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New combination med for severe mental illness tied to less weight gain
, new research suggests. However, at least one expert says the weight difference between the two drugs is of “questionable clinical benefit.”
Last year, the Food and Drug Administration approved the drug for the treatment of adults with schizophrenia or bipolar I disorder, as a maintenance monotherapy or as either monotherapy or an adjunct to lithium or valproate for acute manic or mixed episodes.
In the ENLIGHTEN-Early trial, researchers examined weight-gain profiles of more than 400 patients with early schizophrenia, schizophreniform disorder, or bipolar I disorder.
Results showed those given combination treatment gained just over half the amount of weight as those given monotherapy. They were also 36% less likely to gain at least 10% of their body weight during the 12-week treatment period.
They indicate that the weight-mitigating effects shown with olanzapine plus samidorphan are “consistent, regardless of the stage of illness,” Dr. Kahn added.
He presented the findings at the annual congress of the Schizophrenia International Research Society.
Potential benefit
“Early intervention with antipsychotic treatment is critical in shaping the course of treatment and the disease trajectory,” coinvestigator Christine Graham, PhD, with Alkermes, which manufactures the drug, told this news organization.
Olanzapine is a “highly effective antipsychotic, but it’s really avoided a lot in this population,” Dr. Graham said. Therefore, patients “could really stand to benefit” from a combination that delivers the same amount of antipsychotic effect, but “reduces the propensity” for clinically significant weight gain, she added.
Dr. Kahn noted in his meeting presentation that antipsychotics are the “cornerstone” of the treatment of serious mental illness, but that “many are associated with concerning weight gain and cardiometabolic effects.”
While olanzapine is an effective medication, it has “one of the highest weight gain” profiles of the available antipsychotics and patients early on in their illness are “especially vulnerable,” Dr. Kahn said.
Previous studies have shown the combination of olanzapine plus samidorphan is similarly effective as olanzapine, but is associated with less weight gain.
To determine its impact in recent-onset illness, the current researchers screened patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. The patients were aged 16-39 years and had an initial onset of active phase symptoms less than 4 years previously. They had less than 24 weeks’ cumulative lifetime exposure to antipsychotics.
Participants were randomly assigned to receive olanzapine plus samidorphan or olanzapine alone for 12 weeks, and then followed up for safety assessment for a further 4 weeks.
A total of 426 patients were recruited and 76.5% completed the study. The mean age was 25.8 years, 66.2% were men, 66.4% were White, and 28.2% were Black.
The mean body mass index at baseline was 23.69 kg/m2. The most common diagnosis among the participants was schizophrenia (62.9%) followed by bipolar I disorder (21.6%).
Less weight gain
Results of the 12-week study showed a significant difference in percent change in body weight from baseline between the two treatment groups, with a gain of 4.91% for the olanzapine plus samidorphan group vs. 6.77% for the olanzapine-alone group (between-group difference, 1.87%; P = .012).
Dr. Kahn noted this equates to an average weight gain of 2.8 kg (6.2 pounds) with olanzapine plus samidorphan and a gain of about 5 kg (11pounds) with olanzapine.
“It’s not a huge difference, but it’s certainly a significant one,” he said. “I also think it’s clinically important and significant.”
The reduction in weight gain compared with olanzapine was even maintained in patients assigned to olanzapine plus samidorphan who dropped out and did not complete the study, Dr. Kahn reported. “No one really had a weight gain,” he said.
In contrast, patients in the olanzapine groups who dropped out of the study had weight gain larger than their counterparts who stayed in it.
Further analysis showed the proportion of patients who gained 10% or more of their body weight by week 12 was 21.9% for those receiving olanzapine plus samidorphan vs. 30.4% for those receiving just olanzapine (odds ratio, 0.64; P = .075).
As expected, the improvement in Clinical Global Impression–Severity scale scores was almost identical between the olanzapine + samidorphan and olanzapine-only groups.
For safety, Dr. Kahn said the adverse event rates were “very, very similar” between the two treatment arms, which was a pattern that was repeated for serious AEs. This led him to note that “nothing out of the ordinary” was observed.
Clinical impact 'questionable'
Commenting on the study, Laura LaChance, MD, a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said the actual amount of weight loss shown in the study “is of questionable clinical significance.”
On the other hand, Dr. LaChance said she has achieved “better results with metformin, which has a great safety profile and is cheap and widely available.
“Cost is always a concern in patients with psychotic disorders,” she concluded.
The study was funded by Alkermes. Dr. Kahn reported having relationships with Alkermes, Angelini, Janssen, Sunovion, Otsuka, Merck, Minerva Neuroscience, Roche, and Teva. Dr. Graham is an employee of Alkermes.
A version of this article first appeared on Medscape.com.
, new research suggests. However, at least one expert says the weight difference between the two drugs is of “questionable clinical benefit.”
Last year, the Food and Drug Administration approved the drug for the treatment of adults with schizophrenia or bipolar I disorder, as a maintenance monotherapy or as either monotherapy or an adjunct to lithium or valproate for acute manic or mixed episodes.
In the ENLIGHTEN-Early trial, researchers examined weight-gain profiles of more than 400 patients with early schizophrenia, schizophreniform disorder, or bipolar I disorder.
Results showed those given combination treatment gained just over half the amount of weight as those given monotherapy. They were also 36% less likely to gain at least 10% of their body weight during the 12-week treatment period.
They indicate that the weight-mitigating effects shown with olanzapine plus samidorphan are “consistent, regardless of the stage of illness,” Dr. Kahn added.
He presented the findings at the annual congress of the Schizophrenia International Research Society.
Potential benefit
“Early intervention with antipsychotic treatment is critical in shaping the course of treatment and the disease trajectory,” coinvestigator Christine Graham, PhD, with Alkermes, which manufactures the drug, told this news organization.
Olanzapine is a “highly effective antipsychotic, but it’s really avoided a lot in this population,” Dr. Graham said. Therefore, patients “could really stand to benefit” from a combination that delivers the same amount of antipsychotic effect, but “reduces the propensity” for clinically significant weight gain, she added.
Dr. Kahn noted in his meeting presentation that antipsychotics are the “cornerstone” of the treatment of serious mental illness, but that “many are associated with concerning weight gain and cardiometabolic effects.”
While olanzapine is an effective medication, it has “one of the highest weight gain” profiles of the available antipsychotics and patients early on in their illness are “especially vulnerable,” Dr. Kahn said.
Previous studies have shown the combination of olanzapine plus samidorphan is similarly effective as olanzapine, but is associated with less weight gain.
To determine its impact in recent-onset illness, the current researchers screened patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. The patients were aged 16-39 years and had an initial onset of active phase symptoms less than 4 years previously. They had less than 24 weeks’ cumulative lifetime exposure to antipsychotics.
Participants were randomly assigned to receive olanzapine plus samidorphan or olanzapine alone for 12 weeks, and then followed up for safety assessment for a further 4 weeks.
A total of 426 patients were recruited and 76.5% completed the study. The mean age was 25.8 years, 66.2% were men, 66.4% were White, and 28.2% were Black.
The mean body mass index at baseline was 23.69 kg/m2. The most common diagnosis among the participants was schizophrenia (62.9%) followed by bipolar I disorder (21.6%).
Less weight gain
Results of the 12-week study showed a significant difference in percent change in body weight from baseline between the two treatment groups, with a gain of 4.91% for the olanzapine plus samidorphan group vs. 6.77% for the olanzapine-alone group (between-group difference, 1.87%; P = .012).
Dr. Kahn noted this equates to an average weight gain of 2.8 kg (6.2 pounds) with olanzapine plus samidorphan and a gain of about 5 kg (11pounds) with olanzapine.
“It’s not a huge difference, but it’s certainly a significant one,” he said. “I also think it’s clinically important and significant.”
The reduction in weight gain compared with olanzapine was even maintained in patients assigned to olanzapine plus samidorphan who dropped out and did not complete the study, Dr. Kahn reported. “No one really had a weight gain,” he said.
In contrast, patients in the olanzapine groups who dropped out of the study had weight gain larger than their counterparts who stayed in it.
Further analysis showed the proportion of patients who gained 10% or more of their body weight by week 12 was 21.9% for those receiving olanzapine plus samidorphan vs. 30.4% for those receiving just olanzapine (odds ratio, 0.64; P = .075).
As expected, the improvement in Clinical Global Impression–Severity scale scores was almost identical between the olanzapine + samidorphan and olanzapine-only groups.
For safety, Dr. Kahn said the adverse event rates were “very, very similar” between the two treatment arms, which was a pattern that was repeated for serious AEs. This led him to note that “nothing out of the ordinary” was observed.
Clinical impact 'questionable'
Commenting on the study, Laura LaChance, MD, a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said the actual amount of weight loss shown in the study “is of questionable clinical significance.”
On the other hand, Dr. LaChance said she has achieved “better results with metformin, which has a great safety profile and is cheap and widely available.
“Cost is always a concern in patients with psychotic disorders,” she concluded.
The study was funded by Alkermes. Dr. Kahn reported having relationships with Alkermes, Angelini, Janssen, Sunovion, Otsuka, Merck, Minerva Neuroscience, Roche, and Teva. Dr. Graham is an employee of Alkermes.
A version of this article first appeared on Medscape.com.
, new research suggests. However, at least one expert says the weight difference between the two drugs is of “questionable clinical benefit.”
Last year, the Food and Drug Administration approved the drug for the treatment of adults with schizophrenia or bipolar I disorder, as a maintenance monotherapy or as either monotherapy or an adjunct to lithium or valproate for acute manic or mixed episodes.
In the ENLIGHTEN-Early trial, researchers examined weight-gain profiles of more than 400 patients with early schizophrenia, schizophreniform disorder, or bipolar I disorder.
Results showed those given combination treatment gained just over half the amount of weight as those given monotherapy. They were also 36% less likely to gain at least 10% of their body weight during the 12-week treatment period.
They indicate that the weight-mitigating effects shown with olanzapine plus samidorphan are “consistent, regardless of the stage of illness,” Dr. Kahn added.
He presented the findings at the annual congress of the Schizophrenia International Research Society.
Potential benefit
“Early intervention with antipsychotic treatment is critical in shaping the course of treatment and the disease trajectory,” coinvestigator Christine Graham, PhD, with Alkermes, which manufactures the drug, told this news organization.
Olanzapine is a “highly effective antipsychotic, but it’s really avoided a lot in this population,” Dr. Graham said. Therefore, patients “could really stand to benefit” from a combination that delivers the same amount of antipsychotic effect, but “reduces the propensity” for clinically significant weight gain, she added.
Dr. Kahn noted in his meeting presentation that antipsychotics are the “cornerstone” of the treatment of serious mental illness, but that “many are associated with concerning weight gain and cardiometabolic effects.”
While olanzapine is an effective medication, it has “one of the highest weight gain” profiles of the available antipsychotics and patients early on in their illness are “especially vulnerable,” Dr. Kahn said.
Previous studies have shown the combination of olanzapine plus samidorphan is similarly effective as olanzapine, but is associated with less weight gain.
To determine its impact in recent-onset illness, the current researchers screened patients with schizophrenia, schizophreniform disorder, or bipolar I disorder. The patients were aged 16-39 years and had an initial onset of active phase symptoms less than 4 years previously. They had less than 24 weeks’ cumulative lifetime exposure to antipsychotics.
Participants were randomly assigned to receive olanzapine plus samidorphan or olanzapine alone for 12 weeks, and then followed up for safety assessment for a further 4 weeks.
A total of 426 patients were recruited and 76.5% completed the study. The mean age was 25.8 years, 66.2% were men, 66.4% were White, and 28.2% were Black.
The mean body mass index at baseline was 23.69 kg/m2. The most common diagnosis among the participants was schizophrenia (62.9%) followed by bipolar I disorder (21.6%).
Less weight gain
Results of the 12-week study showed a significant difference in percent change in body weight from baseline between the two treatment groups, with a gain of 4.91% for the olanzapine plus samidorphan group vs. 6.77% for the olanzapine-alone group (between-group difference, 1.87%; P = .012).
Dr. Kahn noted this equates to an average weight gain of 2.8 kg (6.2 pounds) with olanzapine plus samidorphan and a gain of about 5 kg (11pounds) with olanzapine.
“It’s not a huge difference, but it’s certainly a significant one,” he said. “I also think it’s clinically important and significant.”
The reduction in weight gain compared with olanzapine was even maintained in patients assigned to olanzapine plus samidorphan who dropped out and did not complete the study, Dr. Kahn reported. “No one really had a weight gain,” he said.
In contrast, patients in the olanzapine groups who dropped out of the study had weight gain larger than their counterparts who stayed in it.
