cadherin, a characteristic feature of ILC. Patients with estrogen receptor (ER)-positive (ER+) disease could be included, but they had to be proven to be resistant to endocrine therapies. No more than two prior lines of palliative chemotherapy were allowed, and all participants had to have lactose dehydrogenase levels of less than 2 times the upper limit of normal.

Patients were then treated with up to 12 cycles of weekly carboplatin (AUC = 1.5 mg/mL/min), with atezolizumab (1,200 mg) added in from cycle 3 onward. Treatment was continued until disease progression or unacceptable toxicity occurred.

“Baseline characteristics were mainly as expected for this patient population,” Ms. Voorwerk stated. Patients were aged 45-89 years, with a median of 60 years. Around half each had a WHO performance status of 0 or 1, and around half each had one to two or three or more metastatic sites; 78% had liver metastases.

“But I want to highlight that we included five patients with the triple-negative ILC,” said Ms. Voorwerk, also highlighting that approximately 50% of patients had received prior palliative chemotherapy. Later in her presentation she noted that four out of the six patients that showed any clinical benefit had triple negative disease.
 

Key findings and next steps

The primary endpoint was progression-free survival (PFS) at 6 months, with secondary endpoints of the best overall response rate, PFS at 1 year, overall survival, and safety.

While details of the latter three endpoints are yet to be reported, Ms. Voorwerk noted that there was a median duration of response of 12 weeks and the median PFS was 15 weeks. The primary endpoint of PFS was met as four patients were free of progression at 6 months and the statistical method used called for patients to be progression free at this time point.

“We observed that stromal TILs and CD8+ cells were not associated with clinical benefits,” said Ms. Voorwerk. There was, however, “a slight trend” toward higher PD-L1 expression in responding patients.

“Further translational research is needed to provide the rationale for new strategies to improve checkpoint blockade in patients with lobular breast cancer,” she concluded.

Dr. Adams concurred, adding that a future research question was whether either atezolizumab or carboplatin was contributing to the response. This is “difficult to tell as the study was a single arm trial.”

Another question, said Dr. Adams, is are “anti-CDK 4/6 inhibitors helpful in improving response rates and durability?” In the trial, 70% of patients had prior exposure to CDK 4/6 inhibitors.

The GELATO trial was sponsored by the Netherlands Cancer Institute with funding from Roche Pharma AG. Ms. Voorwerk had nothing to disclose. Dr. Adams disclosed uncompensated consulting or advisory roles with Bristol-Myers Squibb, Genentech, and Merck from whom she has received research funding. Dr. Adams also disclosed research funding from Amgen, Celgene, and Novartis.

The PD-L1 inhibitor atezolizumab (Tecentriq) combined with carboplatin has shown signs of clinical activity in women with metastatic invasive lobular breast cancer (ILC) according to the first results to come from the ongoing GELATO trial.

The 6-month objective response rate was 19%, based on 4 of 21 patients who could be evaluated exhibiting a partial response to the chemoimmunotherapy. A further two (10%) patients had stable disease, meaning that clinical benefit rate was 29%.

GELATO (AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular Breast Cancer) is a phase 2 trial being conducted at four Dutch centers. The primary premise of the study is that “there’s an immune-related subtype of ILC,” researcher Leonie Voorwerk, BSc, reported at the European Society for Medical Oncology: Breast Cancer virtual meeting (Abstract LBA3).

This ILC subtype is “characterized by high expression of immune-related genes and high levels of TILs [tumor-infiltrating lymphocytes] and PDL-1,” said Ms. Voorwerk, a PhD student working with medical oncologist Marleen Kok, MD, PhD, at the Netherlands Cancer Institute in Amsterdam.

Furthermore, she added, in vitro data suggest sensitivity of immune-related-ILCs to platinum and there is preclinical work showing that there is synergy between platinum-based chemotherapy and checkpoint blockade.
 

First chemoimmunotherapy trial in lobular cancer setting

GELATO is a significant trial as it is “the first chemoimmunotherapy trial in metastatic lobular breast cancer,” said Sylvia Adams, MD, professor of medicine and director of the Breast Cancer Center at NYU Langone Health in New York City.

“Of note, the further research should include the immune-related genes and TMB [tumor mutational burden],” proposed Dr. Adams, who was not involved in the trial.

“We should look to tumor mutational burden because while it is not typically high in early disease, metastatic lesions can have higher TMB,” she explained. “Also, metastatic ILC is known to have higher tumor mutational burden compared to IDC [invasive ductal carcinoma], so this is an important thing along with the clinical factors as described in looking at outcomes.”
 

Trial design and patient characteristics

GELATO is a single-arm, nonrandomized trial in which 37 patients with metastatic ILC were screened for inclusion between November 2017 and January 2021. A total of 26 of these patients were registered for the trial, and 23 have so far received at least one cycle of atezolizumab.

Prerequisites for entry into the trial were that patients had to have negative or aberrant E-cadherin, a characteristic feature of ILC. Patients with estrogen receptor (ER)-positive (ER+) disease could be included, but they had to be proven to be resistant to endocrine therapies. No more than two prior lines of palliative chemotherapy were allowed, and all participants had to have lactose dehydrogenase levels of less than 2 times the upper limit of normal.

Patients were then treated with up to 12 cycles of weekly carboplatin (AUC = 1.5 mg/mL/min), with atezolizumab (1,200 mg) added in from cycle 3 onward. Treatment was continued until disease progression or unacceptable toxicity occurred.

“Baseline characteristics were mainly as expected for this patient population,” Ms. Voorwerk stated. Patients were aged 45-89 years, with a median of 60 years. Around half each had a WHO performance status of 0 or 1, and around half each had one to two or three or more metastatic sites; 78% had liver metastases.

“But I want to highlight that we included five patients with the triple-negative ILC,” said Ms. Voorwerk, also highlighting that approximately 50% of patients had received prior palliative chemotherapy. Later in her presentation she noted that four out of the six patients that showed any clinical benefit had triple negative disease.
 

Key findings and next steps

The primary endpoint was progression-free survival (PFS) at 6 months, with secondary endpoints of the best overall response rate, PFS at 1 year, overall survival, and safety.

While details of the latter three endpoints are yet to be reported, Ms. Voorwerk noted that there was a median duration of response of 12 weeks and the median PFS was 15 weeks. The primary endpoint of PFS was met as four patients were free of progression at 6 months and the statistical method used called for patients to be progression free at this time point.

“We observed that stromal TILs and CD8+ cells were not associated with clinical benefits,” said Ms. Voorwerk. There was, however, “a slight trend” toward higher PD-L1 expression in responding patients.

“Further translational research is needed to provide the rationale for new strategies to improve checkpoint blockade in patients with lobular breast cancer,” she concluded.

Dr. Adams concurred, adding that a future research question was whether either atezolizumab or carboplatin was contributing to the response. This is “difficult to tell as the study was a single arm trial.”

Another question, said Dr. Adams, is are “anti-CDK 4/6 inhibitors helpful in improving response rates and durability?” In the trial, 70% of patients had prior exposure to CDK 4/6 inhibitors.

The GELATO trial was sponsored by the Netherlands Cancer Institute with funding from Roche Pharma AG. Ms. Voorwerk had nothing to disclose. Dr. Adams disclosed uncompensated consulting or advisory roles with Bristol-Myers Squibb, Genentech, and Merck from whom she has received research funding. Dr. Adams also disclosed research funding from Amgen, Celgene, and Novartis.