Further analysis showed the proportion of patients who gained 10% or more of their body weight by week 12 was 21.9% for those receiving olanzapine plus samidorphan vs. 30.4% for those receiving just olanzapine (odds ratio, 0.64; P = .075).
As expected, the improvement in Clinical Global Impression–Severity scale scores was almost identical between the olanzapine + samidorphan and olanzapine-only groups.
For safety, Dr. Kahn said the adverse event rates were “very, very similar” between the two treatment arms, which was a pattern that was repeated for serious AEs. This led him to note that “nothing out of the ordinary” was observed.
Clinical impact 'questionable'
Commenting on the study, Laura LaChance, MD, a psychiatrist at St. Mary’s Hospital Centre, McGill University, Montreal, said the actual amount of weight loss shown in the study “is of questionable clinical significance.”
On the other hand, Dr. LaChance said she has achieved “better results with metformin, which has a great safety profile and is cheap and widely available.
“Cost is always a concern in patients with psychotic disorders,” she concluded.
The study was funded by Alkermes. Dr. Kahn reported having relationships with Alkermes, Angelini, Janssen, Sunovion, Otsuka, Merck, Minerva Neuroscience, Roche, and Teva. Dr. Graham is an employee of Alkermes.
A version of this article first appeared on Medscape.com.
FROM SIRS 2022
Pandemic prompts spike in eating disorder hospitalization for adolescents
Hospital admission for children with eating disorders approximately tripled during the COVID-19 pandemic, based on data from 85 patients.
Eating disorders are common among adolescents and often require hospital admission for nutritional restoration, according to May Shum of Yale University, New Haven, Conn., and colleagues
During the COVID-19 pandemic, the volume of hospital admissions for adolescents with eating disorders has increased, the researchers wrote in a poster presented at the annual meeting of the Pediatric Academic Societies. This increase may be driven both by interruptions in medical care and increased psychological distress, but data on changes in patient characteristics and hospitalization course are lacking, they said.
The researchers reviewed charts from patients with eating disorders admitted to a single center between Jan. 1, 2017, and June 30, 2021. The majority of the patients were female (90.6%), and White (78.8%), had restrictive eating behaviors (97.2%), and had private insurance (80.0%).
Overall, the number of monthly admissions increased from 1.4 before the onset of the pandemic to 3.6 during the pandemic (P < .001).
Length of stay increased significantly from before to during pandemic cases (12.8 days vs. 17.3 days, P = .04) and age younger than 13 years was significantly associated with a longer length of stay (P < .001).
The number of patients for whom psychotropic medications were initiated or changed increased significantly (12.5% vs. 28.3%, P = .04); as did the proportion of patients discharged to partial hospitalization, residential, or inpatient psychiatric treatment rather than discharged home with outpatient therapy (56.2% vs. 75.0%, P = .04).
No significant differences were noted in demographics, comorbidities, admission parameters, EKG abnormalities, electrolyte repletion, or tube feeding.
The study findings were limited by the use of data from a single center. However, the results suggest an increase in severity of hospital admissions that have implications for use of hospital resources, the researchers said.
“In addition to an increase in hospital admissions for eating disorder management during the pandemic, longer inpatient stays of younger children with higher acuity at discharge is an added strain on hospital resources and warrants attention,” they concluded.
Considerations for younger patients
The current study is especially important at this time, Margaret Thew, DNP, FNP-BC, medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee, said in an interview. “There have been reports of the rising numbers in eating disorders, but until research has been conducted, we cannot quantify the volumes,” said Ms. Thew, who was not involved in the study. “There have been many reports of the rise in mental health issues during the pandemic, so it seems accurate that the rate of eating disorders would rise,” she said. “Additionally, from a clinical perspective there seemed to be many younger-age patients with eating disorders presenting to the inpatient units who seemed sicker,” she noted.
Ms. Thew said she was not surprised by the study findings. “Working with adolescents with eating disorders we saw the increased numbers of both hospitalizations and outpatient referrals during the pandemic,” said Ms. Thew. “Length of stay was higher across the nation regarding admissions for concerns of eating disorders. These patients are sicker and fewer went home after medical stabilization,” she emphasized.
“Clinicians should be more aware of the rise in patients presenting with eating disorders at younger ages to their clinics and provide early interventions to prevent severe illness and medical instability,” said Ms. Thew. Clinicians also should be more proactive in managing younger children and adolescents who express mood disorders, disordered eating, or weight loss, given the significant rise in eating disorders and mental health concerns, she said.
Additional research is needed to continue following the rate of eating disorders into 2022, said Ms. Thew. More research is needed on early interventions and recognition of eating disorders for preteens and teens to prevent severe illness, as is research on how the younger patient with an eating disorder may present differently to the primary care doctor or emergency department, she said.
“We may need to study treatment of the younger population, as they may not do as well with admissions into behavioral health facilities,” Ms. Thew added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
Hospital admission for children with eating disorders approximately tripled during the COVID-19 pandemic, based on data from 85 patients.
Eating disorders are common among adolescents and often require hospital admission for nutritional restoration, according to May Shum of Yale University, New Haven, Conn., and colleagues
During the COVID-19 pandemic, the volume of hospital admissions for adolescents with eating disorders has increased, the researchers wrote in a poster presented at the annual meeting of the Pediatric Academic Societies. This increase may be driven both by interruptions in medical care and increased psychological distress, but data on changes in patient characteristics and hospitalization course are lacking, they said.
The researchers reviewed charts from patients with eating disorders admitted to a single center between Jan. 1, 2017, and June 30, 2021. The majority of the patients were female (90.6%), and White (78.8%), had restrictive eating behaviors (97.2%), and had private insurance (80.0%).
Overall, the number of monthly admissions increased from 1.4 before the onset of the pandemic to 3.6 during the pandemic (P < .001).
Length of stay increased significantly from before to during pandemic cases (12.8 days vs. 17.3 days, P = .04) and age younger than 13 years was significantly associated with a longer length of stay (P < .001).
The number of patients for whom psychotropic medications were initiated or changed increased significantly (12.5% vs. 28.3%, P = .04); as did the proportion of patients discharged to partial hospitalization, residential, or inpatient psychiatric treatment rather than discharged home with outpatient therapy (56.2% vs. 75.0%, P = .04).
No significant differences were noted in demographics, comorbidities, admission parameters, EKG abnormalities, electrolyte repletion, or tube feeding.
The study findings were limited by the use of data from a single center. However, the results suggest an increase in severity of hospital admissions that have implications for use of hospital resources, the researchers said.
“In addition to an increase in hospital admissions for eating disorder management during the pandemic, longer inpatient stays of younger children with higher acuity at discharge is an added strain on hospital resources and warrants attention,” they concluded.
Considerations for younger patients
The current study is especially important at this time, Margaret Thew, DNP, FNP-BC, medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee, said in an interview. “There have been reports of the rising numbers in eating disorders, but until research has been conducted, we cannot quantify the volumes,” said Ms. Thew, who was not involved in the study. “There have been many reports of the rise in mental health issues during the pandemic, so it seems accurate that the rate of eating disorders would rise,” she said. “Additionally, from a clinical perspective there seemed to be many younger-age patients with eating disorders presenting to the inpatient units who seemed sicker,” she noted.
Ms. Thew said she was not surprised by the study findings. “Working with adolescents with eating disorders we saw the increased numbers of both hospitalizations and outpatient referrals during the pandemic,” said Ms. Thew. “Length of stay was higher across the nation regarding admissions for concerns of eating disorders. These patients are sicker and fewer went home after medical stabilization,” she emphasized.
“Clinicians should be more aware of the rise in patients presenting with eating disorders at younger ages to their clinics and provide early interventions to prevent severe illness and medical instability,” said Ms. Thew. Clinicians also should be more proactive in managing younger children and adolescents who express mood disorders, disordered eating, or weight loss, given the significant rise in eating disorders and mental health concerns, she said.
Additional research is needed to continue following the rate of eating disorders into 2022, said Ms. Thew. More research is needed on early interventions and recognition of eating disorders for preteens and teens to prevent severe illness, as is research on how the younger patient with an eating disorder may present differently to the primary care doctor or emergency department, she said.
“We may need to study treatment of the younger population, as they may not do as well with admissions into behavioral health facilities,” Ms. Thew added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
Hospital admission for children with eating disorders approximately tripled during the COVID-19 pandemic, based on data from 85 patients.
Eating disorders are common among adolescents and often require hospital admission for nutritional restoration, according to May Shum of Yale University, New Haven, Conn., and colleagues
During the COVID-19 pandemic, the volume of hospital admissions for adolescents with eating disorders has increased, the researchers wrote in a poster presented at the annual meeting of the Pediatric Academic Societies. This increase may be driven both by interruptions in medical care and increased psychological distress, but data on changes in patient characteristics and hospitalization course are lacking, they said.
The researchers reviewed charts from patients with eating disorders admitted to a single center between Jan. 1, 2017, and June 30, 2021. The majority of the patients were female (90.6%), and White (78.8%), had restrictive eating behaviors (97.2%), and had private insurance (80.0%).
Overall, the number of monthly admissions increased from 1.4 before the onset of the pandemic to 3.6 during the pandemic (P < .001).
Length of stay increased significantly from before to during pandemic cases (12.8 days vs. 17.3 days, P = .04) and age younger than 13 years was significantly associated with a longer length of stay (P < .001).
The number of patients for whom psychotropic medications were initiated or changed increased significantly (12.5% vs. 28.3%, P = .04); as did the proportion of patients discharged to partial hospitalization, residential, or inpatient psychiatric treatment rather than discharged home with outpatient therapy (56.2% vs. 75.0%, P = .04).
No significant differences were noted in demographics, comorbidities, admission parameters, EKG abnormalities, electrolyte repletion, or tube feeding.
The study findings were limited by the use of data from a single center. However, the results suggest an increase in severity of hospital admissions that have implications for use of hospital resources, the researchers said.
“In addition to an increase in hospital admissions for eating disorder management during the pandemic, longer inpatient stays of younger children with higher acuity at discharge is an added strain on hospital resources and warrants attention,” they concluded.
Considerations for younger patients
The current study is especially important at this time, Margaret Thew, DNP, FNP-BC, medical director of the department of adolescent medicine at Children’s Wisconsin in Milwaukee, said in an interview. “There have been reports of the rising numbers in eating disorders, but until research has been conducted, we cannot quantify the volumes,” said Ms. Thew, who was not involved in the study. “There have been many reports of the rise in mental health issues during the pandemic, so it seems accurate that the rate of eating disorders would rise,” she said. “Additionally, from a clinical perspective there seemed to be many younger-age patients with eating disorders presenting to the inpatient units who seemed sicker,” she noted.
Ms. Thew said she was not surprised by the study findings. “Working with adolescents with eating disorders we saw the increased numbers of both hospitalizations and outpatient referrals during the pandemic,” said Ms. Thew. “Length of stay was higher across the nation regarding admissions for concerns of eating disorders. These patients are sicker and fewer went home after medical stabilization,” she emphasized.
“Clinicians should be more aware of the rise in patients presenting with eating disorders at younger ages to their clinics and provide early interventions to prevent severe illness and medical instability,” said Ms. Thew. Clinicians also should be more proactive in managing younger children and adolescents who express mood disorders, disordered eating, or weight loss, given the significant rise in eating disorders and mental health concerns, she said.
Additional research is needed to continue following the rate of eating disorders into 2022, said Ms. Thew. More research is needed on early interventions and recognition of eating disorders for preteens and teens to prevent severe illness, as is research on how the younger patient with an eating disorder may present differently to the primary care doctor or emergency department, she said.
“We may need to study treatment of the younger population, as they may not do as well with admissions into behavioral health facilities,” Ms. Thew added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
FROM PAS 2022
Water, water everywhere leads to leaner students
Elementary schools that provide easy access to drinking water and education about its benefits may help their students maintain a healthy weight, a new study found.
Researchers examined the health and drinking habits of 1,249 children in 26 low-income, ethnically diverse elementary schools in the San Francisco Bay Area. In half of the schools, water stations were placed throughout, along with signs explaining why water is healthier than sugary drinks. In addition, assemblies were held explaining the advantages of water over sugary drinks.
That simple message seemed to have had an outsized effect. Schools with water stations had significantly fewer overweight students than the other schools by the end of the 15-month study, according to Anisha Patel, MD, MSPH, MSHS, associate professor of pediatrics at Stanford (Calif.) University, who will be presenting the findings at the Pediatric Academic Societies (PAS) 2022 Meeting, Denver.
“Sugar-sweetened beverages are a huge contributor to obesity,” Dr. Patel told this news organization. “This provides a key strategy for schools to adopt, and the time is right for this type of work – in the pandemic period we’ve seen significant increases in obesity. Investments like this could help stem that.”
According to the U.S. Centers for Disease Control and Prevention, 14.4 million children aged 2-19 years in the United States – about 19% of all kids in that age range – were obese in 2017-2018. The agency said the rate of increase in body mass index among this group nearly doubled during the COVID-19 pandemic.
Children with obesity are at higher risk for chronic health problems, including diabetes, heart disease, depression, and high blood pressure.
Dr. Patel’s study, funded by the National Institutes of Health, was the culmination of a decade of interest in the area, she said.
Water stations and compostable or recyclable cups were placed in high-traffic areas of the schools, including playgrounds and cafeterias. The water was tested for lead, and if needed, researchers worked with school districts to remediate, Dr. Patel said in an interview.
The intervention included a kickoff assembly about the health benefits of water intake, and students who were seen drinking water with their lunches were given small prizes.
The researchers assessed body weight, height, and dietary intake of students throughout the study, including their consumption of water, sodas, fruit juices, and flavored and unflavored milk.
Promoting water didn’t lead to magical weight loss. At the start of the study, 49.5% of students in the intervention group were overweight – a figure that nudged up to 49.8% by the end of the study. In the control group, however, 47.7% of students began the study overweight – a number that climbed to 51.4% by the end of the trial (odds ratio, 0.3; P = .01), according to the researchers, who credited the increase to the lack of emphasis on opting for water over sweetened drinks.
“We were very excited the effect sizes were nearly double previous studies, which was great news,” Dr. Patel said.
Water intake began to decline at about the 15-month mark, signaling the need for more long-term, consistent education and incentive to foster lasting habits, Dr. Patel said.
The researchers noted that they were unable to collect data from eight of the target schools because of the pandemic. In addition, the study focused on schools with heavily Latino student populations, so the results might not be generalizable to other communities, they said.
Angie Cradock, a principal research scientist at the Harvard T. H. Chan School of Public Health, Boston, said the study “offers an important and practical strategy to promote student health.”
Ms. Cradock serves as deputy director of the Harvard Prevention Research Center on Nutrition and Physical Activity, which focuses on improving population nutrition, increasing physical activity, reducing obesity and chronic disease, and improving health equity.
Dr. Patel and her colleagues’ three-pronged approach of using education, promotion, and accessibility to increase student interest in drinking water could be employed at countless other schools, said Ms. Cradock, who was not involved in the study.
“Negative perceptions of tap water and drinking fountains are common,” she said. “Not all students have access to safe and appealing drinking water while at school, and this strategy seems like a recipe for success.”
Dr. Patel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Elementary schools that provide easy access to drinking water and education about its benefits may help their students maintain a healthy weight, a new study found.
Researchers examined the health and drinking habits of 1,249 children in 26 low-income, ethnically diverse elementary schools in the San Francisco Bay Area. In half of the schools, water stations were placed throughout, along with signs explaining why water is healthier than sugary drinks. In addition, assemblies were held explaining the advantages of water over sugary drinks.
That simple message seemed to have had an outsized effect. Schools with water stations had significantly fewer overweight students than the other schools by the end of the 15-month study, according to Anisha Patel, MD, MSPH, MSHS, associate professor of pediatrics at Stanford (Calif.) University, who will be presenting the findings at the Pediatric Academic Societies (PAS) 2022 Meeting, Denver.
“Sugar-sweetened beverages are a huge contributor to obesity,” Dr. Patel told this news organization. “This provides a key strategy for schools to adopt, and the time is right for this type of work – in the pandemic period we’ve seen significant increases in obesity. Investments like this could help stem that.”
According to the U.S. Centers for Disease Control and Prevention, 14.4 million children aged 2-19 years in the United States – about 19% of all kids in that age range – were obese in 2017-2018. The agency said the rate of increase in body mass index among this group nearly doubled during the COVID-19 pandemic.
Children with obesity are at higher risk for chronic health problems, including diabetes, heart disease, depression, and high blood pressure.
Dr. Patel’s study, funded by the National Institutes of Health, was the culmination of a decade of interest in the area, she said.
Water stations and compostable or recyclable cups were placed in high-traffic areas of the schools, including playgrounds and cafeterias. The water was tested for lead, and if needed, researchers worked with school districts to remediate, Dr. Patel said in an interview.
The intervention included a kickoff assembly about the health benefits of water intake, and students who were seen drinking water with their lunches were given small prizes.
The researchers assessed body weight, height, and dietary intake of students throughout the study, including their consumption of water, sodas, fruit juices, and flavored and unflavored milk.
Promoting water didn’t lead to magical weight loss. At the start of the study, 49.5% of students in the intervention group were overweight – a figure that nudged up to 49.8% by the end of the study. In the control group, however, 47.7% of students began the study overweight – a number that climbed to 51.4% by the end of the trial (odds ratio, 0.3; P = .01), according to the researchers, who credited the increase to the lack of emphasis on opting for water over sweetened drinks.
“We were very excited the effect sizes were nearly double previous studies, which was great news,” Dr. Patel said.
Water intake began to decline at about the 15-month mark, signaling the need for more long-term, consistent education and incentive to foster lasting habits, Dr. Patel said.
The researchers noted that they were unable to collect data from eight of the target schools because of the pandemic. In addition, the study focused on schools with heavily Latino student populations, so the results might not be generalizable to other communities, they said.
Angie Cradock, a principal research scientist at the Harvard T. H. Chan School of Public Health, Boston, said the study “offers an important and practical strategy to promote student health.”
Ms. Cradock serves as deputy director of the Harvard Prevention Research Center on Nutrition and Physical Activity, which focuses on improving population nutrition, increasing physical activity, reducing obesity and chronic disease, and improving health equity.
Dr. Patel and her colleagues’ three-pronged approach of using education, promotion, and accessibility to increase student interest in drinking water could be employed at countless other schools, said Ms. Cradock, who was not involved in the study.
“Negative perceptions of tap water and drinking fountains are common,” she said. “Not all students have access to safe and appealing drinking water while at school, and this strategy seems like a recipe for success.”
Dr. Patel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Elementary schools that provide easy access to drinking water and education about its benefits may help their students maintain a healthy weight, a new study found.
Researchers examined the health and drinking habits of 1,249 children in 26 low-income, ethnically diverse elementary schools in the San Francisco Bay Area. In half of the schools, water stations were placed throughout, along with signs explaining why water is healthier than sugary drinks. In addition, assemblies were held explaining the advantages of water over sugary drinks.
That simple message seemed to have had an outsized effect. Schools with water stations had significantly fewer overweight students than the other schools by the end of the 15-month study, according to Anisha Patel, MD, MSPH, MSHS, associate professor of pediatrics at Stanford (Calif.) University, who will be presenting the findings at the Pediatric Academic Societies (PAS) 2022 Meeting, Denver.
“Sugar-sweetened beverages are a huge contributor to obesity,” Dr. Patel told this news organization. “This provides a key strategy for schools to adopt, and the time is right for this type of work – in the pandemic period we’ve seen significant increases in obesity. Investments like this could help stem that.”
According to the U.S. Centers for Disease Control and Prevention, 14.4 million children aged 2-19 years in the United States – about 19% of all kids in that age range – were obese in 2017-2018. The agency said the rate of increase in body mass index among this group nearly doubled during the COVID-19 pandemic.
Children with obesity are at higher risk for chronic health problems, including diabetes, heart disease, depression, and high blood pressure.
Dr. Patel’s study, funded by the National Institutes of Health, was the culmination of a decade of interest in the area, she said.
Water stations and compostable or recyclable cups were placed in high-traffic areas of the schools, including playgrounds and cafeterias. The water was tested for lead, and if needed, researchers worked with school districts to remediate, Dr. Patel said in an interview.
The intervention included a kickoff assembly about the health benefits of water intake, and students who were seen drinking water with their lunches were given small prizes.
The researchers assessed body weight, height, and dietary intake of students throughout the study, including their consumption of water, sodas, fruit juices, and flavored and unflavored milk.
Promoting water didn’t lead to magical weight loss. At the start of the study, 49.5% of students in the intervention group were overweight – a figure that nudged up to 49.8% by the end of the study. In the control group, however, 47.7% of students began the study overweight – a number that climbed to 51.4% by the end of the trial (odds ratio, 0.3; P = .01), according to the researchers, who credited the increase to the lack of emphasis on opting for water over sweetened drinks.
“We were very excited the effect sizes were nearly double previous studies, which was great news,” Dr. Patel said.
Water intake began to decline at about the 15-month mark, signaling the need for more long-term, consistent education and incentive to foster lasting habits, Dr. Patel said.
The researchers noted that they were unable to collect data from eight of the target schools because of the pandemic. In addition, the study focused on schools with heavily Latino student populations, so the results might not be generalizable to other communities, they said.
Angie Cradock, a principal research scientist at the Harvard T. H. Chan School of Public Health, Boston, said the study “offers an important and practical strategy to promote student health.”
Ms. Cradock serves as deputy director of the Harvard Prevention Research Center on Nutrition and Physical Activity, which focuses on improving population nutrition, increasing physical activity, reducing obesity and chronic disease, and improving health equity.
Dr. Patel and her colleagues’ three-pronged approach of using education, promotion, and accessibility to increase student interest in drinking water could be employed at countless other schools, said Ms. Cradock, who was not involved in the study.
“Negative perceptions of tap water and drinking fountains are common,” she said. “Not all students have access to safe and appealing drinking water while at school, and this strategy seems like a recipe for success.”
Dr. Patel reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Substance use disorders increase risk for death from COVID-19
MADRID, Spain – – compared with the general population. Such are the findings of a line of research led by Mexican psychiatrist Nora Volkow, MD, director of the U.S. National Institute on Drug Abuse (NIDA).
A pioneer in the use of brain imaging to investigate how substance use affects brain functions and one of Time magazine’s “Top 100 People Who Shape Our World,” she led the Inaugural Conference at the XXXI Congress of the Spanish Society of Clinical Pharmacology “Drugs and Actions During the Pandemic.” Dr. Volkow spoke about the effects that the current health crisis has had on drug use and the social challenges that arose from lockdowns. She also presented and discussed the results of studies being conducted at NIDA that “are aimed at reviewing what we’ve learned and what the consequences of COVID-19 have been with respect to substance abuse disorder.”
As Dr. Volkow pointed out, drugs affect much more than just the brain. “In particular, the heart, the lungs, the immune system – all of these are significantly harmed by substances like tobacco, alcohol, cocaine, and methamphetamine. This is why, since the beginning of the pandemic, we’ve been worried about seeing what consequences SARS-CoV-2 was going to have on users of these substances, especially in light of the great toll this disease takes on the respiratory system and the vascular system.”
Pulmonary ‘predisposition’ and race
Dr. Volkow and her team launched several studies to get a more thorough understanding of the link between substance abuse disorders and poor COVID-19 prognoses. One of them was based on analyses from electronic health records in the United States. The purpose was to determine COVID-19 risk and outcomes in patients based on the type of use disorder (for example, alcohol, opioid, cannabis, cocaine).
“The results showed that regardless of the drug type, all users of these substances had both a higher risk of being infected by COVID-19 and a higher death rate in comparison with the rest of the population,” said Dr. Volkow. “This surprised us, because there’s no evidence that drugs themselves make the virus more infectious. However, what the results did clearly indicate to us was that using these substances was associated with behavior that put these individuals at a greater risk for infection,” Dr. Volkow explained.
“In addition,” she continued, “using, for example, tobacco or cannabis causes inflammation in the lungs. It seems that, as a result, they end up being more vulnerable to infection by COVID. And this has consequences, above all, in terms of mortality.”
Another finding was that, among patients with substance use disorders, race had the largest effect on COVID risk. “From the very start, we saw that, compared with White individuals, Black individuals showed a much higher risk of not only getting COVID, but also dying from it,” said Dr. Volkow. “Therefore, on the one hand, our data show that drug users are more vulnerable to COVID-19 and, on the other hand, they reflect that within this group, Black individuals are even more vulnerable.”
In her presentation, Dr. Volkow drew particular attention to the impact that social surroundings have on these patients and the decisive role they played in terms of vulnerability. “It’s a very complex issue, what with the various factors at play: family, social environment. ... A person living in an at-risk situation can more easily get drugs or even prescription medication, which can also be abused.”
The psychiatrist stressed that when it comes to addictive disorders (and related questions such as prevention, treatment, and social reintegration), one of the most crucial factors has to do with the individual’s social support structures. “The studies also brought to light the role that social interaction has as an inhibitory factor with regard to drug use,” said Dr. Volkow. “And indeed, adequate adherence to treatment requires that the necessary support systems be maintained.”
In the context of the pandemic, this social aspect was also key, especially concerning the high death rate among substance use disorder patients with COVID-19. “There are very significant social determinants, such as the stigma associated with these groups – a stigma that makes these individuals more likely to hesitate to seek out treatment for diseases that may be starting to take hold, in this case COVID-19.”
On that note, Dr. Volkow emphasized the importance of treating drug addicts as though they had a chronic disease in need of treatment. “In fact, the prevalence of pathologies such as hypertension, diabetes, cancer, and dementia is much higher in these individuals than in the general population,” she said. “However, this isn’t widely known. The data reflect that not only the prevalence of these diseases, but also the severity of the symptoms, is higher, and this has a lot to do with these individuals’ reticence when it comes to reaching out for medical care. Added to that are the effects of their economic situation and other factors, such as stress (which can trigger a relapse), lack of ready access to medications, and limited access to community support or other sources of social connection.”
Opioids and COVID-19
As for drug use during the pandemic, Dr. Volkow provided context by mentioning that in the United States, the experts and authorities have spent two decades fighting the epidemic of opioid-related drug overdoses, which has caused many deaths. “And on top of this epidemic – one that we still haven’t been able to get control of – there’s the situation brought about by COVID-19. So, we had to see the consequences of a pandemic crossing paths with an epidemic.”
The United States’s epidemic of overdose deaths started with the use of opioid painkillers, medications which are overprescribed. Another issue that the United States faces is that many drugs are contaminated with fentanyl. This contamination has caused an increase in deaths.
“In the United States, fentanyl is everywhere,” said Dr. Volkow. “And what’s more concerning: almost a third of this fentanyl comes in pills that are sold as benzodiazepines. With this comes a high risk for overdose. In line with this, we saw overdose deaths among adolescents nearly double in 1 year, an increase which is likely related to these contaminated pills. It’s a risk that’s just below the surface. We’ve got to be vigilant, because this phenomenon is expected to eventually spread to Europe. After all, these pills are very cheap, hence the rapid increase in their use.”
To provide figures on drug use and overdose deaths since the beginning of the pandemic, Dr. Volkow referred to COVID-19 data provided by the National Center for Health Statistics (NCHS) at the U.S. Centers for Disease Control and Prevention. The data indicate that of the 70,630 drug overdose deaths that occurred in 2019, 49,860 involved opioids (whether prescribed or illicit). “And these numbers have continued to rise, so much so that the current situation can be classified as catastrophic – because this increase has been even greater during the pandemic due to the rise in the use of all drugs,” said Dr. Volkow.
Dr. Volkow referred to an NCHS study that looked at the period between September 2020 and September 2021, finding a 15.9% increase in the number of drug overdose deaths. A breakdown of these data shows that the highest percentage corresponds to deaths from “other psychostimulants,” primarily methamphetamines (35.7%). This category is followed by deaths involving synthetic opioids, mostly illicit fentanyl (25.8%), and deaths from cocaine (13.4%).
“These figures indicate that, for the first time in history, the United States had over 100,000 overdose deaths in 1 year,” said Dr. Volkow. “This is something that has never happened. We can only infer that the pandemic had a hand in making the overdose crisis even worse than it already was.”
As Dr. Volkow explained, policies related to handling overdoses and prescribing medications have been changed in the context of COVID-19. Addiction treatment consequently has been provided through a larger number of telehealth services, and measures such as greater access to treatment for comorbid conditions, expanded access to behavioral treatments, and the establishment of mental health hotlines have been undertaken.
Children’s cognitive development
Dr. Volkow also spoke about another of NIDA’s current subjects of research: The role that damage or compromise from drugs has on the neural circuits involved in reinforcement systems. “It’s important that we make people aware of the significance of what’s at play there, because the greatest damage that can be inflicted on the brain comes from using any type of drug during adolescence. In these cases, the likelihood of having an addictive disorder as an adult significantly increases.”
Within this framework, her team has also investigated the impact of the pandemic on the cognitive development of infants under 1 year of age. One of these studies was a pilot program in which pregnant women participated. “We found that children born during the pandemic had lower cognitive development: n = 112 versus n = 554 of those born before January 2019.”
“None of the mothers or children in the study had been infected with SARS-CoV-2,” Dr. Volkow explained. “But the results clearly reflect the negative effect of the circumstances brought about by the pandemic, especially the high level of stress, the isolation, and the lack of stimuli. Another study, currently in preprint, is based on imaging. It analyzed the impact on myelination in children not exposed to COVID-19 but born during the pandemic, compared with pre-pandemic infants. The data showed significantly reduced areas of myelin development (P < .05) in those born after 2019. And the researchers didn’t find significant differences in gestation duration or birth weight.”
The longitudinal characteristics of these studies will let us see whether a change in these individuals’ social circumstances over time also brings to light cognitive changes, even the recovery of lost or underdeveloped cognitive processes, Dr. Volkow concluded.
Dr. Volkow has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MADRID, Spain – – compared with the general population. Such are the findings of a line of research led by Mexican psychiatrist Nora Volkow, MD, director of the U.S. National Institute on Drug Abuse (NIDA).
A pioneer in the use of brain imaging to investigate how substance use affects brain functions and one of Time magazine’s “Top 100 People Who Shape Our World,” she led the Inaugural Conference at the XXXI Congress of the Spanish Society of Clinical Pharmacology “Drugs and Actions During the Pandemic.” Dr. Volkow spoke about the effects that the current health crisis has had on drug use and the social challenges that arose from lockdowns. She also presented and discussed the results of studies being conducted at NIDA that “are aimed at reviewing what we’ve learned and what the consequences of COVID-19 have been with respect to substance abuse disorder.”
As Dr. Volkow pointed out, drugs affect much more than just the brain. “In particular, the heart, the lungs, the immune system – all of these are significantly harmed by substances like tobacco, alcohol, cocaine, and methamphetamine. This is why, since the beginning of the pandemic, we’ve been worried about seeing what consequences SARS-CoV-2 was going to have on users of these substances, especially in light of the great toll this disease takes on the respiratory system and the vascular system.”
Pulmonary ‘predisposition’ and race
Dr. Volkow and her team launched several studies to get a more thorough understanding of the link between substance abuse disorders and poor COVID-19 prognoses. One of them was based on analyses from electronic health records in the United States. The purpose was to determine COVID-19 risk and outcomes in patients based on the type of use disorder (for example, alcohol, opioid, cannabis, cocaine).
“The results showed that regardless of the drug type, all users of these substances had both a higher risk of being infected by COVID-19 and a higher death rate in comparison with the rest of the population,” said Dr. Volkow. “This surprised us, because there’s no evidence that drugs themselves make the virus more infectious. However, what the results did clearly indicate to us was that using these substances was associated with behavior that put these individuals at a greater risk for infection,” Dr. Volkow explained.
“In addition,” she continued, “using, for example, tobacco or cannabis causes inflammation in the lungs. It seems that, as a result, they end up being more vulnerable to infection by COVID. And this has consequences, above all, in terms of mortality.”
Another finding was that, among patients with substance use disorders, race had the largest effect on COVID risk. “From the very start, we saw that, compared with White individuals, Black individuals showed a much higher risk of not only getting COVID, but also dying from it,” said Dr. Volkow. “Therefore, on the one hand, our data show that drug users are more vulnerable to COVID-19 and, on the other hand, they reflect that within this group, Black individuals are even more vulnerable.”
In her presentation, Dr. Volkow drew particular attention to the impact that social surroundings have on these patients and the decisive role they played in terms of vulnerability. “It’s a very complex issue, what with the various factors at play: family, social environment. ... A person living in an at-risk situation can more easily get drugs or even prescription medication, which can also be abused.”
The psychiatrist stressed that when it comes to addictive disorders (and related questions such as prevention, treatment, and social reintegration), one of the most crucial factors has to do with the individual’s social support structures. “The studies also brought to light the role that social interaction has as an inhibitory factor with regard to drug use,” said Dr. Volkow. “And indeed, adequate adherence to treatment requires that the necessary support systems be maintained.”
In the context of the pandemic, this social aspect was also key, especially concerning the high death rate among substance use disorder patients with COVID-19. “There are very significant social determinants, such as the stigma associated with these groups – a stigma that makes these individuals more likely to hesitate to seek out treatment for diseases that may be starting to take hold, in this case COVID-19.”
On that note, Dr. Volkow emphasized the importance of treating drug addicts as though they had a chronic disease in need of treatment. “In fact, the prevalence of pathologies such as hypertension, diabetes, cancer, and dementia is much higher in these individuals than in the general population,” she said. “However, this isn’t widely known. The data reflect that not only the prevalence of these diseases, but also the severity of the symptoms, is higher, and this has a lot to do with these individuals’ reticence when it comes to reaching out for medical care. Added to that are the effects of their economic situation and other factors, such as stress (which can trigger a relapse), lack of ready access to medications, and limited access to community support or other sources of social connection.”
Opioids and COVID-19
As for drug use during the pandemic, Dr. Volkow provided context by mentioning that in the United States, the experts and authorities have spent two decades fighting the epidemic of opioid-related drug overdoses, which has caused many deaths. “And on top of this epidemic – one that we still haven’t been able to get control of – there’s the situation brought about by COVID-19. So, we had to see the consequences of a pandemic crossing paths with an epidemic.”
The United States’s epidemic of overdose deaths started with the use of opioid painkillers, medications which are overprescribed. Another issue that the United States faces is that many drugs are contaminated with fentanyl. This contamination has caused an increase in deaths.
“In the United States, fentanyl is everywhere,” said Dr. Volkow. “And what’s more concerning: almost a third of this fentanyl comes in pills that are sold as benzodiazepines. With this comes a high risk for overdose. In line with this, we saw overdose deaths among adolescents nearly double in 1 year, an increase which is likely related to these contaminated pills. It’s a risk that’s just below the surface. We’ve got to be vigilant, because this phenomenon is expected to eventually spread to Europe. After all, these pills are very cheap, hence the rapid increase in their use.”
To provide figures on drug use and overdose deaths since the beginning of the pandemic, Dr. Volkow referred to COVID-19 data provided by the National Center for Health Statistics (NCHS) at the U.S. Centers for Disease Control and Prevention. The data indicate that of the 70,630 drug overdose deaths that occurred in 2019, 49,860 involved opioids (whether prescribed or illicit). “And these numbers have continued to rise, so much so that the current situation can be classified as catastrophic – because this increase has been even greater during the pandemic due to the rise in the use of all drugs,” said Dr. Volkow.
Dr. Volkow referred to an NCHS study that looked at the period between September 2020 and September 2021, finding a 15.9% increase in the number of drug overdose deaths. A breakdown of these data shows that the highest percentage corresponds to deaths from “other psychostimulants,” primarily methamphetamines (35.7%). This category is followed by deaths involving synthetic opioids, mostly illicit fentanyl (25.8%), and deaths from cocaine (13.4%).
“These figures indicate that, for the first time in history, the United States had over 100,000 overdose deaths in 1 year,” said Dr. Volkow. “This is something that has never happened. We can only infer that the pandemic had a hand in making the overdose crisis even worse than it already was.”
As Dr. Volkow explained, policies related to handling overdoses and prescribing medications have been changed in the context of COVID-19. Addiction treatment consequently has been provided through a larger number of telehealth services, and measures such as greater access to treatment for comorbid conditions, expanded access to behavioral treatments, and the establishment of mental health hotlines have been undertaken.
Children’s cognitive development
Dr. Volkow also spoke about another of NIDA’s current subjects of research: The role that damage or compromise from drugs has on the neural circuits involved in reinforcement systems. “It’s important that we make people aware of the significance of what’s at play there, because the greatest damage that can be inflicted on the brain comes from using any type of drug during adolescence. In these cases, the likelihood of having an addictive disorder as an adult significantly increases.”
Within this framework, her team has also investigated the impact of the pandemic on the cognitive development of infants under 1 year of age. One of these studies was a pilot program in which pregnant women participated. “We found that children born during the pandemic had lower cognitive development: n = 112 versus n = 554 of those born before January 2019.”
“None of the mothers or children in the study had been infected with SARS-CoV-2,” Dr. Volkow explained. “But the results clearly reflect the negative effect of the circumstances brought about by the pandemic, especially the high level of stress, the isolation, and the lack of stimuli. Another study, currently in preprint, is based on imaging. It analyzed the impact on myelination in children not exposed to COVID-19 but born during the pandemic, compared with pre-pandemic infants. The data showed significantly reduced areas of myelin development (P < .05) in those born after 2019. And the researchers didn’t find significant differences in gestation duration or birth weight.”
The longitudinal characteristics of these studies will let us see whether a change in these individuals’ social circumstances over time also brings to light cognitive changes, even the recovery of lost or underdeveloped cognitive processes, Dr. Volkow concluded.
Dr. Volkow has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
MADRID, Spain – – compared with the general population. Such are the findings of a line of research led by Mexican psychiatrist Nora Volkow, MD, director of the U.S. National Institute on Drug Abuse (NIDA).
A pioneer in the use of brain imaging to investigate how substance use affects brain functions and one of Time magazine’s “Top 100 People Who Shape Our World,” she led the Inaugural Conference at the XXXI Congress of the Spanish Society of Clinical Pharmacology “Drugs and Actions During the Pandemic.” Dr. Volkow spoke about the effects that the current health crisis has had on drug use and the social challenges that arose from lockdowns. She also presented and discussed the results of studies being conducted at NIDA that “are aimed at reviewing what we’ve learned and what the consequences of COVID-19 have been with respect to substance abuse disorder.”
As Dr. Volkow pointed out, drugs affect much more than just the brain. “In particular, the heart, the lungs, the immune system – all of these are significantly harmed by substances like tobacco, alcohol, cocaine, and methamphetamine. This is why, since the beginning of the pandemic, we’ve been worried about seeing what consequences SARS-CoV-2 was going to have on users of these substances, especially in light of the great toll this disease takes on the respiratory system and the vascular system.”
Pulmonary ‘predisposition’ and race
Dr. Volkow and her team launched several studies to get a more thorough understanding of the link between substance abuse disorders and poor COVID-19 prognoses. One of them was based on analyses from electronic health records in the United States. The purpose was to determine COVID-19 risk and outcomes in patients based on the type of use disorder (for example, alcohol, opioid, cannabis, cocaine).
“The results showed that regardless of the drug type, all users of these substances had both a higher risk of being infected by COVID-19 and a higher death rate in comparison with the rest of the population,” said Dr. Volkow. “This surprised us, because there’s no evidence that drugs themselves make the virus more infectious. However, what the results did clearly indicate to us was that using these substances was associated with behavior that put these individuals at a greater risk for infection,” Dr. Volkow explained.
“In addition,” she continued, “using, for example, tobacco or cannabis causes inflammation in the lungs. It seems that, as a result, they end up being more vulnerable to infection by COVID. And this has consequences, above all, in terms of mortality.”
Another finding was that, among patients with substance use disorders, race had the largest effect on COVID risk. “From the very start, we saw that, compared with White individuals, Black individuals showed a much higher risk of not only getting COVID, but also dying from it,” said Dr. Volkow. “Therefore, on the one hand, our data show that drug users are more vulnerable to COVID-19 and, on the other hand, they reflect that within this group, Black individuals are even more vulnerable.”
In her presentation, Dr. Volkow drew particular attention to the impact that social surroundings have on these patients and the decisive role they played in terms of vulnerability. “It’s a very complex issue, what with the various factors at play: family, social environment. ... A person living in an at-risk situation can more easily get drugs or even prescription medication, which can also be abused.”
The psychiatrist stressed that when it comes to addictive disorders (and related questions such as prevention, treatment, and social reintegration), one of the most crucial factors has to do with the individual’s social support structures. “The studies also brought to light the role that social interaction has as an inhibitory factor with regard to drug use,” said Dr. Volkow. “And indeed, adequate adherence to treatment requires that the necessary support systems be maintained.”
In the context of the pandemic, this social aspect was also key, especially concerning the high death rate among substance use disorder patients with COVID-19. “There are very significant social determinants, such as the stigma associated with these groups – a stigma that makes these individuals more likely to hesitate to seek out treatment for diseases that may be starting to take hold, in this case COVID-19.”
On that note, Dr. Volkow emphasized the importance of treating drug addicts as though they had a chronic disease in need of treatment. “In fact, the prevalence of pathologies such as hypertension, diabetes, cancer, and dementia is much higher in these individuals than in the general population,” she said. “However, this isn’t widely known. The data reflect that not only the prevalence of these diseases, but also the severity of the symptoms, is higher, and this has a lot to do with these individuals’ reticence when it comes to reaching out for medical care. Added to that are the effects of their economic situation and other factors, such as stress (which can trigger a relapse), lack of ready access to medications, and limited access to community support or other sources of social connection.”
Opioids and COVID-19
As for drug use during the pandemic, Dr. Volkow provided context by mentioning that in the United States, the experts and authorities have spent two decades fighting the epidemic of opioid-related drug overdoses, which has caused many deaths. “And on top of this epidemic – one that we still haven’t been able to get control of – there’s the situation brought about by COVID-19. So, we had to see the consequences of a pandemic crossing paths with an epidemic.”
The United States’s epidemic of overdose deaths started with the use of opioid painkillers, medications which are overprescribed. Another issue that the United States faces is that many drugs are contaminated with fentanyl. This contamination has caused an increase in deaths.
“In the United States, fentanyl is everywhere,” said Dr. Volkow. “And what’s more concerning: almost a third of this fentanyl comes in pills that are sold as benzodiazepines. With this comes a high risk for overdose. In line with this, we saw overdose deaths among adolescents nearly double in 1 year, an increase which is likely related to these contaminated pills. It’s a risk that’s just below the surface. We’ve got to be vigilant, because this phenomenon is expected to eventually spread to Europe. After all, these pills are very cheap, hence the rapid increase in their use.”
To provide figures on drug use and overdose deaths since the beginning of the pandemic, Dr. Volkow referred to COVID-19 data provided by the National Center for Health Statistics (NCHS) at the U.S. Centers for Disease Control and Prevention. The data indicate that of the 70,630 drug overdose deaths that occurred in 2019, 49,860 involved opioids (whether prescribed or illicit). “And these numbers have continued to rise, so much so that the current situation can be classified as catastrophic – because this increase has been even greater during the pandemic due to the rise in the use of all drugs,” said Dr. Volkow.
Dr. Volkow referred to an NCHS study that looked at the period between September 2020 and September 2021, finding a 15.9% increase in the number of drug overdose deaths. A breakdown of these data shows that the highest percentage corresponds to deaths from “other psychostimulants,” primarily methamphetamines (35.7%). This category is followed by deaths involving synthetic opioids, mostly illicit fentanyl (25.8%), and deaths from cocaine (13.4%).
“These figures indicate that, for the first time in history, the United States had over 100,000 overdose deaths in 1 year,” said Dr. Volkow. “This is something that has never happened. We can only infer that the pandemic had a hand in making the overdose crisis even worse than it already was.”
As Dr. Volkow explained, policies related to handling overdoses and prescribing medications have been changed in the context of COVID-19. Addiction treatment consequently has been provided through a larger number of telehealth services, and measures such as greater access to treatment for comorbid conditions, expanded access to behavioral treatments, and the establishment of mental health hotlines have been undertaken.
Children’s cognitive development
Dr. Volkow also spoke about another of NIDA’s current subjects of research: The role that damage or compromise from drugs has on the neural circuits involved in reinforcement systems. “It’s important that we make people aware of the significance of what’s at play there, because the greatest damage that can be inflicted on the brain comes from using any type of drug during adolescence. In these cases, the likelihood of having an addictive disorder as an adult significantly increases.”
Within this framework, her team has also investigated the impact of the pandemic on the cognitive development of infants under 1 year of age. One of these studies was a pilot program in which pregnant women participated. “We found that children born during the pandemic had lower cognitive development: n = 112 versus n = 554 of those born before January 2019.”
“None of the mothers or children in the study had been infected with SARS-CoV-2,” Dr. Volkow explained. “But the results clearly reflect the negative effect of the circumstances brought about by the pandemic, especially the high level of stress, the isolation, and the lack of stimuli. Another study, currently in preprint, is based on imaging. It analyzed the impact on myelination in children not exposed to COVID-19 but born during the pandemic, compared with pre-pandemic infants. The data showed significantly reduced areas of myelin development (P < .05) in those born after 2019. And the researchers didn’t find significant differences in gestation duration or birth weight.”
The longitudinal characteristics of these studies will let us see whether a change in these individuals’ social circumstances over time also brings to light cognitive changes, even the recovery of lost or underdeveloped cognitive processes, Dr. Volkow concluded.
Dr. Volkow has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNUAL MEETING OF SPANISH SOCIETY OF CLINICAL PHARMACOLOGY
Wearable sensors deemed reliable for home gait assessment in knee OA
Remote gait assessment in people with knee osteoarthritis using wearable sensors appears reliable but yields results slightly different from those achieved in the laboratory, researchers from Boston University have found.
As reported at the OARSI 2022 World Congress, there was “good to excellent reliability” in repeated measures collected by patients at home while being instructed via video teleconferencing.
Agreement was “moderate to excellent” when the findings were compared with those recorded in the lab, Michael J. Rose of Boston University reported at the congress, sponsored by the Osteoarthritis Research Society International.
“People walked faster and stood up faster in the lab,” Mr. Rose said. “Later we found that the difference in gait speed was statistically significant between the lab and home environment.”
This has been suggested previously and implies that data collected at home may have “greater ecological validity,” he observed.
Accelerated adoption of telehealth
Assessing how well someone walks or can stand from a seated position are well known and important assessments in knee OA, but these have but have traditionally only been done in large and expensive gait labs, Mr. Rose said.
Wearable technologies, such as the ones used in the study he presented, could help move these assessments out into the community. This is particularly timely considering the increased adoption of telehealth practices during the COVID-19 pandemic.
To look at the reliability measurements obtained via wearable sensors versus lab assessments, Mr. Rose and associates set up a substudy within a larger ongoing, single-arm trial looking at the use of digital assessments to measure the efficacy of an exercise intervention in reducing knee pain and improving knee function.
For inclusion in the main trial (n = 60), and hence the substudy (n = 20), participants had to have physician-diagnosed knee OA, be 50 years of age or older, have a body mass index of 40 kg/m2 or lower, be able to walk at for a least 20 minutes, and have a score of three or higher on the Knee Injury and Osteoarthritis Outcome Score pain subscale for weight-bearing items.
Acceptance of in-lab versus home testing
The substudy participants (mean age, 70.5 years) all underwent in-person lab visits in which a wearable sensor was placed on each foot and one around the lower back and the participant asked to perform walking and chair stand tests. The latter involved standing from a seated position as quickly as possible without using the arms five times, while the former involved walking 28 meters in two laps of a 7-meter path defined by two cones. These tests were repeated twice.
Participants were then given the equipment to repeat these tests at home; this included the three sensors, a tablet computer, and chair and cones. The home assessments were conducted via video conferencing, with the researchers reminding how to place the sensors correctly. The walking and chair stand tests were then each performed four times: Twice in a row and then a 15-minute rest period before being performed twice in a row again.
The researchers collected participants’ feedback about the process on questionnaires and Likert scales that showed an overall positive experience for the remote home visit, with the median rating being “very likely” to participate in another home visit and that the time commitment required was “very manageable.”
Good correlation found
To determine the correlation and the test-retest reliability of the data obtained during the repeated home tasks, Mr. Rose and collaborators used Pearson’s correlation R2 and the intra-class correlation coefficients (ICC).
ICCs for various gait and chair stand variables obtained with the sensors were between 0.85 and 0.96 for the test-retest reliability during the remote home visit, and R2 ranged between 0.81 and 0.95. Variables include stance, cadence (steps per minute), step duration and length, speed, and chair stand duration.
With regard to the agreement between the home versus lab results, ICCs ranged between 0.63 and 0.9.
“There were some logistical and technological challenges with the approach,” Mr. Rose conceded. “Despite written and verbal instructions, 2 of the 20 participants ended up having gait data that was unusable in the home visit.”
Another limitation is that the study population, while “representative,” contained a higher number of individuals than the general population who identified as being White (95%) and female (85%), and 90% had a college degree.
“Individuals typically representative of an OA population were generally accepting and willing to participate in remote visits showing the feasibility of our approach,” Mr. Rose said.
“We need to determine the responsiveness of gait and chair stand outcomes from wearable sensors at home to change over time.”
The study was sponsored by Boston University with funding from Pfizer and Eli Lilly. The researchers used the OPAL inertial sensor (APDM Wearable Technologies) in the study. Mr. Rose made no personal disclosures. Four of his collaborators were employees of Pfizer and one is an employee of Eli Lilly & Company, all with stock or stock options.
Remote gait assessment in people with knee osteoarthritis using wearable sensors appears reliable but yields results slightly different from those achieved in the laboratory, researchers from Boston University have found.
As reported at the OARSI 2022 World Congress, there was “good to excellent reliability” in repeated measures collected by patients at home while being instructed via video teleconferencing.
Agreement was “moderate to excellent” when the findings were compared with those recorded in the lab, Michael J. Rose of Boston University reported at the congress, sponsored by the Osteoarthritis Research Society International.
“People walked faster and stood up faster in the lab,” Mr. Rose said. “Later we found that the difference in gait speed was statistically significant between the lab and home environment.”
This has been suggested previously and implies that data collected at home may have “greater ecological validity,” he observed.
Accelerated adoption of telehealth
Assessing how well someone walks or can stand from a seated position are well known and important assessments in knee OA, but these have but have traditionally only been done in large and expensive gait labs, Mr. Rose said.
Wearable technologies, such as the ones used in the study he presented, could help move these assessments out into the community. This is particularly timely considering the increased adoption of telehealth practices during the COVID-19 pandemic.
To look at the reliability measurements obtained via wearable sensors versus lab assessments, Mr. Rose and associates set up a substudy within a larger ongoing, single-arm trial looking at the use of digital assessments to measure the efficacy of an exercise intervention in reducing knee pain and improving knee function.
For inclusion in the main trial (n = 60), and hence the substudy (n = 20), participants had to have physician-diagnosed knee OA, be 50 years of age or older, have a body mass index of 40 kg/m2 or lower, be able to walk at for a least 20 minutes, and have a score of three or higher on the Knee Injury and Osteoarthritis Outcome Score pain subscale for weight-bearing items.
Acceptance of in-lab versus home testing
The substudy participants (mean age, 70.5 years) all underwent in-person lab visits in which a wearable sensor was placed on each foot and one around the lower back and the participant asked to perform walking and chair stand tests. The latter involved standing from a seated position as quickly as possible without using the arms five times, while the former involved walking 28 meters in two laps of a 7-meter path defined by two cones. These tests were repeated twice.
Participants were then given the equipment to repeat these tests at home; this included the three sensors, a tablet computer, and chair and cones. The home assessments were conducted via video conferencing, with the researchers reminding how to place the sensors correctly. The walking and chair stand tests were then each performed four times: Twice in a row and then a 15-minute rest period before being performed twice in a row again.
The researchers collected participants’ feedback about the process on questionnaires and Likert scales that showed an overall positive experience for the remote home visit, with the median rating being “very likely” to participate in another home visit and that the time commitment required was “very manageable.”
Good correlation found
To determine the correlation and the test-retest reliability of the data obtained during the repeated home tasks, Mr. Rose and collaborators used Pearson’s correlation R2 and the intra-class correlation coefficients (ICC).
ICCs for various gait and chair stand variables obtained with the sensors were between 0.85 and 0.96 for the test-retest reliability during the remote home visit, and R2 ranged between 0.81 and 0.95. Variables include stance, cadence (steps per minute), step duration and length, speed, and chair stand duration.
With regard to the agreement between the home versus lab results, ICCs ranged between 0.63 and 0.9.
“There were some logistical and technological challenges with the approach,” Mr. Rose conceded. “Despite written and verbal instructions, 2 of the 20 participants ended up having gait data that was unusable in the home visit.”
Another limitation is that the study population, while “representative,” contained a higher number of individuals than the general population who identified as being White (95%) and female (85%), and 90% had a college degree.
“Individuals typically representative of an OA population were generally accepting and willing to participate in remote visits showing the feasibility of our approach,” Mr. Rose said.
“We need to determine the responsiveness of gait and chair stand outcomes from wearable sensors at home to change over time.”
The study was sponsored by Boston University with funding from Pfizer and Eli Lilly. The researchers used the OPAL inertial sensor (APDM Wearable Technologies) in the study. Mr. Rose made no personal disclosures. Four of his collaborators were employees of Pfizer and one is an employee of Eli Lilly & Company, all with stock or stock options.
Remote gait assessment in people with knee osteoarthritis using wearable sensors appears reliable but yields results slightly different from those achieved in the laboratory, researchers from Boston University have found.
As reported at the OARSI 2022 World Congress, there was “good to excellent reliability” in repeated measures collected by patients at home while being instructed via video teleconferencing.
Agreement was “moderate to excellent” when the findings were compared with those recorded in the lab, Michael J. Rose of Boston University reported at the congress, sponsored by the Osteoarthritis Research Society International.
“People walked faster and stood up faster in the lab,” Mr. Rose said. “Later we found that the difference in gait speed was statistically significant between the lab and home environment.”
This has been suggested previously and implies that data collected at home may have “greater ecological validity,” he observed.
Accelerated adoption of telehealth
Assessing how well someone walks or can stand from a seated position are well known and important assessments in knee OA, but these have but have traditionally only been done in large and expensive gait labs, Mr. Rose said.
Wearable technologies, such as the ones used in the study he presented, could help move these assessments out into the community. This is particularly timely considering the increased adoption of telehealth practices during the COVID-19 pandemic.
To look at the reliability measurements obtained via wearable sensors versus lab assessments, Mr. Rose and associates set up a substudy within a larger ongoing, single-arm trial looking at the use of digital assessments to measure the efficacy of an exercise intervention in reducing knee pain and improving knee function.
For inclusion in the main trial (n = 60), and hence the substudy (n = 20), participants had to have physician-diagnosed knee OA, be 50 years of age or older, have a body mass index of 40 kg/m2 or lower, be able to walk at for a least 20 minutes, and have a score of three or higher on the Knee Injury and Osteoarthritis Outcome Score pain subscale for weight-bearing items.
Acceptance of in-lab versus home testing
The substudy participants (mean age, 70.5 years) all underwent in-person lab visits in which a wearable sensor was placed on each foot and one around the lower back and the participant asked to perform walking and chair stand tests. The latter involved standing from a seated position as quickly as possible without using the arms five times, while the former involved walking 28 meters in two laps of a 7-meter path defined by two cones. These tests were repeated twice.
Participants were then given the equipment to repeat these tests at home; this included the three sensors, a tablet computer, and chair and cones. The home assessments were conducted via video conferencing, with the researchers reminding how to place the sensors correctly. The walking and chair stand tests were then each performed four times: Twice in a row and then a 15-minute rest period before being performed twice in a row again.
The researchers collected participants’ feedback about the process on questionnaires and Likert scales that showed an overall positive experience for the remote home visit, with the median rating being “very likely” to participate in another home visit and that the time commitment required was “very manageable.”
Good correlation found
To determine the correlation and the test-retest reliability of the data obtained during the repeated home tasks, Mr. Rose and collaborators used Pearson’s correlation R2 and the intra-class correlation coefficients (ICC).
ICCs for various gait and chair stand variables obtained with the sensors were between 0.85 and 0.96 for the test-retest reliability during the remote home visit, and R2 ranged between 0.81 and 0.95. Variables include stance, cadence (steps per minute), step duration and length, speed, and chair stand duration.
With regard to the agreement between the home versus lab results, ICCs ranged between 0.63 and 0.9.
“There were some logistical and technological challenges with the approach,” Mr. Rose conceded. “Despite written and verbal instructions, 2 of the 20 participants ended up having gait data that was unusable in the home visit.”
Another limitation is that the study population, while “representative,” contained a higher number of individuals than the general population who identified as being White (95%) and female (85%), and 90% had a college degree.
“Individuals typically representative of an OA population were generally accepting and willing to participate in remote visits showing the feasibility of our approach,” Mr. Rose said.
“We need to determine the responsiveness of gait and chair stand outcomes from wearable sensors at home to change over time.”
The study was sponsored by Boston University with funding from Pfizer and Eli Lilly. The researchers used the OPAL inertial sensor (APDM Wearable Technologies) in the study. Mr. Rose made no personal disclosures. Four of his collaborators were employees of Pfizer and one is an employee of Eli Lilly & Company, all with stock or stock options.
FROM OARSI 2022
OARSI sets sights on classifying early-stage knee OA
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
FROM OARSI 2022
Majority of pandemic pediatric visits managed with telemedicine
Approximately two-thirds of pediatric acute care concerns managed in telemedicine visits required no additional visits or follow-up, based on data from more than 600 visits.
The increase in use of telemedicine during the first year of the COVID-19 pandemic enabled access to care and connection to doctors for many pediatric patients, said Kristina Kissiova, MD, of Children’s National Health System, Washington, and colleagues. Some advantages of telemedicine include enhanced medical homes, reduced health care costs, and less crowding and wait time for patients in offices and emergency departments; however, the optimal use of telemedicine for acute primary care has not been examined, they said.
In a study presented at the annual meeting of the Pediatric Academic Societies, the researchers conducted a retrospective chart review of 638 acute care telemedicine visits conducted by 21 health care providers at a single practice in Washington in October 2020 and November 2020. Approximately half of the patients were male, 65% were white, and 89% had commercial insurance. The most common age group was 6-12 years (23%), followed by 2-3 years (16%), 3-6 years (15%), and 12-18 years (14%).
The primary outcome was the number and nature of visits completed via telemedicine without the need for referral or a subsequent in-person visit. Telemedicine visits for well-child checks and follow-up visits were excluded.
Overall, 60% of the visits (384 of 638) were completed over telemedicine with no need for additional visits or referrals. The most common acute complaints were upper respiratory infections, dermatologic issues, gastrointestinal issues, COVID-19 related issues, and fever (18.7%, 16.3%, 12.9%, 11.9%, and 10.3%, respectively).
Of these, dermatologic and GI concerns were most often completed via telemedicine (93.3% and 81.7%, respectively), while upper respiratory tract infections and fever issues were the least likely to be completed via telemedicine (22.7% and 13.6%), mainly because of the need to report for in-person COVID-19 testing, the researchers said.
Among other less common chief complaints, 100% of breathing concerns, behavior/mental health concerns, and head trauma or falls were addressed via telemedicine without additional referrals or follow-up visits. In addition, 90.9% of urgent care or emergency department follow-ups, 88.9% of ear concerns, and 87.5% of eye concerns were completely resolved via telemedicine visits.
Overall, 3% of patients who were not referred after a telemedicine visit presented in person for worsening symptoms. Of these who were referred after a telemedicine visit, 90% were seen in person within 48 hours.
The study findings were limited by the inclusion of data from only a single center. However, “These early findings provide insight into the utility of telehealth in the primary care setting for a broad array of urgent concerns,” the researchers concluded.
Pandemic propelled telemedicine to improve patient care
The widespread adoption of telemedicine in primary care has been a beneficial side effect of the COVID-19 pandemic, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“Toward the end of World War II and in the push to form the United Nations, Winston Churchill was credited with the saying, ‘Never let a good crisis go to waste,’” said Dr. Joos, who was not connected with the study.
“As awful as this pandemic has been, it has propelled health care delivery at an unprecedented pace into the digital age,” he noted.
The current study is important because it highlights the number of complaints that can be successfully resolved through telemedicine, offering patients and families quicker access and more options for care, Dr. Joos said.
“I feel that giving patients and families an open choice for either telemedicine or in-person visits improves the likelihood that the issue will be resolved efficiently and satisfactorily with fewer visits,” he added.
Approximately two-thirds of pediatric acute care concerns managed in telemedicine visits required no additional visits or follow-up, based on data from more than 600 visits.
The increase in use of telemedicine during the first year of the COVID-19 pandemic enabled access to care and connection to doctors for many pediatric patients, said Kristina Kissiova, MD, of Children’s National Health System, Washington, and colleagues. Some advantages of telemedicine include enhanced medical homes, reduced health care costs, and less crowding and wait time for patients in offices and emergency departments; however, the optimal use of telemedicine for acute primary care has not been examined, they said.
In a study presented at the annual meeting of the Pediatric Academic Societies, the researchers conducted a retrospective chart review of 638 acute care telemedicine visits conducted by 21 health care providers at a single practice in Washington in October 2020 and November 2020. Approximately half of the patients were male, 65% were white, and 89% had commercial insurance. The most common age group was 6-12 years (23%), followed by 2-3 years (16%), 3-6 years (15%), and 12-18 years (14%).
The primary outcome was the number and nature of visits completed via telemedicine without the need for referral or a subsequent in-person visit. Telemedicine visits for well-child checks and follow-up visits were excluded.
Overall, 60% of the visits (384 of 638) were completed over telemedicine with no need for additional visits or referrals. The most common acute complaints were upper respiratory infections, dermatologic issues, gastrointestinal issues, COVID-19 related issues, and fever (18.7%, 16.3%, 12.9%, 11.9%, and 10.3%, respectively).
Of these, dermatologic and GI concerns were most often completed via telemedicine (93.3% and 81.7%, respectively), while upper respiratory tract infections and fever issues were the least likely to be completed via telemedicine (22.7% and 13.6%), mainly because of the need to report for in-person COVID-19 testing, the researchers said.
Among other less common chief complaints, 100% of breathing concerns, behavior/mental health concerns, and head trauma or falls were addressed via telemedicine without additional referrals or follow-up visits. In addition, 90.9% of urgent care or emergency department follow-ups, 88.9% of ear concerns, and 87.5% of eye concerns were completely resolved via telemedicine visits.
Overall, 3% of patients who were not referred after a telemedicine visit presented in person for worsening symptoms. Of these who were referred after a telemedicine visit, 90% were seen in person within 48 hours.
The study findings were limited by the inclusion of data from only a single center. However, “These early findings provide insight into the utility of telehealth in the primary care setting for a broad array of urgent concerns,” the researchers concluded.
Pandemic propelled telemedicine to improve patient care
The widespread adoption of telemedicine in primary care has been a beneficial side effect of the COVID-19 pandemic, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“Toward the end of World War II and in the push to form the United Nations, Winston Churchill was credited with the saying, ‘Never let a good crisis go to waste,’” said Dr. Joos, who was not connected with the study.
“As awful as this pandemic has been, it has propelled health care delivery at an unprecedented pace into the digital age,” he noted.
The current study is important because it highlights the number of complaints that can be successfully resolved through telemedicine, offering patients and families quicker access and more options for care, Dr. Joos said.
“I feel that giving patients and families an open choice for either telemedicine or in-person visits improves the likelihood that the issue will be resolved efficiently and satisfactorily with fewer visits,” he added.
Approximately two-thirds of pediatric acute care concerns managed in telemedicine visits required no additional visits or follow-up, based on data from more than 600 visits.
The increase in use of telemedicine during the first year of the COVID-19 pandemic enabled access to care and connection to doctors for many pediatric patients, said Kristina Kissiova, MD, of Children’s National Health System, Washington, and colleagues. Some advantages of telemedicine include enhanced medical homes, reduced health care costs, and less crowding and wait time for patients in offices and emergency departments; however, the optimal use of telemedicine for acute primary care has not been examined, they said.
In a study presented at the annual meeting of the Pediatric Academic Societies, the researchers conducted a retrospective chart review of 638 acute care telemedicine visits conducted by 21 health care providers at a single practice in Washington in October 2020 and November 2020. Approximately half of the patients were male, 65% were white, and 89% had commercial insurance. The most common age group was 6-12 years (23%), followed by 2-3 years (16%), 3-6 years (15%), and 12-18 years (14%).
The primary outcome was the number and nature of visits completed via telemedicine without the need for referral or a subsequent in-person visit. Telemedicine visits for well-child checks and follow-up visits were excluded.
Overall, 60% of the visits (384 of 638) were completed over telemedicine with no need for additional visits or referrals. The most common acute complaints were upper respiratory infections, dermatologic issues, gastrointestinal issues, COVID-19 related issues, and fever (18.7%, 16.3%, 12.9%, 11.9%, and 10.3%, respectively).
Of these, dermatologic and GI concerns were most often completed via telemedicine (93.3% and 81.7%, respectively), while upper respiratory tract infections and fever issues were the least likely to be completed via telemedicine (22.7% and 13.6%), mainly because of the need to report for in-person COVID-19 testing, the researchers said.
Among other less common chief complaints, 100% of breathing concerns, behavior/mental health concerns, and head trauma or falls were addressed via telemedicine without additional referrals or follow-up visits. In addition, 90.9% of urgent care or emergency department follow-ups, 88.9% of ear concerns, and 87.5% of eye concerns were completely resolved via telemedicine visits.
Overall, 3% of patients who were not referred after a telemedicine visit presented in person for worsening symptoms. Of these who were referred after a telemedicine visit, 90% were seen in person within 48 hours.
The study findings were limited by the inclusion of data from only a single center. However, “These early findings provide insight into the utility of telehealth in the primary care setting for a broad array of urgent concerns,” the researchers concluded.
Pandemic propelled telemedicine to improve patient care
The widespread adoption of telemedicine in primary care has been a beneficial side effect of the COVID-19 pandemic, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“Toward the end of World War II and in the push to form the United Nations, Winston Churchill was credited with the saying, ‘Never let a good crisis go to waste,’” said Dr. Joos, who was not connected with the study.
“As awful as this pandemic has been, it has propelled health care delivery at an unprecedented pace into the digital age,” he noted.
The current study is important because it highlights the number of complaints that can be successfully resolved through telemedicine, offering patients and families quicker access and more options for care, Dr. Joos said.
“I feel that giving patients and families an open choice for either telemedicine or in-person visits improves the likelihood that the issue will be resolved efficiently and satisfactorily with fewer visits,” he added.
FROM PAS 2022
Depression strikes more than half of obese adolescents
More than 50% of obese adolescents met criteria for depression, which also was associated with several components of metabolic syndrome, based on data from 160 individuals.
Previous research shows that the metabolic consequences of obesity are worsened with the coexistence of depression in adults, but a similar relationship in obese adolescents has not been explored, according to Nisha Gupta, a medical student at the University of Texas Health Science Center, Houston, and colleagues.
“This relationship is explained by an overactive stress response and adoption of unhealthy lifestyle habits,” both of which increased during the COVID-19 pandemic, the researchers noted in their abstract.
In a study presented at the Pediatric Academic Societies annual meeting, the researchers reviewed data from 160 obese adolescents seen at a pediatric weight management clinic between July 1, 2018, and Dec. 3, 2021. The data included anthropometric, clinical, and laboratory information. Depression was assessed using the Patient Health Questionnaire–9 (PHQ-9). The goal of the study was to compare the prevalence of metabolic syndrome components in obese youth with and without diagnosed depression.
Overall, 46% of the patients had PHQ-9 scores less than 5, which was defined as no clinically significant depression. A total of 26% had current or prior diagnoses of depression, and 25% met the criteria for moderate to severe depression, with PHQ-9 scores of 10 or higher. Notably, 18% of individuals with no prior history of depression met criteria for moderate to severe depression, the researchers wrote.
Teens who reported daytime fatigue or trouble sleeping, and those who reported eating out seven or more times a week had higher scores than those without these reports.
In laboratory analyses, higher PHQ-9 scores were significantly associated with increasing weight, body mass index, body fat percentage, diastolic blood pressure, and fasting blood insulin (P < .02 for all).
The study findings were limited by the relatively small sample size, the researchers noted. However, the results suggest that depression is common, but often underdiagnosed in obese adolescents, and depression screening should be part of obesity management.
Study highlights need to screen
The current study is important because of the overall increase in obesity in the United States, which extends to children and teens, Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, said in an interview.
“With skyrocketing rates of obesity among children and teens over the last decades, we are seeing more ‘adult’ diseases seep into the younger ages, including type 2 diabetes, high blood pressure and now, depression,” he said.
“The results are a wake-up call for the need for better system-wide prevention and management of obesity in adolescents and the importance of screening and managing depression in obese teenagers,” he emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
More than 50% of obese adolescents met criteria for depression, which also was associated with several components of metabolic syndrome, based on data from 160 individuals.
Previous research shows that the metabolic consequences of obesity are worsened with the coexistence of depression in adults, but a similar relationship in obese adolescents has not been explored, according to Nisha Gupta, a medical student at the University of Texas Health Science Center, Houston, and colleagues.
“This relationship is explained by an overactive stress response and adoption of unhealthy lifestyle habits,” both of which increased during the COVID-19 pandemic, the researchers noted in their abstract.
In a study presented at the Pediatric Academic Societies annual meeting, the researchers reviewed data from 160 obese adolescents seen at a pediatric weight management clinic between July 1, 2018, and Dec. 3, 2021. The data included anthropometric, clinical, and laboratory information. Depression was assessed using the Patient Health Questionnaire–9 (PHQ-9). The goal of the study was to compare the prevalence of metabolic syndrome components in obese youth with and without diagnosed depression.
Overall, 46% of the patients had PHQ-9 scores less than 5, which was defined as no clinically significant depression. A total of 26% had current or prior diagnoses of depression, and 25% met the criteria for moderate to severe depression, with PHQ-9 scores of 10 or higher. Notably, 18% of individuals with no prior history of depression met criteria for moderate to severe depression, the researchers wrote.
Teens who reported daytime fatigue or trouble sleeping, and those who reported eating out seven or more times a week had higher scores than those without these reports.
In laboratory analyses, higher PHQ-9 scores were significantly associated with increasing weight, body mass index, body fat percentage, diastolic blood pressure, and fasting blood insulin (P < .02 for all).
The study findings were limited by the relatively small sample size, the researchers noted. However, the results suggest that depression is common, but often underdiagnosed in obese adolescents, and depression screening should be part of obesity management.
Study highlights need to screen
The current study is important because of the overall increase in obesity in the United States, which extends to children and teens, Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, said in an interview.
“With skyrocketing rates of obesity among children and teens over the last decades, we are seeing more ‘adult’ diseases seep into the younger ages, including type 2 diabetes, high blood pressure and now, depression,” he said.
“The results are a wake-up call for the need for better system-wide prevention and management of obesity in adolescents and the importance of screening and managing depression in obese teenagers,” he emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
More than 50% of obese adolescents met criteria for depression, which also was associated with several components of metabolic syndrome, based on data from 160 individuals.
Previous research shows that the metabolic consequences of obesity are worsened with the coexistence of depression in adults, but a similar relationship in obese adolescents has not been explored, according to Nisha Gupta, a medical student at the University of Texas Health Science Center, Houston, and colleagues.
“This relationship is explained by an overactive stress response and adoption of unhealthy lifestyle habits,” both of which increased during the COVID-19 pandemic, the researchers noted in their abstract.
In a study presented at the Pediatric Academic Societies annual meeting, the researchers reviewed data from 160 obese adolescents seen at a pediatric weight management clinic between July 1, 2018, and Dec. 3, 2021. The data included anthropometric, clinical, and laboratory information. Depression was assessed using the Patient Health Questionnaire–9 (PHQ-9). The goal of the study was to compare the prevalence of metabolic syndrome components in obese youth with and without diagnosed depression.
Overall, 46% of the patients had PHQ-9 scores less than 5, which was defined as no clinically significant depression. A total of 26% had current or prior diagnoses of depression, and 25% met the criteria for moderate to severe depression, with PHQ-9 scores of 10 or higher. Notably, 18% of individuals with no prior history of depression met criteria for moderate to severe depression, the researchers wrote.
Teens who reported daytime fatigue or trouble sleeping, and those who reported eating out seven or more times a week had higher scores than those without these reports.
In laboratory analyses, higher PHQ-9 scores were significantly associated with increasing weight, body mass index, body fat percentage, diastolic blood pressure, and fasting blood insulin (P < .02 for all).
The study findings were limited by the relatively small sample size, the researchers noted. However, the results suggest that depression is common, but often underdiagnosed in obese adolescents, and depression screening should be part of obesity management.
Study highlights need to screen
The current study is important because of the overall increase in obesity in the United States, which extends to children and teens, Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, said in an interview.
“With skyrocketing rates of obesity among children and teens over the last decades, we are seeing more ‘adult’ diseases seep into the younger ages, including type 2 diabetes, high blood pressure and now, depression,” he said.
“The results are a wake-up call for the need for better system-wide prevention and management of obesity in adolescents and the importance of screening and managing depression in obese teenagers,” he emphasized.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.
FROM PAS 2022
Preop nivolumab plus chemo ‘a quantum leap’ in NSCLC therapy
NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further
The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.
Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.
“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.
The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.
Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”
“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”
Importance of Neoadjuvant Immunotherapy
New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.
Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).
In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).
Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.
“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
Neoadjuvant slow to catch on
About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.
Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.
The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.
In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.
In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.
“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”
Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.
“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
Fears of delaying surgery
In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.
“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”
In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
CheckMate 816 details
In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.
After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.
At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.
Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.
In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.
The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.
The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.
Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.
CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further
The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.
Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.
“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.
The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.
Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”
“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”
Importance of Neoadjuvant Immunotherapy
New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.
Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).
In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).
Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.
“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
Neoadjuvant slow to catch on
About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.
Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.
The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.
In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.
In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.
“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”
Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.
“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
Fears of delaying surgery
In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.
“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”
In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
CheckMate 816 details
In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.
After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.
At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.
Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.
In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.
The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.
The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.
Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.
CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – For patients with resectable non–small cell lung cancer (NSCLC), further
The combination resulted in significantly longer event-free survival and a 14-fold greater chance of having a pathological complete response compared with chemotherapy alone.
Adding immunotherapy (IO) to chemotherapy in the neoadjuvant setting represents “a quantum leap in lung cancer therapy,” commented David P. Carbone, MD, PhD, director of the James Thoracic Center at Ohio State University, Columbus.
“Combining IO with surgery I think is a new standard of care and will almost certainly improve overall survival [OS] in early-stage disease, for the first time in decades, in my entire career,” he said while discussing the new data at the annual meeting of the American Association for Cancer Research.
The data come from the phase 3 CheckMate 816 study, an open-label trial involving patients with stage IB-IIIA resectable NSCLC. The study was published in the New England Journal of Medicine to coincide with the presentation.
Results from this trial were the basis of the Food and Drug Administration’s recent approval of neoadjuvant therapy with nivolumab (Opdivo) and platinum-based chemotherapy in this population, which one expert described as “a turning point in how we treat resectable NSCLC.”
“Neoadjuvant IO has multiple theoretical advantages of over adjuvant IO,” commented Dr. Carbone. “CheckMate 816 suggests that practice will prove this theory correct.”
Importance of Neoadjuvant Immunotherapy
New details of the results were presented at the meeting by Nicolas Girard, MD, from Institut Curie in Paris.
Among 358 patients in the trial, the median event-free survival (EFS) was 31.6 months for patients randomly assigned to the combination of the immune checkpoint inhibitor nivolumab and platinum-base chemotherapy, compared with 20.8 months for patients assigned to chemotherapy alone. This translated into a hazard ratio for disease recurrence, progression, or death of 0.63 (P = .005).
In addition, 24% of patients assigned to the nivolumab plus chemotherapy arm had a pathological complete response (pCR) to neoadjuvant therapy, compared with only 2.2% of those assigned to chemotherapy alone (P < .001).
Dr. Girard said the study provided important clues to the importance of neoadjuvant therapy for improving objective responses.
“Event-free survival was improved in patients with a pathological complete response, compared with those without, suggesting pCR is a surrogate endpoint for long-term outcomes in resectable non–small cell lung cancer, and this is the first time [this has been shown] in a randomized, phase 3 study,” he said.
Neoadjuvant slow to catch on
About one -fourth of all patients who are diagnosed with NSCLC have resectable disease, Dr. Girard and colleagues noted. However, 30%-55% of patients who undergo surgery with curative intent ultimately experience recurrence and die from their disease.
Neoadjuvant therapy may improve chances for complete resection and prevent or delay recurrence after surgery, but the absolute difference in 5-year recurrence-free survival and OS with neoadjuvant chemotherapy alone is only about 6%, they noted.
The new results suggest that adding neoadjuvant immunotherapy to chemotherapy will improve upon this, although so far, the OS data from this trial are immature.
In an interim analysis, the median OS rate was 83% at 2 years for patients treated with nivolumab plus chemotherapy, compared with 71% for patients treated with chemotherapy alone. The published results show a significant improvement in the two primary endpoints – EFS and pCR.
In an editorial accompanying the study, Christine M. Lovly, MD, PhD, from the Vanderbilt-Ingram Cancer Center at Vanderbilt University in Nashville, Tenn., commented that the results of the trial are expected to change practice.
“However, several issues remain to be addressed,” she wrote. “First, is a pathological complete response predictive of event-free survival? Can event-free survival be used as a surrogate endpoint for overall survival? Second, although not mandated for this trial, approximately 20% of the patients received postoperative therapy. Is adjuvant therapy necessary? What criteria should be used to select patients to receive adjuvant therapy?”
Dr. Lovly also pointed out that patients with tumors harboring mutations in the genes EGFR or ALK were excluded from the trial.
“Therefore, implementation of neoadjuvant therapies requires biomarker testing for patients with early-stage disease at the time of diagnosis, a considerable alteration in the routine practice of lung-cancer medicine,” she wrote.
Fears of delaying surgery
In an interview, Upal Basu Roy, PhD, MPH, executive director of research at the LUNGevity Foundation, who was not involved in the study, gave a reason why neoadjuvant therapy is not more widely prescribed for patients with resectable NSCLC.
“Clinicians are always scared, and I think patients are as well, that giving a treatment before surgery would delay surgery,” he said. “When patients are diagnosed with lung cancer and they’re told that surgery offers the potential of cure and then hear that you’re giving them a treatment before surgery and that treatment may potentially delay surgery, that is a huge source of anxiety.”
In addition, clinicians until recently were unsure about which patients were most likely to benefit from neoadjuvant therapy when the only option was chemotherapy, “but that’s changing, obviously, with the recent approval of neoadjuvant nivolumab through CheckMate 816,” he said.
CheckMate 816 details
In the CheckMate 816 study, investigators enrolled patients with newly diagnosed resectable NSCLC (stage IB-IIIA) who had good performance status and no known sensitizing EGFR mutations or ALK alterations.
After stratification by stage, programmed death–1 status, and sex, the team randomly assigned patients to receive either nivolumab 360 mg plus platinum-based chemotherapy every 3 weeks for a total of three cycles or chemotherapy alone.
At the end of neoadjuvant therapy, patients underwent radiologic restaging and surgery within 6 weeks. Patients could also receive optional adjuvant chemotherapy with or without radiotherapy.
Of the 179 patients in each arm, 176 received the assigned treatment. In all, 149 (83%) of those assigned to the combination had definitive surgery, as did 135 (75%) of those assigned to chemotherapy alone.
In addition, 35 patients (20%) of those assigned to nivolumab-chemo and 56 (32%) assigned to chemotherapy alone received adjuvant therapy.
The coprimary endpoints of EFS and pCR favored the combination, both in the overall population and across most subgroups, including patients younger than 65, men and women, Asian patients, those with stage IIIA disease, nonsquamous histology, current smokers and never-smokers, and patients with higher levels of PD–ligand 1 expression.
The rates of grade 3 or 4 treatment-related adverse events were similar between the groups, at 33.5% with the combination and 36.9% with chemotherapy alone.
Rates of adverse events leading to study discontinuation, treatment-related adverse events, and surgery-related adverse events were similar between the groups. There were two treatment-related deaths, both in the chemotherapy-alone arm.
CheckMate 816 was funded by Bristol-Myers Squibb (manufacturer of nivolumab). Girard has consulted for and has received grant support from Bristol-Myers Squibb and other companies. Dr. Carbone has consulted for Bristol-Myers Squibb and other companies. Dr. Lovly has consulted for various companies. Dr. Roy has received grants from Bristol-Myers Squibb to the LUNGevity Foundation.
A version of this article first appeared on Medscape.com.
AT AACR 2022
Made-to-order TILs effective against metastatic melanoma
NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents,
The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.
The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.
“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).
He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.
Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.
However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.
The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.
“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
Patient-derived product
Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.
Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
Details from clinical trial
At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.
These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.
Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.
After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.
Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.
The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.
All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.
The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.
“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.
The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
Remaining questions, next steps
Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.
“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.
Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.
Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.
The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents,
The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.
The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.
“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).
He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.
Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.
However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.
The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.
“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
Patient-derived product
Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.
Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
Details from clinical trial
At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.
These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.
Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.
After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.
Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.
The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.
All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.
The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.
“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.
The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
Remaining questions, next steps
Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.
“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.
Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.
Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.
The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.
A version of this article first appeared on Medscape.com.
NEW ORLEANS – In just over one-third of patients with metastatic melanoma who had experienced disease progression while receiving multiple prior lines of therapy, including immunotherapy and targeted agents,
The product, called lifileucel, is custom made for each patient and utilizes tumor-infiltrating lymphocytes (TILs) extracted from tumor lesions. This approach differs from other cell-based therapies, such as chimeric antigen receptor (CAR) T cell therapy, which utilizes T cells collected from the patient’s blood.
The new results come from a phase 2 trial conducted in 66 patients with previously treated unresectable or metastatic melanoma who received a single dose of the product. The objective response rate was 36.4%.
“Lifileucel has demonstrated efficacy and durability of response for patients with metastatic melanoma and represents a viable therapeutic option warranting further investigation,” commented Jason Alan Chesney, MD, PhD, from the James Graham Brown Cancer Center, the University of Louisville (Ky.).
He presented the new data at the virtual American Association for Cancer Research (AACR) Annual Meeting 2021.
Customized cell therapy with TILs has been explored for the treatment of melanoma for more than a decade. Some researchers have reported durable response in 25% of patients.
However, “generalizing TIL therapy has been hampered by the complex and really not absolutely defined process for generating cells,” commented Philip Greenberg, MD, professor and head of the program in immunology in the Clinical Research Division of the Fred Hutchinson Cancer Center, Seattle, who was the invited discussant.
The current study demonstrates that cell generation can be performed at a centralized facility that has the required technical expertise. The patient-specific products are then disseminated to multiple centers, he said. The study also demonstrates that TILs can be successfully generated from tumor sites other than skin or lymph nodes.
“Toxicity was, however, significant, although it was generally manageable, and it did occur early, generally within the first 2 weeks,” he noted.
Patient-derived product
Lifileucel is a tailor-made immunotherapy product created from melanoma tumor tissues resected from lesions in skin, lymph nodes, liver, lung, peritoneum, musculoskeletal system, breast, or other visceral organs. The cells are shipped to a central manufacturing facility, whre the TILs are isolated, cultured, expanded, and reinvigorated. The cells are then harvested and cryopreserved. The process takes about 22 days. The cryopreserved product is then shipped back to the treating facility.
Prior to receiving the expanded and rejuvenated TILs, patients undergo myeloablative conditioning with cyclophosphamide followed by fludarabine. The TILs are then delivered in a single infusion, followed by administration of up to six doses of interleukin-2 (IL-2).
Details from clinical trial
At the meeting, Dr. Chesney reported details on the 66 patients in the trial. They had metastatic melanoma that was progressing on treatment. The mean number of prior lines of therapy was 3.3. All of the patients had received prior anti–programmed cell death protein–1 (PD-1) or programmed cell death–ligand-1 (PD-L1) agents; 53 had received a cytotoxic T lymphocyte protein 4 (CTLA-4) inhibitor; and 15 had received a BRAF/MEK inhibitor.
These patients had a mean of six baseline target and nontarget lesions, and 28 patients had liver and/or brain metastases.
Just over a third of patients (24 of 66, 36.4%) had an objective response; three patients had a complete response; and 21 had a partial response. In addition, 29 patients had stable disease, and nine experienced disease progression. Four patients had not undergone the first assessment at the time of data cutoff.
After a median follow-up of 28.1 months, the median duration of response was not reached. It ranged from 2.2 to > 35.2 months.
Since the data cutoff in April 2020, reduction of tumor burden has occurred in 50 of 62 evaluable patients. Reductions in the target lesion sum of diameters has occurred in 11 patients. In one patient, a partial response converted to a complete response 24 months after infusion, Dr. Chesney noted.
The mean number of TILs infused was 27.3 billion (27.3 x 109). Appropriate amounts of TILs were manufactured from tumor samples acquired across all sites, and reductions in target lesion sum of diameter were seen across the range of TIL total cell doses.
All patients experienced at least one adverse event of any grade; all but two experienced grade 3 or 4 adverse events. Two patients died, one as a result of intra-abdominal hemorrhage considered possibly related to TIL therapy, and one from acute respiratory failure deemed not related to TILs.
The most common grade 3 or 4 adverse events were thrombocytopenia, anemia, febrile neutropenia, neutropenia, hypophosphatemia, and lymphopenia.
“The adverse event profile was manageable and was consistent with the underlying and the known profiles of the nonmyeloblative depletion regimen and IL-2,” Dr. Chesney said.
The decreasing frequency of adverse events over time reflects the potential benefit of the one-time infusion, and no new safety risks have been identified during more than 2 years of follow-up, he added.
Remaining questions, next steps
Dr. Greenberg commented that the one of the limitations of the study is that the investigators did not characterize the TIL product.
“Studies have predicted that there’s a particular type of cell, a stemlike T cell, that’s responsible for mediating the efficacy,” he commented. He referred to research from Steven Rosenberg, MD, PhD, and colleagues at the National Cancer Institute, where TILs were first used in 2002.
Dr. Greenberg also raised the question of whether high-dose IL-2 was required post infusion, given that the patients were lymphodepleted before receiving lifileucel.
Future steps for TIL therapy, he said, should include identification of biomarkers for success or failure; strategies to enhance generation and expansion of tumor-reactive T cells; postinfusion strategies, such as using vaccines and/or checkpoint inhibitors to increase therapeutic activity; genetic modifications to enhance the function of TILs in the tumor microenvironment; and research into other tumor types that may be effectively treated with TILs.
The study was supported by Iovance Biotherapeutics. Dr. Chesney has received research funding from Iovance and other companies and has consulted for Amgen and Replimune. Dr. Greenberg has served on scientific advisory boards, has received grant/research support, and owns stock in several companies that do not include Iovance.
A version of this article first appeared on Medscape.com.
AT AACR 2